Clinical prognostic factors for disabling Crohn's disease: A systematic review and meta-analysis

AIM: To identify demographic and clinical factors asso-ciated with disabling Crohn's disease (CD). METHODS: A systematic review and meta-analysisof observational studies, focusing on the factors that can predict the prognosis of different outcomes of CD was undertaken. PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigat-ing the above mentioned factors in adult patients with CD. Studies were eligible for inclusion if they describe prognostic factors in CD, with inclusion and exclusion criteria defined as follows. Studies with adult patients and CD, written in English and studying association between clinical factors and at least one prognosis out-come were included. Meta-analysis of effects was un-dertaken for the disabling disease outcome, using odds ratio (OR) to assess the effect of the different factors in the outcome. The statistical method used was Mantel-Haenszel for fixed effects. The 16-item quality assess-ment tool (QATSDD) was used to assess the quality of the studies (range: 0-42). RESULTS: Of the 913 papers initially selected, sixty studies were reviewed and three were included in the systematic review and meta-analysis. The global QA-TSDD scores of papers were 18, 21 and 22. Of a total of 1961 patients enrolled, 1332 (78%) were classified with disabling disease five years after diagnosis. In two studies, age at diagnosis was a factor associated with disabling disease five years after diagnosis. Individu-als under 40 years old had a higher risk of developing disabling disease. In two studies, patients who were treated with corticosteroids on the first flare developed disabling disease five years after diagnosis. Further, perianal disease was found to be relevant in all of the studies at two and five years after diagnosis. Finally, one study showed localization as a factor associated with disabling disease five years after diagnosis, with L3 being a higher risk factor. This meta-analysis showed a significantly higher risk of developing disabling dis-ease at five years after initial diagnosis among patients younger than 40 years of age (OR=2.47, 95%CI: 1.74-3.51), with initial steroid treatment for first flare (OR=2.42, 95%CI: 1.87-3.11) and with perianal dis-ease (OR = 2.00, 95%CI: 1.41-2.85).CONCLUSION: Age at diagnosis, perianal disease, ini-tial use of steroids and localization seem to be indepen-dent prognostic factors of disabling disease.

Anxiety and pre-symptomatic testing for neurodegenerative disorders

In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD)?and familial amyloidotic polyneuropathy (FAP)?V30MTTR. The study included 686 subjects: 586 (85.4%) were the offspring at risk for FAP, 92 (13.4%) for HD and 8 (1.2%) to MJD. Of these, 352 received the carrier result and 305 the non-carrier result. As indicator of anxiety distress was taken the Self-Rating Anxiety Scale of Zung (SAS), applied in the pre-test and the three post-test moments: three weeks, 6 months and one year after notification of test results. Values decreased significantly along the four evaluation moments, regardless the studied disease or test result. For female population, SAS means cores revealed results of clinical anxiety at pre-test, only decreasing to non clinical scores a year after PST disclosure.

Predictive testing for two neurodegenerative disorders(FAP and HD):A psychological point of view

In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 53 subjects: 40 (75.5%) were the offspring at risk for FAP and 13 (24.5%) for HD. Of these, 38 (73.1%) received the carrier result and 12 (23.1%) the noncarrier result;3 of them did not want to know the result. The indicators taken for emotional distress were the subscales and global indexes of psychopathological Behavior Symptoms Inventory (BSI), applied in the pre-test and post-test, one-year after notification of results. Values decreased significantly one year after the implementation of the PST, regardless of the studied disease or test result;this seems to corroborate previous studies showing that testing does not increase pre-symptomatic levels of emotional disturbance in individuals. However, the subjects studied showed, for all subscales and global indexes of the BSI, significantly higher values than those of control groups.

Neuroinflammation revisited through the microglial lens

Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new therapies.We challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial activation.By dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s progression.This article calls for a significant paradigm shift towards an integrative,multi-omics approach to neuroimmunology.Adopting such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.

Venous thrombosis and prothrombotic factors in inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) may have an increased risk of venous thrombosis (VTE). PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigating the risk of VTE and the prevalence of acquired and genetic VTE risk factors and prothrombotic abnormalities in IBD. Overall, IBD patients have a two- to fourfold increased risk of VTE compared with healthy controls, with an overall incidence rate of 1%-8%. The majority of studies did not show significant differences in the risk of VTE between Crohn’s disease and ulcerative colitis. Several acquired factors are responsible for the increased risk of VTE in IBD: inflammatory activity, hospitalisation, surgery, pregnancy, disease phenotype (e.g., fistulising disease, colonic involvement and extensive involvement) and drug therapy (mainly steroids). There is also convincing evidence from basic science and from clinical and epidemiological studies that IBD is associated with several prothrombotic abnormalities, including initiation of the coagulation system, downregulation of natural anticoagulant mechanisms, impairment of fibrinolysis, increased platelet count and reactivity and dysfunction of the endothelium. Classical genetic alterations are not generally found more often in IBD patients than in non-IBD patients, suggesting that genetics does not explain the greater risk of VTE in these patients. IBD VTE may have clinical specificities, namely an earlier first episode of VTE in life, high recurrence rate, decreased efficacy of some drugs in preventing further episodes and poor prognosis. Clinicians should be aware of these risks, and adequate prophylactic actions should be taken in patients who have disease activity, are hospitalised, are submitted to surgery or are undergoing treatment.

