If You're Not Confused, You're Not Paying Attention: Ochrobactrum Is Not Brucella.

Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged the brucellae with the primarily free-living, phylogenetically related Ochrobactrum spp. in the genus Brucella. This change, founded only on global genomic analysis and the fortuitous isolation of some opportunistic Ochrobactrum spp. from medically compromised patients, has been automatically included in culture collections and databases. We argue that clinical and environmental microbiologists should not accept this nomenclature, and we advise against its use because (i) it was presented without in-depth phylogenetic analyses and did not consider alternative taxonomic solutions; (ii) it was launched without the input of experts in brucellosis or Ochrobactrum; (iii) it applies a non-consensus genus concept that disregards taxonomically relevant differences in structure, physiology, population structure, core-pangenome assemblies, genome structure, genomic traits, clinical features, treatment, prevention, diagnosis, genus description rules, and, above all, pathogenicity; and (iv) placing these two bacterial groups in the same genus creates risks for veterinarians, medical doctors, clinical laboratories, health authorities, and legislators who deal with brucellosis, a disease that is particularly relevant in low- and middle-income countries. Based on all this information, we urge microbiologists, bacterial collections, genomic databases, journals, and public health boards to keep the Brucella and Ochrobactrum genera separate to avoid further bewilderment and harm.

Multi-omics analysis reveals that co-exposure to phthalates and metals disturbs urea cycle and choline metabolism.

This study aimed to evaluate the response of HepaRG cells after co-exposure to phthalates and heavy metals, using a high-dimensional biology paradigm (HDB). Liver is the main metabolism site for the majority of xenobiotics. For this reason, the HepaRG cell line was used as an in vitro model, and cells were exposed to two characteristic mixtures of phthalates and heavy metals containing phthalates (DEHP, DiNP, BBzP) and metals (lead, methylmercury, total mercury) in a concentration-dependent manner. The applied chemical mixtures were selected as the most abundant pollutants in the REPRO_PL and PHIME cohorts, which were studied using the exposome-wide approach in the frame of the EU project HEALS. These studies investigated the environmental causation of neurodevelopmental disorders in neonates and across Europe. The INTEGRA computational platform was used for the calculation of the effective concentrations of the chemicals in the liver through extrapolation from human biomonitoring data and this dose (and a ten-times higher one) was applied to the hepatocyte model. Multi-omics analysis was performed to reveal the genes, proteins, and metabolites affected by the exposure to these chemical mixtures. By extension, we could detect the perturbed metabolic pathways. The generated data were analyzed using advanced bioinformatic tools following the HEALS connectivity paradigm for multi-omics pathway analysis. Co-mapped transcriptomics and proteomics data showed that co-exposure to phthalates and heavy metals leads to perturbations of the urea cycle due to differential expression levels of arginase-1 and -2, argininosuccinate synthase, carbamoyl-phosphate synthase, ornithine carbamoyltransferase, and argininosuccinate lyase. Joint pathway analysis of proteomics and metabolomics data revealed that the detected proteins and metabolites, choline phosphate cytidylyltransferase A, phospholipase D3, group XIIA secretory phospholipase A2, α-phosphatidylcholine, and the a 1,2-diacyl-sn-glycero-3-phosphocholine, are responsible for the homeostasis of the metabolic pathways phosphatidylcholine biosynthesis I, and phospholipases metabolism. The urea, phosphatidylcholine biosynthesis I and phospholipase metabolic pathways are of particular interest since they have been identified also in human samples from the REPRO_PL and PHIME cohorts using untargeted metabolomics analysis and have been associated with impaired psychomotor development in children at the age of two. In conclusion, this study provides the mechanistic evidence that co-exposure to phthalates and metals disturb biochemical processes related to mitochondrial respiration during critical developmental stages, which are clinically linked to neurodevelopmental perturbations.

[Endoscopy after bariatric surgery: what the endoscopist must know]. / Endoscopía luego de cirugía bariátrica: Lo que debe saber el endoscopista.

