Aim
The aim of this study was to analyze the association and susceptibility of Single Nucleotide Polymorphisms (SNPs) in the DRD2 and
BDNF
genes with BED in patients with weight regain in the ...postoperative period of bariatric surgery.
Methods
One hundred and seventy-seven individuals who underwent bariatric surgery with weight regain were evaluated and divided into two groups according to the BED diagnostic. The individuals were submitted to an anthropometric evaluation, analysis of the presence of BED using a validated questionnaire, and blood collection for genotyping of the polymorphisms rs6265 (
BDNF
) and rs1800497 (
DRD2
) by real-time polymerase chain reaction (RT-PCR).
Results
The presence of wild-type alleles for rs1800497 (CC) and rs6265 (GG) was more frequent in patients without BED. Nevertheless, the presence of one or two variant alleles for rs1800497 (CT + TT) and rs6265 (GA + AA) was more frequent in patients with BED. The combination of the two studied SNPs prevailed in patients with BED.
Conclusions
The presence of allele frequency of rs1800497 SNP in the
DRD2
gene and rs6265 SNP in the
BDNF
gene, isolated and/or combined, indicated an additional risk for the development of BED in patients with obesity, especially in the context of weight regain.
Level of evidence
III (evidence obtained from the case–control analytic study).
It was the aim of this study to develop a sustained parenteral peptide (DALCE) delivery system by the immobilization of DALCE to thiolated carboxymethyl dextran-cysteine (CMD-Cys) via disulfide bond ...formation. The resulting CMD-Cys–DALCE conjugate displayed a 22.6±7.9% (m/m) of DALCE (mean±S.D.; n=3). The conjugation of DALCE with CMD-Cys was confirmed by FTIR-ATR spectroscopy. In vitro release studies of conjugate CMD-Cys–DALCE in the presence of 2μM/ml reduced glutathione (GSH) being also available in the plasma showed a sustained peptide release over a time period of 8h, because of thiol/disulfide exchange reactions. For in vivo pharmacokinetic study, DALCE and CMD-Cys–DALCE were administered intravenously to male Sprague–Dawley rats at a dose of 1mg/kg. The AUC0-8 (ng.min/ml) was determined to be 268848±924 and 40019±495 for CMD-Cys–DALCE and DALCE, respectively. The mean residence time (MRT) was determined to be 256±8 and 53.1±9.5min for CMD-Cys–DALCE and for DALCE, respectively. CMD-Cys–DALCE showed a more than 5-fold increased elimination half-life (p<0.01), 3-fold decreased volume of distribution (p<0.01) and a 6.7-fold decreased plasma clearance rate (p<0.01) compared to DALCE. According to these findings, CMD-Cys–DALCE seems to act as prodrug by improving half-life and decreasing plasma clearance.
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CD44v6, the CD44 isoform mostly involved in cancer cell migration and invasion, has been identified as a functional biomarker and therapeutic target in colon cancer stem cells. We here provide ...evidence that baseline CD44v6-positive CTC predict treatment failure in patients with metastatic colorectal cancer undergoing first-line chemotherapy. We suggest that CD44v6-positive CTC can be used to early detect intrinsic drug resistance in this cancer type.
Over the last few years, considerable effort has been spent by Embrapa in the construction of a plant disease database representative enough for the development of effective methods for automatic ...plant disease detection and recognition. In October of 2016, this database, called PDDB, had 2326 images of 171 diseases and other disorders affecting 21 plant species. PDDB size, although considerable, is not enough to allow the use of powerful techniques such as deep learning. In order to increase its size, each image was subdivided according to certain criteria, increasing the number of images to 46,513. Both the original (PDDB) and subdivided (XDB) databases are now being made freely available for academic research purposes, thus supporting new studies and contributing to speed up the advances in the area. Both collections are expected to grow continuously in order to expand their reach. PDDB and XDB can be accessed in the link https://www.digipathos-rep.cnptia.embrapa.br/.
