Genomic Characterization of Piscicolin CM22 Produced by Carnobacterium maltaromaticum CM22 Strain Isolated from Salmon (Salmo salar).

Carnobacterium maltaromaticum is a species of lactic acid bacteria (LAB) that has been isolated from various natural environments. It is well-known for producing a diverse spectrum of bacteriocins with potential biotechnological applications. In the present study, a new psychrotolerant strain of C. maltaromaticum CM22 is reported, isolated from a salmon gut sample and producing a variant of the bacteriocin piscicolin 126 that has been named piscicolin CM22. After identification by 16S rRNA gene, this strain has been genomically characterized by sequencing and assembling its complete genome. Moreover, its bacteriocin was purified and characterized. In vitro tests demonstrated that both the strain and its bacteriocin possess antimicrobial activity against several Gram-positive bacteria of interest in human and animal health, such as Listeria monocytogenes, Clostridium perfringens, or Enterococcus faecalis. However, this bacteriocin did not produce any antimicrobial effect on Gram-negative species. The study of its genome showed the genetic structure of the gene cluster that encodes the bacteriocin, showing a high degree of homology to the gene cluster of piscicolin 126 described in other C. maltaromaticum. Although more studies are necessary concerning its functional properties, this new psychrotolerant strain C. maltaromaticum CM22 and its bacteriocin could be considered an interesting candidate with potential application in agri-food industry.

Endogenous LXR signaling controls pulmonary surfactant homeostasis and prevents lung inflammation.

Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRß, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRß as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases.

Cross-cultural evaluation of the Michigan Hand Outcomes Questionnaire: a systematic review.

This systematic review aims to provide a comprehensive synthesis and in-depth analysis of the quality of the different cross-cultural versions of the MHQ. This study was conducted using Pubmed, Web of Science, CINAHL and SCOPUS databases to identify cross-cultural validation studies of the MHQ. Methodological quality, quality of evidence and criteria for good measurement properties of these studies were applied for each psychometric property. Quality assessment and data extraction were performed independently by two reviewers according to the COnsensus-based Standards for selection of health Measurement INstruments (COSMIN) guidelines. A total of 493 articles were identified, of which 22 were included and 20 were analysed.Of the six properties analysed, responsiveness and hypothesis testing for construct validity had the highest methodological quality and quality of evidence, and met the criteria for good measurement properties. The lowest quality properties were measurement error and internal consistency. The different cross-cultural versions of the MHQ were found to be reliable, valid and able to detect clinical change. The lack of development of measurement error, formulation of an a priori hypothesis or structural validity affects the detection of small clinical changes and their discriminative capacity.

Psychometric Properties of the Spanish Version of the Parental Feeding Style Questionnaire.

BACKGROUND: There are no validated instruments in Spain for measuring parental feeding styles. The aim was to validate the Parental Feeding Styles Questionnaires (PFSQ) in a Spanish sample. METHOD: A total of 523 mothers of 523 school-children participated. The children had a mean age of 4.4 years (SD = 1.3), with 51% being boys (M = 4.3 years, SD = 1.4) and 49% girls (M = 4.5 years, = SD 1.3). The PFSQ and the Comprehensive General Parenting Styles Questionnaire (CGPQ) were used. RESULTS: A model of four correlated factors was identified: Prompting/encouraging eating, emotional feeding, instrumental feeding, and control over eating. Cronbach's alpha for the subscales ranged from 0.64 to 0.86, and McDonald's Omega coefficient ranged from 0.66 to 0.86. Emotional feeding and prompting/encouraging eating had values above 0.70, control over eating had a value of 0.68 and instrumental feeding had an alpha coefficient of 0.64 and omega coefficient of 0.66. The factor structure was similar to the original and to other adapted versions. The Spanish sample used more control over eating and prompting/encouraging to eat. CONCLUSIONS: The adapted PFSQ is a suitable instrument for assessing the feeding styles of Spanish parents.

Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. METHODS: We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS: Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09-1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case-control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS: Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT: This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.

