Helminth-derived proteins as immune system regulators: a systematic review of their promise in alleviating colitis.

Helminth-derived proteins have immunomodulatory properties, influencing the host's immune response as an adaptive strategy for helminth survival. Helminth-derived proteins modulate the immune response by inducing anti-inflammatory cytokines, promoting regulatory T-cell development, and ultimately favouring a Th2-biased immune response. This systematic review focused on helminth-derived proteins and explored their impact on reducing inflammatory responses in mouse models of colitis. A systematic search across Medline, EMBASE, Web of Science, and Cochrane Library identified fourteen relevant studies. These studies reported immunomodulatory changes, including increased production of anti-inflammatory cells and cytokines. In mouse models of colitis treated with on helminth-derived proteins, significant improvements in pathological parameters such as body weight, colon length, and microscopic inflammatory scores were observed compared to control groups. Moreover, helminth-derived proteins can enhance the function of Tregs and alleviate the severity of inflammatory conditions. The findings underscore the pivotal role of helminth-derived proteins in immunomodulation, specifically in the axis of cytokine secretion and immune cell polarization. The findings offer new opportunities for treating chronic inflammatory conditions such Crohn's disease.

Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus.

Herein, we measured the antidiabetic and nephroprotective effects of the sodium-glucose cotransporter-2 inhibitor (empagliflozin; SGLT2i) and synthetic active vitamin D (paricalcitol; Pcal) mono- and co-therapy against diabetic nephropathy (DN). Fifty mice were assigned into negative (NC) and positive (PC) control, SGLT2i, Pcal, and SGLT2i+Pcal groups. Following establishment of DN, SGLT2i (5.1 mg/kg/day) and/or Pcal (0.5 µg/kg/day) were used in the designated groups (5 times/week/day). DN was affirmed in the PC group by hyperglycaemia, dyslipidaemia, polyuria, proteinuria, elevated urine protein/creatinine ratio, and abnormal renal biochemical parameters. Renal SREBP-1 lipogenic molecule, adipokines (leptin/resistin), pro-oxidant (MDA/H2O2), pro-inflammatory (IL1ß/IL6/TNF-α), tissue damage (iNOS/TGF-ß1/NGAL/KIM-1), and apoptosis (TUNEL/Caspase-3) markers also increased in the PC group. In contrast, renal lipolytic (PPARα/PPARγ), adiponectin, antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL10) molecules decreased in the PC group. Both monotherapies increased insulin levels and mitigated hyperglycaemia, dyslipidaemia, renal and urine biochemical profiles alongside renal lipid regulatory molecules, inflammation, and oxidative stress. While SGLT2i monotherapy showed superior effects to Pcal, their combination demonstrated enhanced remedial actions related to metabolic control alongside renal oxidative stress, inflammation, and apoptosis. In conclusion, SGLT2i was better than Pcal monotherapy against DN, and their combination revealed better nephroprotection, plausibly by enhanced glycaemic control with boosted renal antioxidative and anti-inflammatory mechanisms.

Profiling estrogen, progesterone, and androgen receptors in colorectal cancer in relation to gender, menopausal status, clinical stage, and tumour sidedness.

