Vinpocetine mitigates methotrexate-induced duodenal intoxication by modulating NF-κB, JAK1/STAT-3, and RIPK1/RIPK3/MLKL signals.

OBJECTIVES: Methotrexate (MTX) is an antimetabolite agent widely used to manage a variety of tumors and autoimmune diseases. Nonetheless, MTX-induced intestinal intoxication is a serious adverse effect limiting its clinical utility. Inflammation and oxidative stress are possible mechanisms for MTX-induced intestinal toxicity. Vinpocetine (VNP) is a derivative of the alkaloid vincamine with potent anti-inflammatory and antioxidant effects. The current study investigated the protective intestinal impact of VNP in attenuating MTX-induced intestinal intoxication in rats. MATERIALS AND METHODS: VNP was administered orally in a dose of 20 mg/kg, while MTX was injected intraperitoneal in a dose of 20 mg/kg. RESULTS: VNP administration attenuated drastic histological changes induced by MTX and preserved both normal villus and crypt histology. VNP significantly attenuated oxidative injury by upregulating intestinal Nrf2 and HO-1 expression. VNP attenuated inflammation by reducing MPO, NO2-, TNF-α, and IL-1ß levels mediated by downregulating NF-κB, NDAPH-oxidase, IRF3, p-JAK-1, and p-STAT-3 expressions. Moreover, VNP potently counteracted intestinal necroptosis by effectively downregulating RIPK1, RIPK3, MLKL, and caspase-8 proteins. CONCLUSION: Therefore, VNP may represent a promising approach that can attenuate intestinal toxicity in patients receiving MTX.

Gut microbiota analyses of inflammatory bowel diseases from a representative Saudi population.

BACKGROUND: Crohn's diseases and ulcerative colitis, both of which are chronic immune-mediated disorders of the gastrointestinal tract are major contributors to the overarching Inflammatory bowel diseases. It has become increasingly evident that the pathological processes of IBDs results from interactions between genetic and environmental factors, which can skew immune responses against normal intestinal flora. METHODS: The aim of this study is to assess and analyze the taxa diversity and relative abundances in CD and UC in the Saudi population. We utilized a sequencing strategy that targets all variable regions in the 16 S rRNA gene using the Swift Amplicon 16 S rRNA Panel on Illumina NovaSeq 6000. RESULTS: The composition of stool 16 S rRNA was analyzed from 219 patients with inflammatory bowel disease and from 124 healthy controls. We quantified the abundance of microbial communities to examine any significant differences between subpopulations of samples. At the genus level, two genera in particular, Veillonella and Lachnoclostridium showed significant association with CD versus controls. There were significant differences between subjects with CD versus UC, with the top differential genera spanning Akkermansia, Harryflintia, Maegamonas and Phascolarctobacterium. Furthermore, statistically significant taxa diversity in microbiome composition was observed within the UC and CD groups. CONCLUSIONS: In conclusion we have shown that there are significant differences in gut microbiota between UC, CD and controls in a Saudi Arabian inflammatory bowel disease cohort. This reinforces the need for further studies in large populations that are ethnically and geographically diverse. In addition, our results show the potential to develop classifiers that may have add additional richness of context to clinical diagnosis of UC and CD with larger inflammatory bowel disease cohorts.

Autonomy and paternalism in shared decision-making in a Saudi Arabian tertiary hospital: A cross-sectional study.

Medical paternalism has long been a common medical practice. However, patient autonomy in healthcare has been recently adopted by doctors and patients alike. This study explored whether doctors and patients in a tertiary care hospital in Saudi Arabia preferred autonomy or paternalism in shared decision-making. A total of 118 participants (51 patients requiring total knee replacement, owing to stages 3-4 of osteoarthritis, and 67 doctors) from the Eastern province, Saudi Arabia. responded to a 17-question category-based questionnaire involving four scales of autonomy. Descriptive statistics and chi-square test results revealed that in this hospital, patients preferred a paternalistic approach toward their medical care along with a full disclosure of the risks related to surgical procedures. We recommend health education regarding the specific autonomy subscales (doctor knows best, patient should decide, right to non-participation, and obligatory risk information), and the implementation of protocols that protect patients' rights and enhance personal autonomy.

