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Abstract The diversity in genome resources is fundamental to designing genomic strategies for local breed improvement and utilisation. These resources also support gene discovery and enhance our understanding of the mechanisms of resilience with applications beyond local breeds. Here, we report the genome sequences of 555 cattle (208 of which comprise new data) and high-density (HD) array genotyping of 1,082 samples (537 new samples) from indigenous African cattle populations. The new sequences have an average genome coverage of ~30X, three times higher than the average (~10X) of the over 300 sequences already in the public domain. Following variant quality checks, we identified approximately 32.3 million sequence variants and 661,943 HD autosomal variants mapped to the Bos taurus reference genome (ARS-UCD1.2). The new datasets were generated as part of the Centre for Tropical Livestock Genetics and Health (CTLGH) Genomic Reference Resource for African Cattle (GRRFAC) initiative, which aspires to facilitate the generation of this livestock resource and hopes for its utilisation for complete indigenous breed characterisation and sustainable global livestock improvement.

The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility whereas others regulate the microbiota. We have found that peptide YY (PYY1-36), but not endocrine PYY3-36, acts as an antimicrobial peptide (AMP) expressed by gut epithelial paneth cells (PC). PC-PYY is packaged into secretory granules and is secreted into and retained by surface mucus, which optimizes PC-PYY activity. Although PC-PYY shows some antibacterial activity, it displays selective antifungal activity against virulent Candida albicans hyphae-but not the yeast form. PC-PYY is a cationic molecule that interacts with the anionic surfaces of fungal hyphae to cause membrane disruption and transcriptional reprogramming that selects for the yeast phenotype. Hence, PC-PYY is an antifungal AMP that contributes to the maintenance of gut fungal commensalism.

Objectives:. The objective of this study was to compare short-term outcomes of pancreatoduodenectomy between patients with and without liver cirrhosis (LC). Background:. It is not uncommon to encounter a patient with LC and with an indication for pancreatoduodenectomy; however, the knowledge on the outcomes after pancreatoduodenectomy in patients with LC is poorly developed. Methods:. A systematic review and meta-analysis was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards. Short-term outcomes of pancreatoduodenectomy between patients with and without LC were compared using random effects modeling and the certainty of the evidence was assessed using the GRADE system. Results:. Analysis of 18,184 patients from 11 studies suggested LC increased the risk of postoperative mortality (odds ratio [OR]: 3.94, P < 0.00001), major complications (OR: 2.25, P = 0.0002), and pancreatic fistula (OR: 1.73, P = 0.03); it resulted in more blood loss (mean difference [MD]: 204.74 ml, P = 0.0003) and longer hospital stay (MD: 2.05 days, P < 0.00001). LC did not affect delayed gastric emptying (OR: 1.33, P = 0.21), postoperative bleeding (OR: 1.28, P = 0.42), and operative time (MD: 3.47 minutes, P = 0.51). Among the patients with LC, Child-Pugh B or C class increased blood loss (MD: 293.33 ml, P < 0.00001), and portal hypertension increased postoperative mortality (OR: 2.41, P = 0.01); the other outcomes were not affected. Conclusions:. Robust evidence with high certainty suggests LC of any severity with or without portal hypertension results in at least a fourfold increase in mortality and a twofold increase in morbidity after pancreatoduodenectomy. Whether such risks increase with the severity of the liver disease or decrease with optimization of underlying liver disease should be the focus of future research.

BACKGROUND: Functional constipation (FC) is a common condition in children, and information on the clinical characteristics of FC in Saudi children is scarce. OBJECTIVE: Describe the clinical profile of FC in Saudi children. DESIGN: Retrospective SETTING: Hospital that provides primary, intermediate and tertiary care. PATIENTS AND METHODS: All children diagnosed with FC according to the Rome IV criteria were included and had at least one follow-up clinic visit. Demographic and clinical data collected from medical records included the age at onset, duration of constipation, clinical features, treatment modalities, and factors associated with clinical response. Descriptive statistics and Pearson's chi-squared test were used in the statistical analysis to see how categorical study variables were linked to clinical response. A P value of ≤.05 was used to report statistical significance. MAIN OUTCOME MEASURE: Compliance and clinical response to polyethylene glycol (PEG) compared with lactulose. SAMPLE SIZE: 370 children from 0.1 to 13 years of age. RESULTS: The median (IQR) age of onset was 4 (5) years and less than one year in 14%. The median (IQR) duration of constipation was 4 months (11) and less than two months in 93/370 (25%). Abdominal pain was the most commonly associated feature (44%). Screening for celiac disease and hypothyroidism was negative. A Fleet enema was the most common disimpaction method (54%) and PEG was the most common maintenance medication (63.4%). PEG was significantly better tolerated (P=.0008) and more effective than lactulose (P

