Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest.

The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC = 1·33, 1·4 and 5·2 µg ml-1 , respectively) and Cryptococcus gattii strains (MIC = 5·3, 2·8 and 9·2 µg ml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.

A laboratory evaluation of cell viability, radiopacity and tooth discoloration induced by regenerative endodontic materials.

AIM: To analyse the cytotoxicity, colour change and radiopacity of MTA Flow (MTA), UltraCal XS (UC) and Bio-C Temp (BT). METHODOLOGY: Human dental pulp cells (hDPCs) stimulated with lipopolysaccharide (LPS) were placed in contact with several dilutions of culture media previously exposed to the experimental materials and tested for cell viability using MTT. Bovine teeth were prepared to simulate an open apex and to mimic extensive crown fracture. The roots were filled with a mixture of agar and blood, and the materials placed over this mixture. The control group consisted of teeth filled only with agar and blood. Colour assessment analyses were performed before and immediately after material insertion and repeated at 30, 45 and 60 days using a spectrophotometer. The total colour change (ΔEab , ΔE00 and whiteness index (WI)) was calculated based on the CIELAB colour space. Digital radiographs were acquired for radiopacity analysis. Cell viability was analysed by one-way anova, whilst differences in colour parameters (ΔEab , ΔE00 and WI) were assessed by two-way repeated measures anova (α = 0.05). Tukey's test was used to compare the experimental groups, and Dunnett's test was used to compare the experimental groups with the control group. RESULTS: MTA, UC and BT had similar cell viability to that of the control group (DMEM) (P > 0.05), except for the BT group at the 1 : 1 and 1 : 2 dilutions, which had significantly lower viability (P < 0.001). All materials were associated with discoloration values greater than what is considered to be the acceptable threshold, and BT resulted in less or similar tooth colour change than MTA and UC, respectively. Decreasing radiopacity over time was observed only in the MTA group (P = 0.007). Lower values of radiopacity were found in the BT group compared with the UC and MTA groups (P < 0.001). CONCLUSIONS: The new bioceramic material (BT) had acceptable cell viability, similar to that of MTA and UC at the highest dilutions, and BT resulted in less tooth colour change than MTA and UC. Despite its lower radiopacity, BT was identified radiographically.

Curcumin enhances the activity of fluconazole against Cryptococcus gattii-induced cryptococcosis infection in mice.

AIM: The aim of this study was to investigate the in vitro and in vivo activities of pure curcumin, as well as its combination with fluconazole, against Cryptococcus gattii. METHODS AND RESULTS: The minimal inhibitory concentrations (MIC) of curcumin and its interactions with fluconazole against C. gattii were assessed in vitro using standard methods. This same combination was used to treat C. gattii-induced cryptococcosis in mice. The behavioural and functional assessment of the mice during treatment was also performed. The average MIC for curcumin was 19·8 µg ml(-1) . Its combination with fluconazole resulted in FICΣ (fractional inhibitory concentration index) values between 0·79 and 2·29. Curcumin (alone or combined with fluconazole) significantly reduced pulmonary damage and fungal burden in the brain. No colonies were found in the brain following combination treatment, which was also confirmed by the improved behaviour of mice. CONCLUSIONS: The combination therapy with curcumin and fluconazole was the most effective among the treatments tested, as in addition to reducing the fungal burden and damage on lung tissues, it was able to eliminate the fungal burden in the brain, enhancing the survival of mice. SIGNIFICANCE AND IMPACT OF THE STUDY: This study points to the possibility of using curcumin in combination with fluconazole as a clinical treatment of cryptococcosis.

Forensic evaluation of medical liability cases in general surgery.

