Search

Breast cancer (BC) is one of the most significant neoplasms globally due to its high incidence and mortality, particularly among females. As a highly heterogeneous pathology, biomarkers are essential for characterizing specific tumors. Currently, several biological processes are well-described in the context of this neoplasm, such as alterations in BRCA1/2, HER, and pathways involving estrogen and progesterone hormone receptors. These studies have enabled the use of these findings as more precise methods for diagnosis, prognosis, and treatment. However, beyond patients who do not exhibit these classic markers, some individuals within the same risk group respond differently to treatment. Therefore, the search for biological markers that can improve diagnosis, aid in stratification, or serve as therapeutic targets is continuous and urgent. Genetic signatures have led to molecular tests currently used in clinical practice, though certain limitations persist. Understanding genetic and epigenetic mechanisms facilitates the identification of potential biomarkers. Biomarker targets must undergo experimental and clinical trials on samples of significant size before reaching clinical utility. In this review, we compile the classical markers and describe the potential use of other markers associated with the biological processes of this neoplasm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Building upon our previous study on peptoid-based antibacterials which showed good activity against Gram-positive bacteria only, herein we report the synthesis of 34 dimeric peptoid compounds and the investigation of their activity against Gram-positive and Gram-negative pathogens. The newly designed peptoids feature a di-hydrophobic moiety incorporating phenyl, bromo-phenyl, and naphthyl groups, combined with variable lengths of cationic units such as amino and guanidine groups. The study also underscores the pivotal interplay between hydrophobicity and cationicity in optimizing efficacy against specific bacteria. The bromophenyl dimeric guanidinium peptoid compound 10j showed excellent activity against S. aureus 38 and E. coli K12 with MIC of 0.8 μg mL -1 and 6.2 μg mL -1 , respectively. Further investigation into the mechanism of action revealed that the antibacterial effect might be attributed to the disruption of bacterial cell membranes, as suggested by tethered bilayer lipid membranes (tBLMs) and cytoplasmic membrane permeability studies. Notably, these promising antibacterial agents exhibited negligible toxicity against mammalian red blood cells. Additionally, the study explored the potential of 12 active compounds to disrupt established biofilms of S. aureus 38. The most effective biofilm disruptors were ethyl and octyl-naphthyl guanidinium peptoids (10c and 10 k). These compounds 10c and 10 k disrupted the established biofilms of S. aureus 38 with 51 % at 4x MIC (MIC = 17.6 μg mL -1 and 11.2 μg mL -1 ) and 56 %-58 % at 8x MIC (MIC = 35.2 μg mL -1 and 22.4 μg mL -1 ) respectively. Overall, this research contributes insights into the design principles of cationic dimeric peptoids and their antibacterial activity, with implications for the development of new antibacterial compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Thirty four compounds were identified in Sorbus torminalis (L.) fruit extracts of different maturity types by means of LC-DAD-MS (ESI+) fragmentation analysis. Both immature and mature fruits were rich in flavonoid glycosides esterified with hydroxycinnamic, phenolic and dicarboxylic acids along with benzoic, phenylpropanoic and cinnamoyl quinic acid derivatives with many of them being detected for the first time in Sorbus species and in literature. Extracts and fractions were tested for their antioxidant activity (DPPH, chemiluminescence, Rancimat assays) and the estimation of the phenolic content was carried out through Folin-Ciocalteu reagent. Ethyl acetate fraction exhibited the highest scavenging activity determined as EC 50  = 1.58 ± 0.22 μg/mL and EC 50  = 1.64 ± 0.24 μg/mL for immature and mature fruits respectively with the DPPH test. Chemiluminescence test indicated the same fraction having the strongest antioxidant activity with an IC 50 0.41 ± 0.06 μg/mL and IC 50 0.50 ± 0.02 μg/mL in both maturity types. The ethyl acetate fraction of the mature fruits is considered the most potent Aldose Reductase 2 (ALR2) inhibitor with 79% demonstrating the high nutritional value of Sorbus torminalis (L.) mature fruits as a defense mechanism against the onset of diabetes mellitus secondary complications leading to the utilization of the plant for nutritional and pharmaceutical purposes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eugene Kokkalou reports financial support was provided by Aristotle University of Thessaloniki. Eugene Kokkalou reports a relationship with Aristotle University of Thessaloniki that includes., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Stimulant-involved overdose deaths are increasing, driven by polysubstance use and adulteration of the illicit drug supply. While emerging evidence for prescription stimulant substitution is promising, there are no approved treatment options for stimulant use disorder that address the realities of an unpredictable drug supply. This study explores treatment experiences of people who use illicit stimulants (PWUS) to identify gaps and perceptions of prospective pharmaceutical stimulant substitution treatments (SST)., Methods: In-depth qualitative interviews were conducted with 86 PWUS in Vancouver, Canada. Thematic analysis focused on experiences of available treatment options for stimulant use and perceptions of prospective SST., Results: Participants identified how primarily behavioral treatment approaches do not meet the unique needs of PWUS, in contrast with the range of medical treatments available for opioid use disorder. Participants anticipated health and social benefits if they were able to access SST, including avoiding the toxic illicit stimulant supply, reduced engagement in criminalized activities, and greater economic security. Perceptions of prospective SST were informed by knowledge of existing opioid treatments. This led some participants to be unsupportive of SST, citing concerns around agency and highly regulated operational contexts that do not align with the lived realities of stimulant use., Conclusion: Findings demonstrate the need for SST pilot programs in real-world settings and underscore the health and social advantages SST may offer; although drawing on existing opioid treatment models to implement SST pilots may limit success. Thus, any novel treatments for stimulant use must centre the lived realities of PWUS., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biotechnological advancements require the physicochemical alteration of molecules to enhance their biological efficacy for the effective treatment of gastric ulcers. The study aimed to produce a polyelectrolytic compound from red angico gum (AG) by carboxymethylation, evaluate its physicochemical characteristics and investigate gastric protection against ethanol-induced ulcers. AG and carboxymethylated angico gum (CAG) were characterized by Fourier transform infrared spectroscopy, determination of the degree of substitution and gel permeation chromatography (GPC) and 13 C NMR techniques. The results demonstrated that the modification of the polymer was satisfactory, presenting conformational changes e improving the interaction with the gastric mucosa. AG and CAG reduced macroscopic and microscopic damage such as edema, hemorrhage and cell loss caused by exposure of the mucosa to alcohol. Both demonstrated antioxidant activity in vitro, and in vivo, pretreatment with gums led to the restoration of superoxide dismutase and glutathione levels compared to the injured group. Concurrently, the levels of malondialdehyde and nitrite decreased. Atomic force microscopy showed that CAG presented better conformational properties of affinity and protection with the gastric mucosa compared to AG in the acidic pH. Based on our findings, it is suggested that this compound holds promise as a prospective product for future biotechnological applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests personal relationshipsthat could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Injectable opioid agonist treatment (iOAT) has recently been expanded in some geographical contexts in Canada as part of a response to the escalating overdose crisis. Complex gendered dynamics, including power differentials, violence, and social norms, shape the overdose crisis and drug treatment programs which can adversely impact women's experiences. This qualitative study examines how social (e.g., gender, income, housing) and structural factors (e.g., program policies) impact women's experiences of iOAT., Methods: Qualitative interviews were completed with 16 women enrolled in four iOAT programs in Vancouver, Canada. Approximately 50 hours of ethnographic observations were conducted. Interview transcripts and ethnographic fieldnotes were analyzed using a critical feminist lens by applying the concepts of embodiment, relationality, and social control to understand women's engagement and self-reported treatment outcomes., Results: Initial iOAT engagement was a relational process, including initiating treatment with a partner and engaging with iOAT to (re)build personal relationships. Relationships with iOAT providers, including flexibility and support with medication administration, were important to women, providing an affirming