Pneumococcal Surface Protein A: A Promising Candidate for the Next Generation of Pneumococcal Vaccines.

Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.

Virulence factors of Candida species isolated from patients with urinary tract infection and obstructive uropathy.

OBJECTIVE: Fungal urinary tract infections due to Candida have increased significantly in recent years. Our research objective was to study Candida species in urine samples of patients with urinary tract infections (UTIs) associated with obstructive uropathy and to investigate the virulence factors of the isolated Candida. METHODS: Patients were divided into two groups: Group I (cases): 50 patients with UTIs and obstructive uropathy. Group II (control): 50 patients with UTIs but with no functional or anatomical obstruction of their urinary tract. Clinical histories and physical examinations, together with laboratory investigations of urine samples were carried out in all patients in this study. Mid stream urine samples were examined microscopically and by fungal cell culture. The isolated Candida species were identified by analytical profile index (API). Candida Virulence factors were determined for the isolated Candida. The susceptibility to fluconazole was evaluated. RESULTS: This study revealed an overall isolation rate of 27% of Candida species among all patient groups. The rate was 36% in cases, and 18% in controls, a difference found to be statistically significant (P<0.05). By API, C.albicans was detected in 44% of Candida species in cases, and in 33% in controls. While C.glabrata was detected in 28% of Candida species in cases, and in 22% in controls. C.tropicalis was detected in 17% of Candida species in cases, and in 22% in controls. Both C.krusei and C.kyfr were detected in 5.5% of Candida species in cases, and in 11% in controls. In terms of virulence factors the study showed that 11 out of 27 (40.5%) of Candida isolates were biofilm positive by tube adherence. Phospholipase activity was demonstrated in 12 out of 27 (44.5%) of Candida isolates. Secretory aspartic proteinase activity was demonstrated in 13 out of 27 (48%) of the Candida isolates. CONCLUSION: Candida is an important cause of UTIs and obstructive uropathy is a major predisposing factor.

Neglected Bilateral Posterior Shoulder Fracture Dislocation in an Uncontrolled Seizure patient.

Posterior dislocation of the shoulder is a rare injury that occurs secondary to trauma and seizures. Diagnosis is often missed and treatment is challenging. Neglected posterior dislocation is associated with Hill-Sachs lesion which leads to locking of dislocation. Correct diagnosis is achieved by history taking, a physical examination and appropriate imaging. In neglected shoulder dislocation with uncontrolled seizure and humeral head defects of up to 45% the McLaughlin procedure shows excellent results at follow-up.

Knowledge and attitudes of Saudi dental undergraduates on oral cancer.

Oral cancer awareness among future dental practitioners may have an impact on the early detection and prevention of oral cancer. A cross-sectional survey was undertaken to assess the current knowledge of future Saudi dentists on oral cancer and their opinions on oral cancer prevention. A pretested questionnaire was sent to 550 undergraduate dental students in the fourth, fifth, and sixth year of the Al-Farabi College for Dentistry and Nursing, Riyadh, Saudi Arabia. Questions relating to knowledge of oral cancer, risk factors, and opinions on oral cancer prevention and practices were posed. Four hundred seventy-nine students returned the questionnaire (87.1 %). Eighty-one percent of respondents correctly answered questions relating to oral cancer awareness. Eighty-seven percent of respondents felt confident in performing a systematic oral examination to detect changes consistent with oral malignancy. Interestingly, 57 % of respondents had seen the use of oral cancer diagnostics aids. Thirty-seven percent of respondents felt inadequately trained to provide tobacco and alcohol cessation advice. There is a need to reinforce the undergraduate dental curriculum with regards to oral cancer education; particularly in its prevention and early detection. Incorporating the use of oral cancer diagnostic aids should be made mandatory.

Assessing oral cancer knowledge among Saudi medical undergraduates.

