Inaya Hajj Hussein

Dismicrobism in inflammatory bowel disease and colorectal cancer: Changes in response of colocytes

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohns disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.

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?

Vaccines Through Centuries: Major Cornerstones of Global Health

Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the “Germ Theory of disease” of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette–Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, “The Decade of vaccines” was launched, and on April 1st 2012, the United Nations launched the “shot@Life” campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history.

Modulation of wound contracture α-smooth muscle actin and multispecific vitronectin receptor integrin αvβ3 in the rabbit's experimental model

The myofibroblast, a major component of granulation tissue, is a key cell during wound healing, tissue repair and connective tissue remodelling. Persistence of myofibroblasts within a fibrotic lesion leads to excessive scarring impairing function and aesthetics. Various wound‐healing cytokines can be modulated by topical application of active agents to promote optimal wound healing and improve scar quality. Thus, the myofibroblast may represent an important target for wound‐healing modulation to improve the evolution of conditions such as hypertrophic scars. The purpose of this work is to study the modulation of myofibroblasts and integrin αvβ3 in a full thickness wound performed on rabbits treated with different topical agents using: (1) saline, (2) Tegaderm occlusive dressing (3) silver sulfadiazine and (4) moist exposed burn ointment (MEBO). The reepithelialisation was 4 days faster in the MEBO group compared with the other therapies with less oedema formation, delayed contraction, less inflammatory cells and the lowest transepidermal water loss (TEWL) resulting in a soft scar. Although α‐smooth muscle actin (α‐SMA) was the highest around day 12 in the MEBO group, wound contraction and myofibroblasts activity were the least for the same period probably because of a downregulation of the integrin αvβ3. It seems that the effect of MEBO could be more pronounced on force transmission rather then on force generation. Greater insight into the pathology of scars may translate into non surgical treatments in the future and further work in myofibroblast biology will eventually result in efficient pharmacological tools, improving the evolution of healing and scar formation.

Behavioral Perceptions of Oakland University Female College Students towards Human Papillomavirus Vaccination

Human Papillomavirus (HPV) vaccination decreases the risk for cervical cancer. However, the uptake of HPV vaccine remains low when compared with other recommended vaccines. This study evaluates the knowledge and attitudes towards HPV infection and vaccination, and the readiness for the uptake of HPV vaccine amongst female students attending Oakland University (OU) in Michigan, United States. This is a cross-sectional study targeting a randomized sample of a 1000 female OU students using an online questionnaire. The data were statistically analyzed using SPSS software. A total of 192 female students, with the mean age of 24 years completed the survey. The majority of participants had previous sexual experience with occasional use of contraceptives (78.1%), were non-smokers (92.7%), and non-alcohol drinkers (54.2%). The participants had a mean knowledge score of 53.0% with a standard error of 2.3% translating to a moderately informed population. The majority agreed that HPV is life threatening (79%), the vaccine prevents cervical cancer (62%), and that side effects would not deter them from vaccination (63%). Although two thirds (67%) believed that, based on sexual practices in the United States, female college students in Michigan have a higher chance of contracting HPV, about 50% did not believe they themselves were at risk. Higher knowledge correlated with increased recommendation for the vaccine (correlation-factor 0.20, p = 0.005). Results suggested that the best predictor for improvement of vaccination was the awareness level and health education. This indicates a need for an educational intervention to raise awareness, increase HPV vaccine uptake, and decrease the incidence of cervical cancer.

Ulcerative Colitis-Associated Colorectal Cancer Prevention by 5-Aminosalicylates: Current Status and Perspectives

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer. This risk increased mainly with longer duration of colitis, greater anatomic extent, and/or association to primary sclerosing cholangitis (PSC). Recent work highlighted also the carcinogenetic role of long-standing – despite if mild or moderate – mucosal inflammation, bringing an additional argument to support the growing concept of mucosal healing as the final target of current and future treatments (Lichtenstein & Rutgeerts, 2010). Until now, repeated colonoscopic surveillance with biopsies targeted on visible lesions associated to multiple random biopsies in endoscopically normal-appearing mucosa, remains the major way to detect mucosal dysplasia (a precancerous lesion), thereby decreasing colitis-associated cancer (CAC) mortality in UC patients. Colorectal cancer chemoprevention is a second promising strategy to reduce CAC risk in this patients’ population. In particular, most of the available epidemiological data indicate a preventive role for 5-aminosalicylic acid derivatives (5-ASA), despite recent work suggested also a protective role for purine derivatives. Although the main mechanisms by which 5-ASA may reduce CAC risk is not exactly known and remains controversial, some interesting

Immunohistochemical expression of apoptotic factors, cytokeratins, and metalloproteinase-9 in periapical and epithelialized gingival lesions

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Re-Emerging Vaccine-Preventable Diseases in War-Affected Peoples of the Eastern Mediterranean Region—An Update

For the past few decades, the Eastern Mediterranean Region has been one area of the world profoundly shaped by war and political instability. On-going conflict and destruction have left the region struggling with innumerable health concerns that have claimed the lives of many. Wars, and the chaos they leave behind, often provide the optimal conditions for the growth and re-emergence of communicable diseases. In this article, we highlight a few of the major re-emerging vaccine preventable diseases in four countries of the Eastern Mediterranean Region that are currently affected by war leading to a migration crisis: Iraq, South Sudan, Syria, and Yemen. We will also describe the impact these infections have had on patients, societies, and national health care services. This article also describes the efforts, both local and international, which have been made to address these crises, as well as future endeavors that can be done to contain and control further devastation left by these diseases.

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 modules

Perceptions of human cadaver dissection by medical students: a highly valued experience

Cadaver dissection remains a cornerstone in the study of anatomical sciences by medical students. However, this activity can cause emotions that may affect learning outcomes. This study, which involved medical students of various cultural backgrounds, assessed their responses to dissection. Medicine I year students (n = 100) at Oakland University William Beaumont School of Medicine were invited to complete a questionnaire after the first week of dissection, and again at the end of the course. The questionnaire asked for demographics, and assessed the students appraisal of their dissection experience, cultural influences, coping activities and learning outcomes. After the first week of dissection, most of the students found the experience challenging, stimulating, exciting and informative, rather than nauseating or unbearable. Still, some students found the experience anxiety-provoking, especially when they thought about human mortality. Cultural background influenced the students emotional development as they worked through the course. Most of the participants agreed that dissection promotes teamwork, familiarity with the human body, and integration of the theoretical knowledge with practical application. At the end of the course, dissection was significantly less anxiety-provoking, and, interestingly, the study found that culture and religious beliefs became more important to the students. Most students agreed that dissection is important, relevant, and necessary, and has the potential to improve learning outcomes that are essential to the development of physicians. The study suggests that an introductory course in social, behavioral and ethical considerations be presented at the beginning of the medical curriculum.