embodied experience and a greater sense of agency. However, program operations (e.g., mandated daily attendance, program crowding) incompatible with women's needs (e.g., employment) could undermine these positive experiences. Women's reported outcomes highlight a tension between achieving more agency and the constraints of intensive and stigmatized treatment., Conclusion: This study highlights how iOAT is both a source of care and control for women from a relational and embodied perspective. Findings underscore the need for gender-attentive and flexible drug treatment services to meet the varied needs of women and the importance of providing relational care for women accessing iOAT., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Patellofemoral pain (PFP) is characterized by anterior knee, which intensifies during functional activities that require the eccentric action of the quadriceps muscle, specially. In ths way, quantitatively measurable functional tests that simulate these activities should be included in the physical therapy evaluation., Objective: To identify which functional tests are most indicated for the evaluation of women with PFD., Method: This study evaluated 100 young women (50 with PFP), during the execution of the following functional performance tests: Triple hop, Vertical Jump, Single leg squat, Step Down, YBalance tests, Lunge test and running. Dynamic valgus was also assessed in the tests. The isometric muscle strength of the following muscle groups: hip abductors, extensors and lateral rotators, knee extensors, evertors, and plantar flexors were evaluated. Functional Perception were evaluated by Anterior Knee Pain Scale and Activities of Daily Living Scale., Results: PFP group showed lower performance during the Y-Balance, triple hop, vertical jump tests and running. Was observed an increase in dynamic valgus during Triple Hop, Vertical Jump tests and running in PFP group, besides a poorer perception of function. For all lower limb muscle groups, the PFP group showed a reduction in peak isometric force., Conclusion: The YBalance, triple hop, vertical jump tests, and running should be included in the physical therapy evaluation, in addition to aspects of lower limb muscle strength., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

SHP2 is a phosphatase/adaptor protein that plays an important role in various signaling pathways. Its mutations are associated with cancers and developmental diseases. SHP2 contains a protein tyrosine phosphatase (PTP) and two SH2 domains. Selective inhibition of these domains has been challenging due to the multitude of homologous proteins in the proteome. Here, we developed a monobody, synthetic binding protein, that bound to and inhibited the SHP2 PTP domain. It was selective to SHP2 PTP over close homologs. A crystal structure of the monobody-PTP complex revealed that the monobody bound both highly conserved residues in the active site and less conserved residues in the periphery, rationalizing its high selectivity. Its epitope overlapped with the interface between the PTP and N-terminal SH2 domains that is formed in auto-inhibited SHP2. By using the monobody as a probe for the accessibility of the PTP active site, we developed a simple, nonenzymatic assay for the allosteric regulation of SHP2. The assay showed that, in the absence of an activating phospho-Tyr ligand, wild-type SHP2 and the "PTP-dead" C459E mutant were predominantly in the closed state in which the PTP active site is inaccessible, whereas the E76K and C459S mutants were in the open, active state. It also revealed that previously developed monobodies to the SH2 domains, ligands lacking a phospho-Tyr, weakly favored the open state. These results provide corroboration for a conformational equilibrium underlying allosteric regulation of SHP2, provide powerful tools for characterizing and controlling SHP2 functions, and inform drug discovery against SHP2., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.K. is a co-founder and holds equity in Revalia Bio and Aethon Therapeutics; has received consultation fees from Black Diamond Therapeutics and Aethon Therapeutics; has received research funding from Puretech Health, Argenx BVBA, Black Diamond Therapeutics and Aethon Therapeutics. A.K. and S.K. are listed as inventors on issued and pending patents on the monobody technology filed by The University of Chicago (US Patent 9512199 B2 and related pending applications). The other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Climate change leads to an increase in water acidification and temperature, two environmental factors that can change fish appetite and metabolism, affecting fish population in both wild and aquaculture facilities. Therefore, our study tested if climate change affects gene expression levels of two appetite-regulating peptides - Neuropeptide Y (NPY) and Cholecystokinin (CCK) - in the brain of tambaqui, Colossoma macropomum. Additionally, we show the distribution of these genes throughout the body. Amino acid sequences of CCK and NPY of tambaqui showed high similarity with other Characiformes, with the closely related order Cypriniformes, and even with the more distantly related order Salmoniformes. High apparent levels of both peptides were expressed in all brain areas, while expression levels varied for peripheral tissues. NPY and CCK mRNA were detected in all peripheral tissues but cephalic kidney for CCK. As for the effects of climate change, we found that fish exposed to extreme climate scenario (800 ppm CO 2 and 4.5 °C above current climate scenario) had higher expression levels of NPY and lower expression levels of CCK in the telencephalon. The extreme climate scenario also increased food intake, weight gain, and body length. These results suggest that the telencephalon is probably responsible for sensing the metabolic status of the organism and controlling feeding behavior through NPY, likely an orexigenic hormone, and CCK, which may act as an anorexigenic hormone. To our knowledge, this is the first study showing the effects of climate change on the endocrine regulation of appetite in an endemic and economically important fish from the Amazon. Our results can help us predict the impact of climate change on both wild and farmed fish populations, thus contributing to the elaboration of future policies regarding their conservation and sustainable use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: A biphasic allergic reaction develops in 0.4-20% of patients with an allergic reaction, but the incidence of severe biphasic reactions is unknown OBJECTIVE: Our objective was to assess the incidence and time of onset of clinically relevant biphasic reactions in a Dutch emergency department (ED) cohort. Furthermore, the characteristics of patients with a biphasic reaction and the mean observation time after an allergy-related ED visit were assessed., Methods: This was a single-center retrospective cohort study. We collected data from clinical records of adult patients presenting with an allergic reaction to the ED between January 2015 and December 2019. We defined clinically relevant biphasic reactions as biphasic reactions in which the criteria for anaphylaxis were met., Results: Five hundred fifty-seven patients were included. Eight patients (1.4%) developed a biphasic reaction, of which 1 (0.2% of the total inclusions) was clinically relevant. In the subgroup of patients with an anaphylactic reaction (n = 258), those percentages were 2.3% and 0.4%, respectively. The mean time between the initial allergic reaction and the biphasic allergic reaction was 25.4 h (95% CI 13.2-37.6 h). The single clinically relevant biphasic reaction occurred 30 h after the initial reaction., Conclusions: The incidence of clinically relevant biphasic reactions in our cohort was low, with a mean time between the initial allergic reaction and the biphasic reaction of > 24 h. Based on these single-center retrospective data, routine inpatient monitoring for several hours does not seem warranted for all patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background & Aims: COVID-19 patients present a high hospitalization rate with a high mortality risk for those requiring intensive care. When these patients have other comorbid conditions and older age, the risk for severe disease and poor outcomes after ICU admission are increased. The present work aims to describe the preliminary results of the ongoing NUTRICOVID study about the nutritional and functional status and the quality of life of adult COVID-19 survivors after ICU discharge, emphasizing the in-hospital and discharge situation of this population., Methods: A multicenter, ambispective, observational cohort study was conducted in 16 public hospitals of the Community of Madrid with COVID-19 survivors who were admitted to the ICU during the first outbreak. Preliminary results of this study include data retrospectively collected. Malnutrition and sarcopenia were screened at discharge using MUST and SARC-F; the use of healthcare resources was measured as the length of hospital stay and requirement of respiratory support and tracheostomy during hospitalization; other study variables were the need for medical nutrition therapy (MNT); and patients' functional status (Barthel index) and health-related quality of life (EQ-5D-5L)., Results: A total of 176 patients were included in this preliminary analysis. Most patients were male and older than 60 years, who suffered an average (SD) weight loss of 16.6% (8.3%) during the hospital stay, with a median length of stay of 53 (27-89.5) days and a median