Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis, insulin signaling and toll-like receptor expression in rats fed a high-fat diet.

Insulin resistance (IR) has been identified as crucial pathophysiological factor in the development and progression of non-alcoholic fatty liver disease (NAFLD). Although mounting evidence suggests that perturbation of gut microflora exacerbates the severity of chronic liver diseases, therapeutic approaches using synbiotic has remained overlooked. Here, we show that a synbiotic composed by Lactobacillus paracasei B21060 plus arabinogalactan and fructo-oligosaccharides lessens NAFLD progression in a rat model of high fat feeding. IR and steatosis were induced by administration of high fat diet (HFD) for 6 weeks. Steatosis and hepatic inflammation, Toll-like receptor (TLR) pattern, glucose tolerance, insulin signaling and gut permeability were studied. Liver inflammatory markers were down-regulated in rats receiving the synbiotic, along with an increased expression of nuclear peroxisome proliferator-activated receptors and expression of downstream target genes. The synbiotic improved many aspects of IR, such as fasting response, hormonal homeostasis and glycemic control. Indeed it prevented the impairment of hepatic insulin signaling, reducing the phosphorylation of insulin receptor substrate-1 in Ser 307 and down-regulating suppressor of cytokine signaling 3. Gene expression analysis revealed that in the liver the synbiotic reduced cytokines synthesis and restored the HFD-dysregulated TLR 2, 4 and 9 mRNAs toward a physiological level of expression. The synbiotic preserved gut barrier integrity and reduced the relative amount of Gram-negative Enterobacteriales and Escherichia coli in colonic mucosa. Overall, our data indicate that the L. paracasei B21060 based synbiotic is effective in reducing the severity of liver injury and IR associated with high fat intake, suggesting its possible therapeutic/preventive clinical utilization

Compatible Paths on Labelled Point Sets

Let P and Q be finite point sets of the same cardinality in R 2 , each labelled from 1 to n. Two noncrossing geometric graphs GP and GQ spanning P and Q, respectively, are called compatible if for every face f in GP , there exists a corresponding face in GQ with the same clockwise ordering of the vertices on its boundary as in f. In particular, GP and GQ must be straightline embeddings of the same connected n-vertex graph G. No polynomial-time algorithm is known for deciding whether two labelled point sets admit compatible geometric graphs. The complexity of the problem is open, even when the graphs are constrained to be triangulations, trees, or simple paths. We give polynomial-time algorithms to find compatible paths or report that none exist in three scenarios: O(n) time for points in convex position; O(n 2 ) time for two simple polygons, where the paths are restricted to remain inside the closed polygons; and O(n 2 log n) time for points in general position if the paths are restricted to be monotonePeer ReviewedPostprint (published version

Post-intubation tracheal lacerations: Risk-stratification and treatment protocol according to morphological classification

BackgroundPost-intubation tracheal laceration (PITL) is a rare condition (0.005% of intubations). The treatment of choice has traditionally been surgical repair. Following our first report in 2010 of treatment protocol tailored to a risk-stratified morphological classification there is now clear evidence that conservative therapy represents the gold standard in the majority of patients. In this paper we aim to validate our risk-stratified treatment protocol through the largest ever reported series of patients. MethodsThis retrospective analysis is based on a prospectively collected series (2003-2020) of 62 patients with PITL, staged and treated according to our revised morphological classification. ResultsFifty-five patients with Level I (#8), II (#36) and IIIA (#11) PITL were successfully treated conservatively. Six patients with Level IIIB injury and 1 patient with Level IV underwent a surgical repair of the trachea. No mortality was reported. Bronchoscopy confirmed complete healing in all patients by day 30. Statistical analysis showed age only to be a risk factor for PITL severity. ConclusionsOur previously proposed risk-stratified morphological classification has been validated as the major tool for defining the type of treatment in PITL

Luminal-like HER2-negative stage IA breast cancer: A multicenter retrospective study on long-term outcome with propensity score analysis

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome

FEBRE HEMORRÁGICA PELO VÍRUS DA DENGUE: ANÁLISE EPIDEMIOLÓGICA DA MORBIDADE HOSPITALAR NA MACRORREGIÃO OESTE DO ESTADO DO PARANÁ, NO PERÍODO DE 2014 A 2024

