Once Upon a Microscopic Slide: The Story of Histology

For centuries, histology has maintained its remarkable place in the medical curriculum. However, its teaching has been influenced by the new technological advancement that has reshaped medicine teaching into a more modern student-friendly form. Since its inception in the 18th century, the discipline of histology has progressed hand in hand with the advancements in microscopy and microscopic technologies, including immunohistochemistry. In the traditional curriculum of USA medical schools, especially after the first Flexner’s report of 1910, histology was considered as very essential topic for a physician studying the “Art and Science” of medicine. In this era, the teaching relied more on the light microscope and to some extent on the electron microscope. However, the field nowadays, after the second Flexner’s report, which stressed the importance of integrating clinical topics in the curriculum, is shifting towards the use of more electronic resources for teaching. Such new resources rely on information technology and electronic imaging modalities which are considered to be more student-friendly, time efficient, consistent in conveying the images, promote self-learning and are less costly. In fact, in the last 25 years, most universities started relying on virtual microscopy with limited use of the light microscopy by the students. Such an approach facilitated curricular integration of histology into histopathology and provided the opportunity to promote self-learning and clinical relevance. In the era of competency-based curriculum, histology remains an essential and indispensable basic science in the integrated module

The Experience of Non-Traditional Medical Students in the Clinical Setting

Purpose: To understand the experience of mature-aged medical students on clinical rotations. Background/Theoretical Framework: Although the mean age of first year medical students is 24, an increasing number of mature-aged students, defined as over age 30, are entering medical school. Most studies of mature-aged medical students have examined academic performance using quantitative research design. Few studies have employed qualitative methodology to determine the experience of mature-aged medical students, especially in the clinical setting. Methods: A recruitment e-mail was sent to all medical students enrolled in clinical rotations; first responders were interviewed until saturation in emerging themes was achieved. Interviews were conducted and recorded in a private office setting, then transcribed into a Word document. Five mature-aged students and four traditional students were interviewed. Using methodology for qualitative research described by Mustakas (1994), the investigators individually coded the transcripts to identify emerging themes. Coded themes underwent peer review, with triangulation of data collection, to determine main themes. Results: Three main themes emerged from our study. First, abundant life experience influences students perception of their role on clinical rotations. A mature student explained, ...having kids... being married and divorced... helps in connecting with patients. Previous work experience shapes expectations as a physician-in-training. While traditional students tend to be intimidated, mature students desire to take the initiative. Age plays a role in the students\u27 ability to relate to senior team members, as well as medical student colleagues. Traditional students note that mature students are more realistic due to their life experience in the workplace. Conclusion: Mature-aged students draw upon previous life experience, which shapes role expectations, as well as medical team dynamics. These differences may have implications in training the growing number of mature-aged medical students. A larger scale qualitative study including multiple medical school sites is being developed

The Mechanism and Potential Therapeutic Effects of Cyclosporin, Cyclophilin, Probiotics and Syndecan-1 in an Animal Model of Inflammatory Bowel Disease

