Adverse Effects Post COVID-19 Vaccination and its Association with Age, Gender and Comorbid Disease in Basrah City Southern of Iraq.

BACKGROUND: Vaccination against COVID-19 virus is the most valuable tool available for protection during the pandemic of coronavirus. The clinical manifestation post-vaccination is a barrier to vaccination for many people in Iraq and worldwide. OBJECTIVES: The objective of this study is identifying various clinical manifestations occurring after receiving vaccines among individuals in Basrah Governorate. Moreover, we examine its association with respondents' demographics and the type of vaccine they received. METHODS: A cross-section study was conducted in Basrah, southern Iraq. Research data were collected through an online questionnaire. The data were analyzed using both descriptive and analytic statistical tools using the SPSS program. RESULTS: Most of the participants (86.68%) received the vaccine. The side effects were reported in 71.61% of vaccinated individuals. Fever and muscle pain were the two most experienced clinical manifestations, while lymph node enlargement and disturbances in taste and/or smell sensations were reported infrequently. Adverse effects were mostly reported with the Pfizer BioNTech vaccine receiver. Females and those in the younger age group also reported a significantly higher incidence of side effects. CONCLUSION: Most adverse effects related to the COVID-19 vaccine were minor and could be tolerated without the need for hospital admission.

Reprogramming the tumor microenvironment to improve the efficacy of cancer immunotherapies.

The immunotherapeutic approaches based on checkpoint inhibitors, tumor vaccination, immune cell-based therapy, and cytokines were developed to engage the patient's immune system against cancer and better survival of them. While potent, however, preclinical and clinical data have identified that abnormalities in the tumor microenvironment (TME) can affect the efficacy of immunotherapies in some cancers. It is therefore imperative to develop new therapeutic interventions that will enable to overcome tumor-supportive TME and restrain anti-tumor immunity in patients that acquire resistance to current immunotherapies. Therefore, recognition of the essential nature of the tolerogenic TME may lead to a shift from the immune-suppressive TME to an immune-stimulating phenotype. Here, we review the composition of the TME and its effect on tumor immunoediting and then present how targeted monotherapy or combination therapies can be employed for reprogramming educated TME to improve current immunotherapies outcomes or elucidate potential therapeutic targets.

Crypt fusion as a homeostatic mechanism in the human colon.

OBJECTIVE: The crypt population in the human intestine is dynamic: crypts can divide to produce two new daughter crypts through a process termed crypt fission, but whether this is balanced by a second process to remove crypts, as recently shown in mouse models, is uncertain. We examined whether crypt fusion (the process of two neighbouring crypts fusing into a single daughter crypt) occurs in the human colon. DESIGN: We used somatic alterations in the gene cytochrome c oxidase (CCO) as lineage tracing markers to assess the clonality of bifurcating colon crypts (n=309 bifurcating crypts from 13 patients). Mathematical modelling was used to determine whether the existence of crypt fusion can explain the experimental data, and how the process of fusion influences the rate of crypt fission. RESULTS: In 55% (21/38) of bifurcating crypts in which clonality could be assessed, we observed perfect segregation of clonal lineages to the respective crypt arms. Mathematical modelling showed that this frequency of perfect segregation could not be explained by fission alone (p<10-20). With the rates of fission and fusion taken to be approximately equal, we then used the distribution of CCO-deficient patch size to estimate the rate of crypt fission, finding a value of around 0.011 divisions/crypt/year. CONCLUSIONS: We have provided the evidence that human colonic crypts undergo fusion, a potential homeostatic process to regulate total crypt number. The existence of crypt fusion in the human colon adds a new facet to our understanding of the highly dynamic and plastic phenotype of the colonic epithelium.

The miR-200 family is increased in dysplastic lesions in ulcerative colitis patients.

