Search

Radical surgery remains the primary treatment option for gall bladder cancer (GBC). Margin-negative liver resection is a critical component of radical cholecystectomy. Anatomical segment IVb and V resection is preferred in primary GBC with liver infiltration and incidental GBC patients with puckering of gall bladder (GB) bed. Despite the initial scepticism, minimally invasive radical cholecystectomy is recommended as a treatment option in selected GBC patients. However, anatomical Segment IVb and V resection using the minimally invasive approach is scarcely reported. The standardised technique of robotic (daVinci®XiTM) anatomical Segment IVb and V liver resection guided by indocyanine green fluorescence is described here. The systematic fluorescence-guided anatomical resection described in this report could facilitate minimally invasive Segment IVb and V resection with radical lymphadenectomy in selected patients with GBC.

Hepatopancreatoduodenectomy (HPD) can offer a survival advantage in selected patients with locally advanced gall bladder cancer (GBC). While the safety and feasibility of minimally invasive radical cholecystectomy have been recently documented, laparoscopic HPD for GBC has not been previously reported. A 73-year-old male with GBC infiltrating the bile duct underwent laparoscopic HPD to achieve R0 resection. The patient had an uneventful post-operative course except for delayed gastric emptying that improved with conservative management. The feasibility of laparoscopic HPD for locally advanced GBC reported in the present case needs to be documented in a large case series.

The article presents a brief overview of the Neighbourhood Game Design Project, a studio-based curriculum intervention aimed at engaging students in the design of place-based mobile games and interactive stories using geo-locative technologies (for example, GPS enabled cell phones). It describes the three curricular components that defined the project, then highlights how a studio method was used to guide students' design work and develop their design literacies. In particular, the article focuses on one of the main design activities students engaged in--collaboratively designing an Augmented Reality simulation--and explores how the embedded design practices align with a socio-cultural view of literacy (Gee, 2004; Jenkins, Purushotma, Clinton, Weigel, & Robison, 2006; Lankshear and Knobel, 2007; Robison, 2009). (Contains 8 figures, 1 table, and 3 footnotes.)

Drain site eviscerations have been reported as a rare complication following abdominal surgery. An 82-year-old women was diagnosed with carcinoma stomach and underwent laparoscopic subtotal gastrectomy. A few hours following removal of the duodenal stump drain, she developed small bowel evisceration through the drain site. It was successfully managed with immediate bedside release of fascial constriction followed by definitive repair later. Although herniations and eviscerations via larger drain sites have been reported, eviscerations from small laparoscopic port sites used for drains are rare. Here, we report the first case of small bowel evisceration with strangulation through a 5-mm port site.

As predictive biomarkers of response to immune checkpoint inhibitors (ICIs) remain a major unmet clinical need in patients with urothelial carcinoma (UC), we sought to identify tissue‐based immune biomarkers of clinical benefit to ICIs using multiplex immunofluorescence and to integrate these findings with previously identified peripheral blood biomarkers of response. Fifty‐five pretreatment and 12 paired on‐treatment UC specimens were identified from patients treated with nivolumab with or without ipilimumab. Whole tissue sections were stained with a 12‐plex mIF panel, including CD8, PD‐1/CD279, PD‐L1/CD274, CD68, CD3, CD4, FoxP3, TCF1/7, Ki67, LAG‐3, MHC‐II/HLA‐DR, and pancytokeratin+SOX10 to identify over three million cells. Immune tissue densities were compared to progression‐free survival (PFS) and best overall response (BOR) by RECIST version 1.1. Correlation coefficients were calculated between tissue‐based and circulating immune populations. The frequency of intratumoral CD3+LAG‐3+ cells was higher in responders compared to nonresponders (p = 0.0001). LAG‐3+ cellular aggregates were associated with response, including CD3+LAG‐3+ in proximity to CD3+ (p = 0.01). Exploratory multivariate modeling showed an association between intratumoral CD3+LAG‐3+ cells and improved PFS independent of prognostic clinical factors (log HR −7.0; 95% confidence interval [CI] −12.7 to −1.4), as well as established biomarkers predictive of ICI response (log HR −5.0; 95% CI −9.8 to −0.2). Intratumoral LAG‐3+ immune cell populations warrant further study as a predictive biomarker of clinical benefit to ICIs. Differences in LAG‐3+ lymphocyte populations across the intratumoral and peripheral compartments may provide complementary information that could inform the future development of multimodal composite biomarkers of ICI response. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Plummer-Vinson syndrome (PVS) also known as Paterson- Brown- Kelly syndrome or sideropenic dysphagia has been known for over a century. The syndrome is characterised by a triad of Iron Deficiency Anaemia (IDA), dysphagia and oesophageal webs. It is seen mostly in middle aged women and is considered pre-cancerous condition as 3-15% of the patients develop squamous cell carcinoma involving upper digestive tract mainly oral cavity, tongue, hypopharynx and oesophagus. However, gastric adenocarcinoma has rarely been reported in PVS. We present a case of gastric carcinoma associated with PVS in a 52 years old male patient, presented with history of progressive dysphagia and severe anaemia requiring transfusion. Further, evaluation revealed oesophageal webs and locally advanced antral adenocarcinoma. Literature review has shed light on five similar cases so far.

