Post COVID-19 Symptoms Among Infected Vaccinated Individuals: A Cross-Sectional Study in Saudi Arabia.

INTRODUCTION: Multiple studies investigated the endurance and occurrence of symptoms three months after SARS-CoV-2 infection. This study examines the possible effects of COVID-19 vaccination on the persistence of post-recovery symptoms. PATIENTS AND METHODS: A cross-sectional survey was conducted in Saudi Arabia to evaluate 14 prevalent long COVID-19 symptoms among vaccinated individuals. Patients self-reported their acute COVID-19 experience, demographic information, chronic conditions, vaccine history, and persistent symptoms. RESULTS: Of the 484 patients, four respondents were excluded from the study as they had not received the vaccine, and 111 (23.1%) were vaccinated but did not get infected and were also excluded. The remaining 369 (76.9%) reported COVID-19 and a vaccination and thus they were included in the study. The occurrence of post-COVID-19 symptoms was reported in 59 (16.1%) for ≤ 3 months, 202 (54.8%) experienced persistent symptoms 3-6 months, and 108 (29.1%) reported symptoms lasting > 6 months. In relation to age group, persistent symptoms 3-6 months after recovery was more common in those > 50 years and symptoms lasting > 6 months were more common in 30-50 years of age (p < 0.001). Persistence of symptoms for 3-6 months was more common in those who were infected prior to vaccination compared to those who were infected after vaccination (P < 0.001). Of the included patients, 323 (87.5%) rated their health as good, 41 (11.1%) considered it fair, and 5 (1.4%) described their well-being as poor or terrible. CONCLUSION: The study provides information of persistent symptoms in vaccinated individuals who had recovered from COVID-19 and highlights the need for targeted interventions to alleviate post-COVID-19 symptoms. The study is limited by its reliance on self-reported data and potential selection bias. Future research is needed to understand the mechanisms underlying persistent symptoms in vaccinated individuals and to identify effective interventions for long COVID.

Evaluation of School-Age Children's Intelligence Quotient and Their Chronic Exposure to Trace Elements in Ambient Air.

Background Children's exposure to different trace elements in their air, water, and food or even present in paints or toys can affect their intelligence quotient (IQ) score. However, this correlation needs to be analyzed and evaluated in different contexts. This study aimed to investigate the associations between airborne concentrations of lead (Pb), manganese (Mn), cadmium (Cd), chromium (Cr), and arsenic (As) and intellectual function in school-age children in Makkah, Kingdom of Saudi Arabia. Methodology Our cohort study aimed to explore the link between exposure to various trace elements in the surrounding air and the IQ scores of children residing in the vicinity of Makkah. We included 430 children in the study and collected information about demographic and lifestyle factors using a structured questionnaire. We employed a mini volume sampler (MiniVol, AirMetrics, Springfield, OR, USA) to collect 24-hour PM10 samples from five locations in Makkah, representing various residential areas with small-to-medium industrial activities and traffic load. We analyzed the samples for Pb, Mn, Cd, Cr, and As concentrations using inductively coupled plasma-mass spectrometry with Perkin Elmer 7300 (Perkin Elmer, Waltham, MA, USA). The combined impact of heavy metals on continuous outcomes was assessed using the Bayesian kernel machine regression model. Results The mean atmospheric concentrations of Pb, Mn, Cd, Cr, and As in summer were 0.093, 0.006, 0.36, 0.15, and 0.017 µg/m3, respectively, while in winter, they were 0.004, 0.003, 0.12, 0.006, and 0.01 µg/m3, respectively. The findings of our study revealed that children's IQ scores were independently associated with co-exposure to the five metals, namely, Pb, Mn, Cd, Cr, and As. Conclusions This study demonstrates a link between combined exposure to five heavy metals (Pb, Mn, Cd, Cr, and As) and children's IQ scores. Regularly evaluating trace elements in children's biological samples is crucial to comprehend their effects on cognitive growth. To explore the possible future health risks of multimetal exposures and their interaction effects, it is imperative to conduct additional studies that involve repeated biological measurements of metal concentrations.