Psychometric Properties of the Spanish Version of the Parental Feeding Style Questionnaire / Propiedades Psicométricas de la Versión Española del Cuestionario de Estilos deAlimentación Parental

Background: There are no validated instruments in Spain for measuring parental feeding styles. The aim was to validate the Parental Feeding Styles Questionnaires (PFSQ) in a Spanish sample. Method: A total of 523 mothers of 523 school-children participated. The children had a mean age of 4.4 years (SD = 1.3), with 51% being boys (M = 4.3 years, SD = 1.4) and 49% girls (M = 4.5 years, SD = 1.3). The PFSQ and the Comprehensive General Parenting Styles Questionnaire (CGPQ) were used. Results: A model of four correlated factors was identified: Prompting/encouraging eating, emotional feeding, instrumental feeding, and control over eating. Cronbach’s alpha for the subscales ranged from 0.64 to 0.86, and McDonald’s Omega coefficient ranged from 0.66 to 0.86. Emotional feeding and prompting/ encouraging eating had values above 0.70, control over eating had a value of 0.68 and instrumental feeding had an alpha coefficient of 0.64 and omega coefficient of 0.66. The factor structure was similar to the original and to other adapted versions. The Spanish sample used more control over eating and prompting/encouraging to eat. Conclusions: The adapted PFSQ is a suitable instrument for assessing the feeding styles of Spanish parents.(AU)

Antecedentes: No hay suficientes instrumentos validados en España para medir los estilos de alimentación parental. El objetivo fue validar el cuestionario de estilos de alimentación Parental (PFSQ) en muestra española. Método: Participaron 523 madres de 523 escolares con una media de edad de 4.4 años (DT = 1.3), siendo el 51% niños (M = 4.3 años, DT = 1.4) y 49% niñas (M = 4.5 años, DT=1.3). Se utilizaron el PFSQ y el cuestionario de estilos de crianza general (CGPQ). Resultados: Se identificó un modelo de cuatro factores correlacionados: persuadirle/animarle a comer, alimentación emocional, alimentación instrumental, y control de la ingesta. El alfa de Cronbach de las subescalas osciló entre 0.64 y 0.86, y el coeficiente omega de McDonald entre 0.66 y 0.86. Alimentación emocional y persuadirle/animarle a comer obtuvieron valores superiores a 0.70, control de la ingesta obtuvo 0.68 y la alimentación instrumental, un coeficiente alfa de 0.64 y un coeficiente Omega de 0.66. La estructura factorial coincide con la versión original y otras versiones adaptadas. La muestra española utilizó más el control de la ingesta y persuadirle/animarle a comer. Conclusiones: El PFSQ es un instrumento adecuado para evaluar los estilos de alimentación de los padres españoles.(AU)

Complete mitochondrial genome of Metathelazia capsulata (Pneumospiruridae) and comparison with other Spiruromorpha species.

Metathelazia capsulata (family Pneumospiruridae) is a lungworm parasitizing the bronchi and bronchioles, described in four species of wild carnivores. Very little molecular data are available on this nematode and none on other species of the Pneumospiruridae family. In this work, we describe for the first time the complete mitogenome (mitochondrial genome) of M. capsulata, being the first described of the family Pneumospiruridae. The mitogenome of M. capsulata has 13,659 bp in length, an A + T content of 79.2%. The mitogenome included 12 protein-coding genes (PCGs) (lacking the atp8 gene), 22 tRNA genes, 2 rRNA genes (all the genes are coded by the heavy strand), and an AT-rich region. The PCGs varied in size (232 bp-1645 bp). Only the tRNA-Trp has the standard cloverleaf secondary structure, while the other 21 do not. The AT-rich region, with a 90.5% A + T content and a length of 389 bp, is located between the cox3 and tRNA-Ala genes. Comparison with the mitogenomes of 29 species of Spiruromorpha infraorder, belonging to different families, demonstrates that M. capsulata mitogenome shared the common characteristics of most of them. The phylogeny constructions yielded phylogenies that were in agreement with the obtained previously by using sequences and gene order data of mitogenomes.

Analysis of different gamification-based teaching resources for physiotherapy students: a comparative study.