Endoscopy is essential in the assessment and treatment of the bariatric patient, especially in the postoperative state. Since bariatric surgery is increasing exponentially, endoscopists should be familiar with the anatomy and how to manage possible complications. New less invasive therapeutic tools will have a major impact on the prognosis of these patients. Dreaded complications such as leaks, stenosis or weight regain can be successfully assessed and treated by endoscopy. Postoperative evaluation of symptoms requires the precise search of details that can change patient's management.

Use of magnets in gastrointestinal surgery.

BACKGROUND: Laparoscopic and endoscopic surgery has undergone vast progress during the last 2 decades, translating into improved patient outcomes. A prime example of this development is the use of magnetic devices in gastrointestinal surgery. Magnetic devices have been developed and implemented for both laparoscopic and endoscopic surgery, providing alternatives for retraction, anchoring, and compression among other critical surgical steps. The purpose of this review is to explore the use of magnetic devices in gastrointestinal surgery, and describe different magnetic technologies, current applications, and future directions. METHODS: IRB approval and written consent were not required. In this review of the existing literature, we offer a critical examination at the use of magnets for gastrointestinal surgery currently described. We show the experiences done to date, the benefits in laparoscopic and endoscopic surgery, and additional future implications. RESULTS: Magnetic devices have been tested in the field of gastrointestinal surgery, both in the contexts of animal and human experimentation. Magnets have been mainly used for retraction, anchoring, mobilization, and anastomosis. CONCLUSION: Research into the use of magnets in gastrointestinal surgery offers promising results. The integration of these technologies in minimally invasive surgery provides benefits in various procedures. However, more research is needed to continually evaluate their impact and implementation into surgical practice.

Fine-grained parallelization of fitness functions in bioinformatics optimization problems: gene selection for cancer classification and biclustering of gene expression data.

BACKGROUND: Metaheuristics are widely used to solve large combinatorial optimization problems in bioinformatics because of the huge set of possible solutions. Two representative problems are gene selection for cancer classification and biclustering of gene expression data. In most cases, these metaheuristics, as well as other non-linear techniques, apply a fitness function to each possible solution with a size-limited population, and that step involves higher latencies than other parts of the algorithms, which is the reason why the execution time of the applications will mainly depend on the execution time of the fitness function. In addition, it is usual to find floating-point arithmetic formulations for the fitness functions. This way, a careful parallelization of these functions using the reconfigurable hardware technology will accelerate the computation, specially if they are applied in parallel to several solutions of the population. RESULTS: A fine-grained parallelization of two floating-point fitness functions of different complexities and features involved in biclustering of gene expression data and gene selection for cancer classification allowed for obtaining higher speedups and power-reduced computation with regard to usual microprocessors. CONCLUSIONS: The results show better performances using reconfigurable hardware technology instead of usual microprocessors, in computing time and power consumption terms, not only because of the parallelization of the arithmetic operations, but also thanks to the concurrent fitness evaluation for several individuals of the population in the metaheuristic. This is a good basis for building accelerated and low-energy solutions for intensive computing scenarios.

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I-II early-stage melanoma.

Like many cancers, an early diagnosis of melanoma is fundamental to ensure a good prognosis, although an important proportion of stage I-II patients may still develop metastasis during follow-up. The aim of this work was to discover serum biomarkers in patients diagnosed with primary melanoma that identify those at a high risk of developing metastasis during the follow-up period. Proteomic and mass spectrophotometry analysis was performed on serum obtained from patients who developed metastasis during the first years after surgery for primary tumors and compared with that from patients who remained disease-free for more than 10 years after surgery. Five proteins were selected for validation as prognostic factors in 348 melanoma patients and 100 controls by ELISA: serum amyloid A and clusterin; immune system proteins; the cell adhesion molecules plakoglobin and vitronectin and the antimicrobial protein dermcidin. Compared to healthy controls, melanoma patients have high serum levels of these proteins at the moment of melanoma diagnosis, although the specific values were not related to the histopathological stage of the tumors. However, an analysis based on classification together with multivariate statistics showed that tumor stage, vitronectin and dermcidin levels were associated with the metastatic progression of patients with early-stage melanoma. Although melanoma patients have increased serum dermcidin levels, the REPTree classifier showed that levels of dermcidin <2.98 µg/ml predict metastasis in AJCC stage II patients. These data suggest that vitronectin and dermcidin are potent biomarkers of prognosis, which may help to improve the personalized medical care of melanoma patients and their survival.

