Role of Nigella sativa and a number of its antioxidant constituents towards azoxymethane-induced genotoxic effects and colon cancer in rats

This study examined the chemopreventive effect of Nigella sativa and some of its antioxidant constituents on a number of colon cancer biomarkers in rats induced with azoxymethane (AOM). Sixty male Sprague-Dawley rats were randomly assigned into ten subgroups: vehicle (1-5) and experimental (6-10). The rats in each group were fed one of the following diets: basal diet, (200 mg/kg) Nigella sativa, (0.2 mg/kg) selenium, (1.2 mg/kg) all-trans-retinol plus (100 mg/kg) DL-alpha-tocopherol and (10 mg/kg) thymoquinone, respectively. Only rats in subgroups 6-10 were injected with AOM (15 mg/kg) once per week for 2 weeks. Both groups were fed their respective diets for 5 weeks. Then they were killed and examined for colonic aberrant crypt foci (ACF). Our result showed that only vitamin supplementation was effective on ACF. Nigella sativa revealed inhibitory effects only on DNA damage (day 34) in the AOM-treated rat group. Alternatively, selenium, thymoquinone and vitamins inhibited the MDA content in the liver. Although the exact mechanisms involved in the protective role of Nigella sativa against the initiation of colon carcinogenesis are not clearly understood, the results suggest that its inhibitory effects might depend on the combined competitive inhibition of various antioxidant constituents of this plant.     

Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets

Endometrial carcinoma (EnCa) is the most common invasive gynaecologic carcinoma. Over 85% of EnCa are classified as endometrioid, expressing steroid hormone receptors and mostly involving pathological prestages. Human endogenous retroviruses (ERV) are chromosomally integrated genes, account for about 8% of the human genome and are implicated in the etiology of carcinomas. The majority of ERV envelope (env) coding genes are either not present or not consistently represented between common gene expression microarrays. The aim of this study was to analyse the absolute gene expression of all known 21 ERV env genes including 19 codogenic and two env genes with premature stop codons in EnCa, endometrium as well as in hyperplasia and polyps. For EnCa seven env genes had high expression with >200 mol/ng cDNA (e.g. envH1-3, Syncytin-1, envT), two middle >50 mol/ng cDNA (envFc2, erv-3) and 12 low <50 mol/ng cDNA (e.g. Syncytin-2, envV2). Regarding tumor parameters, Syncytin-1 and Syncytin-2 were significantly over-expressed in advanced stage pT2 compared to pT1b. In less differentiated EnCa Syncytin-1, erv-3, envT and envFc2 were significantly over-expressed. Syncytin-1, Syncytin-2 and erv-3 were specific to glandular epithelial cells of polyps, hyperplasia and EnCa using immunohistochemistry. An analysis of 10 patient-matched EnCa with endometrium revealed that the ERV-W 5'' long terminal repeat regulating Syncytin-1 was hypomethylated, including the ERE and CRE overlapping MeCP2 sites. Functional analyses showed that 10 env genes were regulated by methylation in EnCa using the RL95-2 cell line. In conclusion, over-expressed env genes could serve as indicators for pathological pre-stages and EnCa.     

Similarity-Dissimilarity Plot for Visualization of High Dimensional Data in Biomedical Pattern Classification

In pattern classification problems, feature extraction is an important step. Quality of features in discriminating different classes plays an important role in pattern classification problems. In real life, pattern classification may require high dimensional feature space and it is impossible to visualize the feature space if the dimension of feature space is greater than four. In this paper, we have proposed a Similarity-Dissimilarity plot which can project high dimensional space to a two dimensional space while retaining important characteristics required to assess the discrimination quality of the features. Similarity-dissimilarity plot can reveal information about the amount of overlap of features of different classes. Separable data points of different classes will also be visible on the plot which can be classified correctly using appropriate classifier. Hence, approximate classification accuracy can be predicted. Moreover, it is possible to know about whom class the misclassified data points will be confused by the classifier. Outlier data points can also be located on the similarity-dissimilarity plot. Various examples of synthetic data are used to highlight important characteristics of the proposed plot. Some real life examples from biomedical data are also used for the analysis. The proposed plot is independent of number of dimensions of the feature space.     

Anticarcinogenic Effects of the Ethanolic Extract of Salix aegyptiaca in Colon Cancer Cells: Involvement of Akt/PKB and MAPK Pathways

The bark from Salix species of plants has been traditionally consumed for its antiinflammatory properties. Because inflammation frequently accompanies the progress of colorectal cancer (CRC), we have evaluated the anticancer properties of the ethanolic extract from the bark (EEB) of S. aegyptiaca, a Salix species endogenous to the Middle East, using HCT-116 and HT29 CRC cell lines. Fresh bark from S. aegyptiaca was extracted with ethanol, fractionated by solvent-solvent partitioning and the fractions were analyzed by tandem mass spectrometry. Catechin, catechol, and salicin were the most abundant constituents of the extract. Interestingly, EEB showed the highest anticancer effect in the colon cancer cells followed by its fractions in ethyl acetate and water, with catechin, catechol, and salicin showing the least efficacy. EEB could strongly reduce the proliferation of the cancer cells, but not of CCD-18Co, normal colon fibroblast cell line. Accompanying this was cell cycle arrest at G1/S independent of DNA damage in the cancer cells, induction of apoptosis through a p53 dependent pathway and an inhibition of PI3K/Akt and MAP Kinase pathways at levels comparable to known commercial inhibitors. We propose that the combination of the polyphenols and flavonoids in EEB contributes toward its potent anticarcinogenic effects.