Although medical liability (disciplinary, civil and criminal) is increasingly becoming an issue, few studies exist, particularly from the perspective of forensic science, which demonstrate the extent to which medical malpractice occurs, or when it does, the reasons for it. Our aims were to evaluate the current situation concerning medical liability in general surgery (GS) in Portugal, the reasons for claims, and the forensic evaluations and conclusions, as well as the association between these issues and the judicial outcomes. We analysed the Medico-Legal Council (CML) reports of the National Institute of Legal Medicine and Forensic Sciences of Portugal related to GS during 2001-2010. The judicial outcomes of each case were requested from the Public Prosecutor Office (PPO) and the court. Alleged cases of medical liability in GS represented 11.2% of the total cases analysed by the CML. We estimated that in Portugal, 4:100,000 surgeries are subject to litigation. The majority of complaints were due to the patient's death (75.4%), with laparoscopic cholecystectomy surgeries representing 55.2% of cases. In 76.1% of the cases, the CML believed that there was no violation of legesartis and in 55.2% of cases, no causal nexus was found between the medical practice and the alleged harm. The PPO prosecuted physicians in 6.4% of the cases and resulted in one conviction. Finally, the importance of the CML reports as a relevant technical-scientific tool for judicial decision was evident because these reports significantly (p < 0.05) influenced the prosecutor's decision, whether to prosecute or not.

Hydroxyaldimines as potent in vitro anticryptococcal agents.

UNLABELLED: Cryptococcosis, a fungal infection that affects both immunocompromised and immunocompetent individuals, contributes to increasing indices of mortality and morbidity. The development of resistance by Cryptococcus spp., the limited number of commercial antifungal drugs and the various side effects of these drugs cause the treatment of cryptococcosis to be a challenge. The in vitro anticryptococcal activity of nine hydroxyaldimines was evaluated against 24 strains of Cryptococcus spp. Antifungal susceptibility was evaluated using a broth microdilution assay following the Clinical and Laboratory Standards Institute guidelines, using fluconazole as a positive control. Parameters such as the minimum inhibitory concentration and the minimum fungicidal concentration (MIC and MFC, respectively) were also determined. Antiproliferative activity on the normal cell line VERO was assessed 48 h post-compound exposure to determine the selectivity index (SI) of the hydroxyaldimines and fluconazole. All hydroxyaldimines were active against Cryptococcus spp. strains. Compounds 3A9 and 3B7 were the most potent against the Cryptococcus gattii and Cryptococcus neoformans strains. Selectivity indices also revealed that 3B10, 3C3, 3D3 and 3D9 are good candidates for in vivo studies. The in vitro anticryptococcal activity of hydroxyaldimines against various strains of C. gattii and C. neoformans indicates the potential of this class of molecules as lead compound for the development of selective and efficient anticryptococcal agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The effectiveness of hydroxyaldimines for inhibition of Cryptococcus spp. growth and their low toxicity against healthy monkey kidney epithelial cells makes them promising lead compounds for the design of new anticryptococcal agents.

PURA syndrome in a child with severe developmental delay: a challenging diagnosis. / Síndrome PURA en una niña con retraso grave del desarrollo: un diagnóstico desafiante.

INTRODUCTION: PURA syndrome is a rare autosomal dominant condition caused by de novo pathogenic variants in PURA gene and characterized by a multisystemic phenotype that includes global neurodevelopmental delay, early hypotonia, absence of speech, feeding difficulties, hypersomnolence, epilepsy and movement disorders. CASE REPORT: We report a 9-year-old girl with hypotonia and feeding difficulties with failure to thrive since the neonatal period. At the age of 3 years motor and intellectual delay were evident, she had a wide-based gait, no speech and an exaggerated acoustic startle response. She developed hand-mouthing stereotypies and epilepsy at 6 years old. The 24 hours continuous electroencephalogram monitoring revealed global slow activity and frequent epileptiform activity in left temporal and centrotemporal areas. The brain MRI revealed delayed myelination. At 6 years old the clinical exome sequencing identified a heterozygous pathogenic variant in the PURA gene, c.153delA p.(Leu54CysfsTer24). CONCLUSION: PURA syndrome has clinical features similar to other neurological disorders but the association with some clinical features, not as common in other neurological entities, like never being able to speak but being able to follow simple orders and exaggerated acoustic startle response, should raise the suspicion of PURA syndrome and genetic analysis must be performed to confirm the diagnosis and provide early multidisciplinary intervention.

