The role of CD8+ T-cell clones in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multidimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterized patients with ITP and compared them with age-matched controls using immunophenotyping, next-generation sequencing of T-cell receptor (TCR) genes, single-cell RNA sequencing, and functional T-cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon gamma, tumor necrosis factor α, and granzyme B, defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the TCR showed expanded T-cell clones in patients with ITP. T-cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon gamma, and trigger platelet activation and apoptosis via the TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP.

Assessing the Diagnostic Values of the Neutrophil-to-Lymphocyte Ratio (NLR) and Systematic Immunoinflammatory Index (SII) as Biomarkers in Predicting COVID-19 Severity: A Multicentre Comparative Study.

COVID-19 has been notoriously unpredictable in its clinical course. Such unpredictability poses a challenge to clinicians in predicting patients who will develop severe cases and possibly die from the infection. This study aims to assess and compare the diagnostic value of the NLR and SII as biomarkers in predicting COVID-19 severity, represented by mortality, with a multicentre comparative study including 855 patients in Saudi Arabia. Descriptive and analytical statistics were used to compare haematological indices between survivors and non-survivors. The median age of patients included was 41 years old, with an almost equal ratio of men to women. Most participants were Saudis, and the mortality rate in the study cohort was 13.22%. Non-survivors, as compared to survivors, were significantly older, had lower RBC counts, haemoglobin and haematocrit levels, as well as significantly higher WBC and neutrophil counts. Both the NLR and SII were capable of differentiating between survivors and non-survivors, with the latter having significantly higher values. However, the NLR was superior to the SII in such differentiation, as it had a larger area under the curve. This study further confirms the diagnostic values of the NLR and SII as biomarkers in predicting COVID-19 severity and mortality, with the NLR being more sensitive and specific. Clinical guidelines on managing COVID-19 cases should benefit from these findings by harnessing the value of the NLR in COVID-19 management.

Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches.

Toll-like receptors (TLR) play an eminent role in the regulation of immune responses to invading pathogens during sepsis. TLR genetic variants might influence individual susceptibility to developing sepsis. The current study aimed to investigate the association of genetic polymorphisms of the TLR2 and TLR4 with the risk of developing sepsis with both a pilot study and in silico tools. Different in silico tools were used to predict the impact of our SNPs on protein structure, stability, and function. Furthermore, in our prospective study, all patients matching the inclusion criteria in the intensive care units (ICU) were included and followed up, and DNA samples were genotyped using real-time polymerase chain reaction (RT-PCR) technology. There was a significant association between TLR2 Arg753Gln polymorphisms and sepsis under the over-dominant model (p = 0.043). In contrast, we did not find a significant difference with the TLR4 Asp299Gly polymorphism with sepsis. However, there was a significant association between TLR4 Asp299Gly polymorphisms and Acinetobacter baumannii infection which is quite a virulent organism in ICU (p = 0.001) and post-surgical cohorts (p = 0.033). Our results conclude that the TLR2 genotype may be a risk factor for sepsis in adult patients.

Challenges and Opportunities in the Clinical Development of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma.

After a decade of stagnation in drug development, therapeutic reversal of immune-exhaustion with immune checkpoint inhibitors (ICPIs) has been shown to be effective in advanced hepatocellular carcinoma (HCC). The clinical development of novel ICPIs continues at a rapid pace, with more than 50 clinical trials of immunotherapeutic agents registered as of May 2018 for this indication. The development of ICPI is particularly challenging in patients with HCC, a population with unique features which impact on safety and efficacy of immune-modulating therapies. In this review, we discuss the biological foundations supporting the development of ICPIs across the advancing stages of HCC, focusing on the rational positioning of ICPIs across the various Barcelona-Clinic Liver Cancer (BCLC) stages of the disease. Translational studies should guide adequate prioritization of those therapeutic agents and combination strategies which are most likely to achieve patient benefit based on solid mechanistic and clinical justifications.

COVID-19 vaccine hesitancy and attitudes of subjects with disability and their carers in Saudi Arabia: a cross-sectional study.