BACKGROUND : Serogroup distribution of sterile site pneumococcal isolates varies between developing and developed countries as well as between different geographical regions. The potential efficacy of any pneumococcal vaccine depends on the degree of representation of the prevalent serogroups in the vaccine. We conducted this study to determine the prevalent pneumococcal serogroups causing invasive infections in Riyadh, Saudi Arabia and to estimate the coverage by the various pneumococcal conjugate vaccines. METHODS : S. pneumoniae isolated between February 2000 and November 2001 from sterile sites of patients of all age groups were collected from 8 major hospitals in Riyadh and serogrouped using the latex agglutination method. RESULTS : Isolates from 78 patients, 72% of whom were children, were studied. Eighty-eight percent of the isolates belonged to only 10 serogroups/serotypes, namely 6 and 19, 1 and 15, 14 and 23, 7, 18 and 22, in descending order of frequency. Potential coverage of the 7-valent, 9-valent, and 11-valent conjugate vaccines were 54%, 65% and 73%, respectively. The rate of reduced penicillin susceptibility in the serogroups represented in the 7-valent conjugate vaccine was significantly higher than in the non-vaccine serogroups (62% vs. 25%; P =0.0023) CONCLUSION : The currently available 7-valent pneumococcal conjugate vaccine provides sub-optimal coverage to serogroups causing invasive diseases in our community. However, this vaccine would be a useful adjunct to penicillin prophylaxis in at-risk patients in the community. The effectiveness of the vaccine would be greater if serotype 15 could be included.

ABSTRACT Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant intestinal epithelium. RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed a higher abundance of cells expressing specific enterocyte, goblet cell, and enteroendocrine cell markers in differentiated infant HIE monolayers, and greater numbers of proliferative cells in undifferentiated 3D cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine. HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an ex vivo model to advance studies of infant-specific diseases and drug discovery for this population.IMPORTANCETissue or biopsy stem cell-derived human intestinal enteroids are increasingly recognized as physiologically relevant models of the human gastrointestinal epithelium. While enteroids from adults and fetal tissues have been extensively used for studying many infectious and non-infectious diseases, there are few reports on enteroids from infants. We show that infant enteroids exhibit both transcriptomic and morphological differences compared to adult cultures. They also differ in functional responses to barrier disruption and innate immune responses to infection, suggesting that infant and adult enteroids are distinct model systems. Considering the dramatic changes in body composition and physiology that begin during infancy, tools that appropriately reflect intestinal development and diseases are critical. Infant enteroids exhibit key features of the infant gastrointestinal epithelium. This study is significant in establishing infant enteroids as age-appropriate models for infant intestinal physiology, infant-specific diseases, and responses to pathogens.

To evaluate the pattern of Helicobacter pylori ( H. pylori ) susceptibility to different antimicrobial agents, we prospectively studied 45 H. pylori isolates by disc diffusion method. These isolates were obtained from patients aged between 16-75 years, of both sexes who had no prior history of metronidazole ingestion. A total of 45 patients were included, of which 36 were males with a mean age of 42.9 years and nine females with a mean age of 36.4 years, 62% of patients were Saudis. Almost all the H. pylori isolates were susceptible to clarithromycin, penicillin, erythromycin, ampicillin, tetracycline, clindamycin and cephradine. However, 64.4% of the isolates were resistant to metronidazole. No significant difference was found either in susceptibility of isolates from Saudi, non-Saudi or male and female patients.