The remarkable growth of multi-platform genomic profiles has led to the challenge of multiomics data integration. In this study, we present a novel network-based multiomics clustering founded on the Wasserstein distance from optimal mass transport. This distance has many important geometric properties making it a suitable choice for application in machine learning and clustering. Our proposed method of aggregating multiomics and Wasserstein distance clustering (aWCluster) is applied to breast carcinoma as well as bladder carcinoma, colorectal adenocarcinoma, renal carcinoma, lung non-small cell adenocarcinoma, and endometrial carcinoma from The Cancer Genome Atlas project. Subtypes were characterized by the concordant effect of mRNA expression, DNA copy number alteration, and DNA methylation of genes and their neighbors in the interaction network. aWCluster successfully clusters all cancer types into classes with significantly different survival rates. Also, a gene ontology enrichment analysis of significant genes in the low survival subgroup of breast cancer leads to the well-known phenomenon of tumor hypoxia and the transcription factor ETS1 whose expression is induced by hypoxia. We believe aWCluster has the potential to discover novel subtypes and biomarkers by accentuating the genes that have concordant multiomics measurements in their interaction network, which are challenging to find without the network inference or with single omics analysis. [ABSTRACT FROM AUTHOR]

Tumorigenesis is a complex process that is heterogeneous and affected by numerous sources of variability. This article proposes a stochastic extension of a biologically grounded tumor growth model, referred to as the Norton–Simon–Massagué (NSM) model. First, we study the uncontrolled version of the model where the effect of the chemotherapeutic drug agent is absent. Conditions on the model’s parameters are derived to guarantee the positivity of the solution of the proposed stochastic NSM model and hence its validity to describe the dynamics of tumor volume. The proof of positivity makes use of a Lyapunov-type method and the classical Feller’s test for explosion. To calibrate the proposed model, we utilize a population mixed-effect modeling formulation and a maximum likelihood-based estimation algorithm. The identification algorithm is tested by fitting previously published tumor volume mice data. Second, we study the controlled version of the model, which includes the effect of chemotherapy treatment. Analysis of the influence of adding the control drug agent into the model and how sensitive it is to the stochastic parameters is performed both in open- and closed-loop viewpoints. The designed closed-loop control strategy that solves an optimal cancer therapy scheduling problem relies on the model predictive control (MPC) combined with extended Kalman filter approaches. The simulation results and concluding guiding principles are provided for both the open-and closed-loop control cases. [ABSTRACT FROM AUTHOR]

Reviews the 12-year history of negotiations concerning governance in institutions of higher education in New York since passage of the Taylor Law. (IRT)

Tris(4-chlorophenyl)methane (TCPME) and tris(4-chlorophenyl)methanol (TCPMOH) have been detected in various biota and human tissues. The current studies were undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in rats and mice. [14C]TCPME was well absorbed (≥66%) in male rats and mice following a single oral administration of 1, 10, or 100 mg/kg. The excretion of [14C]TCPME-derived radioactivity in urine (≤2.5%) and feces (≤18%) was low. The administered dose was retained in tissues (≥ 64%) with adipose containing the highest concentrations. The metabolism of TCPME was minimal. The disposition and metabolism of [14C]TCPME in females was similar to males. The time to reach maximum concentration was ≤7 h, the plasma elimination half-life was ≥31 h, and the bioavailability was ≥82% following a 10 mg/kg oral dose of [14C]TCPME in male rats and mice. The disposition of [14C]TCPMOH was similar to that of [14C]TCPME. Following an intravenous administration of [14C]TCPME or [14C]TCPMOH in male rats and mice, the pattern of disposition was similar to that of oral administration. In conclusion, both TCPME and TCPMOH are readily absorbed and highly bioavailable following a single oral administration pointing to importance of assessing the toxicity of these chemicals. [ABSTRACT FROM AUTHOR]

By Risto Lehtonen. Grand Rapids, Mich.: Eerdmans, 1998. Pp. xxiv, 360. Paperback $20. This book is the unhappy account of the disintegration and virtual demise of the World Student Christian [...]