TITLE: Síndrome PURA en una niña con retraso grave del desarrollo: un diagnóstico desafiante.Introducción. El síndrome PURA es una condición autosómica dominante poco común causada por variantes patogénicas de novo en el gen PURA y que se caracteriza por un fenotipo multisistémico que incluye retraso del neurodesarrollo global, hipotonía temprana, ausencia de habla, dificultades para alimentarse, hipersomnolencia, epilepsia y trastornos del movimiento. Caso clínico. Presentamos una niña de 9 años con hipotonía y dificultades para alimentarse con retraso del crecimiento desde el período neonatal. A la edad de 3 años era evidente el retraso motor e intelectual, tenía una marcha de base amplia, no hablaba y una respuesta de sobresalto acústico exagerada. Desarrolló estereotipias de mano-boca y epilepsia a los 6 años. La monitorización electroencefalográfica continua de 24 horas reveló una actividad lenta global y una actividad epileptiforme frecuente en las áreas temporal izquierda y centrotemporal. La resonancia magnética del cerebro reveló un retraso en la mielinización. A los 6 años, la secuenciación clínica del exoma identificó una variante patógena heterocigótica en el gen PURA, c.153delA p. (Leu54CysfsTer24). Conclusión. El síndrome PURA tiene características clínicas similares a otros trastornos neurológicos, pero la asociación con algunas características clínicas, no tan comunes en otras entidades neurológicas, como no poder hablar, pero poder seguir órdenes simples, y una respuesta de sobresalto acústico exagerado, deben ser factores de sospecha de síndrome PURA y servir para realizar un análisis genético para confirmar el diagnóstico y proporcionar una intervención multidisciplinar precoz.

Antifungal activity of tri- and tetra-thioureido amino derivatives against different Candida species.

The in vitro antifungal activity of six thioureido substituted amines (P1-P6) was evaluated against Candida species, including Candida albicans, C. glabrata, C. krusei and C. parapsilosis. These tri- and tetra-thioureido amino derivatives with different methylation levels were synthesised through easy synthetic routes to evaluate their antifungal properties against Candida species. Among all studied derivatives, the tri-(2-thioureido-ethyl)-amine (P1) was the most active compound inhibiting C. albicans and C. glabrata at a concentration of 0.49 µg ml(-1); P3, the N,N',N'',N'''-hexamethyl-derivative, also showed inhibitory activity against C. albicans and C. glabrata, but in higher concentrations (250 µg ml(-1) ). The N,N',N'',N'''-tetramethylated amine (P5) only inhibited the growth of C. glabrata, but its corresponding N,N',N'',N'''-octamethyl derivative (P6) was also active against C. glabrata (125 µg ml(-1)) and it was the only compound active against C. parapsilosis. P2 and P4 showed no significant antifungal activity. The structure-activity relationship of the thioureido-substituted derivatives indicates that the molecular branching and the alkylation levels can influence the antifungal activity. This study demonstrated that thioureido derivatives exhibited significant antifungal activity against Candida species and that they can be considered as a very promising bioactive lead compound to develop novel antifungal agents.

Rescue and vegetative propagation of Eremanthus erythropappus (DC.) MacLeish in natural stand.