In-and-out Technique: An In-house Efficient Predictive Hole Fabrication Workflow.

Virtual surgical planning (VSP) and three-dimensional (3D) printing can increase precision and reduce surgical time in craniofacial reconstruction. However, the elevated cost and manufacturing time of outsourced workflows is increasing the development of in-house solutions. One of the main challenges in in-house workflows is to create cutting guides that hold plate position information. This is due to the fact that hospitals usually lack the infrastructure required to design and 3D print custom-made plates. Including plate-positioning information in resection guides is especially relevant in complex reconstructions and when tumor extension limits plate placement before resection. Current in-house workflows revolve around the idea of 3D scanning the bent plate's shape and to fuse it with the VSP. The goal of this article is to share our technique to transfer plate position information to resection guides. Our protocol uses a 3D model of the reconstruction as an intermediate step to transfer the plate position of a bent stock reconstruction plate to cutting guides. Two patients who required mandibular reconstruction with fibula flap are presented to illustrate the technique. This workflow requires a 3D-printed model of the desired outcome, cutting guides, and a stock plate. Results were satisfactory in terms of cutting location and angulation, plate adaptation and condylar position. This technique allows for a simple, safe, cheap, and quick alternative to add reconstruction plate information to cutting guides.

Effect of Dentin Irrigants on Push-Out Bond Strength in Resin Cementation Protocols for Fiber Posts in Endodontically Treated Teeth: An In Vitro Study.

The aim of this study is to analyze the effects of different endodontic irrigants and adhesive systems on the resin bond strength of fiber post cementation. In total, 144 single-rooted, unrestored human teeth were endodontically treated and randomly divided into 12 groups according to four endodontic irrigants (distilled water as control; EDTA 17%; NaOCl 5%; chlorhexidine digluconate 2%) and three different adhesive/resin cement systems (etch-and-rinse: orthophosphoric acid, Parabond® A+B/Paracore®; self-etch: ParaBond® Non-Rinse Conditioner, Parabond® A+B/Paracore®; Universal: ClearfilTM Universal Bond/ClearfilTM DC Core Plus). Forty-eight hours after post cementation, ten teeth from each group were cross-sectioned into three discs (cervical, middle and apical regions). Thirty specimens of each group (n = 30) were submitted to a push-out test at a crosshead speed of 1 mm/min. The remaining two teeth of each group were sectioned in the same manner, and the resin-dentin interface was evaluated using scanning electron microscopy (SEM). The results were statistically analyzed with the ANOVA test and Tukey's test (p < 0,01). The adhesive protocols and post space region showed no significant effect on bond strength (p > 0.01). The combination of NaOCl 5% and ClearfilTM Universal Bond reduced the adhesive strength (p < 0.01). The NaOCl 5%, in relation to other irrigants, significantly decreased the push-out bond strength.

Melanoma Clinical Decision Support System: An Artificial Intelligence-Based Tool to Diagnose and Predict Disease Outcome in Early-Stage Melanoma Patients.

