Variable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes.

Alu elements are non-autonomous Short INterspersed Elements (SINEs) derived from the 7SL RNA gene that are present at over one million copies in human genomic DNA. Alu mobilizes by a mechanism known as retrotransposition, which requires the Long INterspersed Element-1 (LINE-1) ORF2-encoded protein (ORF2p). Here, we demonstrate that HeLa strains differ in their capacity to support Alu retrotransposition. Human Alu elements retrotranspose efficiently in HeLa-HA and HeLa-CCL2 (Alu-permissive) strains, but not in HeLa-JVM or HeLa-H1 (Alu-nonpermissive) strains. A similar pattern of retrotransposition was observed for other 7SL RNA-derived SINEs and tRNA-derived SINEs. In contrast, mammalian LINE-1s, a zebrafish LINE, a human SINE-VNTR-Alu (SVA) element, and an L1 ORF1-containing mRNA can retrotranspose in all four HeLa strains. Using an in vitro reverse transcriptase-based assay, we show that Alu RNAs associate with ORF2p and are converted into cDNAs in both Alu-permissive and Alu-nonpermissive HeLa strains, suggesting that 7SL- and tRNA-derived SINEs use strategies to 'hijack' L1 ORF2p that are distinct from those used by SVA elements and ORF1-containing mRNAs. These data further suggest ORF2p associates with the Alu RNA poly(A) tract in both Alu-permissive and Alu-nonpermissive HeLa strains, but that Alu retrotransposition is blocked after this critical step in Alu-nonpermissive HeLa strains.

Arabidopsis leucine-rich repeat malectin receptor-like kinases regulate pollen-stigma interactions.

Flowering plants contain tightly controlled pollen-pistil interactions required for promoting intraspecific fertilization and preventing interspecific hybridizations. In Arabidopsis (Arabidopsis thaliana), several receptor kinases (RKs) are known to regulate the later stages of intraspecific pollen tube growth and ovular reception in the pistil, but less is known about RK regulation of the earlier stages. The Arabidopsis RECEPTOR-LIKE KINASE IN FLOWERS1 (RKF1)/RKF1-LIKE (RKFL) 1-3 cluster of 4 leucine-rich repeat malectin (LRR-MAL) RKs was previously found to function in the stigma to promote intraspecific pollen hydration. In this study, we tested additional combinations of up to 7 Arabidopsis LRR-MAL RK knockout mutants, including RKF1, RKFL1-3, LysM RLK1-INTERACTING KINASE1, REMORIN-INTERACTING RECEPTOR1, and NEMATODE-INDUCED LRR-RLK2. These LRR-MAL RKs were discovered to function in the female stigma to support intraspecific Arabidopsis pollen tube growth and to establish a prezygotic interspecific barrier against Capsella rubella pollen. Thus, this study uncovered additional biological functions for this poorly understood group of RKs in regulating the early stages of Arabidopsis sexual reproduction.

The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies. DESIGN: We used the KPC mouse model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent in vitro coculture assays, in vivo mouse and zebrafish tumorigenesis studies, and in silico database approaches were performed. RESULTS: Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC. CONCLUSIONS: This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.

A Label-Free Approach for Relative Spatial Quantitation of c-di-GMP in Microbial Biofilms.

Microbial biofilms represent an important lifestyle for bacteria and are dynamic three-dimensional structures. Cyclic dimeric guanosine monophosphate (c-di-GMP) is a ubiquitous signaling molecule that is known to be tightly regulated with biofilm processes. While measurements of global levels of c-di-GMP have proven valuable toward understanding the genetic control of c-di-GMP production, there is a need for tools to observe the local changes of c-di-GMP production in biofilm processes. We have developed a label-free method for the direct detection of c-di-GMP in microbial colony biofilms using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). We applied this method to the enteric pathogen Vibrio cholerae, the marine symbiont V. fischeri, and the opportunistic pathogen Pseudomonas aeruginosa PA14 and detected spatial and temporal changes in c-di-GMP signal that accompanied genetic alterations in factors that synthesize and degrade the compound. We further demonstrated how this method can be simultaneously applied to detect additional metabolites of interest from a single sample.

