Short-term trivalent arsenic and hexavalent chromium exposures induce gut dysbiosis and transcriptional alteration in adipose tissue of mice.

BACKGROUND: Inorganic arsenic [As(III)] and hexavalent chromium [Cr(VI)] can potentially affect metabolic functions. These heavy metal(s)/metalloids can also affect the gut microbial architecture which affects metabolic health. Here, we assessed the effects of short-term exposure of As(III) and Cr(VI) on key transcription factors in adipose tissues and on selected gut microbial abundances to understand the possible modulatory role of these toxicants on host metabolic health. METHODS AND RESULTS: qRT-PCR based relative bacterial abundance studies in cecal samples, gene expression analysis for gut wall integrity in ileum and colon and adipogenesis, lipolysis, and thermogenic genes in gonadal white and brown adipose tissue (gWAT and BAT), along with tissue oxidative stress parameters have been performed. As(III) and Cr(VI) exposure reduced beneficial Lactobacilli, Bifidobacteria, Akkermansia, Lachenospiraceae, Fecalibacterium, Eubacterium, and clostridium coccoid group while increasing lipopolysaccharides producing Enterobacteriaceae abundances. It also impaired structural features and expression of key tight junction and mucin production genes in ileum and colon (Cld-2, Cld-4, ZO-1, ZO-2, MUC-2 and - 4). In gWAT it inhibited adipogenesis (PPARγ, FASN, SREBP1a), lipolysis (HSL, ACOX-1), and thermogenesis (UCP-1, PGC1a, PRDM-16, PPARa) related genes expression, whereas in BAT, it enhanced adipogenesis and reduced thermogenesis. These exposures also reduces the endogenous antioxidants levels in these tissues and promote pro-inflammatory cytokines genes expression (TLRs, IL-6, MCP-1). The combinatorial exposure appears to have more deleterious effects. CONCLUSION: These effects of As(III) and Cr(VI) may not directly be linked to their known toxicological effects, instead, more intriguing crosstalk with gut microbial ecosystem hold the key.

A Systematic Comparison between the Ethereum and Hyperledger Fabric Blockchain Platforms for Attribute-Based Access Control in Smart Home IoT Environments.

Despite the lack of blockchain systems being utilized in modern IoT environments, the prevalence of blockchain technology is increasing, due to its high level of security and accountability. The integration of blockchain technology and access control in a decentralized system for smart home networks is a promising solution to this issue. This paper compares the implementation of attribute-based access control (ABAC) with two popular blockchain platforms, Ethereum and Hyperledger Fabric, for a smart home internet of things (IoT) environment. We present a comprehensive summary of access-control and blockchain-access-control methods, to provide the necessary background for this study. Additionally, we present an original ABAC smart contract for Ethereum, and the modification of a pre-existing Hyperledger Fabric ABAC smart contract, for this comparison. Through the simulation of both implementations, the advantages and limitations will be considered, to determine which is better suited for a smart home IoT environment.

The "Colonial Wig" pancreaticojejunostomy: zero leaks with a novel technique for reconstruction after pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains common and morbid after pancreaticoduodenectomy (PD). A major advance in the study of POPF is the fistula risk score (FRS). METHODS: We analyzed 48 consecutive patients undergoing PD. The "Colonial Wig" pancreaticojejunostomy (CWPJ) technique was used in the last 22 PDs, we compared 22 CWPJ to 26 conventional PDs. RESULTS: Postoperative morbidity was 49% (27% Clavien grade >2). The median length of hospital stay was 11 days. In the first 26 PDs, the PJ was performed according to standard techniques and the clinically relevant POPF (CR-POPF) rate was 15%, similar to the FRS-predicted rate (14%). In the next 22 PJs, the CWPJ was employed. Although the FRS-predicted rates were similar in these two groups (14% vs 13%), the CR-POPF rate in the CWPJ group was 0 (P=0.052). CONCLUSION: Early experience with the CWPJ is encouraging, and this anastomosis may be a safe and effective way to lower POPF rates.

Edoxaban versus warfarin in patients with atrial fibrillation.

BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.).

Implications of gallbladder cholesterolosis and cholesterol polyps?