Background: Although estrogen (ERα/ERß), progesterone (PGR), and androgen (AR) receptors are pathologically altered in colorectal cancer (CRC), their simultaneous expression within the same cohort of patients was not previously measured. Methods: ERα/ERß/PGR/AR proteins were measured in archived paired normal and malignant colon specimens (n =120 patients) by immunohistochemistry, and results were analyzed by gender, age (≤50 vs. ≥60 years), clinical stages (early-stage I/II vs. late-stage III/IV), and anatomical location (right; RSCs vs. left; LSCs). Effects of 17ß-estradiol (E2), progesterone (P4), and testosterone alone or combined with the specific blockers of ERα (MPP dihydrochloride), ERß (PHTPP), PGR (mifepristone), and AR (bicalutamide) on cell cycle and apoptosis were also measured in the SW480 male and HT29 female CRC cell lines. Results: ERα and AR proteins increased, whilst ERß and PGR declined markedly in malignant specimens. Moreover, male neoplastic tissues showed highest AR expression, whilst ERß and PGR weakest alongside ERα strongest expression was seen in cancerous tissues from women aged ≥60 years. Late-stage neoplasms also revealed maximal alterations in the expression of sex steroid receptors. By tumor location, LSCs disclosed significant elevations in ERα with marked declines in PGR compared with RSCs, and ERα strongest alongside PGR weakest expression was detected in advanced LSCs from women aged ≥60 years. Late-stage LSCs from females aged ≥60 years also showed weakest ERß and strongest AR expression. In contrast, male RSC and LSC tissues exhibited equal ERß and AR expression in all clinical stages. ERα and AR proteins also correlated positively, whereas ERß and PGR inversely, with tumor characteristics. Concomitantly, E2 and P4 monotherapies triggered cell cycle arrest and apoptosis in the SW480 and HT29 cells, and while pre-treatment with ERα-blocker enhanced the effects of E2, ERß-blocker and PGR-blocker suppressed the E2 and P4 anti-cancer actions, respectively. In contrast, treatment with the AR-blocker induced apoptosis, whilst co-treatment with testosterone hindered the effects. Conclusions: This study advocates that protein expression of sex steroid receptors in malignant tissues could represent prognostic markers, as well as hormonal therapy could provide an alternative strategy against CRC, and their efficacies could be dependent on gender, clinical stage, and tumor location.

Metformin and thymoquinone co-treatment enhance 5-fluorouracil cytotoxicity by suppressing the PI3K/mTOR/HIF1α pathway and increasing oxidative stress in colon cancer cells.

This study investigated the chemotherapeutic effects of 5-fluorouracil (5-FU), metformin (Met), and/or thymoquinone (TQ) single/dual/triple therapies in the HT29, SW480 and SW620 colon cancer (CRC) cell lines. Cell cycle/apoptosis were measured by flow cytometry. The gene and protein expression of apoptosis (PCNA/survivin/BAX/Cytochrome-C/Caspase-3) and cell cycle (CCND1/CCND3/p21/p27) molecules, the PI3K/mTOR/HIF1α oncogenic pathway, and glycolysis regulatory enzymes were measured by quantitative-PCR and Western blot. Markers of oxidative stress were also measured by colorimetric assays. Although all treatments induced anti-cancer effects related to cell cycle arrest and apoptosis, the triple therapy showed the highest pro-apoptotic actions that coincided with the lowest expression of CCND1/CCND3/PCNA/survivin and the maximal increases in p21/p27/BAX/Cytochrome-C/Caspase-3 in all cell lines. The triple therapy also revealed the best suppression of the PI3K/mTOR/HIF1α pathway by increasing its endogenous inhibitors (PTEN/AMPKα) in all cell lines. Moreover, the lowest expression of lactate dehydrogenase and pyruvate dehydrogenase kinase-1 with the highest expression of pyruvate dehydrogenase were seen with the triple therapy, which also showed the highest increases in oxidative stress markers (ROS/RNS/MDA/protein carbonyl groups) alongside the lowest antioxidant levels (GSH/CAT) in all cell lines. In conclusion, this is the first study to reveal enhanced anti-cancer effects for metformin/thymoquinone in CRC that were superior to all monotherapies and the other dual therapies. However, the triple therapy approach showed the best tumoricidal actions related to cell cycle arrest and apoptosis in all cell lines, possibly by enhancing oxidative glycolysis and augmenting oxidative stress through stronger modulation of the PI3K/mTOR/HIF1α oncogenic network.

Trends in hospital admissions and prescribing due to chronic obstructive pulmonary disease and asthma in England and Wales between 1999 and 2020: an ecological study.

