Risk and also bidirectional valence signaling inside the nucleus accumbens key

Here, we highlight how host-pathogen interactions, immune protection, and effectiveness of currently available vaccines shift with increasing age, and how future pneumococcal vaccine strategies could be tailored for the elderly. © 2020 S. Karger AG, Basel.INTRODUCTION Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for 10% of the global cancer burden. Rectal cancer accounts for around 30% of CRC cases, and patients with resectable rectal cancer are often given preoperative radiotherapy (PRT) to reduce the rate of local recurrence. The human plasma proteome is an exceptionally complex proteome and ideal to study due to its ability to reflect the presence of diseases such as cancer and the ease of obtaining blood samples. Previous proteomic studies involving rectal cancer patients have mostly focused on the identification of proteins involved in resistance to radiotherapy. OBJECTIVE The aim of this study was to investigate the overall effects of PRT on plasma protein expression in rectal cancer patients, as there is a lack of such studies. METHODS Here, we have used mass spectrometry and subsequent statistical analyses to analyze the plasma samples of 30 rectal cancer patients according to PRT status (positive or negative) and tumor stage (II or III). RESULTS AND CONCLUSIONS We discovered 42 proteins whose levels differed significantly between stage II and III rectal cancer patients who did or did not receive PRT. This study shows that PRT, although localized to the pelvis, leads to measurable, tumor stage-specific changes in plasma protein expression. Future studies of plasma proteins should, when relevant, take this into account and be aware of the widespread effects that PRT has on the plasma proteome. © 2020 S. Karger AG, Basel.OBJECTIVE Brain microvascular endothelial cells are integral components of the blood-brain barrier and play a role in protecting the brain from invading microbes. CXC motif chemokine ligand 1 (CXCL1) induces the chemotaxis of neutrophils, and neutrophils are important in host defense in the brain. However, dysregulated neutrophil infiltration leads to brain diseases. Toll-like receptor 3 (TLR3) is a pattern recognition receptor that recognizes viral double-stranded RNA (dsRNA). The aim of this study was to investigate the effect of an TLR3 agonist on the expression of CXCL1 in brain vascular endothelial cells. METHODS hCMEC/D3 human cerebral microvascular endothelial cells were cultured and treated with polyinosinic-polycytidylic acid (poly IC), a potent synthetic dsRNA agonist for TLR3. The production of CXCL1 mRNA and protein was assessed by real-time RT-PCR and ELISA. The expression of CXCL1 was compared with that of CXCL8. The effect of pretreatment of cells with a NF-κB inhibitor (SN50), a p38 mitogen-acse against viral infection and various neurological diseases associated with neutrophil accumulation. © 2020 S. Karger AG, Basel.INTRODUCTION/OBJECTIVE Irritable bowel syndrome (IBS) is a bowel disorder characterized by pain accompanying defecation or altered bowel habits, divided into diarrhea-predominant, constipation-predominant, and alternating subtypes, whose pathogenesis is considered to include disordered bowel motility. The hormone ghrelin is a growth hormone secretagogue which furthermore affects gastrointestinal motility. We study the association between its genetic polymorphisms and the risk for IBS. METHODS IBS patients meeting the Rome III criteria and controls similar in age and gender were recruited. Whole blood samples were used for genotyping via polymerase chain reaction and restriction fragment length polymorphism for the polymorphisms rs34911341, rs696217, and rs2075356. RESULTS Participants included 142 patients and 209 controls. The rs696217 GG genotype frequency was higher in patients (78.87%) compared to controls (55.5%). The rs696217 GT genotype was significantly less frequent among patients than in controls (OR 0.31, 95% CI 0.19-0.52), as was the T allele (OR 0.43, 95% CI 0.28-0.66). No significant differences in genotype distribution were found for the rs34911341 and rs2075356 polymorphisms between patients and controls. The genotype frequencies did not significantly differ between IBS subtype groups for any of the polymorphisms studied. CONCLUSIONS The GG and GT genotypes of the rs696217 polymorphism, as well as the G-allele, demonstrate significant association with IBS susceptibility, while the T allele appears to bear a protective effect. Ghrelin's polymorphisms are plausibly involved in IBS pathogenesis, but do not correlate with any distinct IBS subtype. © 2020 S. Karger AG, Basel.BACKGROUND Nasopharyngeal carcinoma (NPC) originates in the nasopharyngeal epithelium. The most common treatments for NPC rT1-4 are radiotherapy and surgery. The pathogenesis of radiation-induced cognitive impairment is complex and includes oxidative stress, mitochondrial dysfunction, neuro-inflammation, and even apoptosis and cell death. Principally, toll-like receptors (TLRs) could regulate the inflammatory/anti-inflammatory balance in patients with radiation-induced brain injury. Vinpocetine has an anti-inflammatory effect as shown in both animal and in vitro studies. Also, dexamethasone is a widely used anti-inflammatory drug. Thus, it is important to test whether addition of vinpocetine could improve the anti-inflammatory properties of dexamethasone for the treatment of NPC patients with radiation-induced brain injuries. METHODS A total of 60 NPC patients with radiation-related brain injury were recruited for this study. All subjects were randomly and blindly assigned to the following groups the dexamethpy, which leads to alleviated cognitive impairment in NPC patients with radiation injury. © 2020 S. Karger AG, Basel.T lymphocytes follow three main stages of differentiation during their lifetime history - memory generation, memory homeostasis, and immunosenescence. Current