BACKGROUND: For health professionals, gamification is a new teaching method that has achieved an important role in recent years, with excellent results in learning and knowledge acquisition. Thus, the objective of this study was to analyze the gaming experience through different gamification resources in the classroom with physiotherapy students. METHODS: A comparative study on gamification-based teaching resources was carried out during the first semester of the 2021-2022 academic year. A total of 33 physiotherapy students participated in this study. After the theoretical topics were taught, the participants were invited to participate in different gamification resources such as Kahoot!, Physiotherapy Party and Escape Room. The gaming experience with the different gamification resources was measured with the GAMEX scale. RESULTS: The Physiotherapy Party showed a higher score in relation to the enjoyment dimension compared to the Kahoot! and Escape Room (p = 0.004). The Escape Room presented higher scores in absorption, creative thinking, activation and dominance compared to Kahoot! and Physiotherapy Party (p < 0.005). CONCLUSIONS: Gamification resources promote enjoyment and creativity in the students in the classroom. The use of new teaching methods based on gamification, such as Escape Room as Physiotherapy Party should be considered as first choice in the use of gamification resources due to the benefits they bring to students.

Removal of heavy metals from mine tailings by in-situ bioleaching coupled to electrokinetics.

This work utilizes a combined biological-electrochemical technique for the in-situ removal of metals from polluted mine tailings. As the main novelty point it is proposed to use electrokinetics (EK) for the in-situ activation of a bioleaching mechanism into the tailings, in order to promote biological dissolution of metal sulphides (Step 1), and for the subsequent removal of leached metals by EK transport out of the tailings (Step 2). Mine tailings were collected from an abandoned Pb/Zn mine located in central-southern Spain. EK-bioleaching experiments were performed under batch mode using a lab scale EK cell. A mixed microbial culture of autochthonous acidophilic bacteria grown from the tailings was used. Direct current with polarity reversal vs alternate current was evaluated in Step 1. In turn, different biological strategies were used: biostimulation, bioaugmentation and the abiotic reference test (EK alone). It was observed that bioleaching activation was very low during Step 1, because it was difficult to maintain acidic pH in the whole soil, but then it worked correctly during Step 2. It was confirmed that microorganisms successfully contributed to the in-situ solubilization of the metal sulphides as final metal removal rates were improved compared to the conventional abiotic EK (best increases of around 40% for Cu, 162% for Pb, 18% for Zn, 13% for Mn, 40% for Ni and 15% for Cr). Alternate current seemed to be the best option. The tailings concentrations of Fe, Al, Cu, Mn, Ni and Pb after treatment comply with regulations, but Pb, Cd and Zn concentrations exceed the maximum values. From the data obtained in this work it has been observed that EK-bioleaching could be feasible, but some upgrades and future work must be done in order to optimize experimental conditions, especially the control of soil pH in acidic values.

TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck.

Objectives: The aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m2 weekly and cetuximab 400 mg/m2 loading dose, and then 250 mg/m2 weekly) as first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who are medically unfit for cisplatin-based (PT) chemotherapy. Materials and methods: This retrospective, non-interventional study involved 16 centers in Spain. Inclusion criteria were to have started receiving ERBITAX regimen from January 2012 to December 2018; histologically confirmed SCCHN including oral cavity, oropharynx, hypopharynx, and larynx; age ≥18 years; and platinum (PT) chemotherapy ineligibility due to performance status, comorbidities, high accumulated dose of PT, or PT refractoriness. Results: A total of 531 patients from 16 hospitals in Spain were enrolled. The median age was 66 years, 82.7% were male, and 83.5% were current/former smokers. Patients were ineligible to receive PT due to ECOG 2 (50.3%), comorbidities (32%), PT cumulative dose ≥ 225 mg/m2 (10.5%), or PT refractoriness (7.2%). Response rate was 37.7%. Median duration of response was 5.6 months (95% CI: 4.4-6.6). With a median follow-up of 8.7 months (95% CI: 7.7-10.2), median PFS and OS were 4.5 months (95% CI: 3.9-5.0) and 8.9 months (95% CI: 7.8-10.3), respectively. Patients treated with immunotherapy after ERBITAX had better OS with a median of 29.8 months compared to 13.8 months for those who received other treatments. The most common grade ≥ 3 toxicities were acne-like rash in 36 patients (6.8%) and oral mucositis in 8 patients (1.5%). Five (0.9%) patients experienced grade ≥ 3 febrile neutropenia. Conclusion: This study confirms the real-world efficacy and tolerability of ERBITAX as first-line treatment in recurrent/metastatic SCCHN when PT is not feasible. Immunotherapy after treatment with ERBITAX showed remarkable promising survival, despite potential selection bias.