The COVID-19 pandemic has caused significant disruption to countries worldwide, including Saudi Arabia. The fast preventative measures and the mass vaccine enrollment were vital to contain the pandemic in the country. However, vaccine hesitancy was a significant obstacle to taking the vaccine but was not previously explored. One hundred eighty-six subjects with disabilities were enrolled in this study in an attempt to explore their hesitancy and attitudes toward COVID-19 vaccines. Most participants were previously diagnosed with COVID-19 and had a close family who was also diagnosed with it. Most of them were willing to be vaccinated but had not received previous vaccinations. Official sources of information, e.g., TV/radio, were an essential factor driving their intention to get vaccinated. Beliefs that drove participants' vaccine acceptance included vaccine safety, sufficient testing before its release, and its ability to protect from infection. The results of this seminal study provide insights to public health policymakers, which should be considered and taken together in light of other studies addressing the population's vaccine hesitancy.

Evaluating COVID-19 vaccine acceptance among parents in Saudi Arabia: a systematic review examining attitudes, hesitancy, and intentions.

Introduction: The COVID-19 pandemic, affecting adults and children equally, has caused significant disruption to countries worldwide, including Saudi Arabia. In Saudi Arabia, the fast preventative measures and mass vaccine enrollment were vital to contain the devastating impact of the pandemic. However, vaccine hesitancy, especially among parents toward vaccinating their children, was a significant obstacle to vaccine uptake. Methods: This systematic review followed PRISMA guidelines to assess parental willingness to vaccinate their children against COVID-19, determine the key determinants influencing such intention and attitudes, and underline the significant concerns and misconceptions regarding the vaccine among parents. The Joanne Briggs Institute (JBI) checklist for prevalence studies was used to assess included studies for risk of bias. Results: Twenty-three studies were included in this systematic review, representing a total of 20,926 participants, with over 66% of them were female. Over 37% of the participants were willing to vaccinate their children against COVID-19. Parents' age, gender, level of education, and income were the main determinants of their intention to vaccinate their children. The parents' main concerns were the potential vaccine side effects, safety, and efficacy. Major misconceptions about the COVID-19 vaccine included it being dangerous to children and that children are at lower risk of severe infection; hence, vaccines were not needed. Discussion: This seminal review provides insights to public health policymakers, which should be considered and taken together in light of other studies addressing parental vaccine hesitancy.

The Effects of COVID-19 on the Mental Health of Children and Adolescents: A Review.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has profoundly affected global health and well-being. As part of the Coronaviridae family, SARS-CoV-2 joins a diverse group of viruses found in both humans and various animal species, including bats, camels, and cats. The pandemic has led to widespread social isolation, reduced physical activity, and significant lifestyle changes, posing potential risks to individuals' mental and emotional health. This review aims to explore the implications of COVID-19 on the mental health of children and adolescents, given the limited attention this population has received in the medical literature. Multiple research studies in several countries have found that the COVID-19 pandemic is associated with greater stress levels, depression, anxiety, insomnia, drug misuse, and other mental health challenges among young individuals. Understanding the long-term effects of the pandemic on mental health is crucial for developing effective interventions and support systems to promote resilience and well-being in children and adolescents. Even after the pandemic ends, it is crucial to prioritize understanding the long-term impacts of the pandemic on mental health, integrating findings into public health strategies, addressing mental healthcare disparities, and fostering resilience in children and adolescents. Achieving these objectives requires collaborative efforts across various sectors to ensure equitable access to mental health resources and the implementation of sustainable solutions for the well-being of young people in the aftermath of the pandemic.

Characterization and Cytotoxicity Assessment of Synthesized Palladium (II) Complex-Encapsulated Zinc Oxide Nanoparticles for Cancer Treatment.

