Left-sided colorectal cancer distinct in indigenous African patients compared to other ethnic groups in South Africa.

INTRODUCTION: A large proportion of indigenous African (IA) colorectal cancer (CRC) patients in South Africa are young (< 50 years), with no unique histopathological or molecular characteristics. Anatomical site as well as microsatellite instability (MSI) status have shown to be associated with different clinicopathological and molecular features. This study aimed to ascertain key histopathological features in microsatellite stable (MSS) and low-frequency MSI (MSI-L) patients, to provide insight into the mechanism of the disease. METHODS: A retrospective cohort (2011-2015) of MSS/MSI-L CRC patient samples diagnosed at Charlotte Maxeke Johannesburg Academic Hospital was analyzed. Samples were categorized by site [right colon cancer (RCC) versus left (LCC)], ethnicity [IA versus other ethnic groups (OEG)] and MSI status (MSI-L vs MSS). T-test, Fischer's exact and Chi-square tests were conducted. RESULTS: IA patients with LCC demonstrated an increased prevalence in males, sigmoid colon, signet-ring-cell morphology, MSI-L with BAT25/26 marker instability and advanced disease association. CONCLUSION: This study revealed distinct histopathological features for LCC, and suggests BAT25 and BAT26 as negative prognostic markers in African CRC patients. Larger confirmatory studies are recommended.

Ingredient bundles and recipe tastings in food pantries: a pilot study to increase the selection of healthy foods.

OBJECTIVE: The present study examined the effect of ingredient bundles (i.e. measured ingredients with recipes) and recipe tastings as a strategy to increase the selection of healthy, target foods (kale, brown rice and whole-wheat pasta). DESIGN: Each of the three conditions was tested once per week for three weeks. The conditions were: Treatment 1 (T1), recipe tastings only; Treatment 2 (T2), ingredient bundle plus recipe tastings; and Control, no intervention. SETTING: A food pantry in Bridgeport, CT, USA.ParticipantsFood pantry clients. RESULTS: Controlling for family size and intervention week, the likelihood of clients in T2 (n 160) selecting at least one target item compared with the Control group (n 160) was 3·20 times higher for kale, 4·76 times higher for brown rice and 7·25 times higher for whole-wheat pasta. Compared with T1 (n 128), T2 clients were 2·67 times more likely to select kale, 7·67 times more likely to select brown rice and 11·43 times more likely to select whole-wheat pasta. No differences between T1 and the Control group were found. CONCLUSIONS: Findings suggest that innovative, nudging strategies such as ingredient bundles may increase appeal of foods and encourage pantry clients to select healthier options.

Giving Economically Disadvantaged, Minority Food Pantry Patrons' a Voice: Implications for Equitable Access to Sufficient, Nutritious Food.

This study provides economically disadvantaged, minority food pantry patrons (hereafter, patrons) a meaning-ful voice by examining their experiences trying to obtain sufficient, nutritious food. Five focus groups were conducted using a semistructured discussion guide. Atlast.ti software was used to manage and analyze the data. Patrons reported that pantry staff who preserved their dignity by showing compassion were highly valued. Stigma and shame associated with pantry use were major concerns. Patrons suggested environmental and policy changes to improve their food acquisition experiences. These findings suggest that multilevel interventions addressing food access, food distribution policies, and patron-staff interactions are warranted.

Defining the Role of Gut Bacteria in the Metabolism of Deleobuvir: In Vitro and In Vivo Studies.

