Personal support networks of young people with and without intellectual disability. A comparative study.

BACKGROUND: Previous studies show that the personal support networks of people with intellectual disability are smaller and less diverse than those of people without intellectual disability. This article aims to compare the characteristics of the personal networks of young people with and without intellectual disability. METHOD: The Personal Network Analysis (McCarty, Revista Hispana Para El Análisis de Redes Sociales, 2010, 19, 242-271) was applied. The participants comprised 51 young people aged between 13 and 19, of whom 27 had an intellectual disability. The Egonet programme was used to compile information, and SPSS v.27 for the statistical analysis. RESULTS: Young people with intellectual disabilities have smaller personal networks than people without disability, while they also comprise more people with disability and fewer 'friends' and support people. CONCLUSIONS: The full social inclusion of people with intellectual disability requires schools, families, the community and the individual to work together to develop activities that help them initiate and maintain relationships, prioritising mainstream contexts.

Polymorphisms and gene expression of metalloproteinases and their inhibitors associated with cerebral ischemic stroke in young patients with sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is a genetic disease with great clinical heterogeneity and few viable strategies for treatment; hydroxyurea (HU) is the only widely used drug. Thus, the study of single nucleotide polymorphisms (SNPs) and the gene expression of MMPs 1, 2, 9, 7 and TIMPs 1 and 2, which are involved in the regulation of extracellular matrix, inflammation, and neuropathies, may provide further insights into the pathophysiology of the disease and elucidate biomarkers and molecules as potential therapeutic targets for patients with SCA. METHODS AND RESULTS: We evaluated 251 young individuals with SCA from northeastern Brazil. The groups were divided according to vaso-occlusive crisis (VOC) and cerebrovascular disease (CVD), compared to control individuals. SNP detection and gene expression assays were performed by real-time PCR, TaqMan system®. Both the expression levels of MMP1 gene, and the SNP MMP1-1607 1G/2G were associated with the risk of cerebral ischemic stroke (IS), and the expression of MMP1 was also associated with a higher frequency of VOC/year. Expression levels of MMP7, TIMP1, and TIMP2 were increased in patients conditioned to IS. The SNP 372T>C (rs4898) TIMP1 T alleles were more frequent in patients with > 5 VOC events/year. The SNP rs17576 of MMP9 showed differences in gene expression levels; it was increased in the genotypes AG, and AG+GG. CONCLUSION: The findings of this study, the SNPs, and expression provide initial support for understanding the role of MMPs-TIMPs in the pathophysiology of SCA in young patients.

Gender Bias When Using Artificial Intelligence to Assess Anorexia Nervosa on Social Media: Data-Driven Study.

BACKGROUND: Social media sites are becoming an increasingly important source of information about mental health disorders. Among them, eating disorders are complex psychological problems that involve unhealthy eating habits. In particular, there is evidence showing that signs and symptoms of anorexia nervosa can be traced in social media platforms. Knowing that input data biases tend to be amplified by artificial intelligence algorithms and, in particular, machine learning, these methods should be revised to mitigate biased discrimination in such important domains. OBJECTIVE: The main goal of this study was to detect and analyze the performance disparities across genders in algorithms trained for the detection of anorexia nervosa on social media posts. We used a collection of automated predictors trained on a data set in Spanish containing cases of 177 users that showed signs of anorexia (471,262 tweets) and 326 control cases (910,967 tweets). METHODS: We first inspected the predictive performance differences between the algorithms for male and female users. Once biases were detected, we applied a feature-level bias characterization to evaluate the source of such biases and performed a comparative analysis of such features and those that are relevant for clinicians. Finally, we showcased different bias mitigation strategies to develop fairer automated classifiers, particularly for risk assessment in sensitive domains. RESULTS: Our results revealed concerning predictive performance differences, with substantially higher false negative rates (FNRs) for female samples (FNR=0.082) compared with male samples (FNR=0.005). The findings show that biological processes and suicide risk factors were relevant for classifying positive male cases, whereas age, emotions, and personal concerns were more relevant for female cases. We also proposed techniques for bias mitigation, and we could see that, even though disparities can be mitigated, they cannot be eliminated. CONCLUSIONS: We concluded that more attention should be paid to the assessment of biases in automated methods dedicated to the detection of mental health issues. This is particularly relevant before the deployment of systems that are thought to assist clinicians, especially considering that the outputs of such systems can have an impact on the diagnosis of people at risk.

Isotemporal Substitution of Sedentary Behavior by Different Physical Activity Intensities on Pain and Disability of Patients With Chronic Low Back Pain: A Cross-Sectional Study.