The treatment of cancer often leads to a range of adverse effects. Encapsulating drugs can mitigate these effects and enhance drug efficacy by enabling a controlled release at the site of interest. This study details the successful synthesis of zinc oxide nanoparticles (ZnONPs) through the precipitation of Zn(NO3)2·6H2O with KOH. A Pd(II) complex drug was synthesized from a Schiff base ligand derived from 2-hydroxybenzohydrazide and (E)-1-(2-(p-tolyl)hydrazono)propan-2-one using potassium tetrachloropalladate(II). This complex was subsequently incorporated into ZnONPs. Characterization of the resulting compounds was performed using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta Potential, Fourier Transform Infrared (FTIR) Spectroscopy, and UV-visible spectroscopy. TEM imaging revealed particle sizes of 160.69 ± 4.74 nm for ZnONPs and 185.28 ± 2.3 nm for the Pd(II) complex-encapsulated ZnONPs. The Zeta potential values were 6.53 mV for ZnONPs and 7.36 mV for Pd(II) complex-encapsulated ZnONPs. UV-visible spectroscopy showed an absorption peak at 360 nm for ZnONPs, while the Pd(II) complex-encapsulated ZnONPs exhibited a peak at 410 nm. FTIR analysis indicated the presence of the Pd(II) complex within the ZnONPs, as evidenced by a consistent Zn-O vibrational band at 832 cm-1 and a shift in another peak from 460 to 413 cm-1. Additionally, the detection of a C = N stretching vibration at 1548 cm-1 and a carbonyl stretch at 1626 cm-1 was observed. The Encapsulation Efficiency (E.E.) of the Pd(II) complex was 97.2%. A drug release experiment conducted at pH 7 showed a steady-state release pattern after 16 h, with a cumulative release of 44.3%. The cytotoxic effects of the Pd(II) complex and its encapsulated form in ZnONPs on the MCF-7 cell line were assessed via MTT test. The Pd(II) complex encapsulated within ZnONPs exhibited decreased toxicity relative to the unencapsulated drug, as evidenced by a higher IC50 value of 418.5 µg/ml. This suggests that the encapsulation facilitates a sustained release, which allows for targeted accumulation within cells. The elevated IC50 value indicates that the drug delivery system may be engineered to modulate the release of the drug in a more controlled manner, potentially resulting in a prolonged release profile rather than an immediate therapeutic impact.

Uneventful Coadministration of Seasonal Influenza and COVID-19 BNT162b2 Vaccines Two Weeks Post-Influenza Vaccination in an Egg-Allergic Subject: A Case Report.

The COVID-19 pandemic took the world by storm, and although it has taken the world's attention, it did not stop the spread of other communicable diseases. Seasonal influenza is a viral infection that could cause severe disease; therefore, annual influenza vaccination is highly recommended, especially among patients with a weakened immune system. However, such vaccination is contraindicated for people with hypersensitivity to the vaccine or any of its components, e.g., eggs. This paper describes a case of an egg-allergic individual who received an influenza vaccine containing egg protein, which only caused mild tenderness at the site of injection. Two weeks later, the subject received a double vaccination of a second booster dose of Pfizer-BioNTech and the seasonal influenza vaccine. The patient reported no local or systemic adverse reactions to the vaccine. This case report suggests vaccination safety for subjects with mild allergies to vaccine components.

The Reasons behind COVID-19 Vaccination Hesitancy among the Parents of Children Aged between 5 to 11 Years Old in Saudi Arabia.

Simultaneously with the development of the COVID-19 vaccination plan for minors, it is critical to understand the reasons related to parental COVID-19 vaccination hesitancy. This study aims to determine the reasons associated with vaccination hesitancy among parents, and the prevalence and the characteristics of the parents who are hesitant to allow their children aged between 5 to 11 years old to be administered the COVID-19 vaccines. A web-based questionnaire was used to perform this study between May 2022 to September 2022 in Saudi Arabia (SA). Several factors, personal and social, affected the participants' willingness to vaccinate their children with the COVID-19 vaccines. The age of the parents was found to have a significant impact on their decision to vaccinate their children. Those between the age of 40-49 years of age were the most willing to vaccinate (almost 41%) compared to those 50 years or older who were most resistant to vaccination. Female participants were more resistant to vaccinating their children compared to their male counterparts. Saudis were more resistant to vaccinating their children compared to the non-Saudi participants. Those private sector-employed parents were the most willing to vaccinate (16.6%), followed by those working in the governmental sector (13.8%). About 40.7% of non-healthcare workers were resistant to vaccinating their minor compared to healthcare workers (8.7%). In conclusion, the study presents several factors that affect the parental willingness to vaccinate their children in SA. These factors should be properly addressed when developing public health strategies to promote the COVID-19 vaccination of children in SA.