Spanish Cross-Cultural Adaptation and Validation of Neck Bournemouth Questionnaire (NBQ) for Neck Pain Patients.

BACKGROUND: Neck pain is highly prevalent and one of the most common musculoskeletal conditions. Instruments that measure the factors involved in neck pain accurately are needed for clinical assessment. Patient-reported outcome measures (PROMs) are reliable, cost-effective, and specific tools for the assessment of musculoskeletal problems at different moments. The Neck Bournemouth Questionnaire (NBQ) assesses pain, function, disability, and psychological and social variables in patients with cervical pathologies. The aim of this study was to perform an adaptation and validation into Spanish of the NBQ (NBQ-Sp). METHODS: A cross-sectional, observational study was carried out through translation, adaptation, and validation. A total of 129 patients with neck pain, of Spanish nationality, and over 18 years of age were included. RESULTS: The NBQ-Sp showed excellent internal consistency, with Cronbach's α of 0.897, test-retest reliability with interclass correlation coefficient (ICC) of 0.866, and standard error of measurement (SEM) and minimum detectable change (MDC) values were 1.302 and 3.038, respectively. A Kaiser-Meyer-Olkin value of 0.857 was obtained, and Bartlett's test yielded p < 0.001, finding one factor in the factor analysis. CONCLUSION: The NBQ-Sp has proven to be a valid and reliable tool for clinicians and researchers to measure neck pain in the Spanish population.

What is the sensitivity and exactness of post-mortem diagnostic method for cardiopulmonary nematodes in wild carnivores? towards the gold standard.

Cardiopulmonary nematodes cause health and fitness disorders in wild and domestic carnivores. The red fox (Vulpes vulpes) participates in the spread of these shared parasites at the domestic-wildlife interface. This study aimed to evaluate the sensitivity of post-mortem diagnostic method for detecting lungworms in carnivores, and its exactness to estimate the parasite intensity of each nematode species. Cardiorespiratory system of fifty-one foxes were examined through three consecutively methodological steps: first, the tracheobronchial tree, pulmonary arteries and their branches were opened (OT); next, lung parenchyma was immersed in water and squeezed (WS); finally, the parenchyma was artificially digested in a pepsin and chlorhydric acid solution (AD). Eucoleus aerophilus, Angiostrongylus vasorum, Crenosoma vulpis and Metathelazia capsulata were identified. The number of recovered nematodes in each step were 454 (OT), 285 (WS) and 141 (AD). The use of OT and WS helped to improve parasite intensity results and decreased false negative cases. Accordingly, when OT and WS were used together, the sensitivity in the detection of parasitized foxes was 96.1%, while the exactness of parasite intensity was 84%. When AD was performed, although sensitivity does not rise, results were more exact, increasing the total number of detected parasites by 16%. Moreover, AD improved the sensitivity in the detection of A. vasorum and M. capsulata, as well as quantifying more exactly the parasite intensity (92.5% and 92.3% of exactness without AD, respectively). Our study provides valuable information that should be taken into account when planning epidemiological studies based on cardiopulmonary nematode detection in carnivores.

LAP1 supports nuclear adaptability during constrained melanoma cell migration and invasion.

Metastasis involves dissemination of cancer cells away from a primary tumour and colonization at distal sites. During this process, the mechanical properties of the nucleus must be tuned since they pose a challenge to the negotiation of physical constraints imposed by the microenvironment and tissue structure. We discovered increased expression of the inner nuclear membrane protein LAP1 in metastatic melanoma cells, at the invasive front of human primary melanoma tumours and in metastases. Human cells express two LAP1 isoforms (LAP1B and LAP1C), which differ in their amino terminus. Here, using in vitro and in vivo models that recapitulate human melanoma progression, we found that expression of the shorter isoform, LAP1C, supports nuclear envelope blebbing, constrained migration and invasion by allowing a weaker coupling between the nuclear envelope and the nuclear lamina. We propose that LAP1 renders the nucleus highly adaptable and contributes to melanoma aggressiveness.

A Case of Sterile Corneal Stromal Infiltration with Hypotonic Maculopathy Under Brimonidine Treatment.