ICU stay of 24.5 (11-43.5) days. At discharge, 83.5% and 86.9% of the patients were at risk of malnutrition and sarcopenia, respectively, but only 38% were prescribed MNT. In addition, more than 70% of patients had significant impairment of their mobility and to conduct their usual activities at hospital discharge., Conclusions: This preliminary analysis evidences the high nutritional and functional impairment of COVID-19 survivors at hospital discharge and highlights the need for guidelines and systematic protocols, together with appropriate rehabilitation programs, to optimize the nutritional management of these patients after discharge., Competing Interests: Conflict of interest Dr. C.C. reports personal fees from Takeda, personal fees from Fresenius Kabi, personal fees from Baxter, personal fees from Nutricia, personal fees from Persan Farma, outside the submitted work. The rest of the authors declare no conflict of interest related to this article. The authors declare that the funding provider was not involved in analyzing and dissemination of the study results, and that no conflict of interest exists with this organization., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Radiation therapy is a standard part of limb conserving therapy for extremity soft tissue sarcoma (STS) at high risk of recurrence. Toxic effects increase with radiation dose and volume of normal tissue irradiated. This study sought to compare dosimetry of volumetric modulated arc therapy (VMAT) with intensity modulated radiation therapy (IMRT) and to investigate the optimal planning technique., Methods and Materials: Twenty patients with extremity STS who underwent preoperative radiation therapy (50 Gy in 25 fractions) between 2016 and 2020 at a specialised sarcoma center were included. The original treatment techniques were sliding window IMRT or 3-dimensional conformal. VMAT plans were retrospectively generated according to the original tumor and organ-at-risk constraints. Quality assurance was performed as per departmental protocol. Wilcoxon signed-rank test was used to compare dosimetric parameters (for planning target volume [PTV], in-field bone, and soft tissue structures), monitor units (MUs), and treatment time., Results: Median patient age was 65 years and the majority were male (n = 14, 70%). The most common subtype was undifferentiated pleomorphic sarcoma (n = 14, 70%), and most tumors were located on the thigh (n = 12, 60%). Median PTV was 1110 cm 3 and median volume of in-field bone 236 cm 3 . VMAT plans had significantly lower average MU (480 vs 862 MU, P < .001) and overall treatment time (300 vs 153 seconds, P < .001). PTV coverage favored VMAT, with marginally higher mean, minimum, and maximum doses and higher conformity index. However, differences were not statistically significant. Dose to infield bone and soft tissue structures were similar or slightly lower with VMAT., Conclusions: In extremity STS, VMAT plans demonstrated a favorable trend toward tumor coverage and dose conformity compared with IMRT along with significantly lower MUs and half the overall treatment time., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

In retroviruses, strand displacement DNA-dependent DNA polymerization catalyzed by the viral reverse transcriptase (RT) is required to synthesize double-stranded proviral DNA. In addition, strand displacement during RNA-dependent DNA synthesis is critical to generate high-quality cDNA for use in molecular biology and biotechnology. In this work, we show that the loss of RNase H activity due to inactivating mutations in HIV-1 RT (e.g. D443N or E478Q) has no significant effect on strand displacement while copying DNA templates, but has a large impact on DNA polymerization in reactions carried out with RNA templates. Similar effects were observed with β-thujaplicinol and other RNase H active site inhibitors, including compounds with dual activity (i.e., characterized also as inhibitors of HIV-1 integrase and/or the RT DNA polymerase). Among them, dual inhibitors of HIV-1 RT DNA polymerase/RNase H activities, containing a 7-hydroxy-6-nitro-2H-chromen-2-one pharmacophore were found to be very potent and effective strand displacement inhibitors in RNA-dependent DNA polymerization reactions. These findings might be helpful in the development of transcriptomics technologies to obtain more uniform read coverages when copying long RNAs and for the construction of more representative libraries avoiding biases towards 5' and 3' ends, while providing valuable information for the development of novel antiretroviral agents., Competing Interests: Competing interests HIV-1 group O RTs mentioned in the manuscript (sold under the commercial name SunScript™) and methods for their use are the subject of patents and patent applications that have been licensed by CSIC to 4Basebio AG. L.M.-A. receives royalty payments for the sales of relevant enzymes and kits., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Associations of arsenic (As) with the sum of 5-mC and 5-hmC levels have been reported; however, As exposure-related differences of the separated 5-mC and 5-hmC markers have rarely been studied., Methods: In this study, we evaluated the association of arsenic exposure biomarkers and 5-mC and 5-hmC in 30 healthy men (43-55 years) from the Aragon Workers Health Study (AWHS) (Spain) and 31 healthy men (31-50 years) from the Folic Acid and Creatinine Trial (FACT) (Bangladesh). We conducted 5-mC and 5-hmC profiling using Infinium MethylationEPIC arrays, on paired standard and modified (ox-BS in AWHS and TAB in FACT) bisulfite converted blood DNA samples., Results: The median for the sum of urine inorganic and methylated As species (ΣAs) (μg/L) was 12.5 for AWHS and 89.6 for FACT. The median of blood As (μg/L) was 8.8 for AWHS and 10.2 for FACT. At a statistical significance p-value cut-off of 0.01, the differentially methylated (DMP) and hydroxymethylated (DHP) positions were mostly located in different genomic sites. Several DMPs and DHPs were consistently found in AWHS and FACT both for urine ΣAs and blood models, being of special interest those attributed to the DIP2C gene. Three DMPs (annotated to CLEC12A) for AWHS and one DHP (annotated to NPLOC4) for FACT remained statistically significant after false discovery rate (FDR) correction. Pathways related to chronic diseases including cardiovascular, cancer and neurological were enriched., Conclusions: While we identified common 5-hmC and 5-mC signatures in two populations exposed to varying levels of inorganic As, differences in As-related epigenetic sites across the study populations may additionally reflect low and high As-specific associations. This work contributes a deeper understanding of potential epigenetic dysregulations of As. However, further research is needed to confirm biological consequences associated with DIP2C epigenetic regulation and to investigate the role of 5-hmC and 5-mC separately in As-induced health disorders at different exposure levels., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Loeys-Dietz syndrome (LDS) is a connective tissue disorder affecting multiple organ systems, including bone., Methods: We defined the bone phenotype and clinical predictors of low bone density and fracture risk in 77 patients with LDS type 1 to type 5., Results: Patients with LDS had dual-energy x-ray absorptiometry (DXA) Z-scores significantly < 0, and 50% of children and 9% of adults had Z-scores < -2. Sixty percent of patients had ≥1 fracture, and 24% of patients with spinal x-rays scans showed spinal compression fractures. Lower body mass index, asthma, male sex and eosinophilic gastrointestinal disease were correlated with lower DXA Z-scores. The count of 5 LDS-associated skeletal features (scoliosis, pes planus, arachnodactyly, spondylolisthesis, and camptodactyly) in patients with LDS was correlated with DXA Z-score. Adults with ≥1 skeletal features had DXA Z-scores significantly < 0, and children with >2 features had DXA Z-score significantly < -2. Bone turnover markers suggest accelerated bone resorption. Data from 5 patients treated with bisphosphonates suggest a beneficial effect., Conclusion: All LDS types are associated with reduced bone density and increased risk of fracture, which may be due to increased bone resorption. Clinical features can predict a subgroup of patients at highest risk of low bone density and fracture risk., Competing Interests: Conflict of Interest The authors declare no conflict of interests., (Copyright © 2021. Published by Elsevier Inc.)

As inflammation plays a critical role in the development and progression of cancer, therapeutic targeting of cytokine pathways involved in both tumorigenesis and dictating response to clinical treatments are of significant interest. Recent evidence has highlighted the importance of the pro-inflammatory cytokine interleukin-1 (IL-1) as a key mediator of tumor growth, metastatic disease spread, immunosuppression, and drug resistance in cancer. IL-1 promotes tumorigenesis through diverse mechanisms, including the activation of oncogenic signaling pathways directly in tumor cells and via orchestrating crosstalk between the cellular constituents of the tumor microenvironment (TME), thereby driving cancer growth. This review will provide an overview of IL-1 signaling and physiology and summarize the disparate mechanisms involving IL-1 in tumorigenesis and cancer progression. Additionally, clinical studies targeting IL-1 signaling in the management of solid organ tumors will be summarized herein., (Copyright © 2021. Published by Elsevier B.V.)