This study set out to assess the performance of an artificial intelligence (AI) algorithm based on clinical data and dermatoscopic imaging for the early diagnosis of melanoma, and its capacity to define the metastatic progression of melanoma through serological and histopathological biomarkers, enabling dermatologists to make more informed decisions about patient management. Integrated analysis of demographic data, images of the skin lesions, and serum and histopathological markers were analyzed in a group of 196 patients with melanoma. The interleukins (ILs) IL-4, IL-6, IL-10, and IL-17A as well as IFNγ (interferon), GM-CSF (granulocyte and macrophage colony-stimulating factor), TGFß (transforming growth factor), and the protein DCD (dermcidin) were quantified in the serum of melanoma patients at the time of diagnosis, and the expression of the RKIP, PIRIN, BCL2, BCL3, MITF, and ANXA5 proteins was detected by immunohistochemistry (IHC) in melanoma biopsies. An AI algorithm was used to improve the early diagnosis of melanoma and to predict the risk of metastasis and of disease-free survival. Two models were obtained to predict metastasis (including "all patients" or only patients "at early stages of melanoma"), and a series of attributes were seen to predict the progression of metastasis: Breslow thickness, infiltrating BCL-2 expressing lymphocytes, and IL-4 and IL-6 serum levels. Importantly, a decrease in serum GM-CSF seems to be a marker of poor prognosis in patients with early-stage melanomas.

Apoptosis-like cell death induction and aberrant fibroblast properties in human incisional hernia fascia.

Incisional hernia often occurs following laparotomy and can be a source of serious problems. Although there is evidence that a biological cause may underlie its development, the mechanistic link between the local tissue microenvironment and tissue rupture is lacking. In this study, we used matched tissue-based and in vitro primary cell culture systems to examine the possible involvement of fascia fibroblasts in incisional hernia pathogenesis. Fascia biopsies were collected at surgery from incisional hernia patients and non-incisional hernia controls. Tissue samples were analyzed by histology and immunoblotting methods. Fascia primary fibroblast cultures were assessed at morphological, ultrastructural, and functional levels. We document tissue and fibroblast loss coupled to caspase-3 activation and induction of apoptosis-like cell-death mechanisms in incisional hernia fascia. Alterations in cytoskeleton organization and solubility were also observed. Incisional hernia fibroblasts showed a consistent phenotype throughout early passages in vitro, which was characterized by significantly enhanced cell proliferation and migration, reduced adhesion, and altered cytoskeleton properties, as compared to non-incisional hernia fibroblasts. Moreover, incisional hernia fibroblasts displayed morphological and ultrastructural alterations compatible with autophagic processes or lysosomal dysfunction, together with enhanced sensitivity to proapoptotic challenges. Overall, these data suggest an ongoing complex interplay of cell death induction, aberrant fibroblast function, and tissue loss in incisional hernia fascia, which may significantly contribute to altered matrix maintenance and tissue rupture in vivo.

Dependent factors in the adult patient and their relationship with post-tonsillectomy bleeding and pain in an outpatient setting.

INTRODUCTION AND OBJECTIVE: Tonsillectomy performed on an outpatient basis in adult patients presents bleeding and pain as main postoperative complications. Following rules such as cold surgical technique, analgesic protocols, preoperative interview, and postoperative follow-up help to better control the process. However, there are patient-dependent factors such as sex, age, indication for tonsillectomy and the time elapsed between the last tonsil infection and surgical intervention that can influence postoperative complications and should be considered. The objective of this work is to evaluate the influence of age, sex, the indication for tonsillectomy and the period elapsed between the last tonsil infection and surgery on bleeding and pain control. METHODS: A prospective, descriptive, and observational study was carried out in 96 adult patients who underwent outpatient surgery under general anaesthesia, using cold surgical technique, evaluating these complications based on age, sex, indication for tonsillectomy and time elapsed after the last tonsillitis. RESULTS: The patients operated on during the 4 weeks after an episode of tonsillitis presented more postoperative pain. No relationship was found between this period and postoperative bleeding. CONCLUSIONS: Male patients had a higher incidence of bleeding than women. The period elapsed between the last tonsil infection and the surgical procedure was associated with greater postoperative pain, but not with greater postoperative bleeding.

Terfenadine induces apoptosis and autophagy in melanoma cells through ROS-dependent and -independent mechanisms.