OBJECTIVE: To investigate the trends in hospital admissions and medication prescriptions related to asthma and chronic obstructive pulmonary disease (COPD) in England and Wales. METHODS: An ecological study was conducted between April 1999 and April 2020 using data extracted from the hospital episode statistics database in England and the patient episode database for Wales. The Office of National Statistics mid-year population estimates for 1999 through 2020 were collected, and medication prescription data for 2004-2020 were extracted from the prescription cost analysis database. RESULTS: The total annual number of COPD and asthma hospital admissions for various causes increased by 82.2%, from 210,525 in 1999 to 383,652 in 2020, representing a 59.1% increase in hospital admission rate (from 403.77 in 1999 to 642.42 per 100,000 persons in 2020, p < 0.05). Chronic obstructive pulmonary disease with acute lower respiratory infection accounted for 38.7% of hospital admissions. Around 34.7% of all hospital admissions involved patients aged 75 and older. Around 53.8% of all COPD and asthma hospital admissions were attributable to females. The annual number of prescriptions dispensed for COPD and asthma medications increased by 42.2%. CONCLUSIONS: Throughout the study period, hospital admissions due to chronic obstructive pulmonary disease and asthma, as well as medication prescriptions, increased dramatically among all age groups. Hospitalization rates were higher for women. Further observational and epidemiological research is required to identify the factors contributing to increased hospitalization rates.

Determination of Chemical Composition and Investigation of Biological Activities of Ocimum basilicum L.

This study aimed to determine the chemical composition of the essential oils (EOs) of Ocimum basilicum L., as well as to evaluate the antibacterial, antidiabetic, dermatoprotective, and anti-inflammatory properties, and the EOs and aqueous extracts of O. basilicum. The antibacterial activity was evaluated against bacterial strains, Gram-positive and Gram-negative, using the well diffusion and microdilution methods, whereas the antidiabetic activity was assessed in vitro using two enzymes involved in carbohydrate digestion, α-amylase and α-glucosidase. On the other hand, the dermatoprotective and anti-inflammatory activities were studied by testing tyrosinase and lipoxygenase inhibition activity, respectively. The results showed that the chemical composition of O. basilicum EO (OBEO) is dominated by methyl chavicol (86%) and trans-anethol (8%). OBEO exhibited significant antibacterial effects against Gram-negative and Gram-positive strains, demonstrated by considerable diameters of the inhibition zones and lower MIC and MBC values. In addition, OBEO exhibited significant inhibition of α-amylase (IC50 = 50.51 ± 0.32 µg/mL) and α-glucosidase (IC50 = 39.84 ± 1.2 µg/mL). Concerning the anti-inflammatory activity, OBEO significantly inhibited lipoxygenase activity (IC50 = 18.28 ± 0.03 µg/mL) compared to the aqueous extract (IC50 = 24.8 ± 0.01 µg/mL). Moreover, tyrosinase was considerably inhibited by OBEO (IC50 = 68.58 ± 0.03 µg/mL) compared to the aqueous extract (IC50 = 118.37 ± 0.05 µg/mL). The toxicological investigations revealed the safety of O. basilicum in acute and chronic toxicity. The finding of in silico analysis showed that methyl chavicol and trans-anethole (main compounds of OBEO) validate the pharmacokinetics of these compounds and decipher some antibacterial targets.

COVID-19 vaccination side effects among the child age group: a large cross-sectional online based survey in Saudi Arabia.

BACKGROUND: Multiple vaccines have been tested in clinical trials for their efficacy and safety. In Saudi Arabia, Pfizer-BioNTech or Moderna were approved for children, however, previous studies to report their safety profile are limited. This research aims to understand the side effect of children's vaccination against SARS-CoV-2 infection in Saudi Arabia. METHODS: This was an observational retrospective cross-sectional study was conducted using an online survey in Saudi Arabia from March to May 2022. The inclusion criteria were parents aged 18 years and above who live in Saudi Arabia and have vaccinated their children. The self-reported questionnaire was adopted from published studies to investigate the study objectives Descriptive statistics were used to describe patients' demographic characteristics, continuous data were reported as mean ± S.D., categorical data were reported as percentages (frequencies), and logistic regression was used to identify predictors of persistent post-COVID-19 symptoms. RESULTS: This study had a total of 4,069 participants. Only 41.9% of the participants reported that their child(ren) had been infected with the coronavirus. 2.00 was the median number of children (IQR: 1.00-4.00). More than half of the study participants (64.2%) reported that a family member had been infected with the coronavirus. Both parents received COVID-19 vaccination, according to most participants (88.7%). Most participants (70.5%) stated that all children who met the vaccination criteria had received the vaccine. Most participants (83.5%) said their child or children had two doses of their vaccine, and about half (50.4%) of those who received the vaccine reported experiencing side effects. In addition, the majority (78.9%) reported that the side effects appeared within one day of receiving the vaccine, and nearly two-thirds (65.7%) reported that the side effects lasted between one and three. A total of 11,831 side effects cases were documented. Pain at the injection site, hyperthermia, and fatigue were the most reported side effects, accounting for 15.3%, 14.1%, and 13.2%, respectively. CONCLUSION: It appears that the side effects of the COVID-19 vaccine for children are minor, tolerable, and like those described previously in clinical trials. Our data should encourage the public about the safety of receiving the COVID-19 vaccine for children.