BACKGROUND: The clinical significance of cholesterolosis has not been well established but there are some provocative, if not robust, studies of the role it may play in the pathophysiology of pancreatitis and biliary dyskinesia, as well as hypercholesterolemia. Our aim was to take advantage of a very large cholecystectomy (CCY) database to support or refute these potentially important reported associations. MATERIALS AND METHODS: A retrospective review of 6868 patients who underwent CCY from 2001-2013 was performed. Comparisons were made using the student t-test for continuous and chi-square analysis for categorical, variables. RESULTS: Among patients for whom the CCY was the primary operation, 1053 (18%) had cholesterolosis and 4596 did not. Compared to those without cholesterolosis, those with cholesterolosis were no more likely to have elevated cholesterol levels (P = 0.64) nor low gallbladder ejection fraction (P = 0.2). To evaluate cholesterolosis as a cause of pancreatitis, all patients with gallstones were eliminated, leaving 639 patients. Among these, not only was cholesterolosis not associated with more pancreatitis, but rather there was not a single patient with or without cholesterolosis who had pancreatitis. CONCLUSIONS: Despite prior reports of associations between cholesterolosis and elevated serum cholesterol, depressed ejection fraction, and increased risk of pancreatitis, careful analysis of this current, larger data set does not support these associations. Any patient with stones or sludge, or with biliary dyskinesia, and appropriate symptoms, should be considered for CCY, with or without suspected cholesterolosis.

Necrotizing pancreatitis: a review of multidisciplinary management.

The objective of this review is to summarize the current state of the art of the management of necrotizing pancreatitis, and to clarify some confusing points regarding the terminology and diagnosis of necrotizing pancreatitis, as these points are essential for management decisions and communication between providers and within the literature. Acute pancreatitis varies widely in its clinical presentation. Despite the publication of the Atlanta guidelines, misuse of pancreatitis terminology continues in the literature and in clinical practice, especially regarding the local complications associated with severe acute pancreatitis. Necrotizing pancreatitis is a manifestation of severe acute pancreatitis associated with significant morbidity and mortality. Diagnosis is aided by pancreas-protocol computed tomography or magnetic resonance imaging, ideally 72 h after onset of symptoms to achieve the most accurate characterization of pancreatic necrosis. The extent of necrosis correlates well with the incidence of infected necrosis, organ failure, need for debridement, and morbidity and mortality. Having established the diagnosis of pancreatic necrosis, goals of appropriately aggressive resuscitation should be established and adhered to in a multidisciplinary approach, ideally at a high-volume pancreatic center. The role of antibiotics is determined by the presence of infected necrosis. Early enteral feeds improve outcomes compared with parenteral nutrition. Pancreatic necrosis is associated with a multitude of complications which can lead to long-term morbidity or mortality. Interventional therapy should be guided by available resources and the principle of a minimally invasive approach. When open debridement is necessary, it should be delayed at least 3-6 weeks to allow demarcation of necrotic from viable tissue.

Are general surgery residents adequately prepared for hepatopancreatobiliary fellowships? A questionnaire-based study.

BACKGROUND: The present study was conducted to assess the preparedness of hepatopancreatobiliary (HPB) fellows upon entering fellowship, identify challenges encountered by HPB fellows during the initial part of their HPB training, and identify potential solutions to these challenges that can be applied during residency training. METHODS: A questionnaire was distributed to all HPB fellows in accredited HPB fellowship programmes in two consecutive academic years (n = 42). Reponses were then analysed. RESULTS: A total of 19 (45%) fellows responded. Prior to their fellowship, 10 (53%) were in surgical residency and the rest were in other surgical fellowships or surgical practice. Thirteen (68%) were graduates of university-based residency programmes. All fellows felt comfortable in performing basic laparoscopic procedures independently at the completion of residency and less comfortable in performing advanced laparoscopy. Eight (42%) fellows cited a combination of inadequate case volume and lack of autonomy during residency as the reasons for this lack of comfort. Thirteen (68%) identified inadequate preoperative workup and management as their biggest fear upon entering practice after general surgery training. A total of 17 (89%) fellows felt they were adequately prepared to enter HPB fellowship. Extra rotations in transplant, vascular or minimally invasive surgery were believed to be most helpful in preparing general surgery residents pursing HPB fellowships. CONCLUSIONS: Overall, HPB fellows felt themselves to be adequately prepared for fellowship. Advanced laparoscopic procedures and the perioperative management of complex patients are two of the challenges facing HPB fellows. General surgery residents who plan to pursue an HPB fellowship may benefit from spending extra rotations on certain subspecialties. Focus on perioperative workup and management should be an integral part of residency and fellowship training.