Developing a COVID-19 Mortality Prediction (CoMPred) Indicator for ICU Diabetic Patients Treated with Tocilizumab in Saudi Arabia: A Proof-of-Concept Study.

Since the beginning of the COVID-19 pandemic, efforts have been made to underline its discourse and identify factors contributing to its severe forms. Clinically, many physicians depended on subjective criteria to determine its severe forms, which varied significantly between practices. However, they did not rely on objective laboratory findings. This study aimed to present a novel and objective laboratory-based indicator to predict mortality among COVID-19 patients. The study included 249 COVID-19 patients who were admitted to the ICU, of which 80 did not survive. The COVID-19 Mortality Prediction (CoMPred) indicator was developed by including the age and the following lab investigations: neutrophil-to-lymphocyte ratio (NLR), D-Dimer, PT, aPTT, ESR, CRP, and urea levels. A CoMPred score of 7.5 or higher carries a sensitivity of 81.10% in predicting mortality, i.e., a patient with a CoMPred score of 7.5 or higher has an 81.10% chance of dying. The CoMPred indicator score directly correlates with mortality, i.e., the higher the score, the higher the possibility of the patient dying. In conclusion, the CoMPred indicator is an objective tool that is affordable and widely available, will assist physicians, and limit the burden on clinical decisions on an unpredicted course of COVID-19 in patients.

Study of novel bidentate heterocyclic amine-based metal complexes and their biological activities: cytotoxicity and antimicrobial activity evaluation.

Metallic antitumor drugs with heterocyclic ligands, such as novel AMI (amino methyl imidazole) complexes [Pd(AMI)Cl2](1), [Cu(AMI)L1](2), and [Cu(AMI)L2·2H2O](3) where L1 = oxalate and L2 = malonate, were synthesized and characterized. Assessments included elemental analyses, mass spectrometry, Fourier transform-infrared spectroscopy, ultraviolet-visible spectroscopy, and thermal analysis. The cytotoxicity of AMI complexes compared to cisplatin was assessed using MTT (3-[4,5-dimethylthiazol-2-yl] 2,5diphenyl tetrazolium bromide) assay with breast (MCF-7) and cervical (HeLa) cancer cell lines. After treating these cells with the AMI complexes' IC50 values for 48 h, malondialdehyde levels and catalase activity were used to assess oxidative stress, antioxidant activity was evaluated with DPPH radical scavenging method, comet assays assessed DNA damage, and DNA fragmentation was evaluated using the gel electrophoresis. In vitro, antimicrobial activity was assessed using a disc diffusion method. The anticancer activity results showed that IC50 (half-maximal inhibitory concentration) values of complex one, two, and three against MCF-7 and HeLa cancer cells are 0.156 ± 0.0006, 0.125 ± 0.001, 0.277 ± 0.002 µM respectively for MCF-7 cells and 0.222 ± 0.0005, 0.126 ± 0.0009, 0.152 ± 0.001 µM respectively for HeLa cells. Complex two demonstrated strong anticancer activity against MCF-7 and Hela cells. The study of oxidative stress parameters revealed that Malondialdehyde levels increased in cancer cell lines treated with complexes compared to untreated cells. Catalase activity decreased in cells treated with palladium chelate. The DPPH radical scavenging assay results identified that complex one was a more potent antioxidant in MCF-7 and Hela cells than other complexes with SC50 values of 227.5 ± 0.28 and 361 ± 1.2 µL/mL, respectively. The comet assay results showed that complex two caused significant DNA damage in MCF-7 and HeLa cancer cells treated. Antimicrobial assays identified complex three as the most effective. Copper complexes give better antifungal activity against A. flavus than the palladium complex. We conclude that complex two is the most active in both cell types and might be assessed as a clinically useful drug for breast cancer treatment. The significance of the current study is the synthesis of antitumor drugs containing heterocyclic ligands, such as novel AMI complexes, and the study of their biological activities.