Pesticides are chemical constituents used to prevent or control pests, including insects, rodents, fungi, weeds, and other unwanted organisms. Despite their advantages in crop production and disease management, the use of pesticides poses significant hazards to the environment and public health. Pesticide elements have now perpetually entered our atmosphere and subsequently contaminated water, food, and soil, leading to health threats ranging from acute to chronic toxicities. Pesticides can cause acute toxicity if a high dose is inhaled, ingested, or comes into contact with the skin or eyes, while prolonged or recurrent exposure to pesticides leads to chronic toxicity. Pesticides produce different types of toxicity, for instance, neurotoxicity, mutagenicity, carcinogenicity, teratogenicity, and endocrine disruption. The toxicity of a pesticide formulation may depend on the specific active ingredient and the presence of synergistic or inert compounds that can enhance or modify its toxicity. Safety concerns are the need of the hour to control contemporary pesticide-induced health hazards. The effectiveness and implementation of the current legislature in providing ample protection for human health and the environment are key concerns. This review explored a comprehensive summary of pesticides regarding their updated impacts on human health and advanced safety concerns with legislation. Implementing regulations, proper training, and education can help mitigate the negative impacts of pesticide use and promote safer and more sustainable agricultural practices.

Ganoderma lucidum is a versatile mushroom. Polysaccharides and triterpenoids are the major bioactive compounds and have been used as traditional medicinal mushrooms since ancient times. They are currently used as nutraceuticals and functional foods. G. lucidum extracts and their bioactive compounds have been used as an alternative to antioxidants and antimicrobial agents. Secondary metabolites with many medicinal properties make it a possible substitute that could be applied as immunomodulatory, anticancer, antimicrobial, anti-oxidant, anti-inflammatory, and anti-diabetic. The miraculous properties of secondary metabolites fascinate researchers for their development and production. Recent studies have paid close attention to the different physical, genetic, biochemical, and nutritional parameters that potentiate the production of secondary metabolites. This review is an effort to collect biologically active constituents from G. lucidum that reveal potential actions against diseases with the latest improvement in a novel technique to get maximum production of secondary metabolites. Studies are going ahead to determine the efficacy of numerous compounds and assess the valuable properties achieved by G. lucidum in favor of antimicrobial and antioxidant outcomes.

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation of non-CCS donor HIOs and inhibition of 5HT production in the CCS HIOs resulted in decreased proliferation, suggesting a link between local epithelial 5HT production and control of epithelial stem cell proliferation. This link was confirmed in genetically engineered HIOs with an increased number of enteroendocrine cells. This work provides a new mechanism to explain the pathogenesis of CCS and illustrates the important contribution of HIO cultures to understanding disease etiology and in the identification of novel therapies. Our work demonstrates the principle of using organoids for personalized medicine and sheds light on how intestinal hormones can play a role in intestinal epithelial proliferation.

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation of non-CCS donor HIOs and inhibition of 5HT production in the CCS HIOs resulted in decreased proliferation, suggesting a link between local epithelial 5HT production and control of epithelial stem cell proliferation. This link was confirmed in genetically engineered HIOs with an increased number of enteroendocrine cells. This work provides a new mechanism to explain the pathogenesis of CCS and illustrates the important contribution of HIO cultures to understanding disease etiology and in the identification of novel therapies. Our work demonstrates the principle of using organoids for personalized medicine and sheds light on how intestinal hormones can play a role in intestinal epithelial proliferation., Introduction In 1955, Leonard Cronkhite and Wilma Canada documented a rare, nonhereditary disease associated with nonadenomatous cystic polyps in the gastrointestinal (GI) tract, ectodermal abnormalities of alopecia, nail dystrophy, and [...]