Background: Inflammatory bowel diseases (IBDs) have several treatment modalities including immunoregulators, like cyclosporine A, an immunosuppressant that interacts with cytoplasmic cyclophilin A, and probiotics. Aims: This study explored and compared the possible role of syndecan-1 in the IBD pathogenic process as well as the effectiveness of cyclophilin A, cyclosporine A, and their combination in the management of IBDs in the presence of probiotics. Methodology: IBD was induced in a total of 112 mice equally divided between syndecan-1 knock-out (KO) and Balb/c wild-type mice, using 2% dextran sulfate sodium (DSS) followed by intraperitoneal treatment with cyclosporine A, cyclophilin A, or a combination of both. In addition, a daily dose of probiotics was given in their drinking water. The animals were monitored for clinical signs and symptoms and checked for gross pathologies in the abdomen after 3 weeks. Descending and sigmoid colon biopsies were collected and fixed for routine microscopy or frozen for protein extraction and molecular testing for IL-6, CD3, CD147, and beta 1 integrins as well as pAkt expression. Results: The data showed that the induction of IBD in the syndecan-1 KO mice was more severe at the clinical, histological, and molecular levels than in the wild type. The combined CypA-CyA treatment showed no added inhibitory effect compared to single-drug treatment in both strains. Probiotics added to the combination was more effective in the wild type and, when used alone, its inhibition of IL-6 was the highest. As for the CD147 marker, there were more suppressions across the various groups in the KO mice except for the probiotics-alone group. Concerning CD3, it was significantly increased by the CypA-CyA complex, which led to more inflammation in the KO mice. Probiotics had little effect with the combination. In relation to beta 1 integrins, the CypA-CyA combination made no significant difference from CyA alone, and adding probiotics to the combination resulted in higher beta 1 integrin expression in the KO mice. As for pAkt, it was very well expressed and upregulated in both strains treated with DSS, but the effect was much larger in the KO mice. In brief, the CypA-CyA complex showed a decrease in the expression of pAkt, but there was no added effect of both drugs. Probiotics along with the complex had a similar reduction effects in both strains, with a greater effect in the wild-type mice, while probiotics alone led to a similar reduction in pAkt expressions in both strains. Conclusions: The differential effects of CyA, CypA, probiotics, and their combinations on the various inflammatory markers, as well as the histological alterations and clinical signs and symptoms, speak in favor of a clear role of syndecan-1 in reducing inflammation. However, probiotics need to be considered after more explorations into the mechanisms involved in the presence of CypA and CyA especially since pAkt is less active in their presence

INFLAMMATORY BOWEL DISEASE AND COLORECTAL CANCER, NUTRACEUTICAL ASPECTS

Nutraceuticals constitute a group of functional foods that provide added health benefits for various disorders including inflammatory bowel disease (IBD) and colorectal cancer (CCR). The main groups of nutraceuticals include probiotics, prebiotics omega 3 and antioxidants. Studies on nutraceutical showed that this type of food possessed similar properties to drugs but with the benefit of not having side effects. This mini review shows that probiotics and prebiotics, when administered simultaneously with traditional therapies, reduce IBD symptoms and reduce synthesis of enzymes probably involved in colorectal carcinogenesis. Moreover, Omega 3 reduces the synthesis of inflammation mediators and prevenents carcinogenesis through interaction interaction with the signaling pathway NOTCH1/MMP9. Moreover, antioxidant reduce the inflammatory process by inhibiting the synthesis of inflammatory mediators, and inhibit the mechanisms of cell proliferation by inducing apoptosis. In brief, nutraceuticals have gained a huge clinical interest since they could be used along with traditional therapy. Bioavailability studies of nutracetical supplements guarantee a correct intake of the substance by oral administration, a matter which would not have been posible to have entirely with the consumprtion of regular food only

COLORECTAL CARCINOGENESIS; ROLE OF OXIDATIVE STRESS AND ANTIOXIDANTS

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanism. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documentes the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yeld definitive results and were performed mostly in vitro on cell population, or in vivo in experimental animal models

Inflammatory bowel disease, colorectal cancer and type 2 diabetes mellitus: The links.