Mirtazapine attenuated cadmium-induced neuronal intoxication by regulating Nrf2 and NF-κB/TLR4 signals.

Cadmium (Cd) is one of the most hazardous metals to the environment and human health. Neurotoxicity is of the most serious hazards caused by Cd. Mirtazapine (MZP) is a central presynaptic α2 receptor antagonist used effectively in treating several neurological disorders. This study investigated the anti-inflammatory and antioxidant activity of MZP against Cd-induced neurotoxicity. In this study, rats were randomly divided into five groups: control, MZP (30 mg/kg), Cd (6.5 mg/kg/day; i.p), Cd + MZP (15 mg/kg), and Cd + MZP (30 mg/kg). Histopathological examination, oxidative stress biomarkers, inflammatory cytokines, and the impact of Nrf2 and NF-κB/TLR4 signals were assessed in our study. Compared to Cd control rats, MZP attenuated histological abrasions in the cerebral cortex and CA1 and CA3 regions of the hippocampus as well as the dentate gyrus. MZP attenuated oxidative injury by upregulating Nrf2. In addition, MZP suppressed the inflammatory response by decreasing TNF-α, IL-1ß, and IL-6 mediated by downregulating TLR4 and NF-κB. It is noteworthy that MZP's neuroprotective actions were dose-dependent. Collectively, MZP is a promising therapeutic strategy for attenuating Cd-induced neurotoxicity by regulating Nrf2, and NF-κB/TLR4 signals, pending further study in clinical settings.

Colostrum knowledge among Saudi mothers in Jeddah, Saudi Arabia.

OBJECTIVE: To assess the knowledge level of Saudi women about colostrum for the newborns. METHODS: The cross-sectional study was conducted from October 2015 to June 2016 at the Gynaecological Clinics of King Abdulaziz University Hospital, Jeddah, Saudi Arabia and comprised lactating mothers in the community. Data was collected using a pretested questionnaire. Data was analysed using SPSS 22. RESULTS: Of the 552 mothers, 301(54.5%) were age >30 years. The source of information about colostrum was friends and family for 367(66.67%) subjects. Overall, 367(66%) had high knowledge about colostrum. A significant correlation was detected between age and knowledge about colostrum composition and duration (p<0.05); as well as between educational level and colostrum composition, colour and form (p<0.05). A significant association between occupational status and knowledge about colostrum colour and form was also noted (p<0.05). CONCLUSIONS: Saudi mothers were found to have a good knowledge about colostrum and its benefits.

Online case-based learning for medical students as a teaching method for biochemistry at King Abdulaziz University amid COVID-19 pandemic (a study conducted in 2021).

Online case-based learning (CBL) is a method used by King Abdulaziz University to teach medical students in their preclinical years. The use of CBL in basic sciences is important for enabling medical students to correlate basic sciences with future clinical practice. This study implemented online CBL for biochemistry teaching as part of the medical genetic module for 3rd-year preclinical students. Teaching during the study was completely online because of restricted precautions caused by the COVID-19 pandemic, except for practical sessions that were held on campus. The case was presented to the students involved in prenatal screening and diagnosis. Students were guided to learn and discuss the biochemical tests used for prenatal screening and diagnosis and their clinical importance. They were divided into two groups: the control group was given an online lecture and the intervention group was given an online CBL session before the lecture. The online lecture was given to both groups simultaneously by the same instructor, and then 10 MCQs tests were distributed to both groups after the lecture, and their test scores were compared. A 10-question survey was administered to the intervention group to assess their perception of the online CBL session after the test. A significant difference was found between the intervention and control groups regarding test scores (p < 0.001), and most students found the online CBL session enjoyable and motivating.

Nanoformulated 3'-diindolylmethane modulates apoptosis, migration, and angiogenesis in breast cancer cells.