Oral cancer is the sixth most common malignancy worldwide with more than 263,000 patients diagnosed in 2008. Nonspecialists' negative attitudes and poor working knowledge of oral cancer significantly contribute to suboptimal detection of early-stage disease which leads to delays in diagnosis. We aimed to assess the working knowledge and views associated with oral cancer prevention among medical students in Saudi Arabia. A cross-sectional questionnaire-based survey of 4th, 5th, and 6th year undergraduate medical students was undertaken. Questions included knowledge of oral cancer, risk factors, and opinions on oral cancer prevention. The overall response rate was 82 % (137/167). Mean score of cancer knowledge was 57.8 % which was below the expected standard of 70 %. Only 53 % correctly answered all questions related to oral cancer. This result had no association with either the academic year (p = 0.23) or gender (p = 0.37). Interestingly, 72 % of the respondents did not feel confident in performing an oral examination. Sixty-three percent of the medical students believed it to be beyond their role to aid patients in smoking cessation measures or to take part in other disease preventative strategies. This study demonstrates a dearth of knowledge relating to the diagnosis and management of oral cancer among clinical students within an established Saudi medical school. An immediate refinement of current medical curricula to address these deficiencies is warranted.

Prevalence of wheat allergy in Al-Kharj, Saudi Arabia.

BACKGROUND: Wheat allergy has been suggested to represent an important allergic disease. This study collates clinical and laboratory aspects in patients with wheat allergy in Al-Kharj city, Saudi Arabia. METHODS: Total and specific IgE were measured in 15 suspected cases of wheat allergy. Protein allergenicity was assessed with Western blotting. RESULTS: Significant elevation of total and specific IgE was found in 4 cases. Basophlia was also demonstrated on blood film. Western blotting results showed 2 bands (83 and 40 kDa). CONCLUSION: Wheat allergy must also be considered when planning treatment of asthma and eczema of adult patients.

Animal allergy among husbandry personnel in Riyadh.

BACKGROUND: The importance of specific animal allergy in immunopathology of asthma and atopic diseases remained to be defined. METHODS: We measured total and specific IgE. Western blotting of some allergens was also characterised. RESULT: There was a significant elevation of IgE in 3 persons among 15 samples collected. Western blotting showed common husbandry allergens from 3 sources that have common allergenicity. CONCLUSION: Exposure to animal products exacerbates allergic asthma in adults, suggesting that preventive measures should be taken to reduce their sensitivity.

Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity.

The recent identification of the involvement of the immune system response in the severity and mortality of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the importance of cytokines and chemokines as important factors in the clinical outcomes of COVID-19. However, the impact and roles of the BAFF/APRIL cytokine system, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), as well as Toll-like receptor (TLR)-3/4 in COVID-19, have not been investigated. We sought to assess the expression levels and roles of TLR3/4, BAFF, APRIL, IFN-ß, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), SARS-CoV-2 IgG and IgM antibodies in patients with critical (ICU) and non-ICU (mild) COVID-19 and their association with mortality and disease severity. Significant high levels of TLR-4 mRNA, IFN-ß, APRIL, CXCL13, and IgM and IgG antibodies were observed in ICU patients with severe COVID-19 compared to non-ICU COVID-19 patients and healthy controls. On the other hand, BAFF and CCL21 expression were significantly upregulated in non-ICU patients with COVID-19 compared with that in critical COVID-19 patients. The two groups did not differ in TLR-3, CXCL12, and CCL19 levels. Our findings show high expression levels of some inflammatory chemokines in ICU patients with COVID-19. These findings highlight the potential utility of chemokine antagonists as an immune-based treatment for the severe form of COVID-19. We also believe that selective targeting of TLR/spike protein interactions might lead to the development of a new COVID-19 therapy.

Cellular and molecular responses of Saudi chronic myeloid leukaemia patients to imatinib (STI-571): ten year experience.

