Notes

Benzo(a)pyrene publicity within utero exacerbates Parkinson's Disease (PD)-like α-synucleinopathy inside A53T human alpha-synuclein transgenic rodents.
CRP treatment significantly increased mRNA and protein expression levels of NCX1 in myocytes (P=0.024), as well as intracellular calcium concentration (P=0.01). These results were significantly attenuated by the NF-κB-specific inhibitor PDTC and a specific inhibitor of the reverse NCX1, KB-R7943. CRP significantly upregulated NCX1 expression and increased intracellular calcium concentration in cardiomyocytes via the NF-κB pathway, suggesting that CRP may serve a pro-arrhythmia role via direct influence on the calcium homeostasis of cardiomyocytes.Renal tubular interstitial injury plays a key role in the progression of diabetic nephropathy (DN) and, thus, the study of renal tubular injury in DN is important. The aim of the present study was to elucidate the role of the NLR family CARD domain containing 4 (NLRC4) inflammasome in renal tubular epithelial cell (RTEC) injury in DN. Human kidney biopsy tissues were obtained from patients with DN, and normal kidney tissues were obtained from nephrectomies performed for renal hamartoma. Human RTECs (HK2 cells) were divided into normal glucose (D-glucose 5.6 mmol/l), high glucose (HG; 30 mmol/l), high osmotic (D-glucose 5.6 mmol/l + D-mannitol 24.4 mmol/l), HG + NLRC4 small interfering (si)RNA or HG + siRNA control groups. Then, the expression levels of NLRC4, PTEN-induced kinase 1 (PINK1) and parkin, as well as the levels of mitochondrial reactive oxygen species, which are associated with mitophagy, were observed. The expression levels of NLRC4, PINK1, parkin and phosphorylated parkin in the RTECs of patients with DN were higher compared with those in normal controls. In HK2 cells, HG stimulated the expression of NLRC4, the secretion of IL-1β and IL-18 and cell death. Moreover, knockdown of NLRC4 expression in HK2 cells treated with HG reduced the secretion of the inflammatory cytokines, IL-1β and IL-18. HSP990 The findings of the present study may provide a rationale for the development of treatments for patients with DN by preventing inflammasome activation.Inflammatory bowel diseases (IBDs) are chronic immune disorders that occur in the intestinal tract. Previous studies have revealed that intestinal epithelial cells (IECs) play critical roles in the development of IBDs, and therapies targeting IECs hold great potential for the treatment of IBDs. However, the roles of microRNAs (miRs) in the regulation of IEC properties and whether they can be used as targets for IEC regulation and IBD treatment are largely unknown. The aim of the present study was to investigate the role of the miR-452-5p/Mcl-1 axis in the regulation of the properties of IECs during the pathology of IBD. A dextran sulfate sodium-induced mouse model of ulcerative colitis (UC) and an in vitro lipopolysaccharide-stimulated IEC-6 cell model were investigated. The results revealed that miR-452-5p expression in the IECs of the mice increased significantly upon UC induction, and the knockdown of miR-452-5p alleviated the IBD symptoms. Furthermore, the suppression of miR-452-5p downregulated the expression of the inflammatory cytokines IL-6, IL-8 and TNFα, and upregulated the expression of intestinal barrier-associated molecules, namely occludin, zona occludens 1 and mucin-2 in IECs in vitro and in vivo. Notably, the results indicated that miR-452-5p modulated the responses of IECs by negatively regulating the expression of Mcl-1, as the knockdown of Mcl-1 abrogated the effects of miR-452-5p suppression on IECs. The present study suggested that miR-452-5p regulated the responsiveness of IECs to influence the development of UC in an Mcl-1-dependent manner. These observations provide important information to improve the understanding of IBD pathogenesis and indicate that targeting the miR-452-5p-Mcl-1 signaling axis in IECs holds potential for IBD treatment.Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia defined by simple or complex abnormal movements occurring in REM state, instead of the physiological muscular atonia. RBD may be idiopathic, or secondary as in the case of Parkinson's disease (PD). Several studies have confirmed that idiopathic RBD may precede with several years the onset of the specific motor characteristics of PD. The high prevalence of RBD in PD (19-70%) may be explained by several common pathophysiological pathways, mainly related to the dopaminergic cell loss. RBD is also associated with several comorbidities, including cognitive impairment, hallucinations, dysautonomia, or daytime sleepiness. The gold standard investigation for the diagnosis and assessment of RBD is video polysomnography, but in clinical practice, the use of clinical scales and questionnaires is reasonable for the screening of this complex parasomnia. Management options include ensuring a safe environment for the patient and pharmacological treatment, incuding clonazepam, melatonin or certain antiparkinsonian drugs.Naringin (NRG) has been reported to exert cardioprotective effects against multiple cardiovascular diseases, including lipopolysaccharide-induced and hyperglycemia-induced myocardial injury. However, the role of NRG in myocardial ischemia/reperfusion (I/R) injury remains unclear. In the present study, the PI3K/Akt pathway was investigated to evaluate the possible mechanisms underlying the roles of NRG in myocardial ischemia/reperfusion (I/R) injury. The levels of cardiac enzymes were measured by ELISA to evaluate the optimal dosage of NRG that could protect against myocardial I/R injury. Rats were administered 100 mg/kg of NRG and activities of myocardial enzymes, the level of cardiac apoptosis and inflammation, oxidant response, autophagy indicators and echocardiography were evaluated. The level of