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. METHODS: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. RESULTS: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07). CONCLUSIONS: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

First record of ectoparasites (Phthiraptera and Acari) from the Andean condor (Vultur gryphus) in Colombia.

Several species of ectoparasites, including chewing lice and mites are closely associated with their hosts. The Andean condor (Vultur gryphus) is globally listed as vulnerable by the IUCN and its population has been steadily declining in recent decades suggesting a potential extinction of associated entomofauna. The purpose of this study was to record the species of ectoparasites infesting three individuals of Andean condor found dead in the 'Páramo del Almorzadero' Santander Department, Northeastern Colombia. One juvenile (male) and two adults (male and female) Andean condors received for necropsy were carefully examined for ectoparasite infestation. Specimens were collected and preserved in ethanol (70%) for taxonomic studies. Morphologic identification and morphometric records were made under light microscopy. Some specimens were also prepared for scanning electron microscopy and others were subjected to DNA extraction to amplify and obtain sequences of the cytochrome-C oxidase subunit I (COI) gene for phylogenetic analyses. Lice were collected from the juvenile condor and the adult female and identified as Falcolipeurus assesor (Phthiraptera: Ischnocera) in the juvenile condor (8 females, 19 males and 8 nymphs) and the adult (1 female); Colpocephalum trichosum (Phthiraptera: Amblycera) in the juvenile (19 females, 24 males and 1 nymph) and the adult (2 females, 2 males and 3 nymphs); and Cuculiphilus zonatus (Phthiraptera: Amblycera) in the juvenile (40 females, 43 males and 15 nymphs) and the adult (1 male and 2 nymphs). Moreover, one mite collected from the juvenile condor was identified as Ancyralges cathartinus (Acari: Astigmata) (1 female). Morphometric data was obtained for the adult stages of F. assesor (6 females and 13 males), C. trichosum (9 females and 9 males) and C. zonatus (10 females and 10 males). We obtained the first DNA sequences of COI for F. assessor, and C. trichosum, where phylogenetic tree analysis showed that F. assessor is more closely related to Falcolipeurus marginalis, and C. trichosum to Colpocephalum kelloggi. This represents the first record of parasites in Andean condor from Colombia and contributes to the knowledge of chewing lice and mites associated with an endemic and endangered bird species. Further studies on Andean condor ectoparasites should be focused on documenting host-parasite interactions and potential health impacts in these wild birds.

Varias especies de ectoparásitos, incluidos piojos masticadores y ácaros están estrechamente asociados a sus hospedadores. El cóndor andino (Vultur gryphus) está catalogado por la UICN como una especie vulnerable y su población ha ido disminuyendo constantemente en las últimas décadas, lo que sugiere una posible extinción de la entomofauna asociada. El propósito de este estudio fue registrar las especies de ectoparásitos infestando a tres individuos de cóndor andino encontrados muertos en el Páramo del Almorzadero, Departamento de Santander, Noreste de Colombia. Un cóndor andino juvenil (macho) y dos adultos (macho y hembra) recibidos para necropsia fueron examinados cuidadosamente para detectar infestación por ectoparásitos. Los especímenes fueron recolectados y preservados en etanol (70%) para estudios taxonómicos. La identificación morfológica y los registros morfométricos se ejecutaron bajo microscopía óptica. Algunas muestras también se prepararon para microscopía electrónica de barrido y otras se sometieron a extracción de ADN para amplificar y obtener secuencias del gen de la subunidad I (COI) del citocromo­C oxidasa para análisis filogenéticos. Los piojos recolectados del cóndor juvenil y de la hembra adulta se identificaron como Falcolipeurus assesor (Phthiraptera: Ischnocera) en el cóndor juvenil (8 hembras, 19 machos y 8 ninfas) y en el adulto (1 hembra); Colpocephalum trichosum (Phthiraptera: Amblycera) en el juvenil (19 hembras, 24 machos y 1 ninfa) y en el adulto (2 hembras, 2 machos y 3 ninfas); y Cuculiphilus zonatus (Phthiraptera: Amblycera) en el juvenil (40 hembras, 43 machos y 15 ninfas) y en el adulto (1 macho y 2 ninfas). Además, un ácaro recolectado del cóndor juvenil fue identificado como Ancyralges cathartinus (Acari: Astigmata) (1 hembra). Se obtuvieron datos morfométricos para los estadios adultos de F. assesor (6 hembras y 13 machos), C. trichosum (9 hembras y 9 machos) y C. zonatus (10 hembras y 10 machos). Secuencias de ADN basadas en COI para las especies F. assesor y C. trichosum son reportadas por la primera vez, donde el análisis filogenetico mostró que F. assesor está más estrechamente relacionado con Falcolipeurus marginalis y C. trichosum con Colpocephalum kelloggi. Este representa el primer registro de parásitos en cóndor andino de Colombia y contribuye al conocimiento de los piojos masticadores y ácaros asociados a una especie de ave endémica de los Andes y en peligro de extinción. Otros estudios sobre los ectoparásitos del cóndor andino deberían centrarse en documentar las interacciones hospedador­parásito y los posibles impactos en la salud de estas aves silvestres.