1,25-Dihydroxycholecalciferol down-regulates 3-mercaptopyruvate sulfur transferase and caspase-3 in rat model of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of liver morbidity and mortality and has multiple unclear pathogenic mechanisms. Vitamin D deficiency was associated with increased incidence and severity of NAFLD. Increased hepatic expression of 3-mercaptopyruvate sulfur transferase (MPST) and dysregulated hepatocyte apoptosis were involved in NAFLD pathogenesis. We aimed to explore the protective effect of 1,25-Dihydroxycholecalciferol (1,25-(OH)2 D3) against development of NAFLD and the possible underlying mechanisms, regarding hepatic MPST and caspase-3 expression. 60 male adult rats were divided into 4 and 12 week fed groups; each was subdivided into control, high-fat diet (HFD), and HFD + VD. Serum levels of lipid profile parameters, liver enzymes, insulin, glucose, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and hepatic levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and reactive oxygen species (ROS) were measured. BMI and HOMA-IR were calculated, and liver tissues were processed for histopathological and immunohistochemical studies. The present study found that 1,25-(OH)2 D3 significantly decreased BMI, HOMA-IR, serum levels of glucose, insulin, liver enzymes, lipid profile parameters, CRP, TNF-α, hepatic levels of MDA, ROS, hepatic expression of MPST, TNF-α, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and caspase-3; and significantly increased hepatic TAC in both HFD-fed groups. In conclusion: Administration of 1,25-(OH)2 D3 with HFD abolished the NAFLD changes associated with HFD in 4-week group, and markedly attenuated the changes in 12-week group. The anti-apoptotic effect via decrement of caspase-3 and MPST expression are novel mechanisms suggested to be implicated in the protective effect of 1,25-(OH)2 D3.

Therapeutic Potential of Quercetin Loaded Nanoparticles: Novel Insights in Alleviating Colitis in an Experimental DSS Induced Colitis Model.

Oxidative stress is considered the main etiologic factor involved in inflammatory bowel disease (IBD). Integration of nanocarriers for natural therapeutic agents with antioxidant and anti-inflammatory potential is a novel promising candidate for curing IBD. Herein, the colonic antioxidant and anti-inflammatory effects of different concentrations of quercetin nanoparticles (QT-NPs) were evaluated using a dextran sulfate sodium (DSS)-induced colitis model. Following colitis induction, the efficacy and mechanistic actions of QT-NPs were evaluated by assessing lesion severity, molecular aids controlling oxidative stress and inflammatory response, and histopathological and immunohistochemistry examination of colonic tissues. Administration of QT-NPs, especially at higher concentrations, significantly reduced the disease activity index and values of fecal calprotectin marker compared to the colitic group. Colonic oxidant/antioxidant status (ROS, H2O2, MDA, SOD, CAT, GPX and TAC) was restored after treatment with higher concentrations of QT-NPs. Moreover, QT-NPs at levels of 20 mg/kg and, to a lesser extent, 15 mg/kg reduced Nrf2 and HO-1 gene expression, which was in line with decreasing the expression of iNOS and COX2 in colonic tissues. Higher concentrations of QT-NPs greatly downregulated pro-inflammatory cytokines; upregulated genes encoding occludin, MUC-2 and JAM; and restored the healthy architectures of colonic tissues. Taken together, these data suggest that QT-NPs could be a promising alternative to current IBD treatments.

Treatment Challenges When Stopping Denosumab.

Introduction Denosumab is commonly used to treat osteoporosis. However, discontinuation results in rebound bone loss and increased vertebral fracture risk. We report a clinical case series, illustrating the dilemma in deciding the best treatment should denosumab be stopped. Cases In eight patients aged 56-89 years, zolendronic acid after stopping denosumab resulted in BTM rises and BMD decline.  In a 68-year-old, two years of oral bisphosphonate after three years of denosumab resulted in elevated bone turnover markers (BTM) and decline in bone mineral density (BMD), necessitating a switch to zoledronic acid.  In a 79-year-old, two annual doses of zolendronic acid after three years of denosumab failed to suppress high BTM, with BMD dropping and denosumab being restarted.  In a 60-year-old, on stopping denosumab after 10 years of oral bisphosphonate, BMD remained stable despite no further therapy. Conclusion Drug holidays are not an option with denosumab, with a risk of bone loss even on transitioning to bisphosphonates. Risk is greater with longer duration of treatment6 and may be mitigated by prior bisphosphonate use. Standard dose zoledronic acid does not prevent bone loss in a significant proportion of patients. BTM may help in monitoring treatment and need for further bisphosphonates.