1.2-Ethylhexyl-p-methoxycinnamate (EHMC) is commonly used as an ingredient in sunscreens, resulting in potential oral and dermal exposure in humans. 2.Clearance and metabolism of EHMC in hepatocytes and disposition and metabolism of EHMC in rodents following oral (8-800 mg/kg) intravenous (IV) (8 mg/kg) or dermal (0.8-80 mg/kg representing 0.1-10% formulation concentration) exposure to [14C]EHMC were investigated in rats and mice. 3.EHMC was rapidly cleared from rat and mouse hepatocytes (half-life ≤3.16 min) and less rapidly (half-life ≤48 min) from human hepatocytes. 4.[14C]EHMC was extensively absorbed and excreted primarily in urine by 72 h after oral administration to rats (65-80%) and mice (63-72%). Oral doses to rats were excreted to a lesser extent (3-8%) in feces and as CO2 (1-4%). Radioactive residues in tissues were <1% of the dose. There were no sex or species differences in disposition in rats. 5.Following dermal application, 34-42% of an 8-mg/kg dose was absorbed in rats, and 54-62% in mice in 72-h. 6.Among numerous urinary metabolites associated with hydrolysis of the ester, two potential reproductive and developmental toxicants, 2-ethylhexanol and 2-ethylhexanoic acid were produced by metabolism of EHMC. [ABSTRACT FROM AUTHOR]

1.Hydroquinone (HQ) is present in some foods and has varied industrial, medical and consumer uses. These studies were undertaken to investigate the disposition of HQ in rats and mice following gavage, intravenous (IV) and dermal exposure. 2.[14 C]HQ administered (0.5, 5 or 50 mg/kg) by gavage or IV routes to male and female Harlan Sprague-Dawley (HSD) rats and B6C3F1/N mice was well absorbed and rapidly excreted primarily in urine. Radioactivity remaining in tissues at 72 h was <1% for both species at all dose levels and routes. No sex, species or route related differences in disposition were found. 3.With dermal application of 2, 10 or 20% [14 C]HQ, mice absorbed higher percentages of the dose than rats (37, 12, 12% versus 18.6, 4.43 and 1.79%, respectively). The HQ mass absorbed by mice increased with dose, while in rats it was more constant over the dose range. Absorbed HQ was rapidly excreted in urine of both species and urinary excretion indicated continued absorption over the exposure period. No sex differences in disposition were found. 4.The oral bioavailability of HQ at 5 mg/kg was low in both rats (1.6%) and mice (3.9%) demonstrating significant first pass metabolism. Dermal bioavailability in mice was 9.4% following application of 2% formulation. 5.Urinary metabolites for both species and all routes included the glucuronide and sulfate conjugates; no parent was found in urine. [ABSTRACT FROM AUTHOR]

The acoustics of a straight annular lined duct containing a swirling mean flow is considered. The classical Ingard-Myers impedance boundary condition is shown not to be correct for swirling flow. By considering behaviour within the thin boundary layers at the duct walls, the correct impedance boundary condition for an infinitely thin boundary layer with swirl is derived, which reduces to the Ingard-Myers condition when the swirl is set to zero. The correct boundary condition contains a spring-like term due to centrifugal acceleration at the walls, and consequently has a different sign at the inner (hub) and outer (tip) walls. Examples are given for mean flows relevant to the interstage region of aeroengines. Surface waves in swirling flows are also considered, and are shown to obey a more complicated dispersion relation than for non-swirling flows. The stability of the surface waves is also investigated, and as in the non-swirling case, one unstable surface wave per wall is found. [ABSTRACT FROM AUTHOR]