A Rare Case of a Child Diagnosed With Multisystem Inflammatory Syndrome After COVID-19 Presenting With Renal Infarctions and Transient Blast Cells: A Case Report and Literature Review.

Multisystem inflammatory syndrome in children (MIS-C) can develop weeks after the Coronavirus disease 2019 (COVID-19). The disease's clinical spectrum includes persistent febrile illness, features resembling Kawasaki disease, and cytokine storm symptoms. In severe cases, multisystem organ failure and death may result if not treated promptly. This report discusses a rare case of a 13-year-old girl presenting with fever and acute kidney injury (AKI) eight weeks after recovering from COVID-19 who was diagnosed with MIS-C. A 13-year-old female presented with a fever and abdominal pain following a recent COVID-19. A physical examination revealed a febrile, ill-looking child with abdominal tenderness. Pancytopenia, transaminitis, AKI, and a hyperinflammatory state were noted in the initial laboratory workup. Furthermore, blast cells were seen on the peripheral blood smear. Despite appropriate empiric antibiotic therapy for sepsis, she did not show signs of clinical improvement. An abdominal computed tomography (CT) scan revealed multiple focal areas of hypoattenuating lesions involving both kidneys, suggestive of bilateral renal infarction. Since she met the criteria of the Centers for Disease Control and Prevention (CDC) for MIS-C diagnosis, a high dose of intravenous immunoglobulin (IVIG) led to a dramatic improvement in the patient's condition and complete recovery from her illness. This case report describes a rare clinical presentation of MIS-C in a child who presented with AKI due to presumably thrombotic events and transient blast cells in blood film secondary to a severe inflammatory process. Further studies are needed to determine the prevalence of thrombotic AKI associated with MIS-C.

Diagnostic accuracy of different bronchoscopic specimens in sputum Xpert MBT/RIF- negative pulmonary TB patients.

Background: Tuberculosis (TB) control remains a critical public health problem worldwide. Rapid diagnosis and proper treatment are beneficial for the effective control of tuberculosis transmission. Diagnostic challenges arise when a patient has a clinical and radiological suspicion of tuberculosis but cannot produce sputum, sputum acid-fast bacilli, or Xpert Mycobacterium tuberculosis/rifampicin (Xpert MTB/RIF) is negative, resulting in suboptimal management. As a result, more invasive techniques must be used on these patients to establish the diagnosis. Methods: A retrospective study recruited 330 suspected pulmonary TB patients with negative sputum of Xpert MBT/RIF who underwent bronchoscopy between March 2018 and December 2021. The diagnostic yields of bronchoalveolar lavage fluid (acid-fast bacilli, Xpert MTB/RIF, and culture) and histopathologic examination (HPE) were calculated and compared to the final diagnosis and culture as a gold standard. Results: Out of 330 suspected pulmonary TB patients, 181 had a final diagnosis of TB, and 149 had non-TB. The sensitivity of BALF (culture, Xpert, acid-fast bacilli) and trans-bronchial lung biopsy (HPE) was 80.7%, 72.9%, 21.1%, and 87.1%, respectively. Multiple nodules were associated with significantly higher BALF Xpert MTB, bronchoalveolar lavage fluid culture, and trans-bronchial lung biopsy (HPE) positivity. Conclusions: Bronchoscopic specimens are essential for accurate and rapid diagnosis of sputum Xpert MBT/RIF negative patients with high clinical and radiological suspicion of tuberculosis.