Effects of natural mineral-rich water consumption on the expression of sirtuin 1 and angiogenic factors in the erectile tissue of rats with fructose-induced metabolic syndrome

Consuming a high-fructose diet induces metabolic syndrome （MS）-Iike features, including endothelial dysfunction. Erectile dysfunction is an early manifestation of endothelial dysfunction and systemic vascular disease. Because mineral deficiency intensifies the deleterious effects of fructose consumption and mineral ingestion is protective against MS, we aimed to characterize the effects of 8weeks of natural mineral-rich water consumption on the structural organization and expression of vascular growth factors and receptors on the corpus cavernosum （CC） in 10% fructose-fed Sprague-Dawley rats （FRUCT）. Differences were not observed in the organization of the CC either on the expression of vascular endothelial growth factor （VEGF） or the components of the angiopoietins/Tie2 system. However, opposing expression patterns were observed for VEGF receptors （an increase and a decrease for VEGFR1 and VEGFR2, respectively） in FRUCT animals, with these patterns being strengthened by mineral-rich water ingestion. Mineral-rich water ingestion （FRUCTMIN） increased the proportion of smooth muscle cells compared with FRUCT rats and induced an upregulatory tendency of sirtuin I expression compared with the control and FRUCT groups. Western blot results were consistent with the dual immunofluorescence evaluation. Plasma oxidized low-density lipoprotein and plasma testosterone levels were similar among the experimental groups, although a tendency for an increase in the former was observed in the FRUCTMIN group. The mineral-rich water-treated rats presented changes similar to those observed in rats treated with MS-protective polyphenol-rich beverages or subjected to energy restriction, which led us to hypothesize that the effects of mineral-rich water consumption may be more vast than those directly observed in this study.

Polymorphism in cardiovascular diseases(CVD)susceptibility loci in the azores islands(Portugal)

Background: Atherosclerosis and thrombosis are the major manifestations underlying cardiovascular diseases (CVD), which are the leading cause of mortality and morbidity worldwide. Both result from an interaction between genetic and environmental risk factors. The goal of our study was to evaluate several polymorphisms identified as predisposing factors to atherosclerosis and thrombosis. Material and Methods: A series of 155 healthy unrelated individuals of Azorean origin were analyzed using the CVD StripAssay (ViennaLab Diagnostics, Austria) for the most established polymorphisms involved in blood coagulation (F2, F5, F13A1, FGB), fibrinolitic system (SERPINE1), platelet adhesion (ITGB3), homocysteine metabolism (MTHFR), reninangio-tensin system (ACE) and lipid metabolism (APOE). Results: No significant differences were observed in allelic frequencies when comparing our data to mainland Portugal. Group stratification according to the number of “increased” risk alleles, demonstrated that 116/155 (75%) individuals belong to the moderate risk group (5 - 10 risk alleles). Conclusions: Although acknowledging the fact that the allelic states at the analysed loci lack predictive value, the fact that a high frequency of individuals presents at least 5 risk alleles (124/155;80%) is important for the establishment of the appropriate preventive measures in the Azorean population.

Comparison of Classical Models for Evaluating the Heat Requirements of Olive(Olea europeae L.) in Portugal

The aim of the present study was to compare the accuracy and reproducibility of six statistical models for the calculation of olive （Olea europeae L.） heat requirements to trigger the onset of flowering in three Portuguese regions： Reguengos de Monsaraz, Valenga do Douro, and Braga. Other alms were to ascertain the date on which the heat-accumulation period started and the threshold temperatures above which the development of reproductive structures starts in olives. The starting and peak dates for the regional O. europeae flowering season were estimated by monitoring airborne pollen from 1998 to 2004 using ＂Cour＂- type samplers. The threshold temperature values calculated for the three regions were very similar （9.0 ℃ for Valenca do Douro, 9.2 ℃ for Reguengos de Monsaraz, and 9.7 ℃ for Braga）. The accumulated daily mean temperature model had less interannual and inter-regional variation, showing best predictive results for 2004, with absolute differences between the observed and predicted dates of 4 d in Reguengos de Monsaraz and 2 d In Valenca do Douro and Braga for the onset of flowering date and of 2 d In Reguengos de Monsaraz, 7 d in Valenca do Douro, and 4 d in Braga for peak flowering dates. This model was the most accurate, reproducible, and operational to calculate heat requirements for olives to flower, with an average mean temperature accumulation of 1 446 ℃ In Reguengos, 1 642 ℃ in Valenga do Douro, and 1 703℃ In Braga to reach the onset of flowering. The best initial date for this accumulation was 1 January.