Deleobuvir is a potent inhibitor of the hepatitis C virus nonstructural protein 5B polymerase. In humans, deleobuvir underwent extensive reduction to form CD 6168. This metabolite was not formed in vitro in aerobic incubations with human liver microsomes or cytosol. Anaerobic incubations of deleobuvir with rat and human fecal homogenates produced CD 6168. Using these in vitro formation rates, a retrospective analysis was conducted to assess whether the fecal formation of CD 6168 could account for the in vivo levels of this metabolite. The formation of CD 6168 was also investigated using a pseudo-germ free (pGF) rat model, in which gut microbiota were largely eradicated by antibiotic treatment. Plasma exposure (area under the curve from 0 to ∞) of CD 6168 was approximately 9-fold lower in pGF rats (146 ± 64 ng·h/ml) compared with control rats (1,312 ± 649 ng·h/ml). Similarly, in pGF rats, lower levels of CD 6168 (1.5% of the deleobuvir dose) were excreted in feces compared with control rats (42% of the deleobuvir dose). In agreement with these findings, in pGF rats, approximately all of the deleobuvir dose was excreted as deleobuvir into feces (105% of dose), whereas only 26% of the deleobuvir dose was excreted as deleobuvir in control rats. These differences in plasma and excretion profiles between pGF and control rats confirm the role of gut bacteria in the formation of CD 6168. These results underline the importance of evaluating metabolism by gut bacteria and highlight experimental approaches for nonclinical assessment of bacterial metabolism in drug development.

Liquid biopsy approaches and immunotherapy in colorectal cancer for precision medicine: Are we there yet?

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, with nearly half of patients detected in the advanced stages. This is due to the fact that symptoms associated with CRC often do not appear until the cancer has reached an advanced stage. This suggests that CRC is a cancer with a slow progression, making it curable and preventive if detected in its early stage. Therefore, there is an urgent clinical need to improve CRC early detection and personalize therapy for patients with this cancer. Recently, liquid biopsy as a non-invasive or nominally invasive approach has attracted considerable interest for its real-time disease monitoring capability through repeated sample analysis. Several studies in CRC have revealed the potential for liquid biopsy application in a real clinical setting using circulating RNA/miRNA, circulating tumor cells (CTCs), exosomes, etc. However, Liquid biopsy still remains a challenge since there are currently no promising results with high specificity and specificity that might be employed as optimal circulatory biomarkers. Therefore, in this review, we conferred the plausible role of less explored liquid biopsy components like mitochondrial DNA (mtDNA), organoid model of CTCs, and circulating cancer-associated fibroblasts (cCAFs); which may allow researchers to develop improved strategies to unravel unfulfilled clinical requirements in CRC patients. Moreover, we have also discussed immunotherapy approaches to improve the prognosis of MSI (Microsatellite Instability) CRC patients using neoantigens and immune cells in the tumor microenvironment (TME) as a liquid biopsy approach in detail.

Case Study 4: Application of Basic Enzyme Kinetics to Metabolism Studies-Real-Life Examples.

An appreciation of enzyme kinetic principles can be applied in a number of drug metabolism applications. The concept for this chapter arose from a simple discussion on selecting appropriate time points to most efficiently assess metabolite profiles in a human Phase 1a clinical study (Subheading 4). By considering enzyme kinetics, a logical approach to the issue was derived. The dialog was an important learning opportunity for the participants in the discussion, and we have endeavored to capture this experience with other questions related to determination of Km and Vmax parameters, a consideration of the value of hepatocytes vs. liver microsomes, and enzyme inhibition parameters.

Descriptive epidemiological study of South African colorectal cancer patients at a Johannesburg Hospital Academic institution.