Immunohistochemical, functional, and anatomical evaluation of patients with idiopathic epiretinal membrane.

PURPOSE: The main purpose of this study was to perform an immunohistochemical, functional, and anatomical evaluation of patients with idiopathic epiretinal membrane (ERM). METHODS: Twenty-four specimens of idiopathic ERM from 24 consecutive patients who underwent 23 G pars plana vitrectomy for ERM and internal limiting membrane (ILM) peeling at the San Juan University Hospital in Alicante (Spain) in 2019 were analyzed. All patients underwent a complete ophthalmological examination including measurement of best corrected visual acuity (BCVA) and macular analysis by spectral-domain optical coherence tomography (SD-OCT) at the time of diagnosis and 3 months after surgery. Specific glial fibrillar acid protein antibodies (GFAP) and S100 calcium-binding protein ß (S100ß) immunostaining markers were used to identify the macroglial component of the ERM, Müller cells, and astrocytes. Ionized calcium-binding adapter molecule 1 protein (Iba1) antibodies were used as specific markers for inflammatory cells, such as microglia and macrophages. RESULTS: Mean preoperative BCVA measured with Snellen chart was 0.3 and 0.6 preoperatively and at 3 months after surgery, respectively. SD-OCT identified 15 patients (62.5%) with a disruption of the outer retinal hyperreflective bands. The immunohistochemical study showed the presence of Müller cells in almost all cases (91.6%), as well of abundant microglia and macrophages. Microglia and macrophages were more frequently present in earlier stages of ERM. Microglia were present in ERM independently of the outer retinal hyperreflective bands integrity as measured by SD-OCT. A greater presence of macrophages was found in those ERMs with no outer retinal hyperreflective band disruption. CONCLUSIONS: Müller cells seem to be the most frequent cell group in ERMs, with also presence of microglia cells and macrophages. Astrocytes were more frequently found in early stages of ERMs. Microglia and macrophages were most frequent in ERMs with early stage (1, 2, or 3) than in advanced stages (4).

Would shared decision-making be useful in breast cancer screening programmes? A qualitative study using focus group discussions to gather evidence from French women with different socioeconomic backgrounds.

BACKGROUND: To inform the development of an online tool to be potentially used in shared decision-making about breast cancer screening, French women were questioned about participation in breast cancer screening, the health professional's role, and their perceptions of the proposed tool. METHODS: We organised focus group discussions with 55 French women. Two different strategies were used to recruit women from high and low socioeconomic backgrounds. We applied both inductive and deductive approaches to conduct a thematic analysis of the discussions. We analysed the responses by using the main determinants from different health behaviour models and compared the two groups. RESULTS: Independently of socioeconomic status, the most important determinant for a woman's participation in breast cancer screening was the perceived severity of breast cancer and the perceived benefits of its early detection by screening. Cues to action reported by both groups were invitation letters; recommendations by health professionals, or group/community activities and public events were reported by women from high and low socioeconomic backgrounds, respectively. Among other positive determinants, women from high socioeconomic backgrounds reported making informed decisions and receiving peer support whereas women from low socioeconomic backgrounds reported community empowerment through group/community events. Fear of cancer was reported as a barrier in both groups. Among other barriers, language issues were reported only by women from low socioeconomic backgrounds; women from high socioeconomic backgrounds reported breast cancer screening-related risks other than overdiagnosis and/or overtreatment. Barriers to accessing the online tool to be developed were mainly reported by women from high socioeconomic backgrounds. CONCLUSION: Limitations in implementing shared decision-making for women from low socioeconomic backgrounds were highlighted. An online tool that is suitable for all women, regardless of socioeconomic status, would provide "on-demand" reliable and tailored information about breast cancer screening and improve access to health professionals and social exchanges.