BACKGROUND: The cyto-genetic hallmark of chronic myeloid leukaemia (CML), the Philadelphia chromosome (Ph), is the first consistent chromosomal abnormality that has been associated to a certain cancer type. In CML, Philadelphia chromosome is present leading to resistance to cell death and rapid proliferation. The aim of this study is to evaluate the different responses, toxicity and survival of Saudi CML patients to imatinib mesylate. METHODS: All newly diagnosed CML patients who were treated with imatinib were included in this study. We investigated haematological, and molecular and cytogenetic responses by CBC, FISH and RT-PCR respectively. Cell proliferation and apoptosis were assayed using AUC and TUNEL respectively. RESULTS: Of the 12 cases, 9 (75%) were males and 3 (25%) were female. Four (33%) of the cases were diagnosed incidentally and 8 cases (67%) presented mainly with fatigue (75%), fever (58%), and splenomegaly (83%). Signs of bleeding and rashes were rare at presentation. The majority of patients had low risk (8, 67%), and 33% had intermediate risk; but none of them had high risk CML. At the last follow up, 11 (92%) were in remissions. One patient (8%) was in remission after 3 years, 4 (33%) were in remission after 6 years, one was in remission after 7 years and 5 (42%) were in remission after 10 years. Only one patient had incomplete major molecular response (MMR) to imatinib after 12 years. The majority of the patients (10, 83%) were in MMR after 6 years and 42% of them were in MMR after 10 years of therapy. Adverse effects of imatinib were not reported by the patients. Imatinib treatment resulted in the reduction of proliferation and induction of apoptosis of CML CFU-GM cells. CONCLUSION: Imatinib mesylate is capable of treating Philadelphia chromosome-positive CP-CML without any adverse effects.

The Prevalence of unexpected antibodies in Saudi's plasma prior blood transfusion and their association with clinical conditions: A cross-sectional study.

Unexpected antibodies, also called irregular antibodies, are not known to exist in a person's serum before testing. This research aims to assess the prevalence of unexpected antibodies and their correlation with several clinical conditions. This cross-sectional prospective study, undertaken from June 2019 to June 2020, included ABO, Rh grouping, cross-matching, and antibody screening. Antibody identification was performed only on patients who tested positive in the screening test. From a total of 9764 participants who were screened for unexpected antibodies, 107 (1.1%) tested positive. The Rh blood group system antibodies were the most frequent, particularly anti-D. There was also a significant correlation between the unexpected antibodies and history of transfusion, pregnancy, and autoimmune diseases as P ≤ 0.05. The most prominent unexpected antibodies in the study belong to the Rh system (Anti-D). Moreover, as a result of the strong correlation between the unexpected antibodies as well as the history of transfusion, pregnancy, and autoimmune diseases, the highest safety criteria must be followed during the transfusion of blood to patients with these clinical conditions.

Complement Anaphylatoxins and Inflammatory Cytokines as Prognostic Markers for COVID-19 Severity and In-Hospital Mortality.

COVID-19 severity due to innate immunity dysregulation accounts for prolonged hospitalization, critical complications, and mortality. Severe SARS-CoV-2 infections involve the complement pathway activation for cytokine storm development. Nevertheless, the role of complement in COVID-19 immunopathology, complement-modulating treatment strategies against COVID-19, and the complement and SARS-CoV-2 interaction with clinical disease outcomes remain elusive. This study investigated the potential changes in complement signaling, and the associated inflammatory mediators, in mild-to-critical COVID-19 patients and their clinical outcomes. A total of 53 patients infected with SARS-CoV-2 were enrolled in the study (26 critical and 27 mild cases), and additional 18 healthy control patients were also included. Complement proteins and inflammatory cytokines and chemokines were measured in the sera of patients with COVID-19 as well as healthy controls by specific enzyme-linked immunosorbent assay. C3a, C5a, and factor P (properdin), as well as interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IgM antibody levels, were higher in critical COVID-19 patients compared to mild COVID-19 patients. Additionally, compared to the mild COVID-19 patients, factor I and C4-BP levels were significantly decreased in the critical COVID-19 patients. Meanwhile, RANTES levels were significantly higher in the mild patients compared to critical patients. Furthermore, the critical COVID-19 intra-group analysis showed significantly higher C5a, C3a, and factor P levels in the critical COVID-19 non-survival group than in the survival group. Additionally, IL-1ß, IL-6, and IL-8 were significantly upregulated in the critical COVID-19 non-survival group compared to the survival group. Finally, C5a, C3a, factor P, and serum IL-1ß, IL-6, and IL-8 levels positively correlated with critical COVID-19 in-hospital deaths. These findings highlight the potential prognostic utility of the complement system for predicting COVID-19 severity and mortality while suggesting that complement anaphylatoxins and inflammatory cytokines are potential treatment targets against COVID-19.