INTRODUCTION: Brimonidine is a commonly used drug for glaucoma treatment, which has been linked to ocular autoimmune disorders like uveitis and conjunctivitis. Corneal pathology under brimonidine is generally less common. CASE DESCRIPTION: Here, we report a 78 -year-old male patient suffering from immune corneal stromal inflammation with hypotony and resulting hypotonic maculopathy after 6 weeks after introduction of brimonidine treatment. Systemic work-up for system autoimmune and infectious diseases was negative. We discontinued brimonidine and administered topical prednisolone under which inflammatory corneal signs and intraocular pressure normalized. Chorioretinal folds persisted after 9 months. CONCLUSION: Our case report suggests monitoring patients under brimonidine for sterile corneal infiltration.

Predictive factors for flea occurrence in red foxes (Vulpes vulpes) from semi-arid Mediterranean environments.

The role of red fox as host for a wide range of parasites, particularly fleas and other arthropods causing vector-borne diseases, in combination with its capability to adapt to anthropized environments, makes this wild canid an epidemiologically remarkable species at the wildlife-domestic-human interface, especially in the present time of rise of emerging and re-emerging diseases. This study evaluated the prevalence and parasite intensity of fleas in 88 foxes from Murcia Region (Southeastern Spain) and determined the geographic distribution of areas with the highest potential risk of flea presence. Pulex irritans, Ctenocephalides felis, Spilopsyllus cuniculi and Nosopsyllus fasciatus were identified. The overall prevalence was 76.13%. This is the first time that N. fasciatus has been reported in foxes from Murcia Region. The predictive model established a certain pattern to determine the areas with the highest risk of acquiring fleas. Positive correlation of daily potential evapotranspiration (ET0 ) in winter and the opposite effect occurring for ET0 in summer were obtained, as well as positive correlations for mean daily temperature (Tmean ) in summer and mean precipitation (Pmean ) in winter and summer. The model was also found positively correlated in the forest habitat ecotone areas and the anthropized areas.

Protein Supplementation with Short Peptides Prevents Early Muscle Mass Loss after Roux-en-Y-Gastric Bypass.

Introduction: A significant reduction in fat-free mass (FFM) following bariatric surgery (BS) has been reported, and adequate protein intake is recommended for FFM preservation. Current guidelines of nutritional management after BS recommend complex protein (CP) compounds. However, Roux-en-Y-gastric bypass (RYGB) has a negative impact on CP digestion, leading to protein malabsorption. At present, there is no data regarding the impact of early supplementation with short peptide-based (SPB) or hydroxy methylbutyrate (HMB)-enriched formulas on the evolution of the FFM after the BS. Aim: The aim of this study is to evaluate the effect of nutritional products based on CP, HBM-enriched, or SPB formulas on the FFM of patients that undergo RYGB. Material and methods: This is a prospective interventional study, including three groups of patients (according to the type of protein product) as candidates for BS, recruited between December 2021 and April 2022, matched by age, gender, and BMI. All patients underwent evaluations at baseline and one month post-BS, including: medical history, physical and anthropometric evaluation, bioimpedance, and biochemical analysis. Results: A total of 60 patients were recruited: 63% women, mean age 43.13 ± 9.4 years, and BMI 43.57 ± 4.1 kg/m2. The % of FFM loss from total weight loss (TWL) was significantly lower in the SPB group than CP and HMB groups despite the major %TWL in this group (40.60 ± 17.27 in CP, 34.57 ± 13.15 in HMB, and 19.14 ± 9.38 in SPB, p < 0.001). TWL% was 9.98 ± 1.82 vs. 9.83 ± 2.71 vs. 13.56 ± 4.30, p < 0.001, respectively. Conclusion: In our study, the SPB supplementation prevented almost 50% FFM lost from the TWL than the CP- or HMB-enriched compounds at one month post-BS. These results are significant in the setting of muscle mass preservation after the BS, and have the potential to change the current guidelines for the management of nutritional supplementation after BS.

Risk Factors, Radiological and Clinical Outcomes in Subclinical and Clinical Pituitary Apoplexy.