BACKGROUND AND AIM: Epidemiological studies of colorectal cancer (CRC) in South Africa (SA) have been poorly characterized. Black and white SA population groups have demonstrated distinct CRC clinical presentations, suggesting that black SA patients follow a different carcinogenic pathway than their white counterparts. Thus, the aim of this study was to identify unique demographic and histopathological features associated with black SA patients to facilitate earlier diagnosis and to improve disease management. METHODS: This preliminary descriptive epidemiological study included 665 retrospective CRC cases diagnosed between the period 2011 and 2015 at the Charlotte Maxeke Johannesburg Academic Hospital. Demographic and histopathological features in black versus other race groups (ORG) were compared, and Student's t-test, Chi-square, and Fischer's exact tests were used for statistical analysis. RESULTS: Statistical analysis demonstrated that patients with left-sided tumors of invasive adenocarcinoma were predominantly black and male. These patients were considerably younger when compared to ORG (median 56 vs 62 years, respectively), P < 0.0001. However, no significant propensity for other histological features was illustrated. Polyps were mostly tubular adenomas (51%) and tubulovillous adenomas (TVAs) (44%). TVAs were mostly high-grade lesions (P < 0.0001) and associated with left-sided CRC (P = 0.0325). CONCLUSION: These findings verify that black SA CRC patients have an earlier disease onset in comparison to ORG; however, no increased tendency for tumor site, precursor lesion, stage of disease, or gender was evident. Thus, a deeper molecular characterization of CRC is required to understand the underlying causes associated with earlier disease onset in black SA CRC patients.

Significant up-regulation of 1-ACBP, B-ACBP and PBR genes in immune cells within the oesophageal malignant tissue and a possible link in carcinogenic angiogenesis.

Oesophageal cancer ranks as the sixth most common malignancy in the world, and recent evidence has shown that its incidence is increasing. ACBPs (Acyl-coA binding proteins) act as intracellular carrier-proteins for medium to long chain acyl-coA, mediating fatty acid transport to the mitochondrion for ß-oxidation. ACBPs are also believed to be putative ligands of PBR (peripheral benzodiazepine receptor), and once they bind to this receptor they facilitate mitochondrial membrane permeabilization, presumably favouring apoptosis. The main aim of the study was to establish the expression patterns of 1- Acyl-coA binding proteins (1-ACBP), B- Acyl-coA binding proteins (B-ACBP), and peripheral bezodiazepine receptor (PBR) in oesophageal cancer, and to link their roles with the disease. In situ hybridization and quantitative real-time PCR methods were performed to determine localization and the expression levels of the three genes in oesophageal cancer. All three genes illustrated substantial up-regulation within the malignant tissue sections as compared to normal oesophageal sections, all three transcripts localized specifically to mast cells, plasma cells and lymphocytes in diseased and normal tissue section. In the diseased tissue B-ACBP and 1-ACBP mRNA localized to endothelial cells of blood vessels in the submucosa. B-ACBP also localized to the nucleus of squamous epithelial cells. PBR localization was indicated in tumour islands of invasive tissue sections. Quantitative RT-PCR also indicated that the expression levels of PBR were higher as compared to the ACBP genes expression in tumours. These results show that 1-ACBP, B-ACBP and PBR play a role in the pathogenesis of oesophageal tumours and possibly in carcinogenic angiogenesis.

Case study 3. Application of basic enzyme kinetics to metabolism studies: real-life examples.

An appreciation of the principles of enzyme kinetics can be applied in a number of drug metabolism applications. The concept for this chapter arose from a simple discussion on selecting appropriate time points to most efficiently assess metabolite profiles in a human Phase 1a clinical study (Subheading 4). By considering enzyme kinetics, a logical approach to the issue was derived. The dialog was an important learning opportunity for the participants in the discussion, and we have endeavored to capture this experience with other questions related to determination of K m and V max parameters, a consideration of the value of hepatocytes versus liver microsomes and enzyme inhibition parameters.

Deriving service costs for a clubhouse psychosocial rehabilitation program.

This article (a) discusses "function cost," a concept to estimate costs where consumers are involved both in delivery and receipt of services; (b) develops a methodology for costing service units for psychosocial rehabilitation clubhouses; and (c) presents a case study of a clubhouse program. Using function cost to estimate the value of member time leads to costs being on average about 10% higher than when using opportunity cost. Because the case-study clubhouse is typical in key dimensions, the methods used here appear generalizable to other programs and should have utility for other rehabilitation-based services for individuals with mental illness.