Review: Stem cells and gene therapy.

Both stem cell and gene therapy research are currently the focus of intense research in institutions and companies around the world. Both approaches hold great promise by offering radical new and successful ways of treating debilitating and incurable diseases effectively. Gene therapy is an approach to treat, cure, or ultimately prevent disease by changing the pattern of gene expression. It is mostly experimental, but a number of clinical human trials have already been conducted. Gene therapy can be targeted to somatic or germ cells; the most common vectors are viruses. Scientists manipulate the viral genome and thus introduce therapeutic genes to the target organ. Viruses, in this context, can cause adverse events such as toxicity, immune and inflammatory responses, as well as gene control and targeting issues. Alternative modalities being considered are complexes of DNA with lipids and proteins. Stem cells are primitive cells that have the capacity to self renew as well as to differentiate into 1 or more mature cell types. Pluripotent embryonic stem cells derived from the inner cell mass can develop into more than 200 different cells and differentiate into cells of the 3 germ cell layers. Because of their capacity of unlimited expansion and pluripotency, they are useful in regenerative medicine. Tissue or adult stem cells produce cells specific to the tissue in which they are found. They are relatively unspecialized and predetermined to give rise to specific cell types when they differentiate. The current review provides a summary of our current knowledge of stem cells and gene therapy as well as their clinical implications and related therapeutic options.

Biomedical research in the Middle Eastern countries: update and insight using SCImago Journal Rank indicator.

BACKGROUND: There is a dire need in the Arab world and Middle Eastern countries to reform the higher education, research policy and planning for improving the quality to meet the needs of modern society. The impact factor (IF) was developed in the 1960s by Eugene Garfield of the Institute for Scientific Information (ISI) in the USA. It has been extensively used for more than 40 years. The SCImago Journal Rank (SJR) indicator belongs to this new family of indicators based on eigenvector centrality was introduced since 2007. The SJR indicator is a size-independent metric aimed at measuring the current 'average prest (se text) per paper' of journals for use in research evaluation processes. METHODS: We present the status o the biomedical scientific research in the Middle Eastern countries through the newly developed SJR indicator showing some of the proposed ways that clearly can be applied for enhancing and development of that field in the Middle Eastern countries. RESULTS: During the period from 1996 to 2008, Northern America, Western Europe and Asiatic region are the major contributors of the scientific research Worldwide. In the Middle East, the prominent two main Arab countries are Egypt and Saudi Arabia, nevertheless, they need more planned strategies for optimal contribution to their Middle East, Arab region and the World, despite the tangible achievements of the Arab states in the higher education and scientific research during the last decade. CONCLUSION: The SJR is seemingly satisfactory for ranking the countries for their scientific contribution and impact.

New mutations of locus control region in Saudi sickle patients.