Abstract
Dysregulation of calcium signaling is emerging as a key feature in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s ...disease (HD), and targeting this process may be therapeutically beneficial. Under this perspective, it is important to study proteins that regulate calcium homeostasis in the cell. Sorcin is one of the most expressed calcium-binding proteins in the human brain; its overexpression increases endoplasmic reticulum (ER) calcium concentration and decreases ER stress in the heart and in other cellular types. Sorcin has been hypothesized to be involved in neurodegenerative diseases, since it may counteract the increased cytosolic calcium levels associated with neurodegeneration. In the present work, we show that Sorcin expression levels are strongly increased in cellular, animal, and human models of AD, PD, and HD, vs. normal cells. Sorcin partially colocalizes with RyRs in neurons and microglia cells; functional experiments with microsomes containing high amounts of RyR2 and RyR3, respectively, show that Sorcin is able to regulate these ER calcium channels. The molecular basis of the interaction of Sorcin with RyR2 and RyR3 is demonstrated by SPR. Sorcin also interacts with other ER proteins as SERCA2 and Sigma-1 receptor in a calcium-dependent fashion. We also show that Sorcin regulates ER calcium transients: Sorcin increases the velocity of ER calcium uptake (increasing SERCA activity). The data presented here demonstrate that Sorcin may represent both a novel early marker of neurodegenerative diseases and a response to cellular stress dependent on neurodegeneration.
•Isotopic variation in algae was assessed to detect pollution sources in coastal lakes.•We applied modelling to eliminate confounding factors on observed isotopic values.•Our protocol allows us to ...compare ecosystems differing in biotic and abiotic conditions.•Pollution hotspots were identified and their statistical significance quantified.
N-stable isotope analysis of macroalgae has become a popular method for the monitoring of nitrogen pollution in aquatic ecosystems. Basing on changes in their δ15N, macroalgae have been successfully used as biological traps to intercept nitrogen inputs. As different nitrogen sources differ in their isotopic signature, this technique provides useful information on the origin of pollutants and their extension in the water body. However, isotopic fractionation potentially resulting from microbial nitrogen processing, and indirect isotopic variations due to effects of physicochemical conditions on algal nutrient uptake and metabolism, may affect anthropogenic N isotopic values during transportation and assimilation. This in turn can affect the observed isotopic signature in the algal tissue, inducing isotopic variations not related to the origin of assimilated nitrogen, representing a “background noise” in isotope-based water pollution studies.
In this study, we focused on three neighbouring coastal lakes (Caprolace, Fogliano and Sabaudia lakes) located south of Rome (Italy). Lakes were characterized by differences in terms of anthropogenic pressure (i.e. urbanization, cultivated crops, livestock grazing) and potential “background noise” levels (i.e. nutrient concentration, pH, microbial concentration). Our aim was to assess nitrogen isotopic variations in fragments of Ulva lactuca specimens after 48h of submersion to identify and locate the origins of nitrogen pollutants affecting each lake. δ15N were obtained for replicated specimens of U. lactuca spatially distributed to cover the entire surface of each lake, previously collected from a benchmark, unpolluted site. In order to reduce the environmental background noise on isotopic observations, a Bayesian hierarchical model relating isotopic variation to environmental covariates and random spatial effects was used to describe and understand the distribution of isotopic signals in each lake.
Our procedure (i) allowed to remove background noise and confounding effects from the observed isotopic signals; (ii) allowed to detect “hidden” pollution sources that would not be detected when not accounting for the confounding effect of environmental background noise; (iii) produced maps of the three lakes providing a clear representation of the isotopic signal variation even where background noise was high. Maps were useful to locate nitrogen pollution sources, identify the origin of the dissolved nitrogen and quantify the extent of pollutants, showing localized organic pollution impacting Sabaudia and Fogliano, but not Caprolace. This method provided a clear characterization of both intra- and inter-lake anthropogenic pressure gradients, representing a powerful approach to the ecological indication and nitrogen pollution management in complex systems, as transitional waterbodies are.
In the common clinical practice the perioperative risk assessment of an acute surgical patient with advanced chronic comorbidities is carried out independently by surgeon and anesthesiologist, ...usually in two different steps. While the surgeon evaluates the risk mainly in relation to the surgical outcome, the perioperative risk assessment regarding the weight of the coexisting medical condition on the quality of recovery in the short- mid- and long-term is all about the anesthesiologist evaluation. When frailty and/or comorbidities are so serious that will make surgery seem futile, the patient's assessment on one hand, and the decisions regarding the further clinical waypoint on the other, have to be discussed firstly between surgeons and anesthesiologists before being shared with the patients and their relatives. This is mostly true in the event of an emergency surgical procedure. In regard, a consensus conference attended by a panel of experts respectively from the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) and the Italian Society of Surgery (SIC) was called for developing a shared clinical pathway aimed to select the best care option - operative vs palliative - in the best interest of the surgical patient with advanced chronic comorbidities, in emergency or elective condition. After two years, the panel of experts developed a position paper recommending, in case of potentially futile surgery, to assess the patient verifying two coexisting conditions ("Two Steps method"): Palliative Performance Scale <50%, and at least one of the following general clinical criteria: 1) more than one hospital admission within the last 12 months; 2) hospital admission from or awaiting admission to long-term care facilities, home care service, hospice; 3) chronic renal failure requiring weekly dialysis sessions; 4) home oxygen use and/or non-invasive ventilation. Under these conditions, the surgeon together with the anesthesiologist can share with the patient and/or his relatives the decision between palliative surgery or palliative care taking into account his wishes and preferences.