Novel In Vivo Assessment of Antimicrobial Efficacy of Ciprofloxacin Loaded Mesoporous Silica Nanoparticles against Salmonella typhimurium Infection.

Salmonella enterica serovar Typhimurium (S. typhimurium) is known for its intracellular survival, evading the robust inflammation and adaptive immune response of the host. The emergence of decreased ciprofloxacin (CIP) susceptibility (DCS) requires a prolonged antibiotic course with increased dosage, leading to threatening, adverse effects. Moreover, antibiotic-resistant bacteria can persist in biofilms, causing serious diseases. Hence, we validated the in vitro and in vivo efficacy of ciprofloxacin-loaded mesoporous silica nanoparticles (CIP-MSN) using a rat model of salmonella infection to compare the oral efficacy of 5 mg/kg body weight CIP-MSN and a traditional treatment regimen with 10 mg/kg CIP postinfection. Our results revealed that mesoporous silica particles can regulate the release rate of CIP with an MIC of 0.03125 mg/L against DCS S. typhimurium with a greater than 50% reduction of biofilm formation without significantly affecting the viable cells residing within the biofilm, and a sub-inhibitory concentration of CIP-MSN significantly reduced invA and FimA gene expressions. Furthermore, oral supplementation of CIP-MSN had an insignificant effect on all blood parameter values as well as on liver and kidney function parameters. MPO and NO activities that are key mediators of oxidative stress were abolished by CIP-MSN supplementation. Additionally, CIP-MSN supplementation has a promising role in attenuating the elevated secretion of pro-inflammatory cytokines and chemokines in serum from S. typhimurium-infected rats with a reduction in pro-apoptotic gene expression, resulting in reduced S. typhimurium-induced hepatic apoptosis. This counteracted the negative effects of the S. typhimurium challenge, as seen in a corrected histopathological picture of both the intestine and liver, along with increased bacterial clearance. We concluded that, compared with a normal ciprofloxacin treatment regime, MSN particles loaded with a half-dose of ciprofloxacin exhibited controlled release of the antibiotic, which can prolong the antibacterial effect.

Post-COVID-19 syndrome: assessment of short- and long-term post-recovery symptoms in recovered cases in Saudi Arabia.

INTRODUCTION: Recent studies investigated the endurance of symptoms and occurrence of complications three months after SARS-CoV-2 infection. This study aims to examine the prevalence, variation, and severity of continual symptoms in the post-COVID-19 using a single-center questionnaire. METHODS: The questionnaire was distributed among population in Saudi Arabia who recovered from COVID-19 between April 1, 2020 and December 31, 2021. RESULTS: A total of 744 participants completed the questionnaire, 318 (42.8%) recovered less than 3 months, 75 (10.1%) recovered 3-6 months, while 351 (47.2%) recovered more than 6 months. About half of the participants 353 (47.5%) had incessant symptoms and of those patients, more than half had two or more symptoms. Common symptoms included fatigue 189 (25.4%), headache 118 (15.9%), and myalgia 63 (8.5%). Of the participants, 189 (21.4%) experienced continual symptoms including anxiety in 98 (13.2%) and depression in 70 (9.5%). CONCLUSION: The current study showed a high proportion of individuals with long-COVID-19 symptoms. Thus, proper assessment of the individuals in the post-recovery period can guide the patients to the relevant clinics for rehabilitation. Moreover, there is a great importance to decrease COVID-19 infection, populations should be targeted to boost vaccine efficiency.

Nano-silica and magnetized-silica mitigated lead toxicity: Their efficacy on bioaccumulation risk, performance, and apoptotic targeted genes in Nile tilapia (Oreochromis niloticus).