Novel palladium(II) and Zinc(II) Schiff base complexes: Synthesis, biophysical studies, and anticancer activity investigation.

BACKGROUND: Schiff base metal complexes are considered promising chemotherapeutic agents due to their potential application in cancer therapy. METHODS: The current work sought to synthesize a brand-new Schiff base ligand obtained from 2-hydroxybenzohydrazide and (E)- 1-(2-(p-tolyl)hydrazono)propan-2-one with metal ions which included Pd(II) and Zn(II) ions. Elemental analyses, FT-IR, mass spectra, 1H NMR, UV-Vis spectrometer, and computational analysis characterized the compound's structure. In vitro, the breast cancer cell line (MCF-7) was tested for its sensitivity to Schiff base (HL) and its Pd(II) and Zn(II) complexes. The half-maximal inhibitory concentration IC50 of the compounds was determined and used to perform the comet assay, which was carried out to reveal the photo-induced DNA damaging ability of the compounds of individual cells. Moreover, the compounds' effects on antioxidant defense systems of enzymes in cells: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant Malondialdehyde (MDA) were examined in MCF-7 cells. RESULTS: The Pd(II) complex displayed approximately the same IC50 as Cisplatin, while Zn(II) complex had better activity than Cisplatin with very low IC50, 1.40 µg/ml. Significant alterations in SOD, CAT, GPx, and MDA production were discovered, inducing oxidative stress, enlarging ROS production, and reducing the antioxidant amount. This change was approximately similar in most compounds. Consequently, it promoted apoptosis, particularly the Zn(II) complex, which demonstrated an improved impact because of its ability to influence the antioxidant defense systems of enzymes, mostly SOD and GPx, besides increasing MDA levels. CONCLUSION: It can be concluded that Zn(II) complex is the most effective anticancer drug since it induced a very similar genotoxic effect as Cisplatin and has a very low IC50 value.

Assessing the Impact of Use and Trust in Different Sources of Information on COVID-19 Vaccination Uptake in Saudi Arabia (SA) Using the COVID-19 Vaccine Hesitancy and Resistance in SA (CoV-HERSA) Tool.

COVID-19 vaccination has been the cornerstone measure to tackle the severe morbidity and mortality of the ongoing global pandemic. However, vaccine hesitancy and resistance were observed in different populations, including Saudi Arabia (SA), yet such hesitancy was not accurately measured, nor were its influencing factors determined. The COVID-19 Vaccine Hesitance and Resistance in SA (CoV-HERSA) tool was developed, validated, and distributed to 387 participants to accurately measure their COVID-19 vaccine hesitancy and its influencing factors. Different chronic conditions affected participants' CoV-HERSA differently, with those having autoimmune disorders having the highest CoV-HERSA scores. Previous exposure to COVID-19 significantly increased the CoV-HERSA scores. The use and trust of the different sources of information had a significant influence on the CoV-HERSA scores. Those who used newspapers and healthcare practitioners as their source of information had the highest CoV-HERSA scores, while those who relied on family/friends had the lowest scores. The CoV-HERSA is a validated tool that accurately reflects participants' willingness and hesitancy to COVID-19 vaccination and can be used to explore the influence of different factors on the participants' attitudes towards the COVID-19 vaccine.

The Cost-Effectiveness of Requesting a Complete Blood Count (CBC) in the Management of COVID-19 in Saudi Arabia.

BACKGROUND: Since the beginning of the COVID-19 pandemic, studies have attempted to determine the value of the different laboratory investigations. This study aims to assess the cost-effectiveness of requesting a complete blood count (CBC) for COVID-19 patients, as opposed to ordering a COVID-19 antibody titer in Saudi Arabia. METHODS: The prices of a CBC, COVID-19 PCR, and antibody titer were obtained from 40 healthcare establishments in Saudi Arabia, between January and February 2022. RESULTS: Requesting a CBC is significantly cheaper than requesting a COVID-19 antibody titer, which was available in almost all of the establishments, as compared to COVID-19 PCR and antibody titer testing. The investigation prices did not differ significantly between hospitals and private laboratories, nor across cities in Saudi Arabia. CONCLUSIONS: CBC, which provides valuable information on the patient's condition and prognosis, is a cost-effective and widely available tool for managing COVID-19. The price and availability of CBC warrant it to be included in the COVID-19 management protocols.