corresponding proteins was measured using western blotting. The results indicated that NRG elicited the best cardioprotective effects at a dose of 100 mg/kg by significantly reducing the levels of myocardial enzymes, apoptosis, inflammation, oxidative response and infarct size. Furthermore, NRG alleviated contractile dysfunction by increasing the left ventricular ejection fraction and fractional shortening. In addition, NRG markedly promoted the phosphorylation of Akt, while decreasing the level of autophagy indicator beclin-1 and the microtubule-associated protein 1B-light chain 3 (LC3B) II/ LC3BI ratio. However, PI3K/Akt inhibitor (LY294002) partially reduced the NRG induced phosphorylation of Akt and the reduction in beclin-1, along with the LC3BII/LC3BI ratio. The results of the present study demonstrated that NRG could attenuate myocardial I/R injury.The health systems of many countries are desperate in the face of Covid-19, which has become a pandemic worldwide and caused the death of hundreds of thousands of people. In order to keep Covid-19, which has a very high propagation rate, under control, it is necessary to develop faster, low-cost and highly accurate methods, rather than a costly Polymerase Chain Reaction test that can yield results in a few hours. In this study, a deep learning-based approach that can detect Covid-19 quickly and with high accuracy on X-ray images, which are common in every hospital and can be obtained at low cost, was proposed. Deep features were extracted from X-Ray images in RGB, CIE Lab and RGB CIE color spaces using DenseNet121 and EfficientNet B0 pre-trained deep learning architectures and then obtained features were fed into a two-stage classifier approach. Each of the classifiers in the proposed approach performed binary classification. In the first stage, healthy and infected samples were separated, and in the second stage, infected samples were detected as Covid-19 or pneumonia. In the experiments, Bi-LSTM network and well-known ensemble approaches such as Gradient Boosting, Random Forest and Extreme Gradient Boosting were used as the classifier model and it was seen that the Bi-LSTM network had a superior performance than other classifiers with 92.489% accuracy.Rapid identification of microorganisms in urine is essential for patients with urinary tract infections (UTIs). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been proposed as a method for the direct identification of urinary pathogens. Our purpose was to compare centrifugation-based MALDI-TOF MS and short-term culture combined with MALDI-TOF MS for the direct identification of pathogens in urine specimens. We collected 965 urine specimens from patients with suspected UTIs, 211/965 isolates were identified as positive by conventional urine culture. Compared with the conventional method, the results of centrifugation-based MALDI-TOF MS were consistent in 159/211 cases (75.4%), of which 135/159 (84.9%) had scores ≥ 2.00; 182/211 cases (86.3%) were detected using short-term culture combined with MALDI-TOF MS, of which 153/182 (84.1%) had scores ≥ 2.00. There were no apparent differences among the three methods (p = 0.135). MALDI-TOF MS appears to accelerate the microbial identification speed in urine and saves at least 24 to 48 hours compared with the routine urine culture. Centrifugation-based MALDI-TOF MS is characterized by faster identification speed; however, it is substantially affected by the number of bacterial colonies. In contrast, short-term culture combined with MALDI-TOF MS has a higher detection rate but a relatively slow identification speed. Combining these characteristics, the two methods may be effective and reliable alternatives to traditional urine culture.In this study, we develop a nonlinear ordinary differential equation to study the dynamics of syphilis transmission incorporating controls, namely prevention and treatment of the infected males and females. We obtain syphilis-free equilibrium (SFE) and syphilis-present equilibrium (SPE). We obtain the basic reproduction number, which can be used to control the transmission of the disease, and thus establish the conditions for local and global stability of the syphilis-free equilibrium. The stability results show that the model is locally asymptotically stable if the Routh-Hurwitz criteria are satisfied and globally asymptotically stable. The bifurcation analysis result reveals that the model exhibits backward bifurcation. We adopted Pontryagin's maximum principle to determine the optimality system for the syphilis model, which was solved numerically to show that syphilis transmission can be optimally best control using a combination of condoms usage and treatment in the primary stage of infection in both infected male and female populations.
To determine the proportion of potentially avoidable deaths in children under five in Colombia, by department and municipality of residence, during the period from 2000 through 2018.

A multi-group and longitudinal ecological study was conducted in 33 departments and 1 118 municipalities over a period of 19 years. The deaths were classified as probably unavoidable or avoidable; the latter were then identified as treatable, preventable, or mixed; and a proportion was calculated relative to the total. Finally, clusters were created by municipality and by department and depicted in coropleth maps.

Between 2000 and 2018, Colombia reported 228 942 deaths of children under five, of which 91.4% were avoidable (68.2% treatable, 6.8% preventable, and 16.5% mixed) with no difference by sex. At the national level, the proportion of avoidability declined from 93.5% to 88.5% during this period. César was the department with the largest proportion of avoidable deaths (94.1%), compared with Santander, which had the smallest (89.
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