Background: North American cities are experiencing intersecting housing and overdose crises as illicit drug markets become marked by the proliferation of fentanyl and methamphetamine. Despite recent research documenting associations between evictions and drug-related risks and harms, including overdose, the mechanisms through which these occur remain poorly understood. This study to examines how evictions shape the drug use practices of people who use drugs in Vancouver's Downtown Eastside - a neighbourhood with an established drug scene - as the illicit drug supply changed., Methods: Qualitative interviews and geo-spatial data collection were conducted with 56 recently evicted PWUD. Data were analyzed by interfacing qualitative and geo-spatial data, and interpreted focusing on how structural vulnerability shaped spatial practices and drug-related risks post-eviction., Results: Findings demonstrate how post-eviction spatial practices and routines produced risk and harm as participants navigated the uncertainties of housing vulnerability and drug supply changes. Post-eviction disruptions complicated participants' ability to engage with trusted drug sellers. Changes to spatial patterns and access to private spaces rendered public drug use inevitable, though this was mitigated to some degree by harm reduction supports. Abrupt changes to drug use patterns occurred due to post-eviction disruptions and included instrumental uses of methamphetamine to increase alertness and navigate survival amidst severe hardship., Conclusions: Findings demonstrate how post-eviction changes to routines and spatial patterns are framed by structural vulnerability and can exacerbate drug-related harms, particularly in the context of a changing drug supply. There is an urgent need for structural interventions and harm reduction responses to mitigate harms associated with evictions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The increase in pesticide use in response to agricultural demands poses a risk to non-target organisms, including fish. Integrated analysis of biochemical, histopathological and genetic parameters in fish exposed to Malathion insecticide provide information on the toxicity mechanisms of this pesticide, which is classified as a probable carcinogen for humans. The present study assessed the biological responses of Colossoma macropomum after exposure to Malathion. We started determining the lethal concentration, which is the concentration capable of killing 50% of the subjects in an acute toxicity test (LC 50 -96 h), which was 15.77 ± 3.30 mgL -1 . The fish were, then, exposed to Malathion during 96 h at a sublethal concentration, 7.30 mgL -1 . Overall, we observed an increased activity of biotransformation and antioxidant enzymes, which reduced production of mitochondrial reactive oxygen species after 96 h exposure, as well as kept constant the mitochondrial respiration, Acetylcholinesterase activity and DNA damage. However, fish exposed to insecticide presented severe gill histopathological damage and increased expression of proto-oncogene ras. Taken together, the results suggest that, after four days of exposure to the Malathion, C. macropomum efficiently activates its defense mechanisms, suggesting that the basal response mechanisms are responsive. On the other hand, histopathologic damages evidenced the adverse effects of Malathion on fish, since it promoted gill necrosis and increased the expression of ras oncogene that is directly related to tumorigenesis events., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Within the context of the ongoing overdose crisis and limitations of conventional opioid treatments, the scale-up of injectable hydromorphone (HDM) and diacetylmorphine (DAM) as evidenced-based treatments is currently underway in some settings in Canada. Past research has underscored the importance of treatment initiation in shaping onward treatment trajectories, however structural factors that influence participants' motivations to access injectable HDM or DAM have not been fully characterized. This study examines peoples' motivations for accessing HDM/DAM treatment and situates these within the social and structural context that shapes treatment delivery by employing the concept of structural vulnerability., Methods: Fifty-two individuals enrolled in injectable HDM/DAM programs were recruited from four community-based clinical programs in Vancouver, Canada to participate in qualitative semi-structured interviews. Approximately 50 h of ethnographic fieldwork was also completed in one clinical setting, and one-on-one with participants public spaces. Interview transcripts and ethnographic fieldnotes were analyzed through a structural vulnerability lens with a focus on treatment initiation., Results: Participants' previous experiences and perceptions of other drug treatments (e.g. methadone) foregrounded their initiation of injectable HDM/DAM. Social and structural factors (e.g. fentanyl-adulterated drug supply, poverty, drug criminalization) influenced participants' motivations to address immediate physical risks and their initial perception of this treatment's ability to align with their opioid use experiences. Similar social and structural factors that drive immediate physical risks, were also evidenced in participants' motivations to make changes in their daily lives and to address broader opioid use goals., Conclusion: Participants descriptions of their motivations to initiate HDM/DAM highlight how structural vulnerabilities shaped participants' experiences initiating injectable HDM/DAM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: North America is experiencing an overdose crisis driven by illicitly-manufactured fentanyl, related analogues, and fentanyl-adulterated drugs. The concept of 'safe supply' has been suggested as a potential measure to address the overdose crisis by providing a regulated alternative to illicit opioids to people at high risk of fatal overdose. In January 2019, a novel hydromorphone tablet distribution program was implemented within an overdose prevention site in Vancouver, Canada's Downtown Eastside neighbourhood. This study explored barriers and facilitators to engagement with this program., Methods: In-depth interviews were conducted with 42 participants enrolled in the hydromorphone tablet distribution program, and over 100 h of ethnographic observation were conducted in and around the study site. Thematic analysis of the interviews and ethnographic observation focused on program operation, including barriers and facilitators to program uptake, access, and engagement., Results: Barriers to program engagement identified include: limited operating hours and dose schedule, co-location within the overdose prevention site (e.g., wait times), and receiving the generic formulation of hydromorphone. Facilitators identified include: having access to a reliable source of opioids, co-location within the overdose prevention site (e.g., low-barrier design), experiences of agency, and program flexibility., Conclusion: Our findings demonstrate key implementation and operational considerations of safe supply programs. In particular, lower-barrier design and operational features should be considered to improve uptake and engagement. Safe opioid supply programs are a promising intervention to address North America's ongoing overdose crisis by providing people at high risk of fatal overdose an alternative to the toxic drug supply., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Given the high incidence of confirmed infection by SARS-CoV-2 and mortality by COVID-19 in the Spanish population, its impact was analysed among persons with Cystic Fibrosis (CF) as a group at risk of a worse evolution. The possible causes of the incidence observed in them are explained and how CF Units have faced this health challenge is detailed., Methods: Retrospective descriptive observational study, for which a Spanish CF Patients with Confirmed COVID-19 Registry is created, requesting information on number of people affected between 8 March-16 May 2020 and their clinical-demographic characteristics from the CF Units participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR). The accumulated incidence is calculated, compared with that of the general population. Additionally, a survey (CF-COVID19-Spain) is carried out on prevention of SARS-CoV-2 infection, workings of CF Units and possible reasons for the incidence observed., Results: COVID-19 was diagnosed in eight CF patients, one of whom had received a lung transplant. The accumulated incidence was 32/10000 in CF patients and 49/10000 in the general population. General death rate was 5.85/10000 while no CF patients included in the ECFSPR died. The characteristics of those affected and the results of the survey are described., Conclusions: Despite being considered a disease at high risk of severe COVID-19, the low incidence and mortality in CF patients in Spain contrasts with the figures for the general population. The possible factors that would explain such findings are discussed, with the help of the results of the CF-COVID19-Spain survey., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Attention to how women are differentially impacted within harm reduction environments is salient amidst North America's overdose crisis. Harm reduction interventions are typically 'gender-neutral', thus failing to address the systemic and everyday racialized and gendered discrimination, stigma, and violence extending into service settings and limiting some women's access. Such dynamics highlight the significance of North America's first low-threshold supervised consumption site exclusively for women (transgender and non-binary inclusive), SisterSpace, in Vancouver, Canada. This study explores women's lived experiences of this unique harm reduction intervention., Methods: Ethnographic research was conducted from May 2017 to June 2018 to explore women's experiences with SisterSpace in Vancouver's Downtown Eastside, an epicenter of Canada's overdose crisis. Data include more than 100 hours of ethnographic fieldwork, including unstructured conversations with structurally vulnerable women who use illegal drugs, and in-depth interviews with 45 women recruited from this site. Data were analyzed in NVivo by drawing on deductive and inductive approaches., Findings: The setting (non-institutional), operational policies (no men; inclusive), and environment (diversity of structurally vulnerable women who use illegal drugs), constituted a space affording participants a temporary reprieve from some forms of stigma and discrimination, gendered and social violence and drug-related harms, including overdose. SisterSpace fostered a sense of safety and subjective autonomy (though structurally constrained) among those often defined as 'deviant' and 'victims', enabling knowledge-sharing of experiences through a gendered lens., Conclusion: SisterSpace demonstrates the value and effectiveness of initiatives that engage with socio-structural factors beyond the often narrow focus of overdose prevention and that account for the complex social relations that constitute such initiatives. In the context of structural inequities, criminalization, and an overdose crisis, SisterSpace represents an innovative approach to harm reduction that accounts for situations of gender inequality not being met by mixed-gender services, with relevance to other settings., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Biodiesel is a sustainable fuel, which consists of a mixture of fatty acid alkyl esters obtained by the transesterification of vegetable oils or animal fats. Due to the diversity of raw materials used in its production, the biofuel can show significant differences in its physicochemical properties, which causes severe matrix effects in biodiesel analysis. In this work, a calibration strategy recently proposed for atomic spectrometry, named multi-energy calibration (MEC), was evaluated as a tool to circumvent matrix effects in molecular spectrometry. The strategy yielded more accurate results in the spectrophotometric determination of the iodine value and free glycerol in biodiesel produced from different raw materials (root mean square error of prediction, RMSEP, values of 6.0 and 8.0, respectively), than both external standard calibration (EC, RMSEP as high as 45.6) and the standard additions method (SAM, RMSEP as high as 25.3). Moreover, results agreed with those obtained by the reference procedures at the 95% confidence level, which was not observed for EC (free glycerol determination) and SAM (iodine value determination). Coefficients of variation (n = 8) and limits of detection (99.7% confidence level) were, respectively, estimated at 1.7% and 5 g I 2 /100 g iodine value and 3.0% and 10 mg kg -1 free glycerol in biodiesel, which are comparable to or better than those achieved using previously proposed procedures. Thus, MEC is a viable alternative for biodiesel quality control, with outstanding minimization of matrix effects, simplicity, practicality, and environmental friendliness., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This study sought to evaluate the delivery of colposcopy assessments and treatments in Ontario from 2009 to 2017 according to specific performance measures, derived from guidelines on colposcopy use., Methods: This population-based descriptive analysis included screen-eligible women ages 21 to 69 in Ontario who underwent cervical screening between 2009 and 2017. Performance measures that describe the quality of colposcopy services in the province were calculated., Results: Five performance measures were used to assess the use of colposcopy in Ontario from 2009 to 2017. From 2013 to 2017, the percentage of women seen for colposcopy after a first diagnosis of atypical squamous cells of undetermined significance (ASCUS), without evidence of repeat cytology, remained stable, ranging from 5.9% to 6.3%. The median wait time to colposcopy for atypical glandular cells (AGC), atypical squamous cells (ASC-H), cannot rule out high-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions (HSIL), remained relatively stable from 2013 to 2017. In addition, the percentage of women with high-grade Pap test results who were seen in colposcopy within 6 months increased from 74.7% to 83.5%. The percentage of women who were not seen in follow-up within 12 months after treatment for cervical dysplasia remained stable, as did the percentage of women who discontinued colposcopy after three normal Pap test results following treatment for cervical dysplasia., Conclusion: This study developed five performance indicators and used them to assess the delivery of colposcopic services in Ontario from 2009 to 2017. Performance indicators have previously been used effectively in the field of colorectal cancer screening to identify strengths and weaknesses in the delivery of healthcare services. This had never previously been done in colposcopy., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