This paper gives a modified Myers boundary condition in swirling inviscid flow, which differs from the standard Myers boundary condition by assuming a small but non-zero boundary layer thickness. The new boundary condition is derived and is shown to have the correct quadratic error behaviour with boundary layer thickness and also to agree with previous results when the swirl is set to zero. The boundary condition is initially derived for swirling flow with constant azimuthal velocity, but easily extends to radially varying swirling flow, with terms depending on the boundary layer model. The modified Myers boundary condition is then given in the time domain rather than in the frequency domain. The effect of the boundary layer profile is then considered, and shown to be small compared to the boundary layer thickness. The boundary condition is then used to analyse the eigenmodes and Green's function in a realistic flow. Modelling the thickness of the boundary layer properly is shown to be essential in order to get accurate results. [ABSTRACT FROM AUTHOR]

1. Bisphenol AF (BPAF) is used as a crosslinking agent for polymers and is being considered as a replacement for bisphenol A (BPA). 2. In this study, comparative clearance and metabolism of BPAF and BPA in hepatocytes and the disposition and metabolism of BPAF in rodents following oral administration of 3.4, 34 or 340 mg/kg [14C]BPAF were investigated. 3. BPAF was cleared more slowly than BPA in hepatocytes with the rate: rat > mouse > human. 4. [14C]BPAF was excreted primarily in feces by 72 h after oral administration to rats (65–80%) and mice (63–72%). Females excreted more in urine (rat, 15%; mouse, 24%) than males (rat, 1–4%; mouse, 10%). Residual tissue radioactivity was <2% of the dose at 72 h. Similar results were observed following intravenous administration. 5. In male rats, 52% of a 340 mg/kg oral dose was excreted in 24 h bile and was mostly comprised of BPAF glucuronide. However, >94% of fecal radioactivity was present as BPAF, suggesting extensive deconjugation in the intestine. 6. Metabolites identified in bile were BPAF-glucuronide, -diglucuronide, -glucuronide sulfate and -sulfate. 7. In conclusion, BPAF was well absorbed following gavage administration and highly metabolized and excreted mostly in the feces as BPAF. [ABSTRACT FROM PUBLISHER]

1. Dimethylamine borane (DMAB) is used as a reducing agent in the manufacturing of a variety of products and in chemical synthesis. National Toxicology Program is evaluating the toxicity of DMAB in rodents following dermal application. The objective of this study was to evaluate the metabolism and disposition of DMAB in male Harlan Sprague Dawley (HSD) rats. 2. Disposition of radioactivity was similar between gavage and intravenous administration of 1.5 mg/kg [14C] DMAB, with nearly 84%-89% of the administered radioactivity recovered in urine 24 h post dosing. At 72 h, only 1% or less was recovered in feces, 0.3% as CO2, and 0.5%-1.4% as volatiles and 0.3%-0.4 % in tissues. 3. The absorption of [14C]DMAB following dermal application was moderate; percent dose absorbed increased with the dose, with 23%, 32% and 46% of dose absorbed at 0.15, 1.5 and 15 mg/kg, respectively. Urinary and fecal excretion ranged from 18%-37% and 2%-4% of dose, respectively, and 0.1%-0.2% as CO2, and 1%-3% as volatiles. Tissue retention of the radiolabel was low ∼1%, but was higher than following the gavage or intravenous administration. 4. Following co-adminsitration of DMAB and sodium nitrite by gavage, N-nitrosodimethylamine was not detected in blood or urine above the limit of quantitation of the analytical method of 10 ng/mL. 5. Absorption of DMAB in fresh human skin in vitro was ∼41% of the applied dose: the analysis of the receptor fluid shows that the intact DMAB complex can be absorbed through the skin. [ABSTRACT FROM AUTHOR]

n-Butyl-p-hydroxybenzoate (n-butylparaben, BPB) is an antioxidant used in foods, pharmaceuticals and cosmetics. This study investigated the disposition of ring-labelled [14C]BPB in Harlan Sprague Dawley rats, and in rat and human hepatocytes. BPB was rapidly cleared in hepatocytes from rat (t1/2 = 3–4 min) and human (t1/2 = 20–30 min). The major metabolites detected in rat hepatocytes were hydroxybenzoic acid and in human hepatocytes were hydroxybenzoic acid and hydroxyhippuric acid. [14C]BPB was administered to male rats orally at 10, 100 or 1000 mg/kg, intravenously at 10 mg/kg and dermally at 10 and 100 mg/kg; female rats were administered oral doses at 10 mg/kg. Oral doses of BPB were well-absorbed (>83%) and eliminated chiefly in urine (83–84%); ≤1% of the radioactivity remained in tissues at 24 h or 72 h after dosing. About 4% and 8%, respectively, of 100 mg/kg dermal doses were absorbed in 24 h and 72 h, and about 50% of a 10 mg/kg dose was absorbed in 72 h. Metabolites detected in urine included those previously reported, BPB-glucuronide, BPB-sulfate, hydroxybenzoic acid and hydroxyhippuric acid, but also novel metabolites arising from ring hydroxylation followed by glucuronidation and sulfation. [ABSTRACT FROM AUTHOR]