Rectal cancer is associated with a high risk of metastases and local recurrence; local recurrence rates after surgical treatment being up to 32%. An accurate local staging at the time of initial diagnosis is therefore very important. Magnetic Resonance Imaging (MRI) is already established as an accurate tool for the preoperative staging of rectal cancer and has resulted in marked improvements in staging accuracy. Material and Methods: This study used MRI in comparing the morphologic features of rectal cancer before and after 8 weeks of chemo-radiation treatment (CRT) and to correlate the post treatment MRI appearances with the histological findings in resected tumors. 45 patients with histo-pathologically proven rectal adenocarcinoma received standardized 8 weeks chemo-radiation therapy and subjected to MRI before and after treatment for clinical staging. A correlation between pathological response and MRI findings was done. Results: The MRI diagnostic accuracy to diagnose T2 is 74.2% with relatively low specificity (64.7%). The diagnostic accuracy of MRI in evaluation of stage T3 and T4, the MRI sensitivity was 96.2% however of low specificity 26.3%. The diagnostic accuracy was 66.7%. Additionally, in evaluation of T2 stage, the sensitivity of MRI was very low 27.3% and specificity relatively high 94.7%. Diagnostic accuracy was 70%. Post RCT, based on downstaging after CRT, the sensitivity of MRI to show no tumor was very low 0% with diagnostic accuracy 88.9%. However, to evaluate stage T2, the sensitivity was 84.6% with low specificity 66.7% and the diagnostic accuracy was 74.2%. Conclusion: MRI had an accuracy average of 81.6% in T stage and 68.9% in N stage in re-staging rectal tumors after CRT. Over-staging results of majority of the inaccuracy. The statistical agreement between post-CRT MRI and the pathologic staging involving T and N stages was not satisfactory. In view of the above, Post CRT, restaging rectal cancer remains a challenge.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant soft tissue tumor that most commonly arises in the extremities. Its occurrence in the genitourinary tract is extremely uncommon. We present an 82-year-old man who was found to have incidental pulmonary metastasis by imaging studies. The biopsy findings from the lung were in favor of metastatic EMC. The primary mass was found to be located at the penile root, which was confirmed to be EMC. This case adds to the few reported cases of EMC arising in the perineal region, and sheds light on the clinical behavior of this soft tissue tumor.

Abstract Autochthonous Sudanese cattle breeds, namely Baggara for beef and Butana and Kenana for dairy, are characterized by their adaptive characteristics and high performance in hot and dry agro-ecosystems. They are thus used largely by nomadic and semi-nomadic pastoralists. We analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus linked to the immune response, for the indigenous cattle of Sudan and in the context of the global cattle repository. Blood samples (n = 225) were taken from three indigenous breeds (Baggara; n = 113, Butana; n = 60 and Kenana; n = 52) distributed across six regions of Sudan. Nucleotide sequences were genotyped using the sequence-based typing method. We describe 53 alleles, including seven novel alleles. Principal component analysis (PCA) of the protein pockets implicated in the antigen-binding function of the MHC complex revealed that pockets 4 and 9 (respectively) differentiate Kenana-Baggara and Kenana-Butana breeds from other breeds. Venn analysis of Sudanese, Southeast Asian, European and American cattle breeds with 115 alleles showed 14 were unique to Sudanese breeds. Gene frequency distributions of Baggara cattle showed an even distribution suggesting balancing selection, while the selection index (ω) revealed the presence of diversifying selection in several amino acid sites along the BoLA-DRB3 exon 2 of these native breeds. The results of several PCA were in agreement with clustering patterns observed on the neighbor joining (NJ) trees. These results provide insight into their high survival rate for different tropical diseases and their reproductive capacity in Sudan's harsh environment.