Delayed Pneumoperitoneum After Percutaneous Endoscopic Gastrostomy (PEG) Tube Placement: A Case Report.

When used for a selected patient population, percutaneous endoscopic gastrostomy (PEG) can provide enteral nutrition percutaneous endoscopic gastrostomy (PEG) safely. PEG tubes generally possess a very low chance of life-threatening complications but due to the patient population that requires PEG tubes, a delayed diagnosis of minor complications could be fatal. In this study, we present a case of delayed pneumoperitoneum, discovered weeks after our patient underwent PEG placement for enteral nutritional needs. The patient recovered without the need for operative intervention. The development of a pneumoperitoneum in the setting of recent PEG needs a thorough clinical evaluation, and caution must be taken before immediately proceeding to operative exploration.

Demonstration of the DNA Fiber Assay for Investigating DNA Damage and Repair Dynamics Induced by Nanoparticles.

Nanomaterial exposure can cause replication stress and genomic instability in cells. The degree of instability depends on the chemistry, size, and concentration of the nanomaterials, the time of exposure, and the exposed cell type. Several established methods have been used to elucidate how endogenous/exogenous agents impact global replication. However, replicon-level assays, such as the DNA fiber assay, are imperative to understand how these agents influence replication initiation, terminations, and replication fork progression. Knowing this allows one to understand better how nanomaterials increase the chances of mutation fixation and genomic instability. We used RAW 264.7 macrophages as model cells to study the replication dynamics under graphene oxide nanoparticle exposure. Here, we demonstrate the basic protocol for the DNA fiber assay, which includes pulse labeling with nucleotide analogs, cell lysis, spreading the pulse-labeled DNA fibers onto slides, fluorescent immunostaining of the nucleotide analogs within the DNA fibers, imaging of the replication intermediates within the DNA fibers using confocal microscopy, and replication intermediate analysis utilizing a computer-assisted scoring and analysis (CASA) software.

Dications of benzylidenefluorene and diphenylmethylidene fluorene: the relationship between magnetic and energetic measures of antiaromaticity.

Oxidation of m- and p-substituted benzylidene fluorenes to antiaromatic dications was attempted by electrochemical and chemical means. Electrochemical oxidation to dications was successful for benzylidene fluorenes with p-methoxy, p-methyl, p-fluoro, and unsubstituted phenyl rings in the 3-position; attempts to oxidize the m-substituted derivatives via electrochemistry were unsuccessful. Chemical oxidation with SbF(5)/SO(2)ClF gave the dication of 9-[(4-methoxyphenyl)methylene]-9H-fluorene cleanly; oxidation of all other substituted benzylidene fluorenes resulted in mixtures of products. The excellent linear relationship between the chemical shifts calculated by the GIAO method and the experimental shifts for the p-methoxy-substituted benzylidene fluorene dication suggests that the calculations satisfactorily reflect the magnetic properties of this dication and potentially those of the other dications studied. The redox potentials from electrochemical oxidation, a measure of the stability of the dications, showed a good linear relationship with another measure of stability, the calculated difference in energy between each dication and its neutral precursor. The dications of benzylidene fluorenes were less stable than the dications of diphenylmethylidene fluorenes; within each type of compound, dications with p-substituted phenyl rings were more stable than dications with m-substituted phenyl rings and dications with phenyl rings substituted with electron-donating groups were more stable than dications with phenyl rings substituted with electron-withdrawing groups. The antiaromaticity of the fluorenyl system was assessed through the nucleus-independent chemical shift (NICS) that was also calculated by the GIAO method. The plot of the NICS values per square area versus the calculated energy difference for the dications showed a moderate degree of linearity; the plot of NICS values per square area versus the oxidation potentials was less linear. Thus, a suggestive, but not conclusive, relationship between magnetic and energetic measures of antiaromaticity was observed.

Impact of childhood maltreatment on outcomes of antidepressant medication in chronic and/or recurrent depression.