abstract 1. The disposition of 2-Methoxy-4-nitroaniline (MNA) was investigated in male and female Harlan Sprague Dawley rats and B6C3F1/N mice following oral, intravenous, and dermal exposure to [14C]MNA at 2, 15, or 150 mg/kg. Clearance of MNA was investigated in male and female rat, mouse, and human hepatocytes. 2. MNA was cleared slowly in hepatocytes from rat (t1/2 = 152–424 min) and human (t1/2 = 118–403 min) but faster in mouse (t1/2= 70–106 min). 3. MNA was well-absorbed in rats and mice following oral administration and eliminated chiefly in urine (rats, 75–79%; mice, 55–68%) 72 h post dosing. Less than 1% of the radioactivity remained in tissues at 72 h. MNA was poorly absorbed following dermal application in rats (5.5%) and mice (10%) over 24 h. 4. The major pathway of metabolism of MNA was via hydroxylation of the phenyl ring to form 6-hydroxy MNA; major metabolites detected were sulfate and glucuronide conjugates of 6-hydroxy MNA. 5. Following oral administration, the percent of total radioactivity bound in tissues bound was highest in liver (43%) and red blood cells (30%), whereas the radioactivity bound to DNA was highest in cecum (160 pmol/mg DNA). [ABSTRACT FROM AUTHOR]

The editor of this volume has undertaken a nearly impossible task: to scan briefly the Methodist perspective on the church's mission. Inevitably it falls short. Like the curate's egg, 'parts [...]

Since the late 1980s, chemotherapy-induced cognitive impairment, also known as “chemobrain”, has been a recognized side effect in patients undergoing cancer treatment (Matsuda et al., 2005). Although products containing Ginkgo biloba may be used by patients undergoing chemotherapy with paclitaxel and other agents, the potential for an herb-drug interaction with this combination has not been adequately explored. This report describes the inhibition of paclitaxel metabolism by Ginkgo preparations in vitro in human hepatocytes. Hydrolyzate of Ginkgo extract (10-100 mM in terpene lactone concentration) caused a dose-dependent inhibition of the 6α -hydroxylation of paclitaxel, the enzymatic activity responsible for the majority of the clearance of that drug in clinical applications; parent extract had no effect. Contrary to the assumed therapeutic benefit of Ginkgo, its concomitant use with paclitaxel could result in elevated blood levels of the chemotherapeutic, with attendant exacerbation of cognitive impairment and other toxic effects associated with cancer therapy. [ABSTRACT FROM AUTHOR]

The development of reliable predictive models for individual cancer cell lines to identify an optimal cancer drug is a crucial step to accelerate personalized medicine, but vast differences in cancer cell lines and drug characteristics make it quite challenging to develop predictive models that result in high predictive power and explain the similarity of cell lines or drugs. Our study proposes a novel network-based methodology that breaks the problem into smaller, more interpretable problems to improve the predictive power of anti-cancer drug responses in cell lines. For the drug-sensitivity study, we used the GDSC database for 915 cell lines and 200 drugs. The theory of optimal mass transport was first used to separately cluster cell lines and drugs, using gene-expression profiles and extensive cheminformatic drug features, represented in a form of data networks. To predict cell-line specific drug responses, random forest regression modeling was separately performed for each cell-line drug cluster pair. Post-modeling biological analysis was further performed to identify potential biological correlates associated with drug responses. The network-based clustering method resulted in 30 distinct cell-line drug cluster pairs. Predictive modeling on each cell-line-drug cluster outperformed alternative computational methods in predicting drug responses. We found that among the four drugs top-ranked with respect to prediction performance, three targeted the PI3K/mTOR signaling pathway. Predictive modeling on clustered subsets of cell lines and drugs improved the prediction accuracy of cell-line specific drug responses. Post-modeling analysis identified plausible biological processes associated with drug responses. [ABSTRACT FROM AUTHOR]

Presents the short story "Cannibals in the Basement," by James Mathews.