Background: It is well-established that specific herbal plants contain natural active ingredients that have demonstrated anti-cancer potential. Therefore, they are considered highly beneficial as a potential adjuvant, alternative or complementary agent in anti-cancer therapy. However, the low chemical stability and limited bioavailability of 3, 3'-Diindolylmethane (DIM), a plant-derived compound used in clinical settings, limit its therapeutic applications. To overcome this challenge, researchers have focused on developing innovative approaches to improve DIM's biological activity, such as utilizing nanoformulations. Here, we investigated the potential benefits of coating DIM nanoparticles (DIM-NPs) with PEG/chitosan in the treatment of breast cancer. Our results demonstrate the molecular mechanism underlying the activity of DIM-NPs, highlighting their potential as an effective therapeutic strategy for breast cancer treatment. Methods: DIM-PLGA-PEG/chitosan NPs were synthesised and characterised using dynamic light scattering (DLS) and evaluated the impact of these NPs on two breast cancer cell models. Results: DIM-NPs had an average diameter of 102.3 nm and a PDI of 0.182. When treated with DIM-NPs for 48 h, both MCF7 and MDA-MB-231 cells displayed cytotoxicity at a concentration of 6.25 g/mL compared to untreated cells. Furthermore, in MDA-MB-231 cells, treatment with 2.5 µg/mL of DIM-NPs resulted in a significant decrease in cell migration, propagation, and angiogenesis which was further enhanced at 10 µg/mL. In chicken embryos, treatment with 5 µg/mL of DIM-NPs on day 2 led to a significant reduction in angiogenesis. Furthermore, this treatment induced cell death through a regulatory pathway involving the upregulation of Bax and p53, as well as the downregulation of Bcl-2. These results were supported by in-silico analysis of DIM's binding affinity to key proteins involved in this pathway, namely Bax, Bcl-2, and p53. Conclusion: Our findings show that DIM-NPs induces apoptosis, inhibit migration, and reduce angiogenesis in breast cancer. However, further research using a preclinical cancer model may be necessary to determine the pharmacokinetics of DIM-NPs and ensure their safety and efficacy in vivo.

Salivary interleukin-17A and interleukin-18 levels in patients with celiac disease and periodontitis.

Background: An increased level of interleukin-17A and interleukin-18 in the serum and intestinal mucosa of celiac disease patients reflecting the severity of villous atrophy and inflammation was documented. Thus, the objective of this study was to evaluate the concentrations of salivary-17A, interleukin-1 beta, and interleukin-18 in patients with celiac disease who are on a gluten-free diet, both with and without periodontitis, and to compare these levels with those in healthy individuals. Methods: The study involved 23 participants with serologically confirmed celiac disease (CD) and 23 control subjects. The CD patients had been following a gluten-free diet (GFD) for a minimum of 1 year and had no other autoimmune disorders. The research involved collecting demographic data, conducting periodontal examinations, gathering unstimulated whole saliva, and performing enzyme-linked immunosorbent assays to measure salivary interleukin-17A, interleukin-1 beta, and interleukin-18 levels. Spearman's correlation analysis was utilized to explore the relationships between CD markers in patients on a GFD and their periodontal clinical findings. Results: The periodontal findings indicated significantly lower values in celiac disease patients adhering to a gluten-free diet compared to control subjects (p = 0.001). No significant differences were found in salivary IL-17A, IL-18, and IL-1B levels between celiac disease patients and control subjects. Nevertheless, the levels of all interleukins were elevated in periodontitis patients in both the celiac and control groups. The IL-1 Beta level was significantly higher in periodontitis patients compared to non-periodontitis patients in the control group (p = 0.035). Significant negative correlations were observed between serum IgA levels and plaque index (r = -0.460, p = 0.010), as well as gingival index (r = -0.396, p = 0.030) in CD patients on a gluten-free diet. Conclusion: Celiac disease patients on gluten-free diet exhibited better periodontal health compared to control subjects. However, increased levels of salivary IL-17A, IL-18 and IL-1B levels were associated with periodontitis. Additionally, serum IgA level was significantly inversely associated with periodontitis clinical manifestations and with salivary inflammatory mediators in CD patients on GFD.

The Influence of Eating Habits on Type 2 Diabetes in Saudi Arabia: A Systematic Review.