Contamination of aquatic systems with heavy metals (HM) is of great concern owing to their deleterious impact on living organism. The current research is focused on application of silica particles with new functionalized properties (magnetic silica; SiMag or Nanoporous silica; SiNPs) and their efficacy to mitigate lead (pb) toxicity in Nile tilapia. One thousand fingerlings were distributed: two control groups (negative; without pb toxicity (NC) positive (with pb toxicity) and other four groups received two silica sources (SiMag or SiNPs) with two levels (400 and 600 mg/kg diet) for 56 days then exposed to pb for 30 days. Before toxicity exposure, maximum growth, and most improved feed conversion ratio and biochemical parameters were noticed with higher SiMag or SiNPs levels. Serum antioxidant enzymes and their transcriptional levels in muscle and liver were boosted in groups received SiMag or SiNPs. After toxicity exposure, hematological and antioxidants biomarkers maintained at adequate levels in SiMag or SiNPs. Prominent reduction of residual pb in gills, liver, kidney, and muscle was observed in SiNPs then SiMag groups. Interestingly, the maximum down-regulation of P450, caspase-3 and HSP-70 and MT were observed in groups received 600 mg/kg diet of SiMag or SiNPs. The higher level of P53 in liver and gills was detected in PC, inversely reduced in SiMag or SiNPs. Severity of the histopathological alterations in examined organs greatly reduced in groups received SiMag or SiNPs, unlike it were induced in PC group. In conclusion, higher SiMag or SiNPs levels not only mitigate negatives impact of pb toxicity in fish but also ensure its safety for human consumption.

Quantitatively characterizing benthic community-habitat relationships in soft-sediment, nearshore environments to yield useful results for management.

Effective management of benthic habitats is important for maintaining heathy and functional aquatic ecosystems. To provide managers with the best possible information, characterizing benthic habitats at the community level is essential; yet, acquiring the data sets needed to achieve this task is resource intensive and, at times, prohibitively expensive. Thus, thoughtful assessments of which data to collect and utilize in benthic habitat characterization studies are needed. Environmental data sets commonly used to characterize benthic habitats include a range of variables from water depth and sediment grain size to seabed features identified by sonar backscatter. The objective of this study was to identify the most useful environmental variables for characterizing infaunal benthic habitats and to determine how to best utilize these variables in analyses (e.g., by comparing continuous vs. categorical explanatory variables). The modeling approach used multivariate regression tree and redundancy analysis along with a critical cross-validation step for model evaluation. Results indicated that models with more than ~7 environmental predictors overfitted the data sets analyzed and that categorizing continuous predictors into categorical ones influenced the proportion of infaunal community variation explained by each model. Habitats identified and characterized on the basis of sonar backscatter explained more of the infaunal community variation than any model that used a combination of other environmental variables (e.g., water depth & sediment grain size) or those constructed using categorical habitat classes from existing classification schemes. We therefore recommend maximizing the potential of sonar-derived variables for characterizing infaunal benthic habitats in nearshore, soft-sediment ecosystems.

Augmentation of DTH reaction of mycobacterial antigenic cocktail using synthetic mycobacterial 19-kDa lipoprotein as a TLR-stimulant.

The current study proposed that previously characterized individual antigenic proteins could represent potential replacement for conventional purified protein derivative (PPD) in tuberculosis skin testing when used in cocktails triggered by suitable TLR-stimulants that would provide the missing pro-inflammatory stimulus. Three different cocktails of previously selected antigens, including C1 (ESAT-6/CPF-10/MPB-83); C2 (ESAT-6/MPB-64/MPB-83); and C3 (CPF-10/MPB-64/MPB-83), were evaluated in vitro using lymphocytic proliferation and IFN-γ production assays, as well as mRNA and protein expression levels of TNF-α, IL-12p40, and IL-2 as pro-inflammatory molecules. C1 showed the highest significant induction of pro-inflammatory molecules as compared to other cocktails, yet still significantly lower than that induced by conventional PPD. Interestingly, inclusion of the synthetic Mycobacterium tuberculosis 19-kDa lipoprotein (Pam3Cys-SSNKSTTGSGETTTA) as a TLR-stimulant resulted in obvious augmentation of C1-induced pro-inflammatory molecules to levels comparable to that of PPD. In addition, skin testing using sensitized guinea pig model revealed comparable significant reaction to that of conventional PPD. ESAT-6/CPF-10/MPB-83 cocktail is suggested as a potential alternative skin-testing reagent when used in combination with the M. tuberculosis 19-kDa lipoprotein as a TLR-stimulant.

Are Tidal Salt Marshes Exposed to Nutrient Pollution more Vulnerable to Sea Level Rise?