OBJECTIVE: To investigate the association of isotemporal substitution modeling (ISM) of time spent in sedentary activities with physical activity in different intensities on pain and disability of patients with chronic low back pain (LBP). DESIGN: Observational and cross-sectional study. Device-measured physical activity levels were assessed using an actigraph. Pain intensity was measured using the 11-point numeric rating scale, and disability was measured using the Roland Morris Disability Questionnaire. The ISM was used to estimate the theoretical substitution association of reallocating time from 1 exposure variable to an equal amount of time in another exposure variable while holding total activity time constant. SETTINGS: Outpatient physical therapy clinic. PARTICIPANTS: This study included data from 358 patients (N=358) with chronic LBP aged between 18 and 60 years. MAIN OUTCOME MEASURES: Pain and disability. RESULTS: Our results suggest that replacing 60 minutes of sedentary behavior with 60 minutes of vigorous activity in a week is significantly associated with a decrease in pain (ß=-1.67; 95% confidence interval [CI], -3.18 to -0.15). Additionally, replacing 60 minutes of light physical activity (ß=-1.67; 95% CI, -3.18 to -0.16) or moderate activity (ß=-1.67; 95% CI, -3.21 to -0.13) with the same amount of time of vigorous activity per week may also favorable reductions in pain. For the analysis of disability, no significant associations (P>.05) for disability in any of the isotemporal models were found. CONCLUSIONS: Our results showed that replacing 60 minutes of sedentary behavior with equal amounts of vigorous activity per week was associated with reductions in pain intensity. Similarly, replacing a light or moderate activities with vigorous activity was also associated with reductions in pain intensity. Finally, no significant associations were observed between time spent in sedentary activities with physical activity in different intensities for disability.

Characterization of Anorexia Nervosa on Social Media: Textual, Visual, Relational, Behavioral, and Demographical Analysis.

BACKGROUND: Eating disorders are psychological conditions characterized by unhealthy eating habits. Anorexia nervosa (AN) is defined as the belief of being overweight despite being dangerously underweight. The psychological signs involve emotional and behavioral issues. There is evidence that signs and symptoms can manifest on social media, wherein both harmful and beneficial content is shared daily. OBJECTIVE: This study aims to characterize Spanish-speaking users showing anorexia signs on Twitter through the extraction and inference of behavioral, demographical, relational, and multimodal data. By using the transtheoretical model of health behavior change, we focus on characterizing and comparing users at the different stages of the model for overcoming AN, including treatment and full recovery periods. METHODS: We analyzed the writings, posting patterns, social relationships, and images shared by Twitter users who underwent different stages of anorexia nervosa and compared the differences among users going through each stage of the illness and users in the control group (ie, users without AN). We also analyzed the topics of interest of their followees (ie, users followed by study participants). We used a clustering approach to distinguish users at an early phase of the illness (precontemplation) from those that recognize that their behavior is problematic (contemplation) and generated models for the detection of tweets and images related to AN. We considered two types of control users-focused control users, which are those that use terms related to anorexia, and random control users. RESULTS: We found significant differences between users at each stage of the recovery process (P<.001) and control groups. Users with AN tweeted more frequently at night, with a median sleep time tweets ratio (STTR) of 0.05, than random control users (STTR=0.04) and focused control users (STTR=0.03). Pictures were relevant for the characterization of users. Focused and random control users were characterized by the use of text in their profile pictures. We also found a strong polarization between focused control users and users in the first stages of the disorder. There was a strong correlation among the shared interests between users with AN and their followees (ρ=0.96). In addition, the interests of recovered users and users in treatment were more highly correlated to those corresponding to the focused control group (ρ=0.87 for both) than those of AN users (ρ=0.67), suggesting a shift in users' interest during the recovery process. CONCLUSIONS: We mapped the signs of AN to social media context. These results support the findings of previous studies that focused on other languages and involved a deep analysis of the topics of interest of users at each phase of the disorder. The features and patterns identified provide a basis for the development of detection tools and recommender systems.

Correction: Characterization of Anorexia Nervosa on Social Media: Textual, Visual, Relational, Behavioral, and Demographical Analysis.

[This corrects the article DOI: 10.2196/25925.].

Implications of kinetically-hindered metals in ecotoxicological studies: Effect of platinum spike aging on its toxicity to Dunaliella salina.

Platinum (Pt) is considered an emerging environmental micro-contaminant due to its increasing use in anthropogenic activities during the past decades. However, there are still important gaps in the understanding of its biogeochemical behavior in the aquatic environment - e.g. its speciation, reactivity and fate - mainly as a result of the analytical challenge of the determination of its typical ultra-trace environmental concentrations. Also, Pt is a kinetically-hindered metal displaying slow reaction kinetics, which has important implications regarding eco-toxicological studies. That is, investigation of its toxicity under laboratory-controlled conditions may therefore require ensuring that equilibrium speciation conditions are reached before starting the experiments. In order to shed further light on this issue, in this study we have monitored the speciation changes during aging of the Pt(IV) spikes in controlled media (seawater) using an UV-Vis spectrophotometry. Platinum toxicity to the green microalgae Dunaliella salina was then compared, using standardized tests, with fresh and aged Pt(IV) spikes at the mg L-1 concentration range. Following 96-hour exposure, ecotoxicological assays consisting in spectrometric measurements of chlorophyll-a concentrations and Effective Concentrations (EC) of Pt resulting in the inhibition of 10% and 50% of algae growth rate were calculated (EC10 and EC50, respectively). Daily monitoring of Pt speciation reflected the transition from PtCl62- (spike) to hydrolyzed species, probably in the form [PtCl3-n(OH)3+n]2-, n = 0-3. Exposure experiments showed that after a short period of aging (10 days), Pt(IV) toxicity increased one order of magnitude compared to freshly spiked media. These results confirm the relevance of considering spike aging to ensure that speciation equilibrium conditions are attained in order to produce environmental realistic eco-toxicological data.