Several dietary factors are associated with an increased risk of diabetes in Saudi Arabia. The increasing consumption of processed and sugary foods, including fast food and sugary beverages, in recent decades along with the rising prevalence of diabetes indicate the necessity of exploring the influence of eating habits on diabetes in Saudi Arabia. That is why the association between eating habits and diabetes in Saudi Arabia has become a topic of increasing interest. Therefore, this systematic literature review aimed to explore the influence of eating habits on the prevalence of diabetes in Saudi Arabia by providing a comprehensive synthesis of existing evidence from studies conducted on this topic in Saudi Arabia. A systematic search was conducted using predefined search terms in electronic databases, including PubMed, Embase, Medline, Google Scholar, and Scopus. Studies investigating the relationship between eating habits and diabetes prevalence among the Saudi Arabian population were included. Data extraction was performed, and the quality of included studies was assessed using appropriate tools. The findings were synthesized and discussed. Understanding the association between eating habits and diabetes in Saudi Arabia is crucial for developing effective preventive and management strategies for diabetes and other non-communicable diseases and promoting healthier eating habits in Saudi Arabia.

Modulation of Insulin Resistance by Silybum marianum Leaves, and its Synergistic Efficacy with Gymnema sylvestre, Momordica charantia, Trigonella-foenum graecum Against Protein Tyrosine Phosphatase 1B.

Prolonged insulin resistance is considered one of the reasons for Type 2 Diabetes Mellitus. Upregulation of Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signalling, has been well studied as a key regulator in prognosis to insulin resistance. It has been widely studied as a desirable molecular therapeutic target. The study aimed to evaluate the efficacy of leaf extract of the medicinal plants Silybum marianum on the inhibition of PTP1B activity. It also explored the synergistic effect with extracts of Gymnema sylvestre (leaves), Momordica charantia (seeds), and Trigonella foenum graecum (seeds). The S. marianum leaves showed dose-dependent inhibition of PTP1B ranging from 9.48-47.95% (25-1000 µg mL-1). Assay with individual plant extracts showed comparatively lesser inhibition of PTP1B as compared to metformin as a control (38% inhibition). However, a synergistic effect showed nearly 45% PTP1B inhibition (higher than metformin) after the assay was done with selected four plant extracts in combination. The effect of leaf extracts of S. marianum was studied for glucose uptake efficiency in yeast cell lines which was found to be increased by 23% as compared to the control (without extract). Metformin improves glucose upake by yeast cells by ~15-31%. GC-MS analysis revealed 23 phytochemicals, some of which possessed anti-diabetic properties. A dose-dependent increase in antioxidant activity of S. marianum leaves extracts was observed (40-53%). The findings of the study highlighted the presence of various phytochemicals in leaves extracts that are effective against PTP1B inhibition and may help in reinvigorating drug development.

Isolation and Characterization of a Novel Lytic Phage, vB_PseuP-SA22, and Its Efficacy against Carbapenem-Resistant Pseudomonas aeruginosa.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a serious public health threat in multiple clinical settings. In this study, we detail the isolation of a lytic bacteriophage, vB_PseuP-SA22, from wastewater using a clinical strain of CRPA. Transmission electron microscopy (TEM) analysis identified that the phage had a podovirus morphology, which agreed with the results of whole genome sequencing. BLASTn search allowed us to classify vB_PseuP-SA22 into the genus Bruynoghevirus. The genome of vB_PseuP-SA22 consisted of 45,458 bp of double-stranded DNA, with a GC content of 52.5%. Of all the open reading frames (ORFs), only 26 (44.8%) were predicted to encode certain functional proteins, whereas the remaining 32 (55.2%) ORFs were annotated as sequences coding functionally uncharacterized hypothetical proteins. The genome lacked genes coding for toxins or markers of lysogenic phages, including integrases, repressors, recombinases, or excisionases. The phage produced round, halo plaques with a diameter of 1.5 ± 2.5 mm on the bacterial lawn. The TEM revealed that vB_PseuP-SA22 has an icosahedral head of 57.5 ± 4.5 nm in length and a short, non-contractile tail (19.5 ± 1.4 nm). The phage showed a latent period of 30 min, a burst size of 300 PFU/infected cells, and a broad host range. vB_PseuP-SA22 was found to be stable between 4-60 °C for 1 h, while the viability of the virus was reduced at temperatures above 60 °C. The phage showed stability at pH levels between 5 and 11. vB_PauP-SA22 reduced the number of live bacteria in P. aeruginosa biofilm by almost five logs. The overall results indicated that the isolated phage could be a candidate to control CRPA infections. However, experimental in vivo studies are essential to ensure the safety and efficacy of vB_PauP-SA22 before its use in humans.