Background: The COVID-19 pandemic presented a unique opportunity for medical education and research training, especially for the unmatched medical graduates (UMGs). At Michigan State University, Family Medicine Department a tele-geriatric research fellowship program was developed to accommodate these UMGs during the pandemic. Objective: Provide a unique virtual research training for UMGs during the COVID-19 pandemic and beyond. The long-term goal is to fill in the gap that is growing in the workforce in geriatric medicine. Study Design: Qualitative study with pre and post-survey. Setting: Virtual meetings and discussions. Approach: Team-based approach. Population: UMGs applying for the MATCH (residency programs). Intervention: Virtual Zoom meetings were held on a weekly basis. Remote Research training was initiated. All learners underwent extensive research training. Different research projects were discussed. Tasks were distributed among UMGs and different research methods were applied. Data collected. Some learners were involved in different projects. Collaboration with other institutions was established. All projects were completed and presented at national and international conferences. Outcome Measures: The number of completed projects. The total number of medical graduates who were matched to a residency program. Results: Two batches of UMGs were enrolled. All learners found this program to be a valuable enriching experience. Most of the UMGs expressed interest in pursuing a career in geriatric medicine. Of all the UMGs participated in this program fourteen were able to match to the residency program from the first batch (Total of 16). Twenty-four oral presentations and abstracts were accepted and presented in eleven national and international conferences and meetings. Conclusions: The virtual research training is found to be an effective training method during the COVID19 pandemic. All UMGs reported an appreciation for the ability to complete their research projects remotely during the training period. The virtual learning experiences that have been utilized during the COVID-19 pandemic have proven their worth in enhancing UMGs' research skills. While virtual research experiences cannot fully take the place of in-person (e.g. bench-side), virtual research training can definitely add value to medical education. Funding: This work was funded by Pearl Aldrich Award., Presenters Nadir Abdelrahman, CMD, Avinash Bakhtiarpuri, MBBS, Sereen Shamoun, MBBS, Abuobieda Alawad, MBBS, Sulafa Elhassan, MPH, Yossra Kambal, MBBS, Rawia [...]

The diversity in genome resources is fundamental to designing genomic strategies for local breed improvement and utilisation. These resources also support gene discovery and enhance our understanding of the mechanisms of resilience with applications beyond local breeds. Here, we report the genome sequences of 555 cattle (208 of which comprise new data) and high-density (HD) array genotyping of 1,082 samples (537 new samples) from indigenous African cattle populations. The new sequences have an average genome coverage of ~30X, three times higher than the average (~10X) of the over 300 sequences already in the public domain. Following variant quality checks, we identified approximately 32.3 million sequence variants and 661,943 HD autosomal variants mapped to the Bos taurus reference genome (ARS-UCD1.2). The new datasets were generated as part of the Centre for Tropical Livestock Genetics and Health (CTLGH) Genomic Reference Resource for African Cattle (GRRFAC) initiative, which aspires to facilitate the generation of this livestock resource and hopes for its utilisation for complete indigenous breed characterisation and sustainable global livestock improvement. [ABSTRACT FROM AUTHOR]

© 2015 Macmillan Publishers Limited. All rights reserved.Mycobacterium tuberculosis, a major global health threat, replicates in macrophages in part by inhibiting phagosome-lysosome fusion, until interferon-γ (IFNγ) activates the macrophage to traffic M. t

Most of reported symptoms of SARS-CoV-2 infection are related to the respiratory system. Extra pulmonary manifestations of this novel virus infection are being increasingly reported in the literature, with increased attention on the gastrointestinal symptoms which might be the only presenting symptoms in some patients. These GI symptoms are nonspecific and little reported cases in the literature of confirmed gastrointestinal manifestations of SARS-CoV-2 infection by imaging. Colitis related to SARS-CoV-2 is even less reported in the literature. We present a case of SARS-CoV-2 infection of a 40-year-old lady who presented with GI manifestations and features of colitis of the caecum and ascending colon on CT scan. The patient did not have respiratory symptoms but had incidental lung changes in the visualized lung bases. These features were completely resolved as evident clinically and on follow-up CT scan after only 2 weeks, with only supportive care for SARS-CoV-2 infection. GI symptoms, in general, are very common presenting complain for many patients visiting the emergency department; hence, early recognition and high index of clinical suspicion for SARS-CoV-2 infection with the presence of supporting laboratory and imaging findings are to be considered for early protective measures to be undertaken to help in reducing the spread of this virus; in particular, in the middle of global pandemic of this virus and the fact that GI symptoms could be the only presenting symptoms without any respiratory symptoms. More studies and further invasive investigations in patients with features of colitis in imaging are needed to further understand the pathogenesis and its relation to SARS-CoV-2 infection

