Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons.

Microglia are activated in many neurological diseases and have been suggested to play an important role in the development of affective disorders including major depression. To investigate how microglial signaling regulates mood, we used bidirectional chemogenetic manipulations of microglial activity in mice. Activation of microglia in the dorsal striatum induced local cytokine expression and a negative affective state characterized by anhedonia and aversion, whereas inactivation of microglia blocked aversion induced by systemic inflammation. Interleukin-6 signaling and cyclooxygenase-1 mediated prostaglandin synthesis in the microglia were critical for the inflammation-induced aversion. Correspondingly, microglial activation led to a prostaglandin-dependent reduction of the excitability of striatal neurons. These findings demonstrate a mechanism by which microglial activation causes negative affect through prostaglandin-dependent modulation of striatal neurons and indicate that interference with this mechanism could milden the depressive symptoms in somatic and psychiatric diseases involving microglial activation.

Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells.

The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the TH17 subset of helper T cells remain unclear. Here we used a novel strategy for the conditional deletion of distinct IL-6-producing cell types to show that dendritic cells (DCs) positive for the signaling regulator Sirpα were essential for the generation of pathogenic TH17 cells. Using their IL-6 receptor α-chain (IL-6Rα), Sirpα+ DCs trans-presented IL-6 to T cells during the process of cognate interaction. While ambient IL-6 was sufficient to suppress the induction of expression of the transcription factor Foxp3 in T cells, trans-presentation of IL-6 by DC-bound IL-6Rα (called 'IL-6 cluster signaling' here) was needed to prevent premature induction of interferon-γ (IFN-γ) expression in T cells and to generate pathogenic TH17 cells in vivo. Our findings should guide therapeutic approaches for the treatment of TH17-cell-mediated autoimmune diseases.

Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor.

The World Health Organization's tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RT-qPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Laparoscopic versus open approach for interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced epithelial ovarian cancer: a matched comparative study.

BACKGROUND: The use of the laparoscopic approach for the treatment of carcinomatosis from epithelial ovarian cancer (EOC) is controversial. The aim of this study was to compare the short-term outcomes of both laparoscopic and open approach for interval CRS+HIPEC in a matched cohort of patients with advanced EOC. METHODS: A retrospective analysis of a prospectively maintained database including 254 patients treated with interval CRS-HIPEC between January 2016 and December 2021 was performed. Patients with primary disease and limited carcinomatosis (PCI ≤ 10) were selected. A comparative analysis of patients treated by either open (O-CRS-HIPEC) or the laparoscopic (L-CRS-HIPEC) approach was conducted. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were analysed. RESULTS: Fifty-three patients were finally selected and enrolled into two comparable groups in this study. Of these, 14 patients were treated by interval L-CRS-HIPEC and 39 by interval O-CRS-HIPEC. The L-CRS-HIPEC group had a shorter hospital stay (5.6 ± 1.9 vs. 9.7 ± 9.8 days; p < 0.001) and a shorter time to return to systemic chemotherapy (4.3 ± 1.9 vs. 10.3 ± 16.8 weeks; p = 0.003). There were no significant differences in postoperative complications between both groups. The 2-year OS and DFS was 100% and 62% in the L-CRS-HIPEC group versus 92% and 60% in the O-CRS-HIPEC group, respectively (p = 0.96; p = 0.786). CONCLUSION: This study suggests that the use of interval L-CRS-HIPEC for primary advanced EOC is associated with shorter hospital stay and return to systemic treatment while obtaining similar oncological results compared to the open approach. Further prospective research is needed to recommend this new approach for these strictly selected patients.

SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities.