Previously we found that terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca(2+) homeostasis. In this report, focusing our attention on the apoptotic mechanisms activated by terfenadine, we show that this drug can potentially activate distinct intrinsic signaling pathways depending on culture conditions. Serum-deprived conditions enhance the cytotoxic effect of terfenadine and caspase-4 and -2 are activated upstream of caspase-9. Moreover, although we found an increase in ROS levels, the apoptosis was ROS independent. Conversely, terfenadine treatment in complete medium induced ROS-dependent apoptosis. Caspase-4, -2, and -9 were simultaneously activated and p73 and Noxa induction were involved. ROS inhibition prevented p73 and Noxa expression but not p53 and p21 expression, suggesting a role for Noxa in p53-independent apoptosis in melanoma cells. Finally, we found that terfenadine induced autophagy, that can promote apoptosis. These findings demonstrate the great potential of terfenadine to kill melanoma cells through different cellular signaling pathways and could contribute to define new therapeutic strategies in melanoma.

Building an empirical mass spectra library for screening of organic pollutants by ultra-high-pressure liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry.

Hybrid quadrupole time-of-flight mass spectrometry (QTOF MS) has gained wide acceptance in many fields of chemistry, for example, proteomics, metabolomics and small molecule analysis. This has been due to the numerous technological advances made to this mass analyser in recent years. In the environmental field, the instrument has proven to be one of the most powerful approaches for the screening of organic pollutants in different matrices due to its high sensitivity in full acquisition mode and mass accuracy measurements. In the work presented here, the optimum experimental conditions for the creation of an empirical TOF MS spectra library have been evaluated. For this model we have used a QTOF Premier mass spectrometer and investigated its functionalities to obtain the best MS data, mainly in terms of mass accuracy, dynamic range and sensitivity. Different parameters that can affect mass accuracy, such as lock mass, ion abundance, spectral resolution, instrument calibration or matrix effect, have also been carefully evaluated using test compounds (mainly pesticides and antibiotics). The role of ultra-high-pressure liquid chromatography (UHPLC), especially when dealing with complex matrices, has also been tested. In addition to the mass accuracy measurements, this analyser allows the simultaneous acquisition of low and high collision energy spectra. This acquisition mode greatly enhances the reliable identification of detected compounds due to the useful (de)protonated molecule and fragment ion accurate mass information obtained when working in this mode. An in-house empirical spectral library was built for approximately 230 organic pollutants making use of QTOF MS in MS(E) mode. All the information reported in this paper is made available to the readers to facilitate screening and identification of relevant organic pollutants by QTOF MS.

The diversity profile of TP53 is influenced by positive selection on the immediately upstream locus WDR79.

BACKGROUND/AIM: TP53 is an efficient central node in a signal transduction network that responds to minimize cancer. However, over 50% of tumors show some mutation in TP53. Thus, one might argue that this single central node network lacks robustness. Therefore, we wanted to investigate if natural selection has played a role in shaping the genomic region containing TP53. METHODS: We have analyzed the HapMap data for evidence of selection using F(ST) pairwise comparisons and the extended haplotype homozygosity test on a 200-kb region encompassing TP53. We have also resequenced 4 kb upstream TP53 in Europeans (including melanoma patients), Asians, Australian Aborigines and Africans. RESULTS: Genetic hitchhiking by a linked, positively selected allele at the nearby gene WDR79 may be partly responsible for the sequence diversity profile of TP53. It can help explain why the TP53 Arg72 allele is the major allele in Europeans even when the alternative allele, 72Pro, has been reported to offer an increased longevity after disease. CONCLUSIONS: Despite the important role of TP53, a complex interplay with other evolutionary forces, which are extrinsic to TP53 function, may have driven the genetic diversity pattern of this locus, and, as a consequence, its structure and function.

Magnetic Liver Retraction Decreases Postoperative Pain and Length of Stay in Bariatric Surgery Compared to Nathanson Device.

