Braddock-Carey Syndrome (BCS) is characterized by microcephaly, congenital thrombocytopenia, Pierre-Robin sequence (PRS), and agenesis of the corpus callosum. BCS has been shown to be caused by a 21q22.11 microdeletion that encompasses multiple genes. Here, we report a BCS genocopy characterized by congenital thrombocytopenia and PRS that is caused by a loss-of-function mutation in KIF15 in a consanguineous Saudi Arabian family. Mutations of mitotic kinesins are a well-established cause of microcephaly. To our knowledge, KIF15 is the first kinesin to be associated with congenital thrombocytopenia.

Introduction: Gut dysbiosis is an imbalance of the gut microbiome. The presence of dysbiosis can be a cause of systemic inflammation in the body or can be a contributing factor to it. Chronic systemic inflammation is a common feature of CLL, creating an environment in which CLL cells have a survival advantage. NF-κB and STAT3, master transcriptional regulators of pro-inflammatory markers, like IL-1 and IL-6, are reported to be involved in this process as are the Toll-like receptors (TLRs), key innate immunity receptors that are implicated in CLL pathophysiology. With increasing evidence for the role of dysbiosis in chronic inflammation, as well as the role of systemic inflammation in CLL, it seems relevant to prove the presence and the possible role of microbiome in the pathophysiology of CLL, to unravel the complex interaction between microbiome, nutrition and the host in patients with CLL. Our research investigate the hypothesis that dysbiosis i.e. the loss of "health-promoting" commensal gut microbes and/or the overgrowth of pathogenic bacteria distinguishes untreated patients with CLL versus aged-matched unaffected individuals. Methodology: Eight untreated CLL patients were with no history of gastrointestinal disorders, other malignancies and have not been on antibiotics for 4 weeks prior to samples collection. Two of them were not followed for logistical reasons. Six healthy volunteers matched for sex and age were also enrolled in the study. Stool samples from six patients and additional six matched healthy controls were collected and stored in a -40 freezer immediately until they were used for DNA isolation. Total genomic DNA was extracted using the Qiamp DNA stool mini kit and sequenced using Next Generation Sequencing and then analysis were done as per the manufacturer recommendations. Results: Our data indicates a reduced diversity and variability in bacterial phyla of gut microbiota in CLL patients as compare to healthy controls. Lower diversity with increase in certain bacterial types is a well-accepted sign of gut dysbiosis, which have been shown in many disorders such as; type-2 diabetes, obesity, and various autoimmune and neurological diseases. An increase in Proteobacteria numbers has been recognized as the signature of gut dysbiosis which we confirmed in our cohort of patients. Proteobacteria, Firmicutes and Bacteriodetes were also the most abundant bacterial phyla in CLL patients of our study which were reported previously in breast cancer patients. An elevated Firmicutes to Bacteroidetes ratio with altered gut microbiota in CLL patients compared with healthy subjects was also suggested in clinical studies involving obese individuals with insulin resistance. We have observed in CLL patients of this study relative increase in the numbers of Firmicutes and reduction in Bacteriodetes which is considered to be an inverted ratio as compared to healthy individuals which were also reported in ulcerative colitis, colonic and ileal crohn's disease as compared to healthy subjects. . Our finding of gut dysbiosis in this study is linked the association between CLL, inflammatory processes and dysbiosis. The microbiota may play a role in promoting malignancy through chronic inflammation, by disturbing the balance of cell proliferation, death and by initiating unwanted innate and adaptive immune responses. Conclusion: Restoring gut microbiota might open a new avenue for future researches as potential therapeutic intervention in CLL patients. Figure Disclosures No relevant conflicts of interest to declare.

Gastric cancer is a heterogeneous, multifactorial, aggressive disease that has been and remains one of the most common causes of cancer-related deaths and a significant public health issue worldwide. Currently, gastric cancer shows decreasing trends in its incidence and mortality in some geographic areas; however, the disease still shows a poor prognosis and remains difficult to cure. The prognosis for gastric cancer patients depends on the stage at which the gastric cancer is detected, and complete excision of the cancer is the only proven curative option. Gastric cancer prevention remains a priority. Patients at higher risk should be screened for early detection and chemoprophylaxis. Surgical resection enhanced by standardized lymphadenectomy remains the gold standard in the treatment of gastric cancer. Systemic therapy improves long-term disease-free survival compared to surgical treatment alone. Palliative chemotherapy in patients with inoperable gastric cancer prolongs survival and improves the quality of life. Demographic, ecological, environmental, cultural, and genetic variables all contribute to the heterogeneity of gastric cancer; however, environmental risk factors play an important role throughout all the stages of the disease progression, management, and surveillance. In this review, we address the role of important environmental risk factors in the onset of gastric cancer and highlight the current treatment modalities and prevention measures.