Hematological malignancies are a highly heterogeneous group of diseases with varied molecular and phenotypical characteristics. SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes play significant roles in the regulation of gene expression, being essential for processes such as cell maintenance and differentiation in hematopoietic stem cells. Furthermore, alterations in SWI/SNF complex subunits, especially in ARID1A/1B/2, SMARCA2/4, and BCL7A, are highly recurrent across a wide variety of lymphoid and myeloid malignancies. Most genetic alterations cause a loss of function of the subunit, suggesting a tumor suppressor role. However, SWI/SNF subunits can also be required for tumor maintenance or even play an oncogenic role in certain disease contexts. The recurrent alterations of SWI/SNF subunits highlight not only the biological relevance of SWI/SNF complexes in hematological malignancies but also their clinical potential. In particular, increasing evidence has shown that mutations in SWI/SNF complex subunits confer resistance to several antineoplastic agents routinely used for the treatment of hematological malignancies. Furthermore, mutations in SWI/SNF subunits often create synthetic lethality relationships with other SWI/SNF or non-SWI/SNF proteins that could be exploited therapeutically. In conclusion, SWI/SNF complexes are recurrently altered in hematological malignancies and some SWI/SNF subunits may be essential for tumor maintenance. These alterations, as well as their synthetic lethal relationships with SWI/SNF and non-SWI/SNF proteins, may be pharmacologically exploited for the treatment of diverse hematological cancers.

Bacillus coagulans GBI-30, 6086 (BC30) improves lactose digestion in rats exposed to a high-lactose meal.

PURPOSE: Bacillus coagulans GBI-30, 6086 (BC30) was previously shown to improve nutrient digestibility and amino acid absorption from milk protein in vitro. However, the effect of supplementation with this probiotic on lactose digestibility has not yet been evaluated in vivo. METHODS: Wistar female rats were exposed to an acute high-lactose diet (LD; 35% lactose) meal challenge after 7 days of administration of BC30 (LD-BC; n = 10) or vehicle (LD-C; n = 10). Rats treated with vehicle and exposed to control diet (CD; 35% corn starch) meal were used as controls (CD-C; n = 10). Carbohydrate oxidation (CH_OX) and lipid oxidation (L_OX) were monitored by indirect calorimetry before and after lactose challenge. After the challenge, rats were treated daily with vehicle or probiotic for an additional week and were fed with CD or LD ad libitum to determine the effects of BC30 administration in a lactose-induced diarrhoea and malnutrition model. RESULTS: LD-C rats showed lower CH_OX levels than CD rats, while LD-BC rats showed similar CH_OX levels compared to CD rats during the lactose challenge, suggesting a better digestion of lactose in the rats supplemented with BC30. BC30 completely reversed the increase in the small intestine length of LD-C animals. LD-BC rats displayed increased intestinal mRNA Muc2 expression. No significant changes were observed due to BC30 administration in other parameters, such as serum calprotectin, intestinal MPO activity, intestinal A1AT and SGLT1 levels or intestinal mRNA levels of Claudin2 and Occludin. CONCLUSION: Treatment with BC30 improved the digestibility of lactose in an acute lactose challenge and ameliorated some of the parameters associated with lactose-induced malnutrition.

Comparison of amoxicillin administered twice and three times daily in children with acute otitis media.

To compare the effectiveness of amoxicillin administered in regimens of two or three daily doses in children with acute otitis media (AOM). As a secondary aim, we measured and compared treatment adherence between the two groups.A prospective observational study was conducted in the emergency department of a children's hospital.We recruited a total of 353 patients having a median age of 1.58 years. Twice-daily dosing was prescribed to 58%, while 42% received three doses per day. The clinical course of AOM was favourable in 92% of the patients who received two doses of amoxicillin and in 95% of those who received three doses (p = 0.25). Four patients (1%) had persistent symptoms beyond day 7. None developed intracranial complications. In the group receiving three doses daily, 31% reported difficulties with the dosing schedule, and 9.6% faced challenges when administering the medication at the specified volume, compared with 5.8% and 25% of those who received the two-dose regimen, respectively.  Conclusion: Twice-daily amoxicillin has similar efficacy to a three-dose daily regimen and can offer advantages for caregivers in terms of administration schedule. What is Known: • Amoxicillin given in two daily doses is as effective as a three doses regimen in the treatment of acute otitis media in children. • The lower the number of daily doses, the higher the adherence to a drug treatment. What is New: • Administration of amoxicillin in twice-daily doses may improve adherence, as it is less frequently associated with family-perceived problems with dosing schedules.

Learning curve for minimal invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures.

