Severe periodontitis is associated with the serum levels of hypersensitive C reactive protein and lipoprotein-associated phospholipase A2 in the patients of acute ischemic stroke

BackgroundPeriodontitis is associated with the pathogenesis of atherosclerotic plaque, and hypersensitive C reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are the serum biomarkers of the stability of atherosclerotic plaque. Whether periodontitis is associated with the serum level of hs-CRP and Lp-PLA2 of acute ischemic stroke remains unclear.Material and MethodsWe recruited 103 cases with acute ischemic stroke within 7 days after stroke onset. Pocket depth and clinical attachment loss were assessed by oral examination to define the severe periodontitis. Demographic information including gender, age and body weight index, income level, education level, past medical history include smoking history, drinking history, ischemic stroke history, coronary heart disease, hypertension, diabetes and hyperlipidemia were collected, and serum biomarkers including white blood cell (WBC), fibrinogen, total cholesterol (TC), triglyceride (TG), lower density lipoprotein (LDL-C), high density lipoprotein (HDL-C), hs-CRP, HemoglobinA1c (HbAlc), Homocysteine (HCY) and Lp-PLA2 were tested.Results65 (63.1%) cases were diagnosed as severe periodontitis. Severe periodontitis group showed more male, age, drinking history, higher levels of hs-CRP and Lp-PLA2. Multivariate logistic regression showed that severe periodontitis was were significantly associated with hs-CRP (OR = 2.367, 95%CI: 1.182–4.738; P = .015) and Lp-PLA2 (OR = 2.577, 95% CI: 1.010–6.574; P = .048).ConclusionsSevere periodontitis is independently associated with the serum Level of hs-CRP and Lp-PLA2 in patients with acute ischemic stroke. Whether the improvement of periodontitis could decrease the occurrence and re-occurrence of ischemic stroke by stablizating atherosclerotic plaque need be further studied in future.     

Bio-accumulation and health risk assessment of heavy metals in different edible fish species from Hurghada City,Red Sea,Egypt

BackgroundHeavy metal contamination has become a serious issue in this century especially detected in fish organs. Due to the presence of radioactive compounds in agricultural and sewage effluent, which destroys aquatic ecosystems, threatening human livelihoods. Health hazards associated with low and high consumption consumers assessed in five commercial fish species collected from Hurghada City, Egypt, during winter and summer, 2020. Atomic absorption spectrophotometer technique used for determination heavy meals in different organs and expressed as μg/g wet weight.ResultsHeavy metal concentrations in muscle ranged between:(0.054–0.109), (0.260–1.043), (0.264–0.897), (5.895–11.898), (0.381–0.970), (13.582–29.133) and (0.332–0.589) µg/g for Cd, Pb, Mn, Zn, Cu, Fe and Ni respectively, which were lower than those of gills and liver. These concentrations were within WHO, FAO/WHO, and EU standards. Consumption of edible species was lower than the (TDIs) established by the (JECFA) and Egyptian Standards. Even though THQ and TTHQ values were < 1 while, in children with highly consumer were> 1.ConclusionThis study concluded that intake of Red Sea fish is safe for human health. It is critical for consumers to be aware of the consequences of excessive fish consumption, particularly children with highly consumer, which represent possible health risks.     

Incidence,risk factors and clinical implications of postoperative urinary tract infection in geriatric hip fractures

IntroductionPostoperative urinary tract infection (UTI) is common in geriatric patients; however, little is known about the impact of UTI in orthopedic trauma. The present study was designed to determine the risk factors and clinical impact of postoperative urinary tract infection (UTI) in acute geriatric hip fractures.Patients and methodsGeriatric patients (≥65 years of age) undergoing hip fracture surgery were identified within the American College of Surgeons National Surgical Quality Improvement Program between 2016 and 2019. Patients presenting with UTI at the time of surgery were excluded. Baseline characteristics and outcomes were compared between patients with and without postoperative UTI. Multivariate logistic regression was performed, controlling for potential confounders.ResultsA total of 46,263 patients included in the study. Overall, 1,397 (3.02%) patients had postoperative UTI. Patients who developed postoperative UTI had higher rates of pneumonia (6.44% vs. 3.76%, p < 0.001), DVT (2.22% vs. 1.04%, p < 0.001), sepsis (7.73% vs. 0.62%, p < 0.001), and more frequently experienced postoperative hospital lengths of stay exceeding 6 days (37.94% vs. 20.33%, p < 0.001). Hospital readmission occurred more frequently in patients with postoperative UTI (24.55% vs. 7.85%, p < 0.001), but surprisingly, these patients had a lower mortality rate (1.36% vs. 2.2%, p < 0.001). Adjusted analysis demonstrated the following variables associated with postoperative UTI: age ≥ 85 (OR = 1.37, 95%CI = 1.08 - 1.73), ASA class ≥ 3 (OR = 1.59, 95%CI = 1.21 – 2.08,), chronic steroid use (OR = 1.451, 95%CI = 1.05 - 1.89), blood transfusion (OR = 1.24, 95%CI = 1.05 - 1.48), and >2 days delay from admission to operation (OR = 1.37, 95%CI = 1.05 - 1.79). Postoperative UTI was significantly associated with sepsis (OR = 7.65, 95%CI = 5.72 – 10.21), postoperative length of stay >2 days (OR = 1.83, 95%CI = 1.07 – 3.13), and readmission (OR = 3, 95%CI = 2.54 – 3.55).ConclusionsIn our study, postoperative UTI was found in 3% of geriatric hip fracture patients. Predictors of postoperative UTI were age ≥ 85, ASA class ≥ 3, chronic steroid use, blood transfusion, and time to operation > 2 days from admission. Results showed that postoperative UTI is independently associated with sepsis, postoperative length of stay beyond 2 days, and hospital readmission. To diminish the risk of UTI and its consequences, we recommend operating geriatric hip fractures in 24–48 hours after admission.     