North America is in the midst of an overdose crisis. In some of the hardest hit areas of Canada, local responses have included the implementation of low-threshold drug consumption facilities, termed Overdose Prevention Sites (OPS). In Vancouver, Canada the crisis and response occur in an urban terrain that is simultaneously impacted by a housing crisis in which formerly 'undesirable' areas are rapidly gentrifying, leading to demands to more closely police areas at the epicenter of the overdose crisis. We examined the intersection of street-level policing and gentrification and how these practices re/made space in and around OPS in Vancouver's Downtown Eastside neighborhood. Between December 2016 and October 2017, qualitative interviews were conducted with 72 people who use drugs (PWUD) and over 200 h of ethnographic fieldwork were undertaken at OPS and surrounding areas. Data were analyzed thematically and interpreted by drawing on structural vulnerability and elements of social geography. While OPS were established within existing social-spatial practices of PWUD, gentrification strategies and associated police tactics created barriers to OPS services. Participants highlighted how fear of arrest and police engagement necessitated responding to overdoses alone, rather than engaging emergency services. Routine policing near OPS and the enforcement of area restrictions and warrant searches, often deterred participants from accessing particular sites. Further documented was an increase in the number of police present in the neighborhood the week of, and the week proceeding, the disbursement of income assistance cheques. Our findings demonstrate how some law enforcement practices, driven in part by ongoing gentrification efforts and buttressed by multiple forms of criminalization present in the lives of PWUD, limited access to needed overdose-related services. Moving away from place-based policing practices, including those driven by gentrification, will be necessary so as to not undermine the effectiveness of life-saving public health interventions amid an overdose crisis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The goal of this study was to assess the occurrence of steroid-associated adverse events (SAAE) in patients with primary proteinuric kidney disease., Methods: The Kidney Research Network Registry consists of children and adults with primary proteinuric kidney disease. SAAEs of interest were hypertension, hyperglycemia and diabetes, overweight and obesity, short stature, ophthalmologic complications, bone disorders, infections, and psychosis. Events were identified using International Classification of Diseases, Ninth Revision/Tenth Revision codes, blood pressures, growth parameters, laboratory values, and medications. Poisson generalized estimating equations tested the association between steroid onset and dose on SAAE risk., Results: A total of 884 participants were included in the analysis; 534 (60%) were treated with steroids. Of these, 62% had at least one SAAE. The frequency of any SAAE after initiation of steroids was 293 per 1000 person-years. The most common SAAEs were hypertension (173.7 per 1000 person-years), diabetes (78.7 per 1000 person-years), obesity (66.8 per 1000 person-years), and infections (46.1 per 1000 person-years). After adjustment for demographics, duration of kidney disease, estimated glomerular filtration rate (eGFR), proteinuria, and other therapies, steroid exposure was associated with a 40% increase in risk of any SAAE (Relative risk [RR]: 1.4; 95% confidence interval [CI]: 1.3-1.6). A 1-mg/kg per day increase in steroid dose was associated with a 2.5-fold increase in risk of any SAAE., Conclusion: Most patients with primary proteinuric kidney disease treated with steroids experienced at least one SAAE. Steroid therapy increased risk of hypertension, diabetes, weight gain, short stature, fractures, and infections after adjusting for disease-related factors. This study highlights the importance of surveillance and management of SAAE and provides rationale for the development of steroid minimization protocols., (© 2019 International Society of Nephrology. Published by Elsevier Inc.)

Although usual in analytical chemistry, separations of volatile analytes by distillation are time-consuming, whereas gas diffusion through membranes is characterized by low efficiency. These limitations directly hinder sample throughput and sensitivity. In this work, a simple and inexpensive approach is proposed for separation of volatile analytes by microdistillation. It consists of an eppendorf type tube containing the acceptor solution suspended inside a 50 mL Falcon ® capped tube containing the sample. The bottom of the sample tube is submitted to controlled heating in a water bath to promote analyte volatilization to the headspace, thus favoring its collection into the acceptor solution. The efficiency of the approach was evaluated by determination of methanol in biodiesel, whose threshold limit is 0.2% (m/m) according the current legislation. Measurements were based on discoloration of an acidic potassium permanganate solution (750 μL), caused by oxidation of methanol with consequent reduction to Mn(II). The analytical measurements were based on intensity of the reflected radiation acquired as digital images by the camera of a smartphone under controlled lighting. Values of the G channel were used as analytical parameter because of the complementarity with the color of the potassium permanganate solution. Under heating at 70 °C for 40 min, the transference of methanol to the acceptor solution was estimated at (98 ± 3)%. A linear response was achieved within 0.025% and 0.200% (m/m) methanol, with coefficient of variation (n = 10) and limit of detection (99.7% confidence level) estimated at 3.7% and 0.009% (m/m) respectively. The procedure requires only 100 μg of potassium permanganate and 200 μL of sample and generates as low as 950 μL of residue per determination. Because of the selectivity provided by microdistillation, the results obtained by the proposed approach agreed with the reference procedure at the 95% confidence level. The proposed approach is a simple, efficient, and cost-effective alternative for separation and determination of volatile species., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Tissue adhesive is widely used in the emergency department to repair minor lacerations but there exists a debate as to whether it should be used for chin lacerations. The main objective of this study was to evaluate the rate of wound dehiscence of chin lacerations repaired with tissue adhesive in comparison to sutures., Methods: This was a retrospective chart review including all children requiring a facial laceration reparation in a single tertiary care paediatric hospital. The primary outcome was wound dehiscence in the 30 days following reparation, comparing the use of tissue adhesive and sutures. The independent variable of interest was the use of tissue adhesive vs suture. A random sample of charts was reviewed in duplicate to insure reliability of the chart review., Results: Among the 2044 children presenting with a facial laceration requiring an intervention, 1804 (88%) were repaired using tissue adhesive. The laceration was located on the chin in 360 (18%) of patients. The use of tissue adhesive was not statistically associated with a higher risk of dehiscence for all facial lacerations (difference: 0.2; 95%CI: -1.9 to 0.8%), nor for chin lacerations (difference 2.2%; 95%CI: -7.5 to 4.4%). However, the probability of dehiscence was higher for chin laceration in comparison to other localizations (difference of 1.6%; 95%CI: 0.5-3.6%)., Conclusion: While the rate of dehiscence was higher for chin lacerations compared to other facial localizations, the risk of dehiscence was not statistically different for chin laceration repaired with tissue adhesive or sutures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The timing of social service benefit issuance is thought to be associated with increased drug overdose fatalities. However, the extent to which this excess mortality is concentrated in communities with higher levels of benefit receipt has not been studied. We sought to examine if benefit receipt at the neighborhood level was associated with spatiotemporal patterns of overdose fatalities., Methods: We conducted a retrospective review of all accidental overdose deaths recorded in Rhode Island from 2014 to 2016 (n = 838). Overdose incident locations were geocoded to the census block group level. Clusters of census block groups with excess overdose mortality at the beginning of a month were identified using spatial scan methods. Logistic regression models were fit to identify characteristics associated with the inclusion of a census block group within a cluster., Results: Increased rates of overdose fatalities at the beginning of a month were observed relative to the end of a preceding month (Ratio: 1.17; 95% CI: 1.04, 1.38). The proportions of residents receiving cash public assistance or Supplemental Security Income were not associated with excess mortality at the beginning of a month; however, the proportion of residents living in unaffordable housing was (OR: 1.42; 95% CI: 1.05, 1.91)., Conclusion: Despite previous research on benefit check issuance and overdose, welfare receipt was not associated with excess overdose mortality at the beginning of a month at the neighborhood level. Future research on housing cost burden and its influence on overdose death risk at the individual level is needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Methanol is used in transesterification reaction for biodiesel production, being an important quality parameter to evaluate the purity of the final product. Methanol concentrations higher than 0.20% (m/m) reduce the biofuel efficiency. The Brazilian, United States, and European standards recommend the reference method based on gas chromatography with flame ionization detection, which involves a time-consuming procedure and requires high-cost equipment. In this work, it is proposed a simple and low cost spot test based on digital images acquired with a smartphone camera for the determination of methanol in biodiesel. The procedure was based on the oxidation of methanol to formaldehyde and subsequent reaction with Schiff reagent, resulting in a violet product. Analytical signals were based on the reflected radiation measured on the G channel (RGB system), which refers to the complementary color of the reaction product. Linear responses were obtained within 20-500 mg kg -1 and 500-2000 mg kg -1 methanol for 600 and 150 µL of sample aqueous extracts, respectively. The coefficient of variation (n = 10) and the limit of detection (99.7% confidence level) were estimated as 4.8% and 10 mg kg -1 (600 µL of sample), respectively. The procedure requires only 75 µg of potassium permanganate, 6 mg of oxalic acid, and 1.5 mg of p-rosaniline and generates ca. 1.2 mL of residue per determination. The results agreed with those obtained by the reference procedure at the 95% confidence level, demonstrating that the proposed method is an alternative for routine analysis of the biofuel., (Copyright © 2018. Published by Elsevier B.V.)