PURPOSE: The benefits of the minimally invasive approach for performing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) have been described previously, associating an early recovery with similar oncologic outcomes in patients with limited peritoneal carcinomatosis. Currently, no studies are focusing on the learning curve for this emerging procedure. This study aimed to evaluate the L-CRS + HIPEC learning curve and its knock-on effect on the perioperative outcomes. METHODS: We identified all consecutive unselected patients who underwent L-CRS + HIPEC by a single surgeon between April 2016 and January 2022 (n = 51). Patients who underwent risk-reducing CRS + HIPEC (PCI = 0) or initial conversion due to an intraoperative PCI > 10 were excluded from the final analysis. To evaluate the learning curve, perioperative data were analysed using the cumulative sum (CUSUM) analysis. RESULTS: Twenty-six patients were included in the final analysis. Major morbidity occurred in one patient (3.8%). The difficulty of the L-CRS + HIPEC procedures was categorised as low in 23.1% (n = 6), intermediate in 19.2% (n = 5), and advanced in 57.7% (n = 15). The mean length of hospital stay was 5.4 ± 1.5 days. No patient had a conversion to open surgery. The learning curve was divided into two distinct phases: the learning phase (1-14) and the consolidation phase (15-26). A significant decrease in the operative time (375 ± 103.1 vs 239.2 ± 63.6 min) was observed with no differences in complexity, the number of peritonectomy procedures, or morbidity. CONCLUSION: L-CRS + HIPEC is a complex procedure that must be performed in a high-volume and experienced oncologic unit, requiring a learning curve to achieve the consolidation condition, which could be established after 14 procedures.

Intraoperative metabolic changes associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) causes considerable hemodynamic, respiratory, and metabolic changes during the perioperative period. OBJECTIVES: To evaluate metabolic changes associated with this procedure. Understanding perioperative factors and their association with morbidity may improve the perioperative management of patients undergoing this treatment. METHODS: A retrospective review of a prospectively maintained database was performed. All consecutive unselected patients who underwent CRS plus HIPEC between January 2018 and December 2020 (n = 219) were included. RESULTS: The mean age was 58 ± 11.7 years and 167 (76.3%) were female. The most frequent histology diagnosis was serous ovarian carcinoma 49.3% (n = 108) and colon carcinoma 36.1% (n = 79). Mean peritoneal cancer index was 14.07 ± 10.47. There were significant variations in pH, lactic acid, sodium, potassium, glycemia, bicarbonate, excess bases, and temperature (p < 0.05) between the pre-HIPEC and post-HIPEC periods. The closed HIPEC technique resulted in higher levels of temperature than the open technique (p < 0.05). Age, potassium level post-HIPEC potassium level, and pre-HIPEC glycemia were identified as prognostic factors for morbidity in multivariate analysis. CONCLUSION: The administration of HIPEC after CRS causes significant changes in internal homeostasis. Although the closed technique causes a greater increase in temperature, it is not related to higher morbidity rates. The patient's age, post-HIPEC potassium level, and pre-HIPEC glycemia are predictive factors for morbidity.

Regulation of adipose tissue inflammation by interleukin 6.

Obesity is associated with a chronic state of low-grade inflammation and progressive tissue infiltration by immune cells and increased expression of inflammatory cytokines. It is established that interleukin 6 (IL6) regulates multiple aspects of metabolism, including glucose disposal, lipolysis, oxidative metabolism, and energy expenditure. IL6 is secreted by many tissues, but the role of individual cell types is unclear. We tested the role of specific cells using a mouse model with conditional expression of the Il6 gene. We found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue. These opposite actions were associated with a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) with increased expression of the ADAM10/17 metalloprotease that promotes trans-signaling by the soluble IL6 receptor α. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.

Long-term effect of chemotherapy after ovarian decortication on the ovarian function in women surviving cancer.