Analyzing COVID-19 Vaccination Side Effects Among the Adult Population in Jeddah, Saudi Arabia.

The COVID-19 pandemic has brought vaccination to the forefront of global attention. The Pfizer-BioNTech vaccine, an mRNA vaccine that encodes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) glycoprotein spike, has emerged as a significant player in global vaccination efforts. It is generated from lipid nanoparticles and has been subject to various regulatory approvals and authorizations. The United Kingdom became the first country to approve the Pfizer vaccine on December 2, 2020. The World Health Organization (WHO) authorized the emergency use of the Pfizer vaccine on December 31, 2020, facilitating its production and distribution worldwide. In Saudi Arabia, as well as globally, concerns about the safety and effectiveness of vaccines have been raised. Several studies have reported side effects of the Pfizer vaccine, including rare conditions such as myocarditis. In our study, we aimed to systematically investigate the symptoms experienced after vaccination, considering the administration of three doses. We also explored the duration of these symptoms and whether they necessitated hospital visits, primary healthcare interventions, or resolved on their own. Our study employed an online cross-sectional design conducted in Jeddah, Saudi Arabia, utilizing an online self-reported survey. A total of 332 participants who met the predefined criteria were recruited for the study. The rate of COVID-19 infection after 1st and 2nd doses of Pfizer and AstraZeneca vaccines was significantly lower in middle-age subgroups (31-45 years), in comparison to young (18-30 years) and upper middle-age subgroups (46-60 years). For the AstraZeneca vaccine, the infection rate in the middle-aged group was higher after 2nd dose as compared to its 1st dose. Overall, greater infection rates were observed in upper-middle-aged subgroups with all doses of Pfizer and AstraZeneca vaccines. Fatigue and fever were the most common generalized side effects while redness/swelling/pain at the injection site, muscle pain, and joint pain were the most important local side-effects. Fatigue, fever, muscle pain, and joint pain were significantly common after 1st dose of Pfizer and fever was a significant side effect after 2nd dose of Pfizer in comparison to AstraZeneca doses. Understanding the spectrum of side effects associated with the vaccine is crucial for healthcare professionals and individuals receiving the vaccine, as it enables informed decision-making and appropriate management of potential adverse reactions.

The Battle between Bacteria and Bacteriophages: A Conundrum to Their Immune System.

Bacteria and their predators, bacteriophages, or phages are continuously engaged in an arms race for their survival using various defense strategies. Several studies indicated that the bacterial immune arsenal towards phage is quite diverse and uses different components of the host machinery. Most studied antiphage systems are associated with phages, whose genomic matter is double-stranded-DNA. These defense mechanisms are mainly related to either the host or phage-derived proteins and other associated structures and biomolecules. Some of these strategies include DNA restriction-modification (R-M), spontaneous mutations, blocking of phage receptors, production of competitive inhibitors and extracellular matrix which prevent the entry of phage DNA into the host cytoplasm, assembly interference, abortive infection, toxin-antitoxin systems, bacterial retrons, and secondary metabolite-based replication interference. On the contrary, phages develop anti-phage resistance defense mechanisms in consortium with each of these bacterial phage resistance strategies with small fitness cost. These mechanisms allow phages to undergo their replication safely inside their bacterial host's cytoplasm and be able to produce viable, competent, and immunologically endured progeny virions for the next generation. In this review, we highlight the major bacterial defense systems developed against their predators and some of the phage counterstrategies and suggest potential research directions.

Phage cocktails - an emerging approach for the control of bacterial infection with major emphasis on foodborne pathogens.

Phage therapy has recently attracted a great deal of attention to counteract the rapid emergence of antibiotic-resistant bacteria. In comparison to monophage therapy, phage cocktails are typically used to treat individual and/or multi-bacterial infections since the bacterial agents are unlikely to become resistant as a result of exposure to multiple phages simultaneously. The bacteriolytic effect of phage cocktails may produce efficient killing effect in comparison to individual phage. However, multiple use of phages (complex cocktails) may lead to undesirable side effects such as dysbiosis, horizontal gene transfer, phage resistance, cross resistance, and/or higher cost of production. Cocktail formulation, therefore, representa compromise between limiting the complexity of the cocktail and achieving substantial bacterial load reduction towards the targeted host organisms. Despite some constraints, the applications of monophage therapy have been well documented in the literature. However, phage cocktails-based approaches and their role for the control of pathogens have not been well investigated. In this review, we discuss the principle of phage cocktail formulations, their optimization strategies, major phage cocktail preparations, and their efficacy in inactivating various food borne bacterial pathogens.