Physicians' Awareness of Depression Among Their Patients in Saudi Arabia.

Background Depression is a global public health burden, and although it is multifactorial, its development is highly associated with chronic diseases. Thus, physicians' knowledge and attitude toward depression are vital for the recognition and treatment of depression among patients with chronic illnesses. This study aims to examine physicians' knowledge and attitude toward depression in Saudi Arabia and to determine factors that significantly influence them. Methodology An online survey using a 12-item questionnaire was completed by 50 physicians between January and June 2020. Knowledge (K) and attitude (A) scores were calculated and compared nonparametrically based on scores by gender and years of experience. Results Participants' years of clinical experience was found to significantly influence the participants' K scores, with those with fewer than one year of experience having the highest K scores of all participants (p < 0.05). Years of experience had a similar influence on the A scores. Furthermore, gender was an influencing factor as male participants had higher A scores than female participants. Years of experience and gender influenced the A scores independently. Male physicians more commonly referred patients to a mental health specialist than female physicians, and had significantly higher A scores and more years of experience. There was a direct correlation between the K and A score, indicating that participants' knowledge of depression positively influenced their attitude toward depression. Conclusions In this study, participants' gender and years of experience have been identified to have a significant impact on their knowledge and attitude toward comorbid depression when treating patients with chronic illnesses. This identifies an important gap and offers preliminary insight into the readiness and practice of holistic care for patients, particularly for those treated by physicians of differing gender and experience levels. Findings further demonstrate that it is most beneficial to patients with chronic illnesses that physicians utilize a holistic approach and consider depression when developing their treatment plans. This would involve being able to detect and manage depression among their patients properly, as well as referring patients to mental health specialists when needed. Clinical guidelines should be updated to emphasize the use of depression screening tools for patients with chronic diseases.

Assessing the Dynamics of COVID-19 Morbidity and Mortality in Response to Mass Vaccination: A Comparative Study Between Saudi Arabia and the United Kingdom.

Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, efforts have been in place to tackle the infection. Mass vaccination programs were regarded as the sole solution to end the pandemic. Here, we compare the differential impact of mass vaccination programs in Saudi Arabia (SA) and the United Kingdom (UK) on COVID-19 morbidity and mortality to determine whether vaccines were solely responsible for the changes observed in the disease dynamics. Methodology We retrospectively collected the number of new cases and deaths throughout 2021 in both SA and the UK. Similarly, the number of vaccine doses delivered in both countries was collected and compared. Results Through 2021, the percentage of daily COVID-19 cases was significantly less in SA than in the UK; however, the percentage of deaths was higher in SA. Interestingly, the percentage of daily cases was significantly reduced in SA upon vaccination. The vaccination coverage of both the first and second doses was higher in the UK compared to SA, and, consequently, the percentage of deaths was significantly reduced in the UK compared to SA. Conclusions The UK vaccination program succeeded in curbing the number of daily deaths compared to SA. SA had better control over the percentage of daily cases, primarily due to the restrictive measures and vaccination, such as the imposed social distancing and mandatory face masks.

Role of MBL2 Polymorphisms in Sepsis and Survival: A Pilot Study and In Silico Analysis.