Deoxynivalenol induces apoptosis in PC12 cells via the mitochondrial pathway

Deoxynivalenol (DON) has broad toxicity in animals and humans. In this study the impact of DON treatment on apoptotic pathways in PC12 cells was determined. The effects of DON were evaluated on (i) typical indicators of apoptosis, including cellular morphology, cell activity, lactate dehydrogenase (LDH) release, and apoptosis ratio in PC12 cells, and on (ii) the expression of key genes and proteins related to apoptosis, including Bcl-2, Bax, Bid, cytochrome C (Cyt C), apoptosis inducing factor (AIF), cleaved-Caspase9, and cleaved-Caspase3. DON treatment inhibited proliferation of PC12 cells, induced significant morphological changes and apoptosis, promoted the release of Cyt C and AIF from the mitochondria, and increased the activities of cleaved-Caspase9 and cleaved-Caspase3. Bcl-2 expression decreased with increasing DON concentrations, in contrast to Bax and Bid, which were increased with increasing DON concentration. These data demonstrate that DON induces apoptosis in PC12 cells through the mitochondrial apoptosis pathway.     

Association of weight-adjusted-waist index with incident hypertension: The Rural Chinese Cohort Study

AimsTo explore the association between WWI and the incidence of HTN in the Rural Chinese Cohort Study.Methods and ResultsWe examined data for 10,338 non-hypertensive participants (39.49% men) aged ≥ 18 years from the Rural Chinese Cohort Study who completed a baseline examination during 2007–2008 and follow-up during 2013–2014. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Multiple logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the probability of HTN across four WWI categories. Restricted cubic splines analysis was used to model the dose–response association of WWI and HTN. A total of 2078 participants had HTN during a median follow-up of 6 years. After adjusting for potential confounders, as compared with the lowest WWI category (<9.94 cm/√kg), with WWI 9.94 to 10.42, 10.42 to 10.91 and ≥ 10.91 cm/√kg, the ORs (95% CIs) for HTN were 1.12 (0.93–1.35), 1.40 (1.17–1.69) and 1.50 (1.24–1.82), respectively. Results of the sensitivity analyses were robust. The ORs were generally consistent on subgroup analysis by sex, smoking status, systolic blood pressure and diastolic blood pressure. Multiple logistic regression models with restricted cubic splines showed a non-linear positive association between WWI and HTN (P_nonlinearity < 0.001).ConclusionThe highest WWI category was significantly associated with increased risk of HTN. Our findings may facilitate the development and promotion of obesity prevention strategies aimed at reducing the risk of HTN and provide evidence for healthcare policy in rural China.     

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)

BackgroundFOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.Patients and MethodsPatients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H₀: 55% and H₁= 75%. Data were analyzed in intention to treat.ResultsForty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.ConclusionAlthough the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.     

CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.     

Novel lipopeptides of ESAT-6 induce strong protective immunity against Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically impact vaccine’s efficacy

Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic. We have designed a novel subunit vaccine for Mtb by using simple lipid (palmitic acid) modified derivatives of peptides from ESAT-6 protein corresponding to dominant human T cell epitopes and examined their ability to stimulate protective immunity against Mtb by intranasal and subcutaneous immunization in mice. We also investigated how individual TLR agonists as adjuvants (PolyI:C, MPL and GDQ) contribute to enhancing the induced immune responses and resulting protective efficacy of our vaccine. We observed that single C-terminal palmitoyl-lysine modified lipopeptides derived from ESAT-6 induce significant cellular immune responses on their own upon mucosal and subcutaneous immunizations. Intriguingly, a combination of immunogenic lipopeptides of ESAT-6 antigen exhibited local (pulmonary) and systemic immune responses along with efficient protective efficacy when administered intranasally or subcutaneously. Surprisingly, combination of ESAT-6 derived lipopeptides with a TLR-4 agonist (MPL) enhanced protection, whereas TLR-3 (Poly I:C) and TLR-7/8 agonists (gardiquimod, GDQ) led to reduced protection associated with specific local and systemic immune modulation. Our studies demonstrate the potential of ESAT-6 derived lipopeptides as a promising vaccine candidate against Mtb, and emphasize that selection of adjuvant is critical for the success of vaccines. These findings demonstrate the promise of synthetic lipopeptides as the basis of a subunit vaccine for TB.