The native stands of 'candeia' (Eremanthus erythropappus) have been explored through management plans due to the economic potential of essential oil. The rescue of adult trees, as well as the application of silvicultural techniques that favor the restoration of the stand, can contribute to the genetic conservation of this species. This study's objective was to assess the efficiency of propagation techniques for the rescue of 26 matrices of 'candeia' in a natural managed stand and discussion about the rhizogenesis. In August 2017, trees were induced to regrowth by coppice, followed by exposure and scarification of roots. The emergence of shoots and morphology were evaluated according to the origin (i.e., stump or root). After that period, 19 matrices had their sprouts collected for the preparation of apical cuttings. Indole-3-butyric acid (IBA) was applied at the base of the cuttings. Cutting survival at greenhouse exit (GE), rooting at shade house exit (SHE), morphology and root anatomy were evaluated. In 189 days, the scarification of roots promoted 76.92% of budding. The percentage of sprouted matrices, number of shoots per matrice, length, diameter, and shoot length/diameter ratio increased over time. Only 12.2% of the cuttings survived in GE, and of these, 7.9% rooted in SHE. The cutting resulted in the formation of a clonal mini-garden of 'candeia', with seven of the 19 matrices submitted to propagation. The anatomical analyses showed that bud formation occurs from cell redifferentiation in the phloem parenchyma, and presence of crystals on the walls of the vessel elements of the secondary xylem. The shoots induction from scarification of roots could be used as a silvicultural practice for the reestablishment of the native fragments handle.

Impact of the internet on veterinary surgery.

The advent of the internet, and the technological innovations associated with it, have driven significant advances in surgical teaching and learning. The ease of access to information and the variety of online resources allow rapid sharing of surgical knowledge, promoting new teaching and learning patterns. Educational content from online platforms adds theoretical and practical knowledge to accelerate the learning curve and continuing education of surgeons. This study reviews how the advent of the Internet has influenced the teaching and dissemination of knowledge in veterinary surgery.

Establishing a minimum postmortem interval of human remains in an advanced state of skeletonization using the growth rate of bryophytes and plant roots.

This paper illustrates the usefulness and efficiency of botanical evidence in establishing a minimum postmortem interval (PMI). The case under analysis refers to the remains of an adult male in an advanced state of skeletonization recovered from a wooded area in northern Portugal. The skeleton showed several taphonomical changes, which included the presence of green algae, bryophytes, and growing shrub roots in, around, and through the remains. By determining the age of both the bryophytes and shrub roots, it was concluded that the minimum amount of time elapsed since death was 3 years, to which several months or a few years have to be added to account for the complete decomposition of the remains. The disappearance of the presumptive individual had occurred 6 years before and is fully consistent with the estimate of the PMI. This report illustrates a novel use of bryophytes in a forensic setting.

Isolation of clinically relevant fungal species from solid waste and environment of dental health services.

AIMS: This study was undertaken to detect, identify and determine antifungal susceptibility of yeast strains isolated from dental solid waste and to evaluate airborne fungi in the Brazilian dental health care environment and in the waste storage room. METHODS AND RESULTS: A group of 17 yeast strains were identified by macroscopic and microscopic characteristics, API 20C Aux system and Multiplex PCR. All 104 airborne fungal colonies were identified by macroscopic and microscopic morphology. The CLSI broth microdilution method was utilized as the susceptibility test. Candida parapsilosis was the prevailing yeast species recovered from waste, followed by Rhodotorula glutinis. Three strains of Candida guilliermondii presented minimal inhibitory concentration values considered to be susceptible dose dependent (2 µg ml(-1)) to voriconazole. Of all airborne fungal species, 69% were recovered from the waste storage room and 31% were recovered from the clinical/surgical environment. Most of them were identified as Cladosporium spp. CONCLUSIONS: These findings reinforce the potential risk of waste handling and point out the need for safe management to minimize the spread of these agents to the environment. Filamentous fungi isolation in almost all sampled environments indicates that a periodic monitoring of airborne microbiota in the dental health care service environment is required. SIGNIFICANCE AND IMPACT OF THE STUDY: The survival of yeast strains for 48 h suggests that dental waste should be carefully controlled and monitored.

Patient-based dengue virus surveillance in Aedes aegypti from Recife, Brazil.