BACKGROUND: Colorectal cancer (CRC) is a life-threatening complication of ulcerative colitis (UC), and patients are routinely screened for the development of precancerous lesions (dysplasia). However, rates of CRC development in patients with confirmed low-grade dysplasia vary widely between studies, suggesting a large degree of heterogeneity between these lesions that is not detectable macroscopically. A better understanding of the underlying molecular changes that occur in dysplasia will help to identify lesions at higher risk of malignancy. MicroRNAs (miRNAs) post-transcriptionally regulate protein expression and cell-signalling networks. Aberrant miRNA expression is a feature of sporadic CRC but much less is known about the changes that occur in dysplasia and in UC. METHODS: Comprehensive microRNA profiling was performed on RNA extracted from UC dysplastic lesions (n = 7) and UC controls (n = 10). The expression of miRNAs in UC post inflammatory polyps (n = 7) was also assessed. Candidate miRNAs were further validated by qPCR, and miRNA in situ hybridization. Serum levels of miRNAs were also assessed with a view to identification of non-invasive biomarkers of dysplasia. RESULTS: UC dysplasia was associated with a shift in miRNA expression profiles that was not seen in inflammatory polyps. In particular, levels of miR-200b-3p were increased in dysplasia, and this miRNA was localised to epithelial cells in dysplastic lesions and in UC cancers. No changes in miRNA levels were detected in the serum. CONCLUSION: UC-Dysplasia is linked to altered miRNA expression in the mucosa and elevated miR-200b-3p levels.

Inflammatory bowel disease and colon cancer.

The inflammatory bowel diseases (IBD); Crohn's and Ulcerative colitis, result from an altered host response to intestinal flora. Recurrent inflammation with ulceration and tissue restitution confers an increased risk of cancer in both UC and Crohns, and genome wide searches have identified a number of disease susceptibility alleles. The carcinogenesis pathway in colitis-associated colorectal cancer (CACRC) is less clearly understood than it's sporadic counterpart. Clonal ordering experiments have indicated the order and timing of chromosomal instability and common genetic mutations. Epigenetic changes such as DNA methylation and histone modification are thought to play an increasingly important role in inflammation induced carcinogenesis. Clonal expansion of procarcinogenic mutations can lead to large fields of mutant tissue from which colitis associated cancers can arise (field cancerisation). Endoscopic screening is the mainstay of surveillance in high-risk patients although the development of appropriate, clinically applicable biomarkers remains a research priority. Despite the expanding field of biological therapy in inflammatory bowel disease the ASA compounds remain the best-studied and most efficacious chemopreventive agents. Colitis associated CRC appears to have a different aetiology, carcinogenesis pathway and clinical course to its sporadic counterpart. Further research including long-term follow up of patient cohorts taking biological therapies will improve the detection and treatment of these important, inflammation-induced malignancies.

Spindles losing their bearings: does disruption of orientation in stem cells predict the onset of cancer?

Recently, Quyn et al. demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene (APC) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti-tumourigenic mechanism. We describe how hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se, with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers.

Biliary Cystadenoma Causing Obstructive Jaundice: Case Report and Literature Review.

Biliary cystadenomas are rare, potentially malignant neoplasms of biliary origin. Presentation is usually with vague and non-specific symptoms. Here, we describe an unusual case of biliary cystadenoma in a woman presenting with acute onset obstructive jaundice and review the relevant literature of 26 such cases reported over the last two decades.

From rabies to transmissible spongiform encephalopathies: an immune-mediated microbial trigger involving molecular mimicry could be the answer.

The concept of experimental allergic encephalomyelitis (EAE) being linked to both rabies post-vaccination encephalomyelitis and multiple sclerosis (MS) has raised the intriguing question whether animal studies carried out for the induction and transmission of transmissible spongiform encephalopathies (TSEs) using brain antigens including prions do have a similar immunopathogenetic mechanism. Although an essential link between autoimmunity and MS has been well established, its role in the pathogenesis of TSEs is generally lacking. However, auto-antibodies to myelin proteins and/or other neuronal antigens such as neurofilaments and prion proteins have been reported in animals with bovine spongiform encephalopathy (BSE) and scrapie as well as in patients with Creutzfeld-Jakob disease (CJD) and kuru. Acinetobacter has been suggested as a possible triggering microbial factor in the initiation of the autoimmune responses in these diseases because bacterial molecular sequences resemble brain antigens, especially in animals affected with BSE and patients with MS and CJD. These possibilities need to be evaluated further with longitudinal prospective studies carried out on larger numbers of animals or humans with such diseases. The transplantation of saline suspensions of brain homogenates will evoke immunological responses and therefore, the results in the study of MS and other neurological diseases have to be interpreted with caution.