The Influence of COVID-19 Pandemic on Influenza Immunization in Saudi Arabia: Cross-Sectional Study.

Introduction: Influenza vaccination is the primary control measure for severe complications caused by influenza viruses. Moreover, in the face of the COVID-19 pandemic, Saudi Arabia recommends vaccinating people at risk against influenza to minimise co-infection risk with SARS-CoV2. Therefore, this study aims to assess the Saudi population's knowledge, attitude, and practice toward influenza vaccination during the COVID-19 pandemic. Moreover, we evaluate the impact of the COVID-19 pandemic on seasonal influenza vaccination. Methods: This cross-sectional study was conducted using an online survey in Saudi Arabia between July to August 2021. Participants were invited to complete the questionnaire through a survey link sent to social media platforms. Results: A total of 2410 participants were included in this study. Our data demonstrate a lack of practice, attitude, and knowledge, especially on the influenza virus's symptoms, viral transmission, and vaccine efficacy. Moreover, this study showed that the COVID-19 pandemic significantly impacted seasonal influenza vaccination in the Saudi population by 1.5-times compared to the previous years. Conclusion: COVID-19 pandemic has increased the hesitancy of Saudi participants in influenza vaccination due to the lack of knowledge. As the pandemic of COVID-19 is fading, awareness campaigns are needed to encourage the public about the importance of receiving the influenza vaccine, especially for those at high risk each year.

Determinants of Post-COVID-19 Conditions among SARS-CoV-2-Infected Patients in Saudi Arabia: A Web-Based Cross-Sectional Study.

Background: Large numbers of people infected with COVID-19 developed acute symptoms. Post-COVID-19 conditions have been reported after recovery or discharge from the hospital. However, little is known about the prevalence and possible risk factors of post-COVID-19 conditions in the Saudi community. Here, we describe the incidence of post-COVID-19 conditions among the general population of Saudi Arabia. Methods: We conducted a cross-sectional, nationwide study using an online survey in Saudi Arabia from 1 September 2021 to 28 February 2022. The survey was distributed using social media platforms, such as Twitter, WhatsApp, and Facebook. Patients with SARS-CoV-2 infection were included in the questionnaire adapted from published studies. Result: The study enrolled 7520 individuals who were previously infected with SARS-CoV-2. Most patients in our study were symptomatic and their acute symptoms may persist for more than six days. On the other hand, long-term complications may develop and continue for an extended period (post-COVID-19 conditions). Most of these complications are respiratory, neurological, psychological, or skin related. The proportion of long-term complications reported in this study is 36% among SARS-CoV-2-infected individuals. In addition, being female, old age, number of chronic complications, long-term medication, length of stay in hospital and intensive care unit, and duration of acute symptoms may be significant predictors of post-COVID-19 symptoms. Conclusion: In conclusion, the incidence of post-COVID-19 conditions among the Saudi population was high, which urges further investigation into the risk factors associated with post-COVID-19 symptoms.

Parental Knowledge and Awareness of Childhood Urinary Tract Infections: A Cross Sectional Survey.