PURPOSE: Ovarian decortication may affect ovarian function. We investigated the status of ovarian reserve after ovarian decortication plus chemotherapy at a stage of presumed stabilized recovery in women surviving cancer. METHODS: We searched our database for cancer survivors subjected to ovarian decortication and chemotherapy at least 3 years previously. Ovarian function was explored for levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2), and menstrual pattern. RESULTS: Forty women (mean age 29.6 (SD, 6.1) years) were assessed at a mean of 4.7 (1.5) years after surgery. The predecortication levels of AMH and FSH changed at post-treatment from 2.2 (1.4) to 0.5 (1.3) ng/mL for AMH (p < 0.001) and from 4.7 (2.1) to 16.7 (21. 6) IU/L for FSH (p < 0.001). Amenorrhea consistent with primary ovarian insufficiency (POI) was diagnosed in 11 women, and normal ovarian reserve (AMH ≥ 1.0 ng/mL) was found in 4 of the 21 women who recovered regular cycles. Logistic regression confirmed AMH as an independent predictor of diminished ovarian reserve (OR = 0.24, 95% CI: 0.04-0.63, p = 0.025) and POI (OR = 0.11, 95% CI: 0.01-0.52, p = 0.027), and age was predictive of POI (OR = 1.36, 95% CI: 1.08-1.96, p = 0.035) and of irregular menstrual cycle (OR = 1.20, 95% CI: 1.03-1.46, p = 0.034). CONCLUSION: Ovarian decortication plus chemotherapy had a deleterious effect when assessed at a stage of stabilized ovarian recovery, but whether ovarian decortication had a specific impact cannot be revealed from our data.

Microglial response promotes neurodegeneration in the Ndufs4 KO mouse model of Leigh syndrome.

Leigh syndrome is a mitochondrial disease characterized by neurodegeneration, neuroinflammation, and early death. Mice lacking NDUFS4, a mitochondrial complex I subunit (Ndufs4 KO mice), have been established as a good animal model for studying human pathology associated with Leigh syndrome. As the disease progresses, there is an increase in neurodegeneration and neuroinflammation, thereby leading to deteriorating neurological symptoms, including motor deficits, breathing alterations, and eventually, death of the animal. However, despite the magnitude of neuroinflammation associated with brain lesions, the role of neuroinflammatory pathways and their main cellular components have not been addressed directly as relevant players in the disease pathology. Here, we investigate the role of microglial cells, the main immune cells of the CNS, in Leigh-like syndrome pathology, by pharmacologically depleting them using the colony-stimulating factor 1 receptor antagonist PLX3397. Microglial depletion extended lifespan and delayed motor symptoms in Ndufs4 KO mice, likely by preventing neuronal loss. Next, we investigated the role of the major cytokine interleukin-6 (IL-6) in the disease progression. IL-6 deficiency partially rescued breathing abnormalities and modulated gliosis but did not extend the lifespan or rescue motor decline in Ndufs4 KO mice. The present results show that microglial accumulation is pathogenic, in a process independent of IL-6, and hints toward a contributing role of neuroinflammation in the disease of Ndufs4 KO mice and potentially in patients with Leigh syndrome.

BEST: a Shiny/R web-based application to easily retrieve cross-related enzyme functional parameters and information from BRENDA.

MOTIVATION: BRENDA is the largest enzyme functional database, containing information of 84 000 experimentally characterized enzyme entries. This database is an invaluable resource for researchers in the biological field, which classifies enzyme-related information in categories that are very useful to obtain specific functional and protein engineering information for enzyme families. However, the BRENDA web interface, the most used by researchers with a non-informatic background, does not allow the user to cross-reference data from different categories or sub-categories in the database. Obtaining information in an easy and fast way, in a friendly web interface, without the necessity to have a deep informatics knowledge, will facilitate and improve research in the enzymology and protein engineering field. RESULTS: We developed the Brenda Easy Search Tool (BEST), an interactive Shiny/R application that enables querying the BRENDA database for complex cross-tabulated characteristics, and retrieving enzyme-related parameters and information readily and efficiently, which can be used for the study of enzyme function or as an input for other bioinformatics tools. AVAILABILITY AND IMPLEMENTATION: BEST and its tutorial are freely available from https://pesb2.cl/best/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Total mutational load and clinical features as predictors of the metastatic status in lung adenocarcinoma and squamous cell carcinoma patients.