Hyperparasitism in bat flies (Diptera: Streblidae): new records and interaction networks in the Neotropics.

Hyperparasitism is defined as the interaction where one parasite is infected by another parasite. In bat flies (Streblidae and Nycteribiidae), both hyperparasites and microparasites (bacteria, viruses, fungi, and arthropods such as mites) have been documented. Fungi belonging to the order Laboulbeniales are microscopic parasites of a wide diversity of arthropod hosts. Three genera exclusively target bat flies: Arthrorhynchus, which parasitizes species within Nycteribiidae in the Eastern Hemisphere, while genus Gloeandromyces and Nycteromyces parasitize Streblidae in the Western Hemisphere. Among the hyperparasitic arthropods, mites of family Neothrombidiidae, particularly the monospecific genus Monunguis, are known to parasitize bat flies. Here we present the first records of the hyperparasites Monunguis streblida and Gloeandromyces pageanus f. polymorphus parasitizing Streblidae bat flies in Colombia and a summary of these hyperparasitic interactions in the Neotropics. We detected fungi and mites parasitizing bat flies that were collected in the Magdalena River Basin, Colombia, in field expeditions in 2018, 2022, and 2023. We identified 17 bat flies and two species of hyperparasites, specifically M. streblida and the fungi Gloeandromyces. Our search for reports of these interactions in the Neotropics revealed that seven species of Trichobius (Streblidae) are parasitized by M. streblida, whereas Paratrichobius longicrus (Streblidae) is parasitized by Gloeandromyces pageanus f. polymorphus. These interactions have been reported in 11 countries, but our records are the first of M. streblida and Laboulbeniales fungi parasitizing bat flies in Colombia. So far, a total of 14 species of fungi and one species of mite have been associated with 19 species of bat flies, which in turn, are linked to 15 species of Neotropical bats.

Continuous Temperature Telemonitoring of Patients with COVID-19 and Other Infectious Diseases Treated in Hospital-at-Home: Viture® System Validation.

Body temperature must be monitored in patients receiving Hospital-at-Home (HaH) care for COVID-19 and other infectious diseases. Continuous temperature telemonitoring (CTT) detects fever and patient deterioration early, facilitating decision-making. We performed a validation clinical study assessing the safety, comfort, and impact on healthcare practice of Viture®, a CTT system, compared with a standard digital axillary thermometer in 208 patients with COVID-19 and other infectious diseases treated in HaH at the Navarra University Hospital (HUN). Overall, 3258 pairs of measurements showed a clinical bias of -0.02 °C with limits of agreement of -0.96/+0.92 °C, a 95% acceptance rate, and a mean absolute deviation of 0.36 (SD 0.30) °C. Viture® detected 3 times more febrile episodes and revealed fever in 50% more patients compared with spot measurements. Febrile episodes were detected 7.23 h (mean) earlier and modified the diagnostic and/or therapeutic approach in 43.2% of patients. Viture® was validated for use in a clinical setting and was more effective in detecting febrile episodes than conventional methods.

Quality of life in adolescent and adult patients with persistent allergic rhinitis after one year of subcutaneous immunotherapy with a modified mite extract.