Background: Parent's misconceptions or lack of knowledge about childhood urinary tract infections (UTIs) can negatively impact their children's health. Therefore, the present study aimed to determine the childhood urinary tract infections awareness and understanding among parents in Saudi Arabia. Patients and Methods: An online validated cross-sectional survey of parents in Saudi Arabia was conducted from August to September 2021. Study participants who met the inclusion criteria were selected using a convenience sampling technique. A questionnaire with two domains was used to assess parental awareness of childhood urinary tract infection symptoms, complications, treatment, prevention, epidemiology, and diagnosis. The total childhood urinary tract infections awareness scores were classified into three categories: low awareness, moderate awareness, and high awareness. Descriptive statistics were used to determine the data distribution. A chi-square test was used to evaluate the relationship between parental awareness about urinary tract infections in children and other variables. Statistical significance was established at 0.05. Results: Of the 1688 parents who completed the survey, 1289 (76.4%) were female, 1581 (93.7%) were married, and 1161 (68.8) had a university degree. Parent's total awareness scores were high; however, individual domain scores indicate a moderate level of knowledge. Statistically significant relationship were observed between total awareness and gender, occupation, and level of educational level ((P=0.004, P=0.001, P=0.007, respectively). Another statistically significant relationship was noted between the history of urinary tract infections and awareness of disease prevention (P=0.009). Conclusion: In Saudi Arabia, parental knowledge about childhood urinary tract infections is moderate to high. However, future studies are needed to investigate gender, educational, and occupational variations in childhood UTI knowledge among parents in Saudi Arabia.

Impact of COVID-19 Pandemic on Medical Education: A Cross-Sectional Study in the Western Region of Saudi Arabia.

Background: As the Coronavirus Disease 2019 (COVID-19) outbreak has made a tremendous impact on medical education and healthcare institutions, we aimed to measure effects of online classes on medical students' comprehension in comparison with attending campus classes during the COVID-19 pandemic. Methods: A cross-sectional survey has been conducted between September 2020 and June 2021 in the western region of Saudi Arabia. The Convenience sampling technique was conducted to collect the data from medical students in their basic and clinical years, using a questionnaire that involved 45 multiple-choice and multiple-answer questions. Results: Out of 3700 questionnaires, 922 completed the questionnaires from 11 different medical schools. Umm AL-Qura University had the highest response rate with 232 responses (25.2%), followed by King Abdulaziz University with 186 responses (20.2%). The majority of institutions preferred Blackboard and Zoom as platforms for e-learning. A total of 355 (38.5%) believed that it resulted in higher academic achievement, whereas 555 (60.2%) of students believed the limitation of clinical access was one of the biggest disadvantages of e-learning. Overall, 518 (56.2%) of students did not want to continue using e-learning on its own in the future. Whereas 668 (72.5%) wished to keep using e-learning in combination with traditional learning. Conclusion: According to our findings, advantages of e-learning vary among students. Most of the students thought e-learning to be an interactive system that provides a learning opportunity. In contrast, many of the students believed that there were many disadvantages regarding online teaching methods.

Haematological, Biochemical, and Inflammatory Biomarkers of COVID-19 Patients Hospitalized in Critical Unit: A Retrospective Study.

BACKGROUND: The World Health Organization declared coronavirus disease 2019 (COVID-19) responsible for a catastrophic global pandemic. The complexity of COVID-19 is centred on the unpredictable course of the disease, which can rapidly develop from patients being asymptomatic to having life-threatening symptoms. The unpredictable disease severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major problem facing the healthcare system during the pandemic. Identifying the laboratory biomarkers would help predict SARS-CoV-2 pathogenicity. This study focused on the previous literature regarding three laboratory biomarker profiles: haematological, inflammatory, and biochemical biomarkers. METHODS: A retrospective study of COVID-19 patients was conducted between May 2020 and September 2020 to determine the predictors of hospitalization (severity) in COVID-19 patients. Patients were divided into two groups: those admitted to an intensive care unit (ICU, severe) and those admitted to a non-ICU (stable). Patients' data were obtained from their medical records at Al Noor Specialist Hospital and East Arafat Hospital in Saudi Arabia. RESULTS: A total of 487 patients with COVID-19, including 304 males and 183 females, were investigated in this study. A total of 217 patients were admitted to the ICU. Patients admitted to the ICU had a higher prevalence of chronic comorbidities than non-ICU patients. D-dimer, white blood cells (WBC), neutrophils, ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were more elevated in patients admitted to the ICU compared to non-ICU patients. CONCLUSION: Chronic comorbidities are a significant predictor for admission to the ICU. Moreover, tests for D-dimer, WBC, neutrophils, lymphocytes, CRP, LDH, and ALT could be used to predict patients' admission to the ICU.