[Supplementary materials are available for this article. Go to the publisher's online edition of Nutrition and Cancer for the following free supplemental resource(s): Supplementary Figure 1 and Supplementary Figure 2.]     

Unusual case of camptocormia triggered by lumbar-disc herniation

A 21-year-old male patient with low back pain and marked forward bending was presented. The exaggerated lumbar flexion was preventing him to stand in erect posture but disappeared while lying. The symptoms had begun after he had lifted a heavy object. Straight-leg-raising test could not be performed properly because of the exaggerated pain. The light-touch sense was decreased on L5 and S1 dermatomes. There was no loss of muscle strength. The deep-tendon reflexes were normal. Plain graph showed mild narrowing in the L4–5 and L5–S1 intervertebral spaces. Lumbar magnetic resonance imaging revealed disc protrusions in L4–5 and L5–S1 levels. During his stay in the department, the patient was given tizanidine and tramadol, and physical therapy was performed. A paravertebral intramuscular injection with lidocaine was applied. Moreover, the patient was referred to psychiatrist for evaluation regarding his medical history of conversive seizures and possible efforts for secondary gain. No response was obtained from all the treatments. The final diagnosis was camptocormia triggered by lumbar-disc herniation. He was applied supportive psychotherapy, psychoeducation regarding secondary gain, strong suggestions to improve posture, positive reinforcement, and behavioral therapy. His postural abnormality resolved and disappeared completely with mild pain. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Pragmatic Trials in Long-Term Care: Implementation and Dissemination Challenges and Opportunities

Randomized controlled trials are considered the most rigorous research design in efficacy and effectiveness research; however, such trials present numerous challenges that limit their applicability in real-world settings. As a consequence, pragmatic trials are increasingly viewed as a research design that overcomes some of these barriers with the potential to produce findings that are more reproducible. Although pragmatic methodology in long-term care is receiving increasing attention as an approach to improve successful dissemination and implementation, pragmatic trials present complexities of their own. To address these complexities and related issues, experts with experience conducting pragmatic trials, developing nursing home policy, participating in advocacy efforts, and providing clinical care in long-term care settings participated in a virtual consensus conference funded by the National Institute on Aging in Spring 2021. Participants identified 4 cross-cutting principles key to dissemination and implementation of pragmatic trial interventions: (1) stakeholder engagement, (2) diversity and inclusion, (3) organizational strain and readiness, and (4) learn from adaptations. Participants emphasized that implementation processes must be grounded in the perspectives of the people who will ultimately be responsible for implementing the intervention once it is proven to be effective. In addition, messaging must speak to long-term care staff and all others who have a stake in its outcomes. Although our understanding of dissemination and implementation strategies remains underdeveloped, this article is designed to guide long-term care researchers and community providers who are increasingly aware of the need for pragmatism in disseminating and implementing evidence-based care interventions.     

Knowledge and attitudes of family doctors,dermatologists, and endocrinologists on sun exposure and vitamin D

Objectives: Vitamin D is an important component of bone metabolism. Skin cells synthesize vitamin D when exposed to the sun. However, prolonged sun exposure damages the skin and increases the risk for skin cancer. The objective is to evaluate and compare the attitudes and recommendations of family doctors, dermatologists, and endocrinologists on exposure to the sun and vitamin D.

Methods: In a cross-sectional study, a questionnaire was completed by personal interview in a study population of 78 family doctors, 21 dermatologists, and 22 endocrinologists.

Results: On a scale of 1–10, the mean score for recommendations to reduce sun exposure was 4.7 for dermatologists, 4.2 for endocrinologists, and 6.4 for family doctors (p < 0.001). Family doctors recommended a mean daily exposure to the sun of 67.4 min compared to 41.4 by dermatologists, and 47.1 by endocrinologists (p = 0.007). Dermatologists and endocrinologists were more likely to recommend protective measures such as hats and long sleeves during sun exposure than family doctors (p < 0.0001). There were no statistically significant differences between male and female doctors for the entire study population.

Conclusions: There is little consensus among these medical practitioners, whether specialists or primary care doctors, concerning sun exposure. Further studies should evaluate the optimal duration and intensity of sun exposure and doctors’ recommendations should be based on the findings.     

Rod-Cone Dystrophy with Initially Preserved Visual Acuity Despite Early Macular Involvement Suggests Recessive CERKL Mutations

Purpose: To highlight that recessive CERKL mutations cause an early-onset rod-cone dystrophy with initially preserved visual acuity despite early macular involvement, an unusual and distinct initial phenotypic presentation.

Methods: A retrospective case series.

Results: Two young Saudi Arabian adults complained of worsening night blindness over the preceding few years, one of whom had been symptomatic since early childhood. Both had retinal pigment epithelium (RPE) mottling/granularity, vascular attenuation, few bone spicules, and frank macular RPE atrophic changes despite relatively preserved visual acuity. Electroretinography was non-recordable, and ocular coherence tomography confirmed retinal thinning, particularly of the outer nuclear layer in the fovea. Each patient harbored a different homozygous CERKL mutation (p.L245P, p.C333*). The few prior reports that detail the presenting phenotype of CERKL mutations describe children or young adults with the similar unusual presenting constellation of findings: rod-cone dystrophy and frank macular atrophy but relatively preserved visual acuity. With time, central vision is affected.

Conclusions: The initial presenting features of CERKL-related retinopathy are distinct and unusual. Recognition of this initial presenting phenotype can facilitate earlier molecular diagnosis and genetic counseling.