Objective: Retrospective case-matched comparison of magnetic liver retraction to a bedrail-mounted liver retractor in bariatric surgery specifically targeting short-term postoperative outcomes, including pain and resource utilization. Background: Retraction of the liver is essential to ensure appropriate visualization of the hiatus in bariatric surgery. Externally mounted retractors require a dedicated port or an additional incision. Magnetic devices provide effective liver retraction without the need of an incision. Methods: The sample consisted of primary and revisional bariatric surgery patients, including Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and biliopancreatic diversion with duodenal switch (BPD-DS) operations. Propensity score analysis was used to match patients with magnetic retraction to patients with a bedrail-mounted retractor with a 1:2 ratio using preoperative characteristics. Baseline characteristics and postprocedure outcomes were compared using two-sample t-tests or Wilcoxon rank sum tests and chi-square or Fisher's exact test as appropriate. Results: One hundred patients met inclusion criteria for the use of magnetic liver retraction (45 RYGB, 35 SG, 20 BPD-DS) with 196 suitable matched external retractor patients identified. Patients were matched and comparable for all preoperative characteristics except for transversus abdominus plane block (27% versus 47%). Patients in the magnet cohort had significantly decreased mean 12-hour postoperative pain scores (2.9 versus 4.2, P = .004) and decreased hospital length of stay (LOS) (1.5 versus 1.9 days, P = .005) while operating room supply were higher in the magnet cohort ($4600 versus $4213, P = .0001). Conclusions: Magnetic liver retraction in bariatric surgery is associated with decreased postoperative pain scores, decreased hospital LOS, and increased operating supply costs.

Endoscopic septotomy as a treatment for leaks after sleeve gastrectomy: Meeting presentations: Digestive Disease Week 2019.

Background and study aims Sleeve gastrectomy (LSG) is the most commonly performed bariatric procedure in the world. Leaks are the most feared complications after this procedure. Endoscopic septotomy has been described as a resolution technique that could be useful in the setting of late and chronic leaks. We present our experience in the management of gastric leaks with this advanced endoscopic technique. Patients and methods Retrospective review of patients who have been admitted to our hospital from January 2016 to December 2018. Results Five patients were found. All had their index surgery in outside hospitals. The average age was 51 years (range 40 - 69), and four patients were female. Mean time from LSG to leak presentation was 15 days (range 7 - 25). Mean time from leak presentation to septotomy procedure was 61 days (range 21 - 110). All patients were treated with sleeve dilatation before septotomy using endoscopic achalasia balloons. Mean procedure time was 79 minutes (range 55 - 125). Success was achieved in 80 % of patients, and no complications related to the procedure were identified. One patient underwent total gastrectomy for definitive management. Mean follow-up time was 14.25 months (range 6 - 26), and the average time for fistula closure was 60.25 days. Conclusion Endoscopic septotomy is safe and effective for management of chronic leaks after LSG. Associated non-selective dilatation may be a crucial step to allow distal patency and axis rectification for appropriate leak closure.

Racial Disparities in Bariatric Surgery Complications and Mortality Using the MBSAQIP Data Registry.

BACKGROUND: Racial disparities in postoperative complications have been demonstrated in bariatric surgery, yet the relationship of race to complication severity is unknown. STUDY DESIGN: Adult laparoscopic primary bariatric procedures were queried from the 2015 and 2016 MBSAQIP registry. Adjusted logistic and multinomial regressions were used to examine the relationships between race and 30-day complications categorized by the Clavien-Dindo grading system. RESULTS: A total of 212,970 patients were included in the regression analyses. For Black patients, readmissions were higher (OR = 1.39, p < 0.0001) and the odds of a Grade 1, 3, 4, or 5 complication were increased compared with White patients (OR = 1.21, p < 0.0001; OR = 1.21, p < 0.0001; OR = 1.22, p = 0.01; and OR = 1.43, p = 0.04) respectively. The odds of a Grade 3 complication for Hispanic patients were higher compared with White patients (OR = 1.59, p < 0.0001). CONCLUSION: Black patients have higher odds of readmission and multiple grades of complications (including death) compared with White patients. Hispanic patients have higher odds of a Grade 3 complication compared with White patients. No significant differences were found with other races. Specific causes of these disparities are beyond the limitations of the dataset and stand as a topic for future inquiry.