Dengue is one of the most common contagious diseases in Brazil, caused by different types of viruses and transmitted mainly by the Aedes aegypti mosquito. Its clinical manifestation varies widely, from asymptomatic cases to severe situations such as hemorrhagic fever, which can result in death. The objective of this study is to carry out an epidemiological analysis of cases of hemorrhagic fever caused by the dengue virus in the Western Macroregion of the state of Paraná, covering the period from 2014 to 2024. This is an ecological, descriptive, quantitative and retrospective study, in the in which the SUS Hospital Morbidity data of patients reported with hemorrhagic fever were analyzed from January 2014 to April 2024, in the Western Macroregion of the state of Paraná, using data contained in the database of the SUS IT Department (DATASUS). During the period and region analyzed, the study sample consisted of 298 patients hospitalized due to hemorrhagic fever. The majority of cases occurred in male adults of white ethnicity. There were 26 deaths, the majority of which were in older age groups, male and white. April was the month with the highest number of hospitalizations during the period studied. The total cost of hospitalizations reached R$279,852.21, indicating a significant financial impact on the public health system. Therefore, hemorrhagic fever represents a challenge for the health system in the Western Macroregion, both in terms of incidence, costs and mortality. Therefore, it is crucial to maintain continuous vigilance and take preventative measures to avoid new cases.A dengue é uma das enfermidades contagiosas mais comuns no Brasil, causada por diferentes tipos de vírus e transmitida principalmente pelo mosquito Aedes aegypti. A sua manifestação clínica varia amplamente, desde casos assintomáticos até situações severas como a febre hemorrágica, que pode resultar em morte. O objetivo deste estudo é realizar uma análise epidemiológica dos casos de febre hemorrágica causada pelo vírus da dengue na Macrorregião Oeste do estado do Paraná, abrangendo o período de 2014 a 2024. Trata-se de um estudo ecológico, descritivo, quantitativo e retrospectivo, no qual foram analisados os dados de Morbidade Hospitalar do SUS dos pacientes notificados com febre hemorrágica no período de janeiro de 2014 a abril de 2024, na Macrorregião Oeste do estado do Paraná, por meio dos dados contidos no banco de dados do Departamento de Informática do SUS (DATASUS). Durante o período e na região analisada, a amostra do estudo consistiu de 298 pacientes hospitalizados devido à febre hemorrágica. A maioria dos casos ocorreu em adultos do sexo masculino e de etnia branca. Houve 26 óbitos, sendo a maioria em indivíduos de faixas etárias avançadas, do sexo masculino e de etnia branca. Abril foi o mês com o maior número de hospitalizações durante o período estudado. O custo total das hospitalizações alcançou R$ 279.852,21, indicando um impacto financeiro significativo para o sistema de saúde pública. Assim sendo, a febre hemorrágica representa um desafio para o sistema de saúde na Macrorregião Oeste, tanto em termos de incidência quanto de custos e mortalidade. Portanto, é crucial manter vigilância contínua e tomar medidas preventivas para evitar novos casos. &nbsp

Laryngopharyngeal reflux diagnosis in obstructive sleep apnea patients using the pepsin salivary test

Background: To investigate the presence of laryngopharyngeal reflux in patients with obstructive sleep apnea (OSA) employing the salivary pepsin concentration method. To compare the results of pepsin concentration with the severity of the pathology. Methods: Seventy-five OSA patients (44 males, 31 females) were enrolled in the study. For each patient, the AHI (apnea–hypopnea index) and the BMI (body mass index) were initially evaluated. All the patients enrolled were assessed using the reflux symptom index (RSI) and the reflux finding score (RFS) in order to perform a clinical diagnosis of laryngopharyngeal reflux. In all patients a salivary sample was taken to estimate the presence of pepsin and its concentration. Results: The incidence of LPR (laryngopharyngeal reflux) in OSA patients, evaluated using the salivary pepsin concentration test (PEP-test), was found to be 32% of cases. Linear regression testing did not show any correlation between AHI and pepsin concentration in salivary samples (p = 0.1). Conclusion: A high number of patients with OSA seem to show positivity for salivary pepsin, correlated to an LPR. There does not appear to be a correlation between the severity of apnea and the grade of salivary pepsin reflux. On the other hand, direct correlation between BMI and the value of pepsin in salivary specimens was observed

RANKL Cytokine: From Pioneer of the Osteoimmunology Era to Cure for a Rare Disease

Since its identification, the RANKL cytokine has been demonstrated to play a crucial role in bone homeostasis and lymphoid tissue organization. Genetic defects impairing its function lead to a peculiar form of autosomal recessive osteopetrosis (ARO), a rare genetic bone disease presenting early in life and characterized by increased bone density due to failure in bone resorption by the osteoclasts. Hematopoietic stem cell transplantation (HSCT) is the only option for the majority of patients affected by this life-threatening disease. However, the RANKL-dependent ARO does not gain any benefit from this approach, because the genetic defect is not intrinsic to the hematopoietic osteoclast lineage but rather to the mesenchymal one. Of note, we recently provided proof of concept of the efficacy of a pharmacological RANKL-based therapy to cure this form of the disease. Here we provide an overview of the diverse roles of RANKL in the bone and immune systems and review the clinical features of RANKL-deficient ARO patients and the results of our preclinical studies. We emphasize that these patients present a continuous worsening of the disease in the absence of a cure and strongly wish that the therapy we propose will be further developed