A child with bronchiectasis, chronic mucocutaneous candidiasis, and hypothyroidism secondary to STAT1 gain-of-function mutation: A case report and review of the literature.

STAT 1 GOF mutations are a rare cause of childhood primary immunodeficiency. Recurrent mucocutaneous candidiasis, chest infections, and autoimmune disease are all classic phenotype presentations. Rapid identification and diagnosis of this debilitating disease using whole exon sequencing may improve outcomes and minimize long-term sequelae.

Polychlorinated Biphenyls and Pulmonary Hypertension.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that were banned because of their potential carcinogenicity. Population studies have shown that PCBs are associated with lung toxicity and hypertension. The objective of this study was to evaluate whether higher exposure to PCB congeners is associated with the risk of pulmonary hypertension. Serum levels of PCBs in 284 subjects with combined risk factors for pulmonary arterial hypertension (PAH) were compared to 4210 subjects with no risk for PAH using the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The major findings from this study include significantly higher PCB levels in PAH subjects compared to non-PAH subjects; for example, the geometric mean (GM) of PCB74 was 15.91 (ng/g) (14.45-17.53) vs. 11.48 (ng/g) (10.84-12.16), respectively. Serum levels of PCB congeners showed an increasing trend in the age group 20-59 years as PCB180 GM was 19.45 (ng/g) in PAH vs. 12.75 (ng/g) in the control. A higher body burden of PCB153 followed by PCB138, PCB180, and PCB118 was observed. Estimated age, race, BMI, and gender-adjusted ORs for PCB congener levels in subjects with the combined risk factors for PAH compared to controls was significant; for example, PCB99 (OR: 1.5 (CI: 1.49-1.50). In summary, these findings indicate that exposure, as well as body burden estimated based on lipid adjustment of PCBs, were higher in people with risk factors for PAH, and PCB congeners accumulated with age. These findings should be interpreted with caution because of the use of cross-sectional self-reported data and a small sample size of subjects with combined risk factors for pulmonary arterial hypertension. Nonetheless, our finding emphasizes a need for a comprehensive environmental molecular epidemiologic study to determine the potential role of environmental exposures to PCBs in the development of pulmonary arterial hypertension.

Enhanced in vitro tumoricidal effects of 5-Fluorouracil, thymoquinone, and active vitamin D3 triple therapy against colon cancer cells by attenuating the PI3K/AKT/mTOR pathway.

AIMS: This study measured the effects of 5-Fluorouracil (5-FU), calcitriol (VD3), and/or thymoquinone (TQ) single/dual/triple therapies on cell cycle progression, apoptosis, inhibition of the PI3K/AKT/mTOR pathway, and oxidative stress against colorectal cancer (CRC). MAIN METHODS: The HT29, SW480 and SW620 cell lines were treated with 5-FU (50 µM), VD3 (25 µM), and TQ (75 µM), alone or combined for 12 h, prior to cell cycle/apoptosis analyses. KEY FINDINGS: TQ monotherapy had greater anticancer effects to active VD3 or 5-FU, revealing higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3 and increased levels of total glutathione, with inhibitions in CCND1/CCND3/BCL-2 and PI3K/AKT/mTOR molecules, alongside higher rates of apoptosis in HT29, SW480 and SW620 cells (P < 0.005 for all markers). Additionally, all combination protocols revealed enhanced modulations of the PI3K/PTEN/Akt/mTOR pathway, higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3, and better anti-oxidant effects, than the monotherapies. Although TQ/5-FU and TQ/VD3 co-therapies were better relative to the VD3/5-FU regimen, the best tumoricidal effects were observed with triple therapy in the HT29 and SW480 cell lines, possibly by boosted attenuations of the PI3K/AKT/mTOR oncogenic pathway. In contrast, TQ single treatment was more effective than the triple therapy regimen in metastatic SW620 cells, suggesting that this protocol would be more useful therapeutically in late-stage CRC. SIGNIFICANCE: In conclusion, this study is the first to demonstrated enhanced anti-tumorigenic effects for VD3, TQ, and 5-FU triple therapy against CRC cells and could represent the best strategy for treating early stages of malignancy, whereas TQ monotherapy could be a better approach for treating metastatic forms of the disease.