To maintain safety conditions in the provision of care and assistance, and to protect healthcare workers (HCWs) and patients, the Italian government required compulsory COVID-19 vaccination for HCWs, ...including medical residents (MRs). The aim of this study was to assess COVID-19 vaccination coverage in MRs in a large tertiary hospital in Italy, before and after the introduction of compulsory vaccination, according to demographic characteristics and specific residency. A database on COVID-19 vaccination status and infection of resident medical doctors was created. Descriptive statistics and logistic regressions were carried out on the data. A total of 1894 MRs were included in the study. Being vaccinated in the same hospital as the residency program was significantly related to the year of residency and being enrolled in a frontline residency. A significant association between compliance with the compulsory primary cycle vaccination and vaccination in the hospital residency was observed. Being enrolled in the second, third, and last years of residency, and in a frontline residency, were predictive of being vaccinated in the residency hospital. Almost 100% of the MRs participating in the study were vaccinated against COVID-19. Compulsory vaccination of HCWs, alongside greater and clearer information about the risks and benefits of vaccination, represents an important booster to ensure public health and to promote quality and safety of care.
The Web is one of the most successful Internet applications. Yet, the quality of Web users' experience is still largely impenetrable. Whereas Web performance is typically studied with controlled ...experiments, in this work we perform a large-scale study of a real site, Wikipedia, explicitly asking (a small fraction of its) users for feedback on the browsing experience. The analysis of the collected feedback reveals that 85% of users are satisfied, along with both expected (e.g., the impact of browser and network connectivity) and surprising findings (e.g., absence of day/night, weekday/weekend seasonality) that we detail in this paper. Also, we leverage user responses to build supervised data-driven models to predict user satisfaction which, despite including state-of-the art quality of experience metrics, are still far from achieving accurate results (0.62 recall of negative answers). Finally, we make our dataset publicly available, hopefully contributing in enriching and refining the scientific community knowledge on Web users' QoE.
Background
No data exist about the changes induced by the transition from first‐generation long‐acting insulins to second‐generation long‐acting analogues in the paediatric population.
Objective
To ...assess changes in insulin/carbohydrate ratio (I:CHO) after the first 6 months of degludec therapy in a paediatric population with type 1 diabetes previously treated with glargine U100.
Subjects
All patients treated with degludec under routine clinical practice conditions were retrospectively analysed.
Methods
Nonprofit observational retrospective study. Changes during the follow‐up in mean CHO/I ratio were assessed using longitudinal linear models for repeated measures. Rate of hypoglycaemia, ketoacidosis and adverse events was evaluated.
Results
Overall, 51 children (mean age 13.8 ± 4.6 years; mean diabetes duration 5.8 ± 3.9 years) started therapy with degludec in the period between April 2017 and April 2018. I:CHO ratio before starting degludec therapy significantly differed among the three meals, being the lowest at breakfast and the highest at dinner. After introducing degludec, I:CHO ratio at lunch (−1.29 95% CI −2.02;−0.57) and at dinner (−3.08 95% CI −4.35;−1.8) significantly decreased, while it slightly increased at breakfast (+1.37 95% CI 0.47;2.28). No episodes of severe hypoglycaemia, ketoacidosis and adverse event were recorded during 6 months.
Conclusions
Our data show that the use of degludec is associated with a significant change in the I:CHO ratio at the different meals compared to the previous glargine therapy. This could derive from the flat and prolonged pharmacokinetic profile of degludec. This has important clinical implications for daily insulin dose adjustments.
No data exist about the changes induced by the transition from first‐generation long‐acting insulins to second‐generation long‐acting analogues in the paediatric population. The study assessed changes in insulin/carbohydrate ratio (I:CHO) after the first 6 months of degludec therapy in a paediatric population with type 1 diabetes previously treated with glargine U100. Our data showed that the use of degludec is associated with a flattening in the I:CHO ratio at the different meals compared to the previous glargine therapy.
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