Sickle cell anemia (SCA) is a common hematological disease affecting humans. Detection of a single base pair mutation in ß-globin gene is an important diagnostic tool for SCA. The aim was to study the molecular survey of locus control regions (LCR) in Saudi patients with sickle cell anemia, and to identify the genetic variables and their clinical manifestations. METHODOLOGY: Blood samples from 69 unrelated sickle cell disease patients were obtained from the KKUH, Riyadh between 2017-2019. In this study, the DNA was extracted and PCR was performed. Additional PCR amplifications reactions covering the LCR were performed by using another different set of primers. Seven specific primer pairs were used to amplify seven regions in the locus control region (LCR) of ß globin family. The generated fragments were sequenced to identify the possible alterations in this region. RESULTS: The results gained from sequencing experiments revealed a wide range of genomic alterations. A total of 69 gene alterations have been recognized in the locus control region;- The first fragment LCR-HS1 shows 20 alterations; The second fragment LCR-HS2 revealed six changes; The third fragment LCR-HS3 shows many changes; The fifth LCR-HS5 region revealed four changes; The sixth fragment LCR-HS6 revealed eight changes; The seventh LCR-HS7 fragment demonstrates ten changes. CONCLUSION: It clear that this study has successfully identified LCR mutations for random Saudi patients with SCD. The above results should be taken further to set up management strategies to improve outcomes.

Biochemical and molecular analysis of the beta-globin gene and LCR region on Saudi ß-thalassemia patients.

INTRODUCTION: Beta-thalassemias are a group of inherited blood disorders caused by reduced or absent synthesis of beta chain of hemoglobin resulting in variable phenotypes ranging from clinically asymptomatic individuals to severe anemia symptoms. The objective of this study is to screen for the whole beta gene globulin and the LCR region and its clinical relevance in ß-Thalassemia patients. METHODS: In this study, we collected 140 blood patients' samples with beta-thalassemia from different areas of Saudi Arabia. DNA was then extracted then the molecular scanning for the whole ß-globin gene and the Locus control region (ß-LCR) for patients' samples, was run using PCR. RESULTS: Sixty one mutations found in this study, including 22 new mutations not recorded in the database before. These deletions including: (*C-1960-1961 ca/-- del in hbb5) and (*c-519C A het in hbb9). Interestingly, the highest percentage in gene deletion occurred in exon 03A by ∼33% of the samples, while the highest percentage in gene addition of the gene occurred in exon 03B by ∼25%. CONCLUSION: This study was unique to show several new mutations that would help in diagnosis and treatment. These results should be taken further to set up better management strategies to improve outcomes.

Prevalence, antibiotic susceptibility pattern and production of extended-spectrum beta-lactamases amongst clinical isolates of Klebsiella pneumoniae at Armed Forces Hospital in Saudi Arabia.

The aim of this descriptive study was to determine the prevalence of Klebsiella pneumoniae from different clinical specimens, their antibiotic susceptibility pattern and the extended-spectrum beta-lactamase (ESBL) production among such isolates at Armed Forces Hospital, Al-Kharaj, Saudi Arabia, from November, 2004 to October, 2007. A total of 328 isolates of K. pneumoniae recovered from 8152 different specimens were studied for ESBL production and antimicrobial susceptibility. The prevalence of K. pneumoniae was 4% (328/8152). We observed a high percentage of K. pneumoniae resistant to ampicillin (100%) and tetracycline (92%). The prevalence of ESBL-producing K. pneumoniae was found to be 10.4% (34/328). The ESBL-producing strains were mostly from aspirates (25%) followed by sputum (20%) and blood (18.2%). These ESBLproducing isolates were highly resistant to gentamicin and ciprofloxacin. All isolates were susceptible to imipenem. Our findings demonstrate a high percentage of ESBL-producers among clinical isolates of K. pneumoniae and a high rate of multidrug resistance. Continued infection control measures and prudent use of antimicrobial agents are essential in reducing the spread of multi-resistant ESBL-producing K. pneumoniae.

Role of airway epithelium in engulfing apoptotic eosinophils.