Purpose: Medical students’ knowledge assessment is a challenge. Multiple-choice questions (MCQs) despite their limitations are commonly used for this purpose. The Concept Retrieval Technique (CRT) is a relatively new knowledge assessment method. In this study we investigated the use of CRT to assess a particular long-term knowledge of medical students from different study levels. Method: One hundred forty-four medical students (50% females) participated in an Endocrinology CRT exam. The students were either in fourth, fifth-or sixth-year of the medical program. Fourth-year students were tested before they received an endocrinology course whereas students from the fifth- and sixth-year respectively took the course ten and twenty-four months before being tested. The CRT was rated by two raters independently. Results: There was strong effect of year of study on the CRT score. Fourth-year students scored significantly lower than fifth- and sixth-year students. No significant differences in CRT score emerged between fifth- and sixth-year students. The inter-rater agreement was acceptable indicating that the CRT is a reliable assessment method. The CRT showed construct validity. Conclusion: The CRT is an assessment tool that could assess long-term knowledge retention properly, and has the ability to differentiate students according to their study level.

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

The ever increasing applications of bioinformatics in providing effective interpretation of large and complex biological data require expertise in the use of sophisticated computational tools and advanced statistical tests, skills that are mostly lacking in the Sudanese research community. This can be attributed to paucity in the development and promotion of bioinformatics, lack of senior bioinformaticians, and the general status quo of inadequate research funding in Sudan. In this paper, we describe the challenges that have encountered the development of bioinformatics as a discipline in Sudan. Additionally, we highlight on specific actions that may help develop and promote its education and training. The paper takes the National University Biomedical Research Institute (NUBRI) as an example of an institute that has tackled many of these challenges and strives to drive powerful efforts in the development of bioinformatics in the country. Author summary Bioinformatics is gaining recognition globally and in Sudan as an important subdiscipline of biological sciences, one that enables researchers to efficiently interpret complex biological data. A limited number of Sudanese academic institutions have acknowledged this field despite its increasingly recognized importance. The development of bioinformatics in the country requires interdisciplinary collaborations involving experts in life sciences, research methodology, healthcare, computer, and data sciences. This can be achieved through designing educational programs and workshops alongside proposing and establishing effective collaborative research projects. In this context, we comprehensively discussed the present state of bioinformatics in Sudan, the challenges faced, as well as the efforts exerted by academic institutions including NUBRI, to upgrade infrastructure and establish local and international collaborations.

There is much interest in the use of mesenchymal stem cells/marrow stromal cells (MSC) to treat neurodegenerative disorders, in particular those that are fatal and difficult to treat, such as Huntington's disease. MSC present a promising tool for cell therapy and are currently being tested in FDA-approved phase I-III clinical trials for many disorders. In preclinical studies of neurodegenerative disorders, MSC have demonstrated efficacy, when used as delivery vehicles for neural growth factors. A number of investigators have examined the potential benefits of innate MSC-secreted trophic support and augmented growth factors to support injured neurons. These include overexpression of brain-derived neurotrophic factor and glial-derived neurotrophic factor, using genetically engineered MSC as a vehicle to deliver the cytokines directly into the microenvironment. Proposed regenerative approaches to neurological diseases using MSC include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation, MSC in the brain promote endogenous neuronal growth, encourage synaptic connection from damaged neurons, decrease apoptosis, reduce levels of free radicals, and regulate inflammation. These abilities are primarily modulated through paracrine actions. Clinical trials for MSC injection into the central nervous system to treat amyotrophic lateral sclerosis, traumatic brain injury, and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of Huntington's disease is discussed.

We report a Saudi girl who presented at birth with neonatal diabetes, duodenal atresia, and progressive cholestasis. After other gene testing was negative, the clinical diagnosis of Mitchell-Riley syndrome was ultimately considered and further genetic analysis revealed a novel missense homozygous variant in RFX6: c.983A>T (p.asp328Val). Despite intensive management, the patient died from severe Klebsiella pneumoniae sepsis at 5 months of age. This rare syndrome should be suspected in any neonate with hyperglycemia complicated by intestinal atresia and/or progressive cholestasis that could suggest biliary hypoplasia. Early recognition and diagnosis through genetic testing are essential for guiding aggressive clinical management as well as family counseling, particularly in light of the high possibility of early death in this highly complex disorder.