Ageing exacerbates damage of systemic and salivary neutrophils from patients presenting Candida-related denture stomatitis

<p>Abstract</p> <p>Background</p> <p>Ageing leads to a decline in the function of the immune system, increasing the body's susceptibility to infections through the impairment of T-cells, macrophages, neutrophils and dendritic cells Denture stomatitis is a primary oral disease affecting elderly denture wearers. The major etiologic factor involved in this pathology is the infection by <it>Candida albicans</it>, an opportunistic pathogen that causes local and disseminated diseases in immunosuppressed humans. Neutrophils play a critical role in the immune response against <it>C. albicans </it>and are continually present in the salivary fluid and in the blood. The aim of this study was to determine ageing-related changes in salivary and blood neutrophils and their potential implications in <it>Candida</it>-related denture stomatitis.</p> <p>Results</p> <p>Our results showed a lower number of neutrophils in the saliva from patients presenting <it>Candida</it>-related denture stomatitis in comparison to their matched controls. Furthermore, fewer neutrophils were isolated from the saliva of aged control individuals in comparison to matched younger subjects. CXCR1, CD62L and CD11b expression were significantly greater on systemic neutrophils from younger control individuals. Elderly individuals showed more apoptotic salivary neutrophils and lower GM-CSF levels than younger ones, regardless of the occurrence of <it>Candida </it>infection. On the other hand, CXCL-8 concentrations were higher in the saliva from elderly individuals. Besides, TNF-α was detected at elevated levels in the saliva from infected elderly subjects. Salivary neutrophils from elderly and young patients presented impaired phagocytic activity against <it>C. albicans</it>. However, just systemic neutrophils from elderly showed decreased phagocytosis when compared to the younger ones, regardless of the occurrence of infection. In addition, neutrophils from aged individuals and young patients presented low fungicidal activity.</p> <p>Conclusion</p> <p>The data suggests that the <it>Candida </it>related-denture stomatitis is associated to neutrophils function deficiency, and ageing drastically appears to alter important characteristics of such cells, facilitating the establishment of this infection.</p

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Impact of early haemodynamic goal-directed therapy in patients undergoing emergency surgery: an open prospective, randomised trial

Haemodynamic goal-directed therapies (GDT) may improve outcome following elective major surgery. So far, few data exist regarding haemodynamic optimization during emergency surgery. In this randomized, controlled trial, 50 surgical patients with hypovolemic or septic conditions were enrolled and we compared two algorithms of GDTs based either on conventional parameters and pressure pulse variation (control group) or on cardiac index, global end-diastolic volume index and stroke volume variation as derived from the PiCCO monitoring system (optimized group). Postoperative outcome was estimated by a composite index including major complications and by the Sequential Organ Failure Assessment (SOFA) Score within the first 3 days after surgery (POD1, POD2 and POD3). Data from 43 patients were analyzed (control group, N = 23; optimized group, N = 20). Similar amounts of fluid were given in the two groups. Intraoperatively, dobutamine was given in 45 % optimized patients but in no control patients. Major complications occurred more frequently in the optimized group [19 (95 %) versus 10 (40 %) in the control group, P < 0.001]. Likewise, SOFA scores were higher in the optimized group on POD1 (10.2 ± 2.5 versus 6.6 ± 2.2 in the control group, P = 0.001), POD2 (8.4 ± 2.6 vs 5.0 ± 2.4 in the control group, P = 0.002) and POD 3 (5.2 ± 3.6 and 2.2 ± 1.3 in the control group, P = 0.01). There was no significant difference in hospital mortality (13 % in the control group and 25 % in the optimized group). Haemodynamic optimization based on volumetric and flow PiCCO-derived parameters was associated with a less favorable postoperative outcome compared with a conventional GDT protocol during emergency surgery

Critical care considerations in the management of the trauma patient following initial resuscitation

<p>Abstract</p> <p>Background</p> <p>Care of the polytrauma patient does not end in the operating room or resuscitation bay. The patient presenting to the intensive care unit following initial resuscitation and damage control surgery may be far from stable with ongoing hemorrhage, resuscitation needs, and injuries still requiring definitive repair. The intensive care physician must understand the respiratory, cardiovascular, metabolic, and immunologic consequences of trauma resuscitation and massive transfusion in order to evaluate and adjust the ongoing resuscitative needs of the patient and address potential complications. In this review, we address ongoing resuscitation in the intensive care unit along with potential complications in the trauma patient after initial resuscitation. Complications such as abdominal compartment syndrome, transfusion related patterns of acute lung injury and metabolic consequences subsequent to post-trauma resuscitation are presented.</p> <p>Methods</p> <p>A non-systematic literature search was conducted using PubMed and the Cochrane Database of Systematic Reviews up to May 2012.</p> <p>Results and conclusion</p> <p>Polytrauma patients with severe shock from hemorrhage and massive tissue injury present major challenges for management and resuscitation in the intensive care setting. Many of the current recommendations for “damage control resuscitation” including the use of fixed ratios in the treatment of trauma induced coagulopathy remain controversial. A lack of large, randomized, controlled trials leaves most recommendations at the level of consensus, expert opinion. Ongoing trials and improvements in monitoring and resuscitation technologies will further influence how we manage these complex and challenging patients.</p

The developmental psychopathology of social anxiety and phobia in adolescents

The highest incidence rates for social anxiety disorder (SAD) occur during the period from late childhood to early adulthood. A number of factors that increase vulnerability for the development of SAD have been proposed in the literature, including genes, temperament, biological factors, cognitive factors, parent factors, life events, peer experiences, performance deficits, general learning mechanisms, and cultural factors. These proposed aetiological factors have been given different weightings in theoretical accounts of the aetiology of SAD. Genes, temperament, cognitive factors, parent factors, life events, and peer experiences are generally emphasised in theoretical accounts, while biological factors, performance deficits, general learning mechanisms, and cultural factors have received less emphasis. The proposed aetiological factors have also been empirically examined to varying extents in the literature. In general, the majority of research into the proposed aetiological factors has been limited by the use of cross-sectional designs and the recruitment of individuals already diagnosed with SAD. Further research is needed to obtain better evidence to evaluate the aetiological role of the proposed factors. Such research will ultimately help to develop efficacious early intervention and prevention strategies for SAD

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

BACKGROUND: The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS: In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS: Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS: Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group