INTRODUCTION: This study aims to investigate which recognition pathways are important in engulfing apoptotic eosinophils. METHODS: Here, two epithelial cell were selected namely (large airway bronchial epithelial cells) LAECs and A549. The inhibition assay was examined by resting and dexamethasone-stimulated epithelial cells. Confocal microscopy confirmed the engulfment of apoptotic eosinophils. RESULTS: Macrophages and LAECs recognized and phagocytosed apoptotic eosinophils. Dexamethasone and IL-1 increased the capacity of LAECs to engulf apoptotic eosinophils. More interestingly, inhibiting monoclonal antibodies (Mabs) abolished the uptake of apoptotic cells by LAECs. CONCLUSION: On the basis of the above findings, the LAECs is capable of recognizing and engulfing apoptotic eosinophils and that enhanced by interleukin-1 (IL-1â) and dexamethasone.

The haemopoietic stem cell: between apoptosis and self renewal.

Self renewal and apoptosis of haemopoietic stem cells (HSC) represent major factors that determine the size of the haemopoietic cell mass. Changes in self renewal above or below the steady state value of 0.5 will result in either bone marrow expansion or aplasia, respectively. Despite the growing body of research that describes the potential role of HSC, there is still very little information on the mechanisms that govern HSC self renewal and apoptosis. Considerable insight into the role of HSC in many diseases has been gained in recent years. In light of their crucial importance, this article reviews recent developments in the understanding of the molecular, biological, and physiological characteristics of haemopoietic stem cells.

Investigation of Helicobacter pylori infection in Jordanian patients using six enzyme immunoassays for immunoglobulin G (IGG) and IGA testing.

Helicobacter pylori (H. pylori) is the etiologic agent of a variety of gastrointestinal disorders. The rationale of the current study is to evaluate six enzyme immunoassays for detection of anti-H. pylori immunoglobulin G (IgG) and IgA in Jordanian patients. Biopsy specimens and blood samples were obtained from patients underwent the endoscopy unit at Al-Bashir hospital in Jordan. The serum samples were investigated for the presence of anti-H. pylori IgG and IgA antibodies in patients with positive H. pylori biopsy samples. The results showed that IgG utilizing kits are more sensitive than of IgA kits and the IgA kits are more specific than of that IgG kits. Moreover, the biopsy is seemingly the gold standard for diagnosis of H. pylori is followed by H. pylori culture on brucella agar medium. An imperfect relation between the presence of H. pylori infection and the antibody response was existed that could be explained either because of the unsatisfactory sensitivities and specificities of the commercial kits used or because of weak immunological response in our patients to H. pylori antigens. Collectively, the H. pylori diagnosis that depends on the detection of anti-H. pylori antibodies in the hospital setting and in the screening programs should consider another test for confirmation the initial diagnosis.

Biochemical and Molecular analysis of the beta-globin gene on Saudi sickle cell anemia.

Sickle cell anemia (SCA) is one of the most common hematologic diseases affecting humans. Detection of a single base pair mutation at 6th codon of ß-globin gene is important for the diagnosis of SCA. The aim was to study the nucleotide sequences and the molecular survey of ß-globin gene in Saudi patients. Blood samples from 77 unrelated SC patients were obtained from the KKUH, between 2015 and 2017. In this study, DNA was extracted then PCR was performed. Twelve overlapping fragments covering ß-globin gene, have been generated by PCR. A total of 47 alterations have been recognized in ß-globin gene. These alterations composed of: deletions, insertion or substitutions as follows:- one mutation identified on the 1st segment; three alterations on 2nd fragment; two alterations on 3rd segment; seven alterations on 4th segment; three substitution on 5th fragment; two changes on 6th fragment; five alterations on 7th fragment; seven substitution changes on 8th fragment; two heterozygous substitution changes on 9th fragment; three changes on 10th fragment and eight substitution changes on 11th fragment, and four changes on 12th fragment. SCA had profound negative effects on many organs, causing many complications. The results should be taken further to set up management strategies to improve outcomes.