BACKGROUND: Recently, extensive cancer genomic studies have revealed mutational and clinical data of large cohorts of cancer patients. For example, the Pan-Lung Cancer 2016 dataset (part of The Cancer Genome Atlas project), summarises the mutational and clinical profiles of different subtypes of Lung Cancer (LC). Mutational and clinical signatures have been used independently for tumour typification and prediction of metastasis in LC patients. Is it then possible to achieve better typifications and predictions when combining both data streams? METHODS: In a cohort of 1144 Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LSCC) patients, we studied the number of missense mutations (hereafter, the Total Mutational Load TML) and distribution of clinical variables, for different classes of patients. Using the TML and different sets of clinical variables (tumour stage, age, sex, smoking status, and packs of cigarettes smoked per year), we built Random Forest classification models that calculate the likelihood of developing metastasis. RESULTS: We found that LC patients different in age, smoking status, and tumour type had significantly different mean TMLs. Although TML was an informative feature, its effect was secondary to the "tumour stage" feature. However, its contribution to the classification is not redundant with the latter; models trained using both TML and tumour stage performed better than models trained using only one of these variables. We found that models trained in the entire dataset (i.e., without using dimensionality reduction techniques) and without resampling achieved the highest performance, with an F1 score of 0.64 (95%CrI [0.62, 0.66]). CONCLUSIONS: Clinical variables and TML should be considered together when assessing the likelihood of LC patients progressing to metastatic states, as the information these encode is not redundant. Altogether, we provide new evidence of the need for comprehensive diagnostic tools for metastasis.

A Proposal for Modification of the PSOGI Classification According to the Ki-67 Proliferation Index in Pseudomyxoma Peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignancy, classified according to the Peritoneal Surface Oncology Group International (PSOGI) classification, whose response to treatment remains highly heterogeneous within the high-grade (HG) category. Molecular profiling of PMP cases might help to better categorize patients and predict treatment responses. METHODS: We studied the Ki-67 proliferation rate and P53 overexpression in tissue samples from our historical cohort of HG-PMP patients. We established as cut-off levels the third quartile of each marker to perform univariate and multivariate Cox regression survival analyses. According to these results, the HG-PMP category was divided into subcategories and a new survival analysis was performed. RESULTS: A total of 90/117 patients with PMP undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were selected for secondary analysis. The survival analysis of the HG-PMP category for preoperative variables showed that a proliferation index defined by Ki-67 >15% is a bad prognostic factor, with a hazard ratio (HR) of 3.20 (95% confidence interval [CI] 1.24-8.25). Accordingly, the HG-PMP group was divided using the Ki-67 15% cut-off. The new PSOGI/Ki-67 variable was an independent prognostic factor for overall survival (OS), with an HR of 3.74 (95% CI 1.88-7.47), and disease-free survival (DFS), with an HR of 4.184 (95% CI 1.79-9.75). The estimated 5-year OS rate was 100%, 70% and 24% for the LG-PMP, HG-PMP ≤15% and HG-PMP >15% groups, respectively (p = 0.0001), while the 5-year DFS rate was 90%, 44% and 0%, respectively (p = 0.0001). CONCLUSION: Division of the HG-PMP category of the PSOGI classification, according to the Ki-67 proliferation index, provides two well-defined subcategories, with significant differences in terms of OS and DFS, and hence high prognostic value.

Evolution of incidence of chilblain-like lesions in children during the first year of COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has brought innumerable reports of chilblains. The relation between pernio-like acral eruptions and COVID-19 has not been fully elucidated because most reported cases have occurred in patients with negative microbiological tests for SARS-CoV-2. METHODS: A retrospective study of 49 cases of chilblains seen during the first year of the pandemic in a children's hospital in Madrid, Spain. The incidence of these skin lesions was correlated with the number of COVID-19 admissions and environmental temperatures. Patients were separated into two groups depending on the day of onset (strict lockdown period vs. outside the lockdown period). RESULTS: Most chilblains cases presented during the first and third waves of the pandemic, paralleling the number of COVID-19 admissions. The first wave coincided with a strict lockdown, and the third wave coincided with the lowest ambient seasonal temperatures of the year. Systemic symptoms preceding chilblains were more frequent in the first wave (45.8% vs. 8.0%, p = .002), as was the co-occurrence with erythema multiforme-like lesions (16.7% vs. 0%, p = .033). Laboratory test and skin biopsies were performed more frequently in the first wave (75.0% vs. 12.0%, p < .001; and 25.0% vs. 0%, p = .007; respectively). Five patients developed recurrent cutaneous symptoms. CONCLUSIONS: An increased incidence of chilblains coincided not only with the two major waves of the pandemic, but also with the strict lockdown period in the first wave and low seasonal temperatures during the third wave. Both increased sedentary behaviors and cold environmental temperatures may have played an additive role in the development of COVID-19-related chilblains.