Apoptosis induction in human hepatoma cell line HepG2 cells by trans- Anethole via activation of mitochondria-mediated apoptotic pathways.

trans-Anethole a valuable compound derived from star anise widely used by ethnic tribals to manage numerous human diseases. In this study antiproliferative activities of trans-Anethole towards human liver cancer (HepG2), cervical cancer (HeLa) and breast cancer (MCF-7) cells were explored. trans-Anethole showed free radical scavenging potential as assessed by DNA nicking assay. trans-Anethole exhibited strong antiproliferative potential towards HepG2 cells compared to other cell lines. trans-Anethole strongly induced apoptosis in HepG2 cells by significantly upregulating the protein expressions of p53, Caspase-3 and Caspase-9 were assessed by western blotting analysis which highlighted apoptosis-inducing capacity of trans-Anethole against HepG2 cells. Rt-qPCR analysis revealed that trans- Anethole upregulated p53, caspase - 3 and - 9 in comparison to untreated HepG2 cancer cells. Moreover, trans-Anethole provoked the generation of ROS and disruption of MMP. Our research suggests that trans-Anethole may have a significant anticancer therapeutic potential for treating liver cancer.

Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells.

BACKGROUND: Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity. METHODS: Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells. RESULTS: The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL (p < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis (p < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells. CONCLUSION: Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.

Curcumin nanoparticles (Cur-NPs) increase the anticancer efficiency of Curcumin against liver cancer cells.Cur-NPs induce apoptotic cell death of Liver cancer cells.Cur-NPs have ant-angiogenesis and metastasis effect.

Comprehensive mapping of mutations in TDP-43 and α-Synuclein that affect stability and binding.

Abnormal aggregation and amyloid inclusions of TAR DNA-binding protein 43 (TDP-43) and α-Synuclein (α-Syn) are frequently co-observed in amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Several reports showed TDP-43 C-terminal domain (CTD) and α-Syn interact with each other and the aggregates of these two proteins colocalized together in different cellular and animal models. Molecular dynamics simulation was conducted to elucidate the stability of the TDP-43 and Syn complex structure. The interfacial mutations in protein complexes changes the stability and binding affinity of the protein that may cause diseases. Here, we have utilized the computational saturation mutagenesis approach including structure-based stability and binding energy calculations to compute the systemic effects of missense mutations of TDP-43 CTD and α-Syn on protein stability and binding affinity. Most of the interfacial mutations of CTD and α-Syn were found to destabilize the protein and reduced the protein binding affinity. The results thus shed light on the functional consequences of missense mutations observed in TDP-43 associated proteinopathies and may provide the mechanisms of co-morbidities involving these two proteins.Communicated by Ramaswamy H. Sarma.

Emergence of Post COVID-19 Vaccine Autoimmune Diseases: A Single Center Study.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) became a major concern since the announcement that it is a pandemic in early 2020. Vaccine trials were started in November 2020, and completed rapidly due to the urgency to get over the infection. Side effects to vaccines started to be reported. There were minor side effects including site of injection pain and heaviness and constitutional symptoms like fever which are considered minor. One of the rare adverse events is post vaccine new onset autoimmune diseases. Methods: Data were obtained from one center in the eastern province of Saudi Arabia (King Fahd Hospital of University). All patient events reported occurred in the study period March 2021 to February 2022. We identified patients presenting with autoimmune diseases with exclusively new onset presentations. Results: We identified 31 cases of immune-mediated disease: 18 females (58%); 13 males (42%). Only 4 of them (13%) had an autoimmune background before COVID-19 vaccination. The average time between vaccination and new-onset disease symptoms was 7 days. Among all the cases in our study, 7 patients (22.5%) had new-onset vasculitis, 2 cases had IgA vasculitis and 5 cases had ANCA vasculitis, 6 cases had neurological diseases (19.3%), 4 cases (12.9%) had new-onset systemic lupus erythematosus (SLE), 3 cases (9.6%) presented with new-onset inflammatory arthritis, and one had Sjogren's syndrome (3.2%). Conclusion: Our study is unique as it is the first study to include the largest number (31 patients) of new onsets of confirmed autoimmune diseases related to Covid-19 vaccines.