Introduction: Allergic rhinoconjunctivitis (AR) is an IgE-mediated inflammation of nasal and ocular mucosa after environmental allergen exposure, mainly by house dust mites (HDM). AR affects more than one third of the population worldwide and it is associated with loss of quality of life (QoL). Aim: To analyse the improvement in the QoL in 50 patients with moderate-persistent AR due to house HDM before and after receiving 1 year of subcutaneous specific aeroallergen immunotherapy treatment (SAIT). Material and methods: A prospective observational study was performed based on clinical practice in 50 patients with moderate-severe persistent AR due to HDM and candidates to SAIT. Forty-one patients completed the study. Patients were evaluated with the ESPRINT short-version QoL questionnaire, a score of medication use and visual analogue scale (VAS) symptom score, prior to and 12 months after SAIT. Results: Forty-one patients (25 women, mean age 26.9 years). Mean ESPRINT values prior to the start SAIT was 3.06 (moderate-severe) and 1 year after starting subcutaneous SAIT the mean value dropped in all patients to 0.88 (mild). The VAS score symptom dropped from 8.26 to 3.68. 97.56% of patients used 3 or more drugs (oral antihistamine, ophthalmic/intranasal antihistamine, intranasal corticosteroid and/or oral antileukotrienes) prior to starting SAIT, and 1 year after it, 58.53% used one on-demand medication to control symptoms, oral antihistamine or nasal spray, and not daily use. Conclusions: Subcutaneous SAIT seems to be a valid treatment in our patients with moderate-persistent AR due to HDM, since it reduces the ESPRINT score, VAS score and the use of medication. An improvement in the quality of life and satisfaction was observed by the patients themselves.

Seeing is Believing: Developing Multimodal Metabolic Insights at the Molecular Level.

This outlook explores how two different molecular imaging approaches might be combined to gain insight into dynamic, subcellular metabolic processes. Specifically, we discuss how matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and stimulated Raman scattering (SRS) microscopy, which have significantly pushed the boundaries of imaging metabolic and metabolomic analyses in their own right, could be combined to create comprehensive molecular images. We first briefly summarize the recent advances for each technique. We then explore how one might overcome the inherent limitations of each individual method, by envisioning orthogonal and interchangeable workflows. Additionally, we delve into the potential benefits of adopting a complementary approach that combines both MSI and SRS spectro-microscopy for informing on specific chemical structures through functional-group-specific targets. Ultimately, by integrating the strengths of both imaging modalities, researchers can achieve a more comprehensive understanding of biological and chemical systems, enabling precise metabolic investigations. This synergistic approach holds substantial promise to expand our toolkit for studying metabolites in complex environments.

Revalorization of Yerba Mate Residues: Biopolymers-Based Films of Dual Wettability as Potential Mulching Materials.

Biodegradable mulching films are a very attractive solution to agronomical practices intended to achieve more successful crop results. And, in this context, the employment of agricultural and industrial food residues as starting material for their production is an alternative with economic and environmental advantages. This work reports the preparation of bilayer films having two different wettability characteristics from three bio-derived biopolymers: TEMPO-oxidized cellulose nanofibers isolated from infused Yerba Mate residues, Chitosan and Polylactic acid. The infused Yerba Mate residues, the isolated and oxidized cellulose nanofibers, and the films were characterized. Nanofibrillation yield, optical transmittance, cationic demand, carboxyl content, intrinsic viscosity, degree of polymerization, specific surface area and length were studied for the (ligno)cellulose nanofibers. Textural and chemical analysis, thermal and mechanical properties studies, as well as water and light interactions were included in the characterization of the films. The bilayer films are promising materials to be used as mulching films.

An in vivo drug screen in zebrafish reveals that cyclooxygenase 2-derived prostaglandin D2 promotes spinal cord neurogenesis.

The study of neurogenesis is essential to understanding fundamental developmental processes and for the development of cell replacement therapies for central nervous system disorders. Here, we designed an in vivo drug screening protocol in developing zebrafish to find new molecules and signalling pathways regulating neurogenesis in the ventral spinal cord. This unbiased drug screen revealed that 4 cyclooxygenase (COX) inhibitors reduced the generation of serotonergic interneurons in the developing spinal cord. These results fitted very nicely with available single-cell RNAseq data revealing that floor plate cells show differential expression of 1 of the 2 COX2 zebrafish genes (ptgs2a). Indeed, several selective COX2 inhibitors and two different morpholinos against ptgs2a reduced the number of serotonergic neurons in the ventral spinal cord and led to locomotor deficits. Single-cell RNAseq data and different pharmacological manipulations further revealed that COX2-floor plate-derived prostaglandin D2 promotes neurogenesis in the developing spinal cord by promoting mitotic activity in progenitor cells. Rescue experiments using a phosphodiesterase-4 inhibitor suggest that intracellular changes in cAMP levels underlie the effects of COX inhibitors on neurogenesis and locomotion. Our study provides compelling in vivo evidence showing that prostaglandin signalling promotes neurogenesis in the ventral spinal cord.