Sepsis is a serious infection-induced syndrome with serious ramifications, especially in intensive care units. Global concern motivated the investigation of the role of related genes' polymorphism in predicting the liability to infection, sepsis, septic shock and survival. Among these genes is the gene encoding mannose-binding lectin (MBL), with its remarkable importance in the immune system. However, the previous studies showed conflicting results and ambiguity that urged us to engage with this issue in the Egyptian population. Prediction of functional and structural impacts of single nucleotide polymorphisms (SNPs) was done using in silico methods. A prospective observational study was conducted in intensive care units; one hundred and thirty patients were followed up. Genotyping was performed using real-time polymerase chain reaction (RT-PCR) technology. MBL SNPs showed a remarkable high frequency in our population, as well. No significant association was found between MBL2 genotypes and any of our analyses (sepsis, septic shock and survival). Only septic shock and age were independently associated with time of survival by Cox regression analysis. Our study may confirm the redundancy of MBL and the absence of significant impact on sepsis liability and mortality in adult patients.

In silico analysis of missense variants of the C1qA gene related to infection and autoimmune diseases.

Objectives: C1q is a key activator of the classical pathway of the complement system and exerts consequences relating to opsonization and phagocytosis. The C1qA gene is one of three genes encoding the C1q molecule. Defects in C1q, and especially in C1qA, have been linked to an increased susceptibility to infection, sepsis, and systemic lupus erythematosus. These defects could arise from missense single nucleotide polymorphisms (SNPs) and their deleterious impacts on protein structure and function. Thus, identifying high-risk missense SNPs in C1qA has become a necessity if we are to identify appropriate measures for prevention and management of affected patients. Methods: A comprehensive in silico study was conducted to screen the 184 missense SNPs in the C1qA gene using different tools with different algorithms and approaches. We investigated the impact of SNPs on protein function, stability, and structure. In addition, we identified the location of the SNPs on protein domains, secondary structure alignment, and the phylogenetic conservation of their positions. Results: Of the 184 missense SNPs, 10 SNPs were predicted to be the most damaging to protein function and structure. Conclusion: Ten missense SNPs were predicted to have the highest risk of damaging protein function and structure, thus leading to infection, sepsis, and systemic lupus erythematosus. These 10 SNPs constitute the best candidates for further experimental investigations.

Al-hijamah (the triple S treatment of prophetic medicine) significantly increases CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio: a clinical trial.

Beta thalassemia is associated with decreased immunity possibly due to iron overload. Al-hijamah (Hijamah) is wet cupping therapy (WCT) of prophetic medicine. Prophet Muhammad Peace be upon him said: "The best among your treatments is Al-hijamah". Al-hijamah is a promising excretory treatment to clear blood of causative pathological substances. Al-hijamah is a three-step technique (skin suction, scarification and suction) i.e. triple S technique). Recently, we introduced Al-hijamah as a novel iron excretion therapy (through pressure-dependent filtration then excretion via the skin dermal capillaries) that significantly decreased serum iron overload and related oxidative stress using a physiological excretory mechanism (Taibah mechanism). Iron overload was reported to impair both humoral immunity and cell mediated immunity in patients with beta thalassemia. In this study, twenty patients having ß-thalassemia major (maintained on iron chelation therapy) underwent a single session of Al-hijamah (30-60 minutes) using 4-5 sucking cups only. Another age and sex-matched control group of thalassemic patients received iron chelation therapy only. Al-hijamah enhanced the immunity of thalassemic patients in the form of increased CD4+ T cell count, from 124.10±36.98 to 326.20±57.94 cells/mm3, and an increased CD8+ T cell count from 100.30±36.98 to 272.40±46.37 cells/mm3. CD4/CD8 ratio significantly increased from 1.29 to 1.7 (P<0.001). There was a significant increase of ten times (P<0.001) in serum TAC/MDA ratio (reflects increased antioxidant capacity vs decreased oxidative load and stress) induced by Al-hijamah. After Al-hijamah, both CD4+ and CD8+ T cell counts significantly increased and positively correlated with TAC/MDA ratio (r = 0.246) and (r = 0.190), respectively. Moreover, CD4/CD8 ratio positively correlated with TAC/MDA after Al-hijamah (r = 0.285). In conclusion, Al-hijamah significantly increased CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio. Our study strongly recommends medical practice of Al-hijamah in hospitals for its immune potentiating effects in agreement with the evidence-based Taibah mechanism. Al-hijamah should be generalized for treating other immune-deficiency conditions. Al-hijamah-induced bloody excretion is so minimal and never aggravates the anaemic status.