Transplacental Transfer of SARS-CoV-2 Receptor-Binding Domain IgG Antibodies from Mothers to Neonates in a Cohort of Pakistani Unvaccinated Mothers.

The presence of COVID-19 antibodies in the maternal circulation is assumed to be protective for newborns against SARS-CoV-2 infection. We investigated whether maternal COVID-19 antibodies crossed the transplacental barrier and whether there was any difference in the hematological parameters of neonates born to mothers who recovered from COVID-19 during pregnancy. The cross-sectional study was conducted at the Saidu Group of Teaching Hospitals, located in Swat, Khyber Pakhtunkhwa. After obtaining written informed consent, 115 healthy, unvaccinated mother-neonate dyads were included. A clinical history of COVID-19-like illness, laboratory-confirmed diagnosis, and contact history were obtained. Serum samples from mothers and neonates were tested for SARS-CoV-2 anti-receptor-binding domain (anti-RBD) IgG antibodies. Hematological parameters were assessed with complete blood counts (CBC) and peripheral blood smear examinations. The study population consisted of 115 mothers, with a mean age of 29.44 ± 5.75 years, and most women (68/115 (59.1%)) were between 26 and 35 years of age. Of these mothers, 88/115 (76.5 percent) tested positive for SARS-CoV-2 anti-RBD IgG antibodies, as did 83/115 (72.2 percent) neonatal cord blood samples. The mean levels of SARS-CoV-2 IgG antibodies in maternal and neonatal blood were 19.86 ± 13.82 (IU/mL) and 16.16 ± 12.90 (IU/mL), respectively, indicating that maternal antibodies efficiently crossed the transplacental barrier with an antibody transfer ratio of 0.83. The study found no significant difference in complete blood count (CBC) parameters between seropositive and seronegative mothers, nor between neonates born to seropositive and seronegative mothers.

Burden of COVID-19 infection and lockdown measures on individuals with chronic diseases in Saudi Arabia: A national population-based study.

BACKGROUND: The recent COVID-19 crisis has placed a huge strain on the global health and economy. The toll of the damage on the human society exceeds the morbidity and mortality of the pandemic and the associated burden, considering the multidimensional impact on all aspects of life. OBJECTIVES: The present study assessed the specific impact of COVID-19 on individuals with chronic diseases including the Years Lost for Disability (YLD) burden of COVID-19 infection, and multidimensional impact on the disease management, adaptive lifestyle, and socioeconomic dimensions. METHOD: A national, population-based cross-sectional study was conducted among adult Saudi population. An internet-based questionnaire was used to collect sociodemographic characteristics, medical history, impact of COVID-19 lockdown on the management of the chronic disease, adaptive lifestyle, and impact of COVID-19 on family members. Additionally, data regarding eventual COVID-19 infection, severity and management were collected. YLD was estimated and normalized per 100,000 persons. RESULT: Having a chronic disease was not associated with a greater risk of COVID-19 (relative risk [RR]=0.83, p = 0.153); however, it was associated with higher risk of declined physical activity (RR=1.30, p < 0.0001), deteriorated eating habit (RR=1.20, p = 0.002), sleep quality (RR=1.25, p < 0.0001), and overall health perception (RR=1.61, p < 0.0001), loss of family members due to COVID-19 (RR=1.96, p = 0.0001), and impacted household income (RR=1.11, p = 0.010). In case of COVID-19 infection, having a chronic disease was associated with increased risk of hospitalization (RR=5.04, p = 0.005) and having a moderate-to-severe form of COVID-19 (RR=6.00, p = 0.013). The overall YLD was estimated to be 17.7 per 100,000 individuals, and there was no significant difference between individuals with chronic diseases and those without. CONCLUSION: COVID-19 entailed a substantial burden on the Saudi society in 2020, and individuals with preexisting chronic diseases suffered more important multidimensional impact, which need further research to assess the real impact of the pandemic and draw the pertinent lessons from the experience for future possible epidemics.