BACKGROUND: Pituitary apoplexy (PA) can be symptomatic, namely acute apoplexy (APA), or asymptomatic or subclinical (SPA). OBJECTIVE: To describe the clinical characteristics and evolution of the patients with APA compared to SPA Patients and methods: Retrospective, longitudinal database analysis. RESULTS: We identified 58 patients with PA, and 37 accomplished the inclusion criteria (17 men, median age 47.7 years). A total of 29 (78.4%) had APA (17 underwent surgery, and 12 were conservatively managed), and 8 (21.6%) had SPA. The presence of non-functioning pituitary adenoma (NFPA) odds ratio (OR): 29.36 (95% confidence interval (CI): 1.86-462.36) and the largest size OR 1.10 (95% CI: 1.01-1.2) elevated the risk of having surgery. Hypopituitarism developed in 35.1% without significant differences between APA and SPA. In non-surgical patients, adenoma volume shrunk spontaneously at one year magnetic resonance imaging (MRI), without statistical differences between the conservatively treated and SPA group. CONCLUSIONS: APA is more frequent in larger NFPAs, and this subset of patients has a higher risk of surgery. Hypopituitarism is quite frequent even in patients with SPA, and, therefore, long-term follow-up is mandatory. In the non-surgical group, the pituitary tumour shrinkage is clinically relevant after one year of PA. Consequently, surgery indication in NFPA should be delayed and reassessed if patients remain asymptomatic.

Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance.

Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, which is supported by an extracellular matrix (ECM). Therefore, we investigated the impact of tissue-matched human ECM in driving PDAC and the role of the ECM in promoting chemotherapy resistance. Decellularized human pancreata and livers were recellularized with PANC-1 and MIA PaCa-2 (PDAC cell lines), as well as PK-1 cells (liver-derived metastatic PDAC cell line). PANC-1 cells migrated into the pancreatic scaffolds, MIA PaCa-2 cells were able to migrate into both scaffolds, whereas PK-1 cells were able to migrate into the liver scaffolds only. These differences were supported by significant deregulations in gene and protein expression between the pancreas scaffolds, liver scaffolds, and 2D culture. Moreover, these cell lines were significantly more resistant to gemcitabine and doxorubicin chemotherapy treatments in the 3D models compared to 2D cultures, even after confirmed uptake by confocal microscopy. These results suggest that tissue-specific ECM provides the preserved native cues for primary and metastatic PDAC cells necessary for a more reliable in vitro cell culture.

Cytokine Profile in Children with Severe Multisystem Inflammatory Syndrome Related to the Coronavirus Disease 2019.

The multisystem inflammatory syndrome in children (MIS-C) is a novel and concerning entity related to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Although MIS-C has been the subject of intensive research efforts, its pathophysiology and optimal treatment remain elusive. We studied the clinical features, laboratory findings, and immunoinflammatory profiles of seven children prospectively admitted to a pediatric intensive care unit (PICU) during the first wave of the pandemic. All patients had immunoglobulin (Ig)-G against SARS-CoV-2, four of seven patients had both IgM and IgG, and in one of the 7 SARS-CoV-2 was detected in a respiratory sample. All patients received intravenous fluid boluses (median: 15 mL/kg) and norepinephrine. The most common form of respiratory support was supplemental oxygen via nasal cannula. None of the patients needed mechanical ventilation. The cardiovascular system was frequently involved. All patients had an elevated troponin-I (median: 107.3 ng/L). Four out of seven patients had coronary artery abnormalities, and two of seven had both abnormal electrocardiogram (EKG) findings and evidence of left ventricular dysfunction on echocardiogram. Ig levels and complement function were normal. Peripheral blood phenotyping with flow cytometry showed decreased T-cell numbers at the expense of CD8+ T-cells. Cytokine profiling showed a heterogeneous increase in interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-18, IL-2Ra, IL-10, and IL-1Ra that tended to normalize after treatment. Our study shows that children with MIS-C have elevated plasma levels of pro- and anti-inflammatory cytokines in the acute phase of the disease without other relevant immunologic disturbances. These findings suggest the presence of a mixed antagonist response syndrome (MARS) similar to that present in pediatric sepsis. Combining a meticulous differential diagnosis with cautiously coordinated immunomodulatory therapy and high-quality supportive care can help clinicians avoid causing iatrogenic harm in patients with MIS-C.