Objective Chronic fatigue syndrome (CFS) patients report limited social support, which can affect symptom severity. Friends are a key source of social support for young adults with CFS, but there is limited research on friends' responses to the CFS label. We explored the potential benefits or harms of the CFS label for shaping the potential for social support from a friend's perspective. Method 207 university students responded to hypothetical scenarios about a close friend experiencing CFS. Participants were randomly allocated to either the CFS-label or no-label conditions. The potential for social support was operationalised as attitude (sympathetic or hostile), intended treatment support and intended behavioural support. Results The CFS label elicited a greater potential for social support, with significantly higher sympathetic responses, lower rejecting responses and greater support for active treatment. These effects were significantly greater in men compared to women. There was no effect on intended behavioural support. Conclusion This study suggests the CFS label may increase the potential for social support. Young adults, particularly men, held more supportive attitudes towards their friend when the CFS label was used. Practical Implications The effects of labels on the potential for social support need to be considered when evaluating the usefulness of a disease label., (Copyright © 2018. Published by Elsevier B.V.)

Crotalus bites are considered a public health problem especially in Latin America. This study was performed to describe the epidemiology, spatial distribution and environmental determinants of Crotalus durissus bites in the Brazilian Amazon. Crotalus durissus envenomings official database included cases reported from 2010 to 2015. A total of 70,816 snakebites were recorded in the Amazon Region, 3058 (4.3%) cases being classified as crotalid, with a mean incidence rate of 11.1/100,000 inhabitants/year. The highest mean incidence rates were reported in Roraima, Tocantins and Maranhão. Area covered by water bodies, precipitation and soil humidity were negatively associated to rattlesnake encountering. Rattlesnake bites incidence was positively associated to tree canopy loss and altitude. In the Amazon, severe manifestations at admission, delayed medical assistance, lack of antivenom administration and ages ≥61 and 0-15 years were predictors of death in C. durissus snakebites. Spatial distribution of rattlesnake bites across the Brazilian Amazon showed higher incidence in areas of transition from the equatorial forest to the savanna, and in the savanna itself. Such results may aid focused policy-making in order to mitigate the burden, clinical complications and death as well as to manage Crotalus rattlesnake populations in the Brazilian Amazon., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The ingestion of detritus by sea turtles results in high mortality and morbidity. The objective of this study was to describe the characteristics of free-living sea turtles that ingested anthropogenic inorganic detritus in comparison to those that did not. A total of 186 necropsy files were analyzed in marine turtles from the beaches of the Microregion dos Lagos, Rio de Janeiro. Among the turtles that ingested detritus, the mean turtle was female and cachectic, with a carapace length of 36,6 cm, detritus accumulated in the large intestine, and fecal compaction. It seems most likely that's low food transit, combined with the multiplicity of ingestion, favored the accumulation of detritus. This ingestion resulted in cachexia associated with fecal compaction, since the greatest accumulation was in the large intestine. The intake of detritus by turtles was not punctual but continuous. These studies demonstrated the vulnerability of these animals to environmental pollution., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: North America is experiencing an opioid overdose epidemic, fuelled by the proliferation of fentanyl, related analogues, and fentanyl-adulterated opioids. British Columbia, Canada has similarly experienced a rapid increase in the proportion of opioid overdose deaths associated with fentanyl. This study builds off of research characterizing fentanyl exposure to further explore the presentation of fentanyl use and related overdoses among people who use drugs., Methods: From December 2016 to April 2017, rapid ethnographic fieldwork was conducted in Vancouver, Canada to examine the implementation of low-threshold overdose prevention sites, where people use drugs under the supervision of staff and peers trained to respond to overdose. Data collection included 185 h of ethnographic observation and in-depth interviews with 72 people who inject drugs, 44 of whom reported experiencing an overdose in the year prior to the interviews., Results: While most participants had experienced previous opioid-related overdose, they characterized how fentanyl was markedly distinct in terms of: potency, and rapid onset. Ethnographic observations and participant narratives highlighted how fentanyl use and related overdoses had implications for frontline response, including: rapid onset, multiple concurrent overdoses, body and chest rigidity, and the need to administer larger doses of naloxone., Conclusions: Participant narratives and observational data documented distinct symptoms for fentanyl-attributed overdoses compared to other opioid related overdose events, which had implications for response. Findings may serve to inform best practices in responding to fentanyl-related overdoses including; the provision of oxygen and effective doses of naloxone, and also considerations regarding overdose identification., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Plant ribosome-inactivating proteins (RIPs) are a family of toxins that inhibit protein synthesis. In this study, we have isolated a novel type 2 ribosome-inactivating protein (RIP) present in seeds of the Abrus fruticulosus, named of fruticulosin. Fruticulosin, shows characteristics common to other type 2 RIPs, as specificity by galactosides (d-galactose, N-acetyl-d-galactosamine, and d-lactose), mass of approximately 60 kDa and presence of the of disulfide bonds. The N-terminal amino acid sequence (26 residues) of A-chain fruticulosin, determined by Edman degradation, revealed high similarity of the A-chain with those of other type 2 RIPs. The secondary structure of fruticulosin was analysed by circular dichroism, which showed that fruticulosin contains α-helices (22.3%), β-sheets (43.5%), and random coils and corners (34.2%). Furthermore, fruticulosin showed high toxicity in Artemia sp. (3.12 μg/mL), inhibited in vitro protein synthesis by a cell-free system and showed RNA N-glycosidase activity. Fruticulosin presented biological activities such as agglutination and antileishmanial activity on promastigote forms of Leishmania major., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Biopsy pick-up (BPU) has been considered a safe method to harvest ovarian fragments from live animals. However, no studies have been reported on the use of BPU to collect in vivo ovarian tissue in goats. The goals of this study were: (i) to test different biopsy needle sizes to collect ovarian tissue in situ using the BPU method (Experiment 1), and (ii) to study ovarian tissue features such as preantral follicle density, morphology, class distribution, and stromal cell density in ovarian fragments obtained in vivo through a laparoscopic BPU method (Experiment 2). In Experiment 1, goat ovaries (n = 20) were collected in a slaughterhouse and subjected to in situ BPU. Three needles (16, 18, and 20G) were tested. In Experiment 2, the most efficient biopsy needle from Experiment 1 was used to perform laparoscopic BPU in goats (n = 8). In Experiment 1, the recovery rate was greater (P < 0.05; range 50-62%) with 16G and 18G needles than the 20G (17%) needle. The mean weight of ovarian fragments collected by the 16G needle was greater (P < 0.05) than the 18G and the 20G needle. In Experiment 2, 62 biopsy attempts were performed and 52 ovarian fragments were collected (90% success rate). Overall, 2054 preantral follicles were recorded in 5882 histological sections analyzed. Mean preantral follicular density was 28.4 ± 1.3 follicles per cm 2 . The follicular density differed (P < 0.05) among animals and ovarian fragments within the same animal. The mean stromal cell density in the ovarian fragments was 37.1 ± 0.5 cells per 2500 μm 2 , and differed (P < 0.05) among animals. Moreover, preantral follicle density and stromal cell density were associated (P < 0.001). The percentage of morphologically normal follicles was 70.1 ± 1.2, and differed (P < 0.05) among animals. The majority (79%) of the morphologically normal follicles was classified as primordial follicles, and differed (P < 0.05) among animals and between ovaries. In summary, a laparoscopic BPU method has been developed to harvest ovarian tissue in vivo with a satisfactory success rate in goats. Furthermore, this study described for the first time that goat ovarian biopsy fragments have a high heterogeneity in follicular density, morphology, class distribution, and stromal cell density., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Parents are critical to ensure sufficient human papillomavirus (HPV) vaccine coverage. No studies to date have examined how mothers and fathers perceive their own, their partners' and their sons' involvement in HPV vaccination decision-making process., Methods: An online survey methodology was used to collect data from a national sample of Canadian parents (33% fathers, 67% mothers, M age =44) who had a 9-16years old son (n=3117)., Main Outcome Measures: Parent's perception of their self-involvement, partner-involvement and son's involvement in the decision to get their son the HPV vaccine were measured on a Likert scale and were classified as 'no involvement', 'moderate involvement' and 'high involvement'., Results: Mothers and fathers both perceive that they themselves and their partners should be highly involved