BACKGROUND: While childhood maltreatment (CMT) is associated with higher rates of chronicity and recurrence in depression, whether CMT results in poorer outcomes with antidepressant medication remains unclear. METHODS: We performed secondary analyses with data from the large, representative, multisite trial Combining Medications to Enhance Depression Outcomes (CO-MED). CO-MED was a randomized, single-blinded, placebo-controlled study with 665 individuals (663 assessed for CMT) with chronic and/or recurrent Major Depressive Disorder (MDD). CMT was determined by a brief self-reported questionnaire assessing the four types of CMT defined by the Centers for Disease Control and Prevention: sexual abuse, emotional abuse, physical abuse, and neglect. Repeated measures and logistic regression analyses were used. RESULTS: Individuals with CMT did not have a differential improvement of depressive symptoms when compared to those without CMT (adjusted p=.203 for continuous analysis; adjusted p=.320 for remission rates). Neither type of antidepressant medication (adjusted p=.302) nor the age at which CMT occurred (adjusted p=.509) affected depressive symptom outcomes. There was no difference in functional improvement between individuals with and without CMT (adjusted p=.228). A history of CMT was associated with greater antidepressant side effects (p=.009). LIMITATIONS: This study investigated treatment-seeking individuals with chronic and/or recurrent MDD. Intensity and duration of CMT were not assessed. CONCLUSION: In a sample of treatment-seeking outpatients with chronic and/or recurrent MDD, a history of CMT was not associated with differential symptomatic or functional response to pharmacological treatment. However, those with CMT reported greater antidepressant side effect burden.

Measured versus Estimated Blood Loss: Interim Analysis of a Prospective Quality Improvement Study.

Estimated blood loss (EBL) is an increasingly important factor used to predict outcomes, such as morbidity and mortality, length of stay, and readmissions, after major abdominal operations. However, blood loss is difficult to estimate, with frequent under- and overestimations, consequences of which can be potentially dangerous for individual patients and confounding for scoring systems relying on EBL. We hypothesized that EBL is often inaccurate and have prospectively enrolled consecutive patients undergoing major elective intra-abdominal operations. Actual hemoglobin levels were measured and used to calculate the measured blood loss (MBL), which was compared with the EBL, as estimated both by surgeons (sEBL) and anesthesiologists (aEBL). Of 23 eligible cases at interim analysis, pancreaticoduodenectomy (n = 8) was the most common, followed by colectomy (n = 3), hepatectomy (n = 3) and gastrectomy (n = 2), biliary excision and reconstruction (n = 2), combined gastrectomy + colectomy (n = 1), radical nephrectomy (n = 1), open cholecystectomy (n = 1), pancreatic debridement (n = 1), and exploratory laparotomy (n = 1). aEBL overestimated MBL by 192 mL (143%) on average. The aEBL was significantly greater than the MBL (P = 0.004), whereas the sEBL was significantly less than the MBL (P = 0.009). In conclusion, surgeons significantly underestimate and anesthesiologists significantly overestimate EBL. This finding impacts not only immediate patient care but also the interpretation of scoring systems relying on EBL.

Childhood maltreatment and impact on clinical features of major depression in adults.

OBJECTIVES: This study examined: 1) the prevalence of childhood maltreatment (CMT) in individuals with chronic and/or recurrent depression, 2) the association between CMT and depressive symptoms, 3) the link between CMT and worse clinical presentation of depression, 4) the effects of accumulation of different types of CMT, and 5) the relationship between the age at CMT and depression. METHODS: We analyzed the baseline data of 663 individuals from the CO-MED study. CMT was determined by a brief self-reported questionnaire assessing sexual abuse, emotional abuse, physical abuse, and neglect. Correlational analyses were conducted. RESULTS: Half of the sample (n = 331) reported CMT. Those with CMT had higher rates of panic/phobic, cognitive and anhedonic symptoms than those without CMT. All individual types of maltreatment were associated with a poorer clinical presentation including: 1) earlier MDD onset; 2) more severe MDD, 3) more suiccidality, 4) worse quality of life, and functioning, and 5) more psychiatric comorbidities. Clinical presentation was worse in participants who reported multiple types of CMT. CONCLUSIONS: In chronic and/or recurrent depression, CMT is common, usually of multiple types and is associated with a worse clinical presentation in MDD. The combination of multiple types of CMT is associated with more impairment.