The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFβ, NFKB, TNFα and ROS among others. This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases. The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array of pro-inflammatory mediators and other related biomolecules are up-regulated, both locally and systematically. Such a persistent or an inadequately resolved chronic inflammation may be a causative agent, in the presence other factors, leading to several pathologies such as IBD, CRC and T2DM. TGFβ plays a crucial role in pancreatic β cell malfunctioning as glucotoxicity stimulates its signaling cascade through smad 3, IL-6 and epithelial to mesenchymal transition. Such a cascade could lead to macrophages and other cells recruitment, inflammation, then IBD and CRC. NFkB is also another key regulator in the crosstalk among the pathways leading to the three disease entities. It plays a major role in linking inflammation to cancer development through its ability to up regulate several inflammatory and tumor promoting cytokines like: IL-6, IL-1 α and TNF α, as well as genes like BCL2 and BCLXL. It activates JAK/STAT signaling network via STAT3 transcription factors and promotes epithelial to mesenchymal transition. It also increases the risk for T2DM in obese people. In brief, NFKB is a matchmaker between inflammation, IBD, cancer and diabetes. In addition, TNFα plays a pivotal role in systemic inflammation. It is increased in the mucosa of IBD patients and has a central role in its pathogenesis. It also activates other signaling pathways like NFKB and MAPK leading to CRC. It is also overexpressed in the adipose tissues of obese patients thus linking it to T2DM, chronic inflammation and consequently CRC. On the other hand, increasing evidence suggests that dysbiosis plays a role in initiating, maintaining and determining the severity of IBD. Actually, among its functions, it modulates genotoxic metabolites which are able to induce CRC, a fact proven to be sustained by stool transfer from patients with CRC. Probiotics, however, may actively prevent CRC as well as IBD and results in a significant decrease in fasting glycemia in T2DM patients. In conclusion, IBD, CRC and T2DM are commonly occurring interrelated clinical problems. They share a common basis influenced by an inflammatory process, an imbalance in intestinal microbiota, and a crosstalk between various signaling pathways. Would probiotics interrupt the crosstalk or orient it in the physiological direction

COLORECTAL CANCER: AN UPDATE ON THE EFFECTS OF LYCOPENE ON TUMOR PROGRESSION AND CELL PROLIFERATION

Colorectal cancer (CRC) is one of the most common cancers worldwide. Various factors, including oxidative stress, where excessive productions of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occur, contribute to its pathogenesis. Numerous studies have investigated the effect of antioxidant substances derived from food such fruits and vegetables; however, data on Lycopene are still rare. Stidies on HT-29 colorectal cancer cells and on animal models have shown that Lycopene has effects on cell proliferation and on the progression of the CRC by interacting with variuos cellular signaling pathways. this analysis of the literature focused on the antioxidant effect of Lycopene, a substance that is found in the tomato

SURGICAL TREATMENT OF SACROCOCCYGEAL PILONIDAL SINUS WITH THE LIMBERG FLAP: REVIEW OF 81 CASES

Pilonidal sinus disease is a complex condition that causes both discomfort and embarassment to suffers. Direct cost through absence from work is high. Controversy still exists regarding the best surgical technique for its treatment in terms of minimizing disease recurrence and patient discomfort. Thus, we conducted this study to evaluate the results of rhomboid excision and Limberg flap reconstruction in the surgical treatment of pilonidal sinus disease. This prospective study included 81 patients who had pilonidal sinus and were treated by the rhomboid excision and Limberg flap. The mean follow-up was 18 months and all patients were satisfied with the procedure. There were lower complication rates, minimal discomfort, patients disharged in 2-3 days and only two recurrences. The Authors recommend the Limberg flap procedure for pilonidal sinus disease. It is effective, with short hospitalization, low recurrence rate and shorter time off work

The Use of Stem Cells in Burn Wound Healing: A Review

Burn wound healing involves a series of complex processes which are subject to intensive investigations to improve the outcomes, in particular, the healing time and the quality of the scar. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. Stem cells have been recently applied in the field to promote superior healing of the wounds. Not only have stem cells been shown to promote better and faster healing of the burn wounds, but also they have decreased the inflammation levels with less scar progression and fibrosis. This review aims to highlight the beneficial therapeutic effect of stem cells in burn wound healing and to discuss the involved pathways and signaling molecules. The review covers various types of burn wound healing like skin and corneal burns, along with the alternative recent therapies being studied in the field of burn wound healing. The current reflection of the attitudes of people regarding the use of stem cells in burn wound healing is also stated