in their son's HPV vaccination decision. Son's involvement was reported as moderate and influenced by age. Significant gender differences were found for self and partner involvement, but the effect sizes were small., Conclusion: Mothers and fathers both perceive that they themselves and their partners should be significantly involved in their son's HPV vaccination decision. A dyad decision-making model involving both parents for HPV vaccine decision-making is suggested with a stronger recommendation for a triad decision-making model involving both parents as well as the child/adolescent. Gender stereotypes of females perceiving themselves as the sole decision-maker or fathers not wanting to be involved in their children's health decision were not supported., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Emergency Department (ED) overcrowding has become a global concern as the number of countries with formalized emergency care systems has expanded, and the burden of trauma and non-communicable diseases in low and middle-income countries increased. In light of this, the international Emergency Medicine literature has outlined the need for operational projects in low and middle income countries which focus on the process of care. Despite this, there is limited published literature describing these types of projects. We share our experience mapping emergency care processes at a teaching hospital in Ghana as a case study of Lean's application in a relatively resource limited setting. From this work, we conclude that process mapping, a critical first step in further process re-design, is a cost effective, low tech activity which can be feasibly used in low resource environments to initiate quality improvement., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: NephCure Accelerating Cures Institute (NACI) is a collaborative organization sponsored by NephCure Kidney International and the University of Michigan. The Institute is composed of 7 cores designed to improve treatment options and outcomes for patients with glomerular disease: Clinical Trials Network, Data Warehouse, Patient-Reported Outcomes (PRO) and Endpoints Consortium, Clinical Trials Consulting Team, Quality Initiatives, Education and Engagement, and Data Coordinating Center., Methods: The Trials Network includes 22 community- and hospital-based nephrology practices, 14 of which are trial-only sites. Eight sites participate in the NACI Registry, and as of October 2017, 1054 patients are enrolled with diagnoses including but not limited to focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, IgA nephropathy, and childhood-onset nephrotic syndrome. By using electronic health record data extraction, robust and efficient clinical data are captured while minimizing the burden to site-based network staff., Results: The Data Warehouse includes her-extracted data from registry patients, PRO development data, and data from completed observational studies and clinical trials. The Clinical Trial Consulting Team provides support for trial design in rare diseases leveraging these data. The PRO and Endpoints Consortium develops shorter-term endpoints while capturing the patient-reported significance of interventions under study. The Quality Initiatives and Education/Engagement cores elevate the level of care for patients. The Data Coordinating Center manages the analysis and operations of the Institute., Conclusion: By engaging with patients, academia, industry, and patient advocate community representatives, including our Patient Advisory Board, NACI strives for better outcomes and treatments using evidence-based support for clinical trial design.

The ester content is an important parameter to be monitored in biodiesel for evaluation of the transesterification reaction yield and for assessing the purity of the final product. This is also a relevant quality parameter in diesel/biodiesel blends to avoid frauds, because legislation establishes a minimum amount of biodiesel to be added to diesel. The official method EN14103 requires the addition of an alternative internal standard (methyl nonadecanoate) for analysis of biodiesel from bovine tallow because the methyl heptadecanoate is found in high amounts in this product. In this work, it is proposed a fast, simple, practical, and environmental friendly flow-based spectrophotometric procedure, which exploits the formation of the violet complex between Fe(III) and the hydroxamate generated by the reactions of the alkyl esters with hydroxylamine. All involved steps are carried out inside the syringe pump of a sequential injection analyzer (lab-in-syringe approach). A single phase is attained by using ethanol as mediator solvent between the organic sample and aqueous soluble reagents. Linear responses for biodiesel samples and diesel/biodiesel blends were obtained from 4-99%(v/v) to 2.0-40%(v/v) methyl esters, described by the equations: A = 0.342 + 0.00305C (r = 0.997) and A = 0.174 + 0.00503C (r = 0.999), respectively. The analytical curve can be obtained by in-line dilution of a methyl linoleate stock solution. For biodiesel samples, the coefficient of variation (n = 10), limit of detection (99.7% confidence level), and sampling rate were estimated at 0.8%, 0.36%(v/v), and 15h -1 , respectively, whereas the corresponding values for the blend samples were 0.20%, 0.03%(v/v), and 12h -1 , respectively. The procedure consumes only 860μg of hydroxylamine, 366μg of Fe 2 (SO 4 ) 3 ·H 2 O, and 2.0mL ethanol and generates ca. 3.0mL of residue per determination. The results agreed with those obtained by official methods EN14103/2011 e EN14078, at the 95% confidence level., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Polyelectrolyte complex (beads) based on N,N,N-trimethyl chitosan/alginate was successful obtained and silver nanoparticles (AgNPs) were loaded within beads. In vitro cytotoxicity assays using beads/silver nanoparticles (beads/AgNPs) provided results, indicating that this material significantly inhibited the growth of colon cancer cells (Caco-2). In vitro release studies showed that the beads stabilized AgNPs and repressed Ag(0) oxidation under gastric conditions (pH 2.0). On the other hand, at physiological condition (pH 7.4) the beads/AgNPs released 3.3 μg of Ag(+) per each beads milligram. These studies showed that the concentration of Ag(+) released (3.3 μg) was cytotoxic for the Caco-2 cells and was not cytotoxic on healthy VERO cells. This result opens new perspectives for the manufacture of biomaterials based on beads/AgNPs with anti-tumor properties., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Unlabelled: A rapid, sensitive and specific method for quantifying propylthiouracil in human plasma using methylthiouracil as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (ethyl acetate). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS) in negative mode (ES-). Chromatography was performed using a Phenomenex Gemini C18 5μm analytical column (4.6mm×150mm i.d.) and a mobile phase consisting of methanol/water/acetonitrile (40/40/20, v/v/v)+0.1% of formic acid. For propylthiouracil and I.S., the optimized parameters of the declustering potential, collision energy and collision exit potential were -60 (V), -26 (eV) and -5 (V), respectively. The method had a chromatographic run time of 2.5min and a linear calibration curve over the range 20-5000ng/mL. The limit of quantification was 20ng/mL. The stability tests indicated no significant degradation. This HPLC-MS/MS procedure was used to assess the bioequivalence of two propylthiouracil 100mg tablet formulations in healthy volunteers of both sexes in fasted and fed state. The geometric mean and 90% confidence interval CI of Test/Reference percent ratios were, without and with food, respectively: 109.28% (103.63-115.25%) and 115.60% (109.03-122.58%) for Cmax, 103.31% (100.74-105.96%) and 103.40% (101.03-105.84) for AUClast., Conclusion: This method offers advantages over those previously reported, in terms of both a simple liquid-liquid extraction without clean-up procedures, as well as a faster run time (2.5min). The LOQ of 20ng/mL is well suited for pharmacokinetic studies. The assay performance results indicate that the method is precise and accurate enough for the routine determination of the propylthiouracil in human plasma. The test formulation with and without food was bioequivalent to reference formulation. Food administration increased the Tmax and decreased the bioavailability (Cmax and AUC)., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Femoral head avascular necrosis (AVN) is a recalcitrant disease of the hip that leads to joint destruction. Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B (RANK) and RANK ligand (RANKL) regulate the balance between osteoclasts-osteoblasts. The expression of these genes affects the maturation and function of osteoblasts-osteoclasts and bone remodeling. In this study, we investigated the molecular pathways leading to AVN by studying the expression profile of OPG, RANK and RANKL genes., Material and Methods: Quantitative Real Time-PCR was performed for evaluation of OPG, RANK and RANKL expression. Analysis was based on parallel evaluation of mRNA and protein levels in normal/necrotic sites of 42 osteonecrotic femoral heads (FHs). OPG and RANKL protein levels were estimated by western blotting., Results: The OPG mRNA levels were higher (insignificantly) in the necrotic than the normal site (p > 0.05). Although the expression of RANK and RANKL was significantly lower than OPG in both sites, RANK and RANKL mRNA levels were higher in the necrotic part than the normal (p < 0.05). Protein levels of OPG and RANKL showed no remarkable divergence., Conclusions: Our results indicate that differential expression mechanisms for OPG, RANK and RANKL that could play an important role in the progress of bone remodeling in the necrotic area, disturbing bone homeostasis. This finding may have an effect on the resulting bone destruction and the subsequent collapse of the hip joint., (Copyright © 2013. Published by Elsevier Inc.)