Parents' Willingness to Vaccinate Their Children Against Seasonal Influenza After the COVID-19 Pandemic in Saudi Arabia: A Retrospective Cross-Sectional Survey.

PURPOSE: To explore the impact of the novel coronavirus (COVID-19) pandemic on caregivers' willingness to vaccinate their children against influenza in 2021 in Saudi Arabia and the factors influencing this decision. PATIENTS AND METHODS: An online survey of 2501 caregivers in Saudi Arabia with children aged 6 months-18 years was conducted between July 15, 2021, and August 2, 2021. A convenience sample of participants that met the inclusion criteria was used as the study sample. Social Science Package Statistical (SPSS) was used for the statistical analysis. Categorical variables were reported as frequencies and percentages. The Chi-square test was used for categorical variables to assess the difference between the variables and the parents' willingness to vaccinate their children against seasonal influenza after the COVID-19 pandemic. RESULTS: Of the 2501 respondents to the survey, 1185 (47.3%) parents plan to give their children the influenza vaccine next year, which is an increase from 745 (29.8%) in the previous year. The following were the main reasons for not giving children the vaccine: children were less likely to get seasonal flu (617, 24.7%), fear of side effects (491, 19.6%), and fear of needles and syringes (484, 19.4%). Among the parents, 1222 (48.9%) were more likely to receive the seasonal flu vaccine themselves the following year, and 1361 (54.4%), which is more than half, were concerned about their children contracting seasonal influenza. CONCLUSION: Parents' decision-making to vaccinate their children against seasonal influenza has been influenced by the COVID-19 pandemic. Numerous factors including a caregiver who had received the seasonal influenza vaccine themselves, who had vaccinated or planned to vaccinate their children during the previous or current seasonal influenza season, and/or who had a higher education level were associated with increased willingness to receive the flu vaccine.

Assessment of caregiver willingness to vaccinate their children against COVID-19 in Saudi Arabia: a cross-sectional study.

BACKGROUND: Vaccination against COVID-19 is the key to controlling the pandemic. Parents are the decision makers in the case of children vaccination as they are responsible for them. This study aims to investigate the acceptability of COVID-19 vaccination for children among parents in Saudi Arabia. METHODS: This cross-sectional study used an online self-administered questionnaire. A 35-items questionnaire was distributed via social media platforms between June 6 and July 9-2021. Descriptive statistics were used to describe the participants' characteristics. Categorical variables were reported as frequencies and percentages. Predictors of vaccination acceptance were identified using binary logistic regression. RESULTS: A total of 581 parents were involved in this study. A majority of parents 63.9% reported that they will vaccinate their children if the vaccine becomes available. Around 40% of them confirmed that they want their child to be among the first to receive the COVID-19 vaccine. Nearly a quarter, 23.9%, reported that they will vaccinate their child against influenza this year. The most commonly reported reason for hesitancy was poor awareness about the vaccine's effectiveness on children. Adequate information about the COVID-19 vaccine was the most agreed cause to accept the vaccine. Having five or more children was a significant predictor for poor vaccination acceptance (OR: 0.42 (95%CI: 0.21-0.86), p < .05). CONCLUSION: An appropriate proportion of parents are willing to vaccinate their children if the vaccine becomes available for children in Saudi Arabia. Public health awareness must be raised to gain public trust in the vaccination and the healthcare system.

Disseminated histoplasmosis in a renal transplantation recipient: Peripheral blood smear was the key.

Disseminated histoplasmosis is common in immunocompromised patients such as patients with AIDS, hematologic malignancies, transplant recipients, and those on prolonged corticosteroid use. We report the case of a 53-year-old man with a history of end-stage renal disease due to uncontrolled hypertension who underwent renal transplantation in 2013. He presented to the hospital with a 5-day history of dyspnea, and blood tests showed pancytopenia. The diagnosis of disseminated histoplasmosis was made rapidly by peripheral blood smear. We encourage clinicians to check peripheral blood smear if disseminated histoplasmosis is suspected.