Over the past four decades, Long Island, NY, USA, has lost coastal wetlands at a rate of 4% per decade due to submergence. In this study, we examined relationships between the rate of tidal salt marsh loss and environmental factors, including marsh elevation, tidal range, and wastewater exposure through analysis of stable isotope ratios of marsh soils and biota. Our goal was to identify factors that increase vulnerability of marshes to sea level rise, with a specific emphasis on the potential role of poor water quality in hastening marsh loss. Our results suggest that wastewater exposure may accelerate loss of intertidal marsh, but does not negatively impact high tidal marsh resilience to sea level rise. And while marsh elevation and tidal range were statistically significant predictors of marsh loss, they similarly displayed opposite relationships among marsh zones. This study suggests that different functional zones of coastal salt marshes may not respond similarly to global change factors, and that elevation may be an important factor mediating eutrophication effects to coastal salt marshes.

A role for the tfs3 ICE-encoded type IV secretion system in pro-inflammatory signalling by the Helicobacter pylori Ser/Thr kinase, CtkA.

Two distinct type IV secretion systems (T4SSs) can be identified in certain Helicobacter pylori strains, encoded on mobile genetic elements termed tfs3 and tfs4. Although their function remains unknown, both have been implicated in clinical outcomes of H. pylori infection. Here we provide evidence that the Tfs3 T4SS is required for activity of the pro-inflammatory Ser/Thr kinase protein, CtkA, in a gastric epithelial cell infection model. Previously, purified recombinant CtkA protein has been shown to upregulate NF-kappaB signalling and induce TNF-alpha and IL-8 cytokine secretion from cultured macrophages suggesting that it may potentiate the H. pylori-mediated inflammatory response. In this study, we show that CtkA expressed from its native host, H. pylori has a similar capacity for stimulation of a pro-inflammatory response from gastric epithelial cells. CtkA interaction was found to be dependent upon a complement of tfs3 T4SS genes, but independent of the T4SSs encoded by either tfs4 or the cag pathogenicity island. Moreover, the availability of CtkA for host cell interaction was shown to be conditional upon the carboxyl-terminus of CtkA, encoding a putative conserved secretion signal common to other variably encoded Tfs3 proteins. Collectively, our observations indicate a role for the Tfs3 T4SS in CtkA-mediated pro-inflammatory signalling by H. pylori and identify CtkA as a likely Tfs3 T4SS secretion substrate.

Detection of desmoplastic melanoma with dermoscopy and reflectance confocal microscopy.

BACKGROUND: Desmoplastic melanoma (DM) is frequently misdiagnosed clinically and often associated with melanoma in situ (MIS). OBJECTIVE: To improve the detection of DM using dermoscopy and reflectance confocal microscopy (RCM). METHODS: A descriptive analysis of DM dermoscopy features and a case-control study within a melanoma population for RCM feature evaluation was performed blindly, using data obtained between 2005 and 2015. After retrospectively identifying all DM cases with RCM data over the study period (n = 16), a control group of non-DM melanoma patients with RCM data, in a ratio of at least 3 : 1, was selected. The control group was matched by age and primary tumour site location, divided into non-DM invasive melanomas (n = 27) and MIS (n = 27). Invasive melanomas were selected according to the melanoma subtypes associated with the DM cases. The main outcomes were the frequency of melanoma-specific features on dermoscopy for DM; and the odds ratios of RCM features to distinguish DM from MIS and/or other invasive melanomas; or MIS from the combined invasive melanoma group. RESULTS: At least one of the 14 melanoma-specific features evaluated on dermoscopy was found in 100% of DMs (n = 15 DM with dermoscopy). Known RCM melanoma predictors were commonly found in the DMs, such as pagetoid cells (100%) and cell atypia (100%). The RCM feature of spindle cells in the superficial dermis was more common in DM compared with the entire melanoma control group (OR 3.82, 95% CI 1.01-14.90), and particularly compared to MIS (OR 5.48, 95% CI 1.11-32.36). Nucleated cells in the dermis and the RCM correlate of dermal inflammation were also significant RCM features favouring DM over MIS, as well as invasive melanoma over MIS. CONCLUSION: Dermoscopy and RCM may be useful tools for the identification of DM. Certain RCM features may help distinguish DM from MIS and other invasive melanomas. Larger studies are warranted.

Scimitar Syndrome-Complex Surgical Revision 3 Decades After Repair.

We present a case of a 39-year-old woman with scimitar syndrome who had a 2-patch repair 3 decades previously and presented with a right-to-left shunt of the inferior vena cava (IVC) to the left atrium resulting from baffle dehiscence. We discuss details of our reoperative repair.