Slipping rib syndrome in childhood. A case series. / Síndrome de la costilla deslizante en la edad pediátrica. Serie de casos.

Among the causes of chest pain, slipping rib has a low prevalence, usually with a history of trauma, and its management is controversial. Slipping rib syndrome should be included in the differential diagnosis of causes of chest pain in children. When not associated with previous trauma and cartilage deformity, it is necessary to consider an alteration in rib development, regardless of the typical traumatic etiology in adults. Here we describe a series of pediatric patients with slipping rib seen at a referral hospital between 2001 and 2022. Nine patients aged 11 to 16 years were included. Only 2 had a history of trauma. All patients described a sudden onset of severe thoracic abdominal pain. The patients underwent open resection of the affected costal cartilages, with resolution of pain.

Entre las causas de dolor torácico, la costilla deslizante presenta baja prevalencia, antecedentes traumáticos y manejo controvertido. Este síndrome merece ser incluido en el diagnóstico diferencial de causas de dolor torácico en niños. Al no asociarse a traumatismos previos y la deformidad de cartílagos, nos induce a pensar en una alteración en el desarrollo costal, al margen de la etiología traumática típica en adultos. Se presenta una serie de pacientes pediátricos intervenidos por costilla deslizante en un centro de referencia entre 2001 y 2022. Se incluyeron nueve pacientes, con un rango de edades de 11 a 16 años. Solo dos casos describen traumatismo previo. Todos presentan un inicio súbito de dolor toracoabdominal intenso. Los pacientes fueron intervenidos mediante resección abierta de cartílagos costales afectos, con resolución del dolor.

Is histological confirmation necessary to avoid futile resections? Comparative of 4 university hospitals.

OBJECTIVES: There is no consensus in the literature on preoperative histological analysis for lung cancer. The objective of this study was to assess 4 diagnostic models used in different hospitals with differing practices regarding preoperative histological diagnosis and the consequences in terms of unnecessary surgery and futile major resection. METHODS: We carried out a retrospective observational study collected from 4 university hospitals in Spain over 3 years (January 2019 to December 2021). We included all patients with a confirmed diagnosis of primary lung cancer and any patients with suspected primary lung cancer who had undergone surgery. All patients underwent computed tomography and positron emission tomography/computed tomography scans. Each multidisciplinary committee was free to choose whether to perform flexible bronchoscopic or transthoracic lung biopsy. Decisions concerning whether to perform intraoperative sample analysis, the surgical approach and the type of resection were left to the surgical team. RESULTS: We included a total of 1642 patients. The use of flexible endoscopy and its diagnostic performance varied substantially between hospitals (range: 23.8-79.3% and 25-60.7%, respectively); and the same was observed for transthoracic biopsy and its performance (range: 16.9-82.3% and 64.6-97%, respectively). Regarding major resection surgery (lobectomy or more extensive resection), the lowest rate was observed in hospital C (1%) and the highest in hospital B (2.8%), with between-hospital differences not reaching significance (P = 0.173). CONCLUSIONS: The rate of histological sampling before lung cancer surgery still varies between hospitals. In spite of very diverse multidisciplinary management, the rate of futile lobectomy is not significantly higher in hospitals with lower rates of preoperative histological analysis.

Non-invasive assessment of sublingual microcirculation using flow derived from green light PPG: evaluation and reference values.