BACKGROUND & OBJECTIVES: Dengue is currently one of the most important arthropod-borne diseases and may be caused by four different dengue virus serotypes (DENV-1 to DENV-4), transmitted mainly by Aedes aegypti (Diptera: Culicidae) mosquitoes. With the lack of a dengue vaccine, vector control strategies constitute a crucial mode to prevent or reduce disease transmission. In this context, DENV detection in natural Ae. aegypti populations may serve as a potential additional tool for early prediction systems of dengue outbreaks, leading to an intensification of vector control measures, aimed at reducing disease transmission. In Brazil, this type of surveillance has been performed sporadically by a few groups and has not been incorporated as a routine activity in control programs. This study aimed at detecting DENV in natural Ae. aegypti from Recife, Pernambuco, to check the circulating serotypes and the occurrence of transovarial transmission in local mosquito populations. METHODS: From January 2005 to June 2006, mosquitoes (adults and eggs) were collected in houses where people with clinical suspicion of dengue infection lived at. RNA was extracted from pooled mosquitoes and RT-PCR was performed in these samples for detection of the four DENV serotypes. RESULTS & CONCLUSION: Out of 83 pools of adult mosquitoes collected in the field, nine were positive for DENV: five for DENV-1, two for DENV-2 and two for DENV-3. From 139 pools of adult mosquitoes reared from collected eggs, there were 17 positive pools: three for DENV-1, 10 for DENV-2, and four for DENV-3. These results are discussed in the paper in regard to the local dengue epidemiological data. The conclusions clearly point to the informative power and sensitivity of DENV entomological surveillance and to the importance of including mosquito immature forms in this strategy.

Post-treatment of UASB reactor effluent in waste stabilization ponds and in horizontal flow constructed wetlands: a comparative study in pilot scale in Southeast Brazil.

The results of a 20-month period study in Brazil were analyzed to compare horizontal-flow constructed wetlands (CW) and waste stabilization pond (WSP) systems in terms of land area requirements and performance to produce effluent qualities for surface water discharge, and for wastewater use in agriculture and/or aquaculture. Nitrogen, E. coli and helminth eggs were more effectively removed in WSP than in CW. It is indicated that CW and WSP require similar land areas to achieve a bacteriological effluent quality suitable for unrestricted irrigation (10(3) E. coli per 100 mL), but CW would require 2.6 times more land area than ponds to achieve quite relaxed ammonia effluent discharge standards (20 mg NH(3) L(-1)), and, by far, more land than WSP to produce an effluent complying with the WHO helminth guideline for agricultural use (< or =1 egg per litre).

Collection of biological samples in forensic toxicology.

Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission.

Curcumin as a promising antifungal of clinical interest.

OBJECTIVES: The antifungal activity of curcumin was evaluated against 23 fungi strains and its in vitro inhibitory effect on the adhesion of Candida species to human buccal epithelial cells (BEC) was also investigated. METHODS: The antifungal susceptibility was evaluated by broth microdilution assay following the CLSI (formerly the NCCLS) guidelines. The inhibitory effect of curcumin on the cell adhesion was performed with Candida species and BEC. RESULTS: Paracoccidioides brasiliensis isolates were the most susceptible to curcumin while the growth of Aspergillus isolates was not affected. Curcumin was much more efficient than fluconazole in inhibiting the adhesion of Candida species to BEC, particularly those strains isolated from the buccal mucosa of AIDS patients. CONCLUSIONS: The lack of antifungal compounds with reduced side effects highlights the importance of studying natural products for this purpose. Curcumin was a more potent antifungal than fluconazole against P. brasiliensis, the causal agent of the neglected disease paracoccidioidomycosis. Curcumin dramatically inhibited the adhesion of Candida species isolated from AIDS patients to BEC, demonstrating that curcumin is a promising lead compound that warrants further investigation into its therapeutical use in immunocompromised patients.

In vitro studies of anticandidal activity of goniothalamin enantiomers.