The IMPACT study: early loss of skeletal muscle mass in advanced pancreatic cancer patients

Abstract Background Pancreatic cancer (PC) patients have multiple risk factors for sarcopenia and loss of skeletal muscle mass (LSMM), which may cause greater treatment toxicities, reduced response to cancer therapy, prolonged hospitalization, impaired quality of life, and worse prognosis. Methods This is a retrospective study on advanced PC patients treated at the Department of Oncology of Udine, Italy, from January 2012 to November 2017. Among 162 patients who received chemotherapy, 94 consecutive patients with an available computed tomography (CT) scan were retrospectively analyzed. The primary objective of our study was to explore if an early LSMM ≥ 10% (measured at first radiological evaluation and compared with baseline) and/or baseline sarcopenia may impact prognosis. Baseline sarcopenia was defined according to Prado's criteria. Skeletal muscle area was measured as cross‐sectional areas (cm2) using CT scan data through the Picture archiving and communication system (PACS) image system. Results In the whole cohort, 48% of patients were ≤70 years old, and 50% had metastatic disease. At baseline, 73% of patients had sarcopenia, and 16% presented a visceral fat area ≥ 44 cm2/m2. Overall, 21% experienced an early LSMM ≥ 10%. Approximately 33% of sarcopenic patients at baseline and ~35% of patients with early LSMM ≥ 10% had a body mass index > 25 kg/m2. Of note, 71% of patients were evaluated by a nutritionist, and 56% received a dietary supplementation (oral and/or parenteral). After a median follow‐up of 30.44 months, median overall survival (OS) was 11.28 months, whereas median progression‐free survival (PFS) was 5.72 months. By multivariate analysis, early LSMM ≥ 10% was significantly associated with worse OS [hazard ratio (HR): 2.16; 95% confidence interval (CI) 1.23–3.78; P = 0.007] and PFS (HR: 2.31; 95% CI 1.30–4.09; P = 0.004). Moreover, an exploratory analysis showed that inflammatory indexes, such as neutrophil–lymphocyte ratio variation, impact early LSMM ≥ 10% (odds ratio 1.31, 95% CI 1.06–1.61, P = 0.010). Conclusions Early LSMM ≥ 10% has a negative prognostic role in advanced PC patients. Further prospective investigations are needed to confirm these preliminary data

Global distribution of organic carbon content and age in submarine canyons: results from the Factors influencing the Accumulation of organic Carbon and its Transfer in Submarine canyons (FACTS) project

6th International Submarine Canyon Symposium (INCISE-2023), 4th to 8th December 2023, Wellington, New ZealandSubmarine canyons are ubiquitous geomorphological features of continental margins that serve as important pathways of organic carbon (OC) transfer from coastal environments to deep-sea basins. Through the FACTS project, we compiled surficial sedimentological (e.g., grain size, mineral surface area) and geochemical (e.g., OC, ẟ13C, Δ14C) data from 48 submarine canyons incising continental margins worldwide to understand the processes that modulate the variations in the quantity, origin, and age of OC. Despite a general fining of surficial sediments with increasing depth, OC content generally decreased downcanyon in all submarine canyons. This trend is attributed to the degradation of OC with increasing transit time, as observed by the general decrease in OC loading. The downcanyon degradation of OC is further supported by the general decrease of Δ14C, indicating an overall ageing of OC with across-margin distance. However, certain submarine canyons (e.g. Calahonda and Mackenzie canyons) did not follow this trend, and instead, presented a general increase in Δ14C, due to the deposition of older (e.g., petrogenic) OC in the canyon head that became progressively diluted by fresh marine OC input offshore. These results reveal that the primary driver of the contrasting OC signatures accumulating in submarine canyons worldwide is the origin and age of the OC delivered into the continental margin, whereas post-depositional processes promote its downcanyon ageing. To better understand the factors that affect the distribution of the origin of OC in submarine canyons, we analysed biomarkers (proteins, lipids and specific fatty acids, carbohydrates, as well as phytopigments) and compound-specific-isotope-analyses (CSIA) in fatty acids of three contrasting submarine canyons incising the Gulf of Palermo, Sicily. Although all canyons presented a decreasing contribution of terrestrially-derived biomarkers downcanyon, Oreto Canyon did not present the greatest terrestrial fraction despite its proximity to a river mouth. Instead, Eleuterio Canyon, located downcurrent within the Gulf, had the greatest terrestrial OM contribution. These results reveal that along-margin hydrodynamic processes also govern the dispersal of OM across these geomorphological features