Original ArticleIntroduction: Gut dysbiosis is an imbalance in the microbial communities of the intestine and has been associated with numerous chronic diseases. Objectives: We aimed to compare gut dysbiosis within and across various disease states (Crohn's disease [CD], colorectal cancer [CRC], irritable bowel syndrome [IBS], and type 2 diabetes mellitus [T2DM], and obesity). Materials and Methods: Assessing comparative studies which examined levels of bacterial phyla in cases and controls. PubMed and Web of Science were searched to identify relevant studies, in which human fecal samples were used to analyze microbial flora. Results: Twenty-one studies were included, which met inclusion and exclusion criteria. Three studies were included assessing IBS, which found a decrease in Bacteroidetes in the IBS population, but inconsistent findings for other phyla. Six studies were included assessing obesity, and no consistent patterns emerged. Five studies were included examining T2DM, which found a consistent decrease in the Firmicutes/Bacteroidetes ratio in cases as compared to controls. No patterns were found for other phyla. Three studies were included examining CD, and five examining CRC. Conclusions: No consistent patterns were found for either of these diseases. While some patterns were found in bacterial phyla distribution, there were few commonalities, even in same-system disorders. However, uncovering underlying dysbiosis patterns shows great promise in furthering the understanding of disease pathogenesis and the potential for new therapeutic and diagnostic interventions. Further systematic reviews and well-controlled studies are warranted.

Review Article introduCtionGut microbiota refers to the community of microorganisms found within the gut, composed of a variety of bacteria, fungi, and viruses. Many of the bacteria found in this broad mix serve integral roles in maintaining homeostasis and immune and physiological functions. The community is thought to consist of 100 trillion archaeal and bacterial cells over 1000 species, with the majority belonging to the Firmicutes and Bacteroidetes families. These microorganisms help the host in various functions including nutrient metabolism, drug metabolism, and immunomodulation. These microorganisms can be regulated and promoted toward effective functioning by altering diet and uptake of substances known as prebiotics. However, if the normal microbiota composition becomes imbalanced, they go into a state termed dysbiosis. This altered, negative state can exacerbate and be the source of various pathologies. Many of these pathologies are naturally related to the gastrointestinal (GI) tract (i.e., inflammatory bowel disease [IBD]); however, they can affect other systems as well, including the neurological system. [1][2][3][4][5] Thus, this article aims to first review the normal function of the gut microbiota and its relationship with the neural system and then examines the hallmarks of Parkinson's disease (PD) and the potential role of the gut microbiota in PD. methodsThis is a nonsystematic review exploring the role of gut microbiota dysbiosis in PD. A search of the literature was done using online databases (PubMed, Google Scholar, and MEDLINE) with the following search terms in various combinations: Gut Microbiota, Dysbiosis, Parkinson's, Parkinson's Disease, Gut Microbiota-Brain Axis, Gut-Brain Axis, Neurodegenerative. Relevant records were retrieved and reviewed.The article aimed to determine the current state of the literature regarding the role of dysbiosis on PD and any pathways which may have been implicated in the pathogenesis. Additionally,The gut microbiota consists of thousands of microbial species sharing a symbiotic relationship with the human host. These microorganisms have a well-defined role in maintaining optimal function through various avenues including metabolism and immunomodulation. A literature search was accomplished using Google Scholar, MEDLINE, PubMed, and relevant articles were nonsystematically reviewed. In states of dysregulation termed dysbiosis, the gut microbiota may play a role and can lead to various pathologies. Interestingly, pathological states are not entirely limited to the gut and have the potential to affect other systems. Notably, dysbiosis has been linked to several neurological pathologies, including Parkinson's disease (PD). Hallmarks of Parkinson's include buildup of Lewy bodies mediated by α-synucleinopathies, aggregation of misfolded proteins, and mitochondrial dysfunction, resulting in various motor and gastrointestinal dysfunctions. The gut microbiota is implicated in contributing to this pathology through communication via the gut-brain axis. While there...