SCHC over LoRaWAN Efficiency: Evaluation and Experimental Performance of Packet Fragmentation.

Low Power Wide Area Networks (LPWAN) are expected to enable the massive connectivity of small and constrained devices to the Internet of Things. Due to the restricted nature of both end devices and network links, LPWAN technologies employ network stacks where there is no interoperable network layer as a general case; instead, application data are usually placed directly into technology-specific two-layer frames. Besides not being able to run standard IP-based protocols at the end device, the lack of an IP layer also causes LPWAN segments to operate in an isolated manner, requiring middleboxes to interface non-IP LPWAN technologies with the IP world. The IETF has standardized a compression and fragmentation scheme, called Static Context Header Compression and Fragmentation (SCHC), which can compress and fragment IPv6 and UDP headers for LPWAN in a way that enables IP-based communications on the constrained end device. This article presents a model to determine the channel occupation efficiency based on the transmission times of SCHC messages in the upstream channel of a LoRaWAN™ link using the ACK-on-Error mode of standard SCHC. The model is compared against experimental data obtained from the transmission of packets that are fragmented using a SCHC over LoRaWAN implementation. This modeling provides a relationship between the channel occupancy efficiency, the spreading factor of LoRa™, and the probability of an error of a SCHC message. The results show that the model correctly predicts the efficiency in channel occupation for all spreading factors. Furthermore, the SCHC ACK-on-Error mode implementation for the upstream channel has been made fully available for further use by the research community.

Characterisation of Endogenous Peptides Present in Virgin Olive Oil.

The low molecular weight peptide composition of virgin olive oil (VOO) is mostly unknown. We aimed to investigate the composition of the endogenous peptides present in VOO, the protein sources from which those peptides originate and their biological activities. A water-soluble extract containing peptides was obtained from VOO. The peptides were separated by size-exclusion using fast protein liquid chromatography, and the low molecular weight fraction (1600-700 kDa) was analysed by nanoscale liquid chromatography Orbitrap coupled with tandem mass spectrometry and de novo sequencing. Nineteen new peptides were identified by Peaks database algorithm, using the available Olea europaea (cv. Farga) genome database. Eight new peptides were also identified by Peaks de novo sequencing. The protein sources of the peptides detected in the database by Peaks DB were identified by BLAST-P search. Seed storage proteins were among the most frequent sources of VOO peptides. BIOPEP software was used to predict the biological activities of peptides and to simulate (in silico) the proteolytic activity of digestive enzymes on the detected peptide sequences. A selection of synthetic peptides was obtained for investigation of their bioactivities. Peptides VCGEAFGKA, NALLCSNS, CPANGFY, CCYSVY and DCHYFL possessed strong ACE-inhibitory and antioxidant activities in vitro. Antioxidant peptides could play a role in VOO quality.

From the Ronnett to the PSOGI Classification System for Pseudomyxoma Peritonei: A Validation Study.

BACKGROUND: Several classifications have been used for pseudomyxoma peritonei (PMP), and among these, the Ronnett classification is the most commonly used. However, a new consensual Peritoneal Surface Oncology Group International (PSOGI) classification has recently been proposed. Nonetheless, to date, the ability of the PSOGI classification to predict survival based on its different disease histologic categories has not been validated. METHODS: This study enrolled 117 patients with PMP who had undergone cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) between 1997 and 2020. Cox proportional hazards regression models and time-dependent curve receiver operating characteristic (ROC) analyses were used to assess the predictive capacity of both classification systems for the overall survival (OS) and disease-free survival (DFS) of these patients. RESULTS: Significant differences in the 5-year OS rate were found for the different histologic grades according to each of the classifications. The completeness of cytoreduction score (CCS) was identified as a factor that predicted patient OS prognosis (p = 0.006). According to the time-dependent ROC curves at the "100" time point, adjusted by the CCS and DFS, the capacity to predict OS was optimal and achieved an area under the curve (AUC) of about 69% for OS and approximately 62% for DFS. CONCLUSIONS: Both the Ronnett and PSOGI classifications were able to predict survival optimally for this patient cohort. However, when the classifications were adjusted by the CCS, the predictive availability for OS was better with the PSOGI classification than with the Ronnett classification.