definitions of T cell immunosenescence now include distinct aspects of both T cell senescence and exhaustion. Multiple studies have indicated a loss of vaccine efficacy in old age, and because this period coincides with the onset of T cell immunosenescence, the latter has often been implicated in the loss of vaccine responsiveness. This chapter examines changes in T cell homeostasis with age, and proposes mechanisms of how these changes, together with senescence and exhaustion, could affect the T cell contribution to the vaccine response. © 2020 S. Karger AG, Basel.INTRODUCTION Exposure to traumatic stressful events in childhood is an important risk factor for the development of posttraumatic symptomatology. From a mentalization-based developmental perspective, childhood adversity can affect attachment in children and may result in insecure attachment and impaired mentalizing abilities, which increase the lifetime risk for psychopathology. The present cross-sectional study examined the potential mediating role of attachment insecurity and impaired mentalizing on the relationship between childhood trauma and posttraumatic symptomatology. METHOD Adults who had experienced childhood neglect and abuse (n = 295, 184 patients with personality disorder and 111 community controls) completed self-report measures of posttraumatic stress disorder (PTSD) symptoms, dissociative experiences, adult attachment insecurity, and mentalizing. RESULTS Structural equation modelling results revealed that attachment insecurity together with lower mentalizing mediated the link between childhood trauma and PTSD symptoms, and lower mentalizing mediated the link between childhood trauma and dissociative experiences. CONCLUSION The findings show that attachment insecurity and lower mentalizing play significant mediating roles in the reporting of posttraumatic symptomatology among survivors of childhood abuse and neglect, with treatment implications for mentalization-based therapy as beneficial for individuals with a history of childhood trauma. © 2020 The Author(s) Published by S. Karger AG, Basel.BACKGROUND/AIMS This study evaluated the relationships of clinical consequences of untreated dental caries, individual characteristics, and environmental factors on self-reported oral health measures in adolescents. METHODS A follow-up prevalence study was conducted involving 406 twelve-year-old adolescents selected from public schools in the eastern area of the city of Manaus, Brazil. Baseline data included clinical consequences of untreated caries (PUFA/pufa index), DMFT, sociodemographic characteristics (sex, parental schooling, and family income), psychosocial factors (sense of coherence [SOC-13 scale], oral health beliefs and self-esteem [Rosenberg Self-Esteem Scale]), and social support (SSA questionnaire). Oral health-related quality of life (OHRQoL [CPQ11-14]) and self-rated oral health were assessed at the 6-month follow-up. Structural equation modelling was used to explore the relationships between variables according to the Wilson and Cleary model. RESULTS The prevalence of PUFA/pufa was 17.8% and ys. © 2020 S. Karger AG, Basel.BACKGROUND Experimental studies indicate that Klotho deficiency is a pathogenic factor for CKD-related complications, including cardiovascular disease (CVD). However, the association between serum Klotho and clinical outcomes in nondiabetic CKD patients needs to be further clarified. We aimed to determine whether serum Klotho levels are associated with CVD events and mortality in predialysis CKD patients without diabetes. METHODS A total of 336 CKD stage 2-5 predialysis patients without diabetes were recruited and followed from the end of 2014 to January 2019 for CVD events and overall mortality. Serum Klotho was detected by ELISA and divided into quartiles (lowest, middle, second highest, and highest quartiles) according to their serum Klotho category. RESULTS After a median follow-up of 3.52 years (IQR 3.34-3.76), Kaplan-Meier analysis showed that, compared to participants with a Klotho level in the highest quartile (the reference category), those in the lowest Klotho quartile were associated with a higher all-cause mortality risk (HR = 7.05; 95% CI 1.59-31.25) and a higher CVD event risk (HR = 3.02; 95% CI 1.45-6.30). selleck In addition, the middle Klotho quartile was also associated with CVD event risk (HR = 2.56; 95% CI 1.21-5.41). Moreover, in the multivariate-adjusted model, the lowest Klotho quartile remained significantly associated with all-cause mortality (HR = 5.17; 95% CI 1.07-24.96), and the middle Klotho quartile maintained a significant association with CVD event risk (HR = 2.32; 95% CI 1.03-5.21). CONCLUSION These results suggest that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients. © 2020 S. Karger AG, Basel.INTRODUCTION Although both glucose and fructose are hexoses, their catabolism is quite different the catabolism of fructose is initiated by ketohexokinase and is not regulated by negative feedback, which results in oxidative stress. OBJECTIVE We hypothesized that fructose impairs endothelium-dependent relaxation via oxidative stress in rat aortic rings. METHODS Sprague-Dawley rats were offered 20% fructose solution or tap water for 2 weeks, after which vascular reactivity was measured in isolated aortic rings. In a separate experiment, vascular reactivity was measured after acute exposure to ∼10 mM fructose in isolated aortic rings from untreated rats. RESULTS Although high-fructose intake statistically significantly increased blood pressure and body weight, it did not affect contraction and relaxation in aortic rings. The substitution of fructose for glucose in Krebs solution inhibited vascular relaxation in aortic rings, which was abolished by pretreatment with antioxidants. Decreasing the glucose concentration in Krebs solution inhibited vascular relaxation, whereas decreasing the fructose concentration in Krebs solution improved vascular relaxation in the aortic rings.