Colonial Wig Pancreaticojejunostomy.

Postoperative pancreatic fistula (POPF) is one of the most problematic complications after pancreaticoduodenectomy (PD). We describe a series of 48 pancreatic-head resections from our institution, in which we compare a new technique to create the pancreaticojejunostomy (PJ) reconstruction with standard techniques. The goal is to achieve a lower rate of POPF. This new PJ is termed the "Colonial Wig" (CW) PJ due to the novel appearance of the jejunum wrapping around the pancreas, resembling a Colonial wig wrapping around the head of a Colonial Whig (e.g., George Washington). In our consecutive series, 22 cases were performed using the new CW technique to perform the PJ and were compared to 26 traditional PDs with traditional reconstruction. There was an incidence of clinically relevant POPF of 0% in the CW group, compared to 15% in 26 conventional PJs. Our proposed CW PJ reconstruction is associated with a lower the incidence of POPF following PD, and hence may be a way to improve outcomes after PD.

The current state of hepatopancreatobiliary fellowship experience in North America.

AIM: The face of hepatopancreatobiliary (HPB) training has changed over the past decade. The growth of focused HPB fellowships, which are vetted with a rigorous accreditation process through the Fellowship Council (FC), has established them as an attractive mode of training in HPB surgery. This study looks at the volumes of HPB cases performed during these fellowships in North America. METHODS: After approval by the FC research committee, data from all HPB fellowships that had 3 years worth of complete fellow case log data were tabulated and reported (n = 12). For 2-year fellowships, the fellow logs were tabulated at the completion of both years. Those programs that had transplant experience (n = 9) were reported. RESULTS: Data for the current fellows' case numbers show that graduating fellows have a median of 26 biliary cases, 19 major liver cases (hemilivers), 28 other liver cases, 40 pancreaticoduodenectomies,18 distal pancreatectomies, and 9 other pancreas cases. The programs that provided transplantation experience had 10 cases for each fellow. CONCLUSION: This study validates that FC-accredited HPB fellowships have a robust exposure to complex HPB surgery. Fellows completing these fellowships should be well versed in the management and surgical treatment of HPB patients.

MRI with gadoxetate disodium for colorectal liver metastasis: is it the new "imaging modality of choice"?

BACKGROUND: Accurate detection of colorectal liver metastasis is paramount in the role of management. This study aims to compare magnetic resonance imaging (MRI) with gadoxetate disodium (a hepatocyte-specific agent-Eovist®) to triple-phase enhanced computed tomography in detecting colorectal liver metastases. METHODS: A retrospective chart analysis of 30 patients from 2011 to 2013 with colorectal liver metastases was performed. Patients with more than 6 weeks or two cycles of chemotherapy between the two imaging modalities were excluded. The number of lesions identified on triple-phase enhanced computed tomography vs. MRI with Eovist® was compared. RESULTS: Of the 30 patients that met the inclusion criteria, 12 (40 %) patients had more lesions identified on MRI with Eovist® compared to triple-phase enhanced computed tomography. Eighteen (60 %) had no change in the number of lesions identified. When MRI with Eovist® detected more lesions, the mean number of additional lesions detected was 1.5. Eovist® MRI changed the surgical management in 36.7 % of patients. CONCLUSION: MRI with Eovist® is superior to enhanced computed tomography in identifying colorectal liver metastases. The increased number of lesion identified on MRI with Eovist® can profoundly change the surgeon's management. It should be considered the "imaging modality of choice" in preoperative imaging for liver metastases in these patients.

A Unique Case of Eosinophilic Pancreatitis and Anencephaly in the Fetus of a Type I Diabetic Mother.

Pancreatic infiltration with eosinophils is an uncommon finding with numerous etiologies. While two rare cases of eosinophilic pancreatitis in infants born to Type I diabetic mothers have been reported once in the English literature and once in the French literature, we present the additional finding of anencephaly in a 34 week old fetus. Although the pancreas was grossly unremarkable, histological inspection demonstrated an eosinophilic infiltrate in the fibrous septae and islets of Langerhans along with hypertrophy and hyperplasia of the pancreatic islets.