This study aimed to dissect the roles played by the autonomic interoreceptors, the carotid bodies (cbs) and the aortic bodies (abs) on the vascular resistances of several organs in anesthetized, paralyzed, artificially ventilated cats challenged by systemic hypoxemia. Two 15 min challenges stimulated each of 5 animals in two different groups: (1) in the intact group hypoxic hypoxia (10% O2 in N2; HH) stimulated both abs and cbs, increasing neural output to the nucleus tractus solitarius (NTS); (2) in this group carbon monoxide hypoxia (30% O2 in N2 with the addition of CO; COH) stimulated only the abs, increasing neural output to the NTS. (3) In the second group in which their bilateral aortic depressor nerves had been transected only the cbs increased neural output to the NTS during the HH challenge; (4) in this aortic body resected group during COH neither abs nor cbs increased neural traffic to the NTS. CO and 10% O2 reduced Hb saturation to the same level. With the use of radiolabeled microspheres blood flow was measured in a variety of organs. Organ vascular resistance was calculated by dividing the aortic pressure by that organ's blood flow. The spleen and pancreas revealed a vasoconstriction in the face of systemic hypoxemia, thought to be sympathetic nervous system (SNS)-mediated. The adrenals and the eyes vasodilated only when cbs were stimulated. Vasodilation in the heart and diaphragm showed no effect of chemoreceptor stimulated increase in SNS output. Different chemoreceptor involvement had different effects on the organs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: In many developing countries pre-eclampsia is under-detected partly due to inadequate training in accurate blood pressure (BP) measurements and insufficient, poorly functioning equipment., Objective: To evaluate whether the introduction of easy to use, low cost novel BP devices (Microlife 3AS1-2; designed by our research group specifically for use in developing countries and validated in pregnancy (B/A grade) according to BHS criteria) into rural clinics in Tanzania, Zimbabwe and Zambia increases referrals for suspected pre-eclampsia to a central referral hospital (as reflected by an increase in mean BP in pregnant women seen in the central referral site)., Methods: International prospective longitudinal pre- and post-intervention pilot study. BP measurements were taken from consecutive women ⩾20 weeks' gestation who accessed care at a referral site (N=694). 20 BP devices were distributed to 20 rural antenatal clinics in each country. Post-intervention data was collected the following year (N=547)., Results: After adjustment for confounders, there was a significant increase in primary outcome; post-intervention mean diastolic BP for all women (2.39mmHg, p<0.001, 95% CI 0.97-3.8), implying an increased proportion of referred hypertensive women; and a reduction in proportion of women (median gestation 35 weeks') who had never previously had a BP taken in pregnancy (25.1% to 16.9%, OR 0.58, p=0.001, CI 0.42-0.79)., Conclusion: Equipping community healthcare providers with this novel validated BP device is feasible, widely accepted and results in increased referrals for suspected pre-eclampsia. A cluster RCT to evaluate the effect of these monitors equipped with a traffic-light 'early warning system' is planned., (Copyright © 2013. Published by Elsevier B.V.)

This study aimed to determine the roles played by the autonomic interoreceptors, the carotid bodies (cbs) and the aortic bodies (abs) in anesthetized, paralyzed, artificially ventilated cats' response to systemic hypoxemia. Four 15min challenges stimulated each of 15 animals: (1) hypoxic hypoxia (10%O₂ in N₂; HH) in the intact (int) cat where both abs and cbs sent neural traffic to the nucleus tractus solitarius (NTS); (2) carbon monoxide hypoxia (30%O₂ in N₂ with the addition of CO; COH) in the intact cat where only the abs sent neural traffic to the NTS; (3) HH in the cat after transection of both aortic depressor nerves, resecting the aortic bodies (HHabr), where only the cbs sent neural traffic to the NTS; (4) COH to the abr cat where neither abs nor cbs sent neural traffic to the NTS. Cardiac output (C.O.), contractility (dP/dt(MAX)), systolic/diastolic pressures, aortic blood pressure, total peripheral resistance, pulmonary arterial pressure, and pulmonary vascular resistance (PVR) were measured. When both cbs and abs were active the maximum increases were observed except for PVR which decreased. Some variables showed the cbs to have a greater effect than the abs. The abs proved to be important during some challenges for maintaining blood pressure. The data support the critically important role for the chemoreceptor-sympathetic nervous system connection during hypoxemia for maintaining viable homeostasis, with some differences between the cbs and the abs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate the use of a collagen-based membrane compared with no treatment on guided bone regeneration by 3-dimensional computerized microtomography (μCT)., Study Design: Defects were created between the mesial and distal premolar roots of the second and third premolars (beagle dogs; n = 8). A collagen-based membrane (Vitala; Osteogenics Biomedical Inc., TX, USA) was placed in one of the defects (membrane group; n = 16), and the other was left untreated (no-membrane group; n = 16). Left and right sides provided healing samples for 2 and 16 weeks. Three-dimensional bone architecture was acquired by μCT and categorized as fully regenerated (F, bone height and width) or nonregenerated (N)., Results: Chi-square tests (95% level of significance) showed that tooth did not have an effect on outcome (P = .5). Significantly higher F outcomes were observed at 16 weeks than 2 weeks (P = .008) and in membrane group than in no-membrane group (P = .008)., Conclusions: The collagen-based membrane influenced bone regeneration at the furcation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Previous evidence indicates a homology of gonadotrophin surge-attenuating factor (GnSAF) to the carboxyl terminal of human serum albumin (HSA) and the ability of human granulosa cells to produce mRNA transcripts corresponding to this fragment, but the underlying mechanism is still unknown. This study investigated the role of FSH in vitro in the expression of the carboxyl terminal of HSA by human luteinized granulosa cells. Cells were cultured on poly-l-lysine-coated microscope slides in the absence or presence of 10 ng/ml FSH, followed by in-situ hybridization and immunocytochemistry. In the presence of FSH, mRNA transcripts corresponding to the carboxyl terminal of the HSA gene and corresponding protein could be detected in comparable intensity to that seen by hepatic HepG2 cells (positive control). Significantly lower expression was detected in granulosa cells cultured without FSH addition (P<0.01), but no expression was detected in HeLa cells. These results demonstrate for the first time that FSH stimulates the expression of the carboxyl terminal fragment of the HSA gene and corresponding protein in human luteinized granulosa cells. Therefore, the carboxyl terminal of HSA has a functional role in the ovary and this further supports the notion that this HSA fragment is a GnSAF-bioactive entity., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)