AIMS: The antifungal activity of (R)-goniothalamin (1) and (S)-goniothalamin (ent-1) was evaluated against six Candida species. The in vitro effect of these compounds on yeast adhesion to human buccal epithelial cells (BEC) and Candida albicans and C. dubliniensis biofilms progression were also investigated. METHODS AND RESULTS: Yeast susceptibility was evaluated by broth microdilution assay and showed that ent-1 exhibited higher potency against all fungal clinical isolated when compared to compound 1. Compounds 1 and ent-1 were as potent as fluconazole in inhibiting the adhesion of C. albicans and C. dubliniensis to BEC. XTT-reducing assay and scanning electron microscopy revealed that 1 and ent-1 were twice as potent as fluconazole in the inhibition of yeast biofilms progression. CONCLUSIONS: Our findings indicate that compounds 1 and ent-1 are potent anticandidal agents. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights goniothalamin enantiomers as promising lead compounds for the design of new antifungal with inhibitory activity on yeast adhesion and biofilm progression.

Silencing an Anopheles gambiae catalase and sulfhydryl oxidase increases mosquito mortality after a blood meal.

Catalase is a potent antioxidant, likely involved in post-blood meal homeostasis in mosquitoes. This enzyme breaks down H2O2, preventing the formation of the hydroxyl radical (HO*). Quiescins are newly classified sulfhydryl oxidases that bear a thioredoxin motif at the N-terminal and an ERV1-like portion at the C-terminal. These proteins have a major role in generating disulfides in intra- or extracellular environments, and thus participate in redox reactions. In the search for molecules to serve as targets for novel anti-mosquito strategies, we have silenced a catalase and a putative quiescin/sulfhydryl oxidase (QSOX), from the African malaria vector Anopheles gambiae, through RNA interference (RNAi) experiments. We observed that the survival of catalase- and QSOX-silenced insects was reduced over controls following blood digestion, most likely due to the compromised ability of mosquitoes to scavenge and/or prevent damage caused by blood meal-derived oxidative stress. The higher mortality effect was more accentuated in catalase-silenced mosquitoes, where catalase activity was reduced to low levels. Lipid peroxidation was higher in QSOX-silenced mosquitoes suggesting the involvement of this protein in redox homeostasis following a blood meal. This study points to the potential of molecules involved in antioxidant response and redox metabolism to serve as targets of novel anti-mosquito strategies and offers a screening methodology for finding targetable mosquito molecules.

WITHDRAWN: Recommendations for evaluation and management of pain in patients with mucopolysaccharidosis in Latin America.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.jpainsymman.2018.03.023. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aß) and Tau) and exacerbates AD pathology. Neuroinflammation can also be induced by systemic influences (factors from outside the central nervous system). However, the role of systemic inflammation in AD pathophysiology is much less understood. Thus, our main objective in this study was to verify whether the presence of serum cytokines (IL-1ß, IL-6, IL-10, IL-12, and TNF-α) affects different AD biomarkers: Aß1-42 and Tau protein levels, hippocampal volumes (HV), and default mode network functional connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this, we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the groups, we found that the mild AD patients presented smaller HV, disrupted DMN FC, and proportionally less IL-1ß than the controls. The aMCI patients only differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD with detectable levels of cytokines (TNF-α, IL-1ß, IL-10, and IL-12) had decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF Aß1-42, and less p-Tau), indicating a possible protective role of these ILs. Our findings indicate a possible relationship between systemic inflammation with DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects with mild AD and aMCI.

Electrocardiographic characteristics in a population with high rates of seropositivity for Trypanosoma cruzi infection.

This study was conducted in Posse, a rural community in Goiàs, Brazil. Persons were recruited into the study through house-to-house sampling of all houses in the sampled area. Blood samples were collected for seropositivity assessments for Trypanosoma cruzi and an electrocardiogram was assessed using a portable system. The results demonstrate significant differences between seropositive and seronegative persons for electrocardiographic (ECG)-derived traits. Seropositive persons had substantially longer QRS and QT intervals than seronegative persons. The PR interval was significantly different between seropositive and seronegative persons. Conduction abnormalities were observed more frequently in seropositive than seronegative persons. Right bundle branch block, an ECG abnormality typical of Chagas disease, was observed in 15% of seropositive persons compared with less than 1% of seronegative persons. Results indicate that T. cruzi infection and subsequent Chagas disease will continue to be major health problems for the foreseeable future in this typical rural area of Brazil.