Significance: The study of sublingual microcirculation offers valuable insights into vascular changes and overcomes some limitations of peripheral microcirculation assessment. Videomicroscopy and pulse oximetry have been used to assess microcirculation, providing insights into organ perfusion beyond macrohemodynamics parameters. However, both techniques have important limitations that preclude their use in clinical practice. Aim: To address this, we propose a non-invasive approach using photoplethysmography (PPG) to assess microcirculation. Approach: Two experiments were performed on different samples of 31 subjects. First, multi-wavelength, finger PPG signals were compared before and while applying pressure on the sensor to determine if PPG signals could detect changes in peripheral microcirculation. For the second experiment, PPG signals were acquired from the ventral region of the tongue, aiming to assess the microcirculation through features calculated from the PPG signal and its first derivative. Results: In experiment 1, 13 out of 15 features extracted from green PPG signals showed significant differences (p<0.05) before and while pressure was applied to the sensor, suggesting that green light could detect flow distortion in superficial capillaries. In experiment 2, 15 features showed potential application of PPG signal for sublingual microcirculation assessment. Conclusions: The PPG signal and its first derivative have the potential to effectively assess microcirculation when measured from the fingertip and the tongue. The assessment of sublingual microcirculation was done through the extraction of 15 features from the green PPG signal and its first derivative. Future studies are needed to standardize and gain a deeper understanding of the evaluated features.

Fallopian Tube-Derived High-Grade Serous Cancers Influence Ovarian Production of Norepinephrine and Generate Specific Metabolomic Signatures.

High-grade serous ovarian cancer is the most common and lethal gynecologic malignancy, which is often attributed to the lack of available screenings, allowing the disease to progress unnoticed until it is diagnosed at more aggressive stages. As such, identifying signals in the tumor microenvironment involved in the primary metastasis of tumorigenic fallopian tube epithelial (FTE) cells to the ovary could provide new avenues for prevention, diagnostics, or therapeutic intervention. Since our previous work identified that the interaction of tumorigenic FTE and the ovary causes the release of norepinephrine (NE) from the ovary, we intended to determine the effects of ovarian NE on signaling and invasion of tumorigenic FTE models and high-grade serous ovarian cancer cell lines. We demonstrate that NE does not universally enhance migration, invasion, or adhesion by using multiple cell types but does alter specific oncogenic protein expression in certain models. In vivo, we found that blocking NE signaling via slow-release propranolol pellets significantly increased survival time in mice injected intraperitoneally with murine FTE cells engineered to stably express shRNA for PTEN and an activated KRAS expression construct. Finally, we identified that the metabolome released from the ovary is variable depending upon which cell type it is cocultured with, suggesting that distinct driver mutations in fallopian tube epithelial tumor models and early lesions can alter specific metabolomes within the surrounding ovarian microenvironment. These metabolomes provide the next frontier for evaluating local signals of the tumor microenvironment that facilitate ovarian spread of FTE lesions.

Presurgical invasive mediastinal staging in lung cancer, unexpected N2 and long-term survival: a registry-based study with data from the Spanish group for video-assisted thoracic surgery.

Background: Mediastinal lymph node staging is a key element in the diagnosis of lung cancer. The combination of computed tomography (CT) and positron emission tomography (PET) has improved staging but some circumstances are known to influence their negative predictive value. The objective of this study was to assess the impact on survival of avoiding invasive mediastinal staging in surgical lung cancer patients with negative mediastinum in CT and PET and intermediate risk of unexpected pN2. Methods: Data were collected from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS), from December 2016 to March 2018. For this study, patients were selected if they had negative mediastinum in CT and PET findings but tumours >3 cm or located centrally, or with cN1 disease. Patients who did and did not undergo invasive staging [invasive group (IG) and non-invasive group (NIG)] were compared, analysing unexpected pN2 and survival with Kaplan-Meier curves and Cox regression. Results: A total of 2,826 patients underwent surgery for primary lung cancer. We selected 1,247 patients who had tumours >3 cm, central tumours or cN1. Invasive staging was performed in 275 (22.1%) cases. The unexpected pN2 rate was 9.6% in the NIG and 13.8% in the IG, but half of them were discovered prior to surgery in the IG. Five-year overall survival (OS) was poorer in the IG (52.4% vs. 64%; P<0.001). In the Cox regression model, male sex, older age, diabetes, synchronous tumour, lower diffusing capacity for carbon monoxide, larger tumour size, higher pathological N-stage, and IG status were significant independent risk factors. Conclusions: Invasive staging recommended by guidelines could be reduced with an appropriate selection in mediastinal CT- and PET-negative patients with risk factors for unexpected pN2, because rates of pN2 and survival did not worsen without invasive staging.