Profiling metal contamination from ultramafic sediments to biota along the Albanian shoreline of Lake Ohrid (Albania/Macedonia).

Ultramafic sediments exhibit high levels of geogenically-derived and potentially toxic metals, with Ni, Cr and Co often exceeding benchmark values. As yet, a holistic understanding of the bioavailability, mobility, potential ecotoxicity and trophic transfer of trace elements in both benthic and pelagic food chains in aquatic ultramafic environments (UME) is lacking. We investigated potential environmental health issues due to metal contamination by jointly implementing chemical, ecological and toxicological tools, along the Albanian shoreline of Lake Ohrid. It is an aquatic system of worldwide importance, representative of temperate UME with a legacy of Ni and Cr contamination from mining activities. Levels of Ni, Cr, Cd, Cu, Co, Fe, Mn and Zn were determined in waters, sediments and native biota. The potential environmental mobility of sediment-bound elements was further assessed using CaCl2, EDTA and acetic acid extractions. Whole-sediment ecotoxicity tests were also carried out using ostracods and chironomids, according to standardized procedures. Despite Ni and Cr concentrations above the sediment quality guidelines for probable effect levels, we did not observe ecotoxic effects in laboratory tests. However, these elements were bioavailable to native organisms under field conditions, especially to benthic primary producers in direct contact with sediments (up to 139 mg Cr kg-1 and 785 mg Ni kg-1). Although biomagnification was not observed, further investigations of metal translocation, metabolism and elemental trophic transfer along benthic food webs appears to be a general research priority in the management of temperate UME. The present study shows that proper management of temperate UME requires not only the integration of data from different lines of evidence, but also laboratory vs. field approaches to understand the subtler, long-term effects of increased elemental body burdens in native organisms.

Zygotorulaspora cariocana sp. nov., a yeast species isolated from tree bark in Brazil.

Six strains of a novel yeast species were isolated from tree bark collected in the Atlantic Forest and the Amazon Rainforest in Brazil. Analyses of the sequences of D1/D2 domains of the large subunit rRNA gene showed that the strains belong to a species in the genus Zygotorulaspora. The species differed by 5.54 % sequence divergence (25 substitutions and five indels out of 542 bp) in the D1/D2 sequences from Zygotorulaspora mrakii, its closest relative. The ITS sequence of the type strain of the novel species differs by 27-69 nucleotide substitutions/indels from the other Zygotorulaspora species. The novel species is able to grow on trehalose, maltose, l-sorbose, inulin and at 37 °C, which are negative in Z. mrakii. The name Zygotorulaspora cariocana sp. nov. is proposed. The holotype of Z. cariocana sp. nov. is CBS 16118T. The MycoBank number is MB 833702.

Detection of Suicidal Ideation on Social Media: Multimodal, Relational, and Behavioral Analysis.

BACKGROUND: Suicide risk assessment usually involves an interaction between doctors and patients. However, a significant number of people with mental disorders receive no treatment for their condition due to the limited access to mental health care facilities; the reduced availability of clinicians; the lack of awareness; and stigma, neglect, and discrimination surrounding mental disorders. In contrast, internet access and social media usage have increased significantly, providing experts and patients with a means of communication that may contribute to the development of methods to detect mental health issues among social media users. OBJECTIVE: This paper aimed to describe an approach for the suicide risk assessment of Spanish-speaking users on social media. We aimed to explore behavioral, relational, and multimodal data extracted from multiple social platforms and develop machine learning models to detect users at risk. METHODS: We characterized users based on their writings, posting patterns, relations with other users, and images posted. We also evaluated statistical and deep learning approaches to handle multimodal data for the detection of users with signs of suicidal ideation (suicidal ideation risk group). Our methods were evaluated over a dataset of 252 users annotated by clinicians. To evaluate the performance of our models, we distinguished 2 control groups: users who make use of suicide-related vocabulary (focused control group) and generic random users (generic control group). RESULTS: We identified significant statistical differences between the textual and behavioral attributes of each of the control groups compared with the suicidal ideation risk group. At a 95% CI, when comparing the suicidal ideation risk group and the focused control group, the number of friends (P=.04) and median tweet length (P=.04) were significantly different. The median number of friends for a focused control user (median 578.5) was higher than that for a user at risk (median 372.0). Similarly, the median tweet length was higher for focused control users, with 16 words against 13 words of suicidal ideation risk users. Our findings also show that the combination of textual, visual, relational, and behavioral data outperforms the accuracy of using each modality separately. We defined text-based baseline models based on bag of words and word embeddings, which were outperformed by our models, obtaining an increase in accuracy of up to 8% when distinguishing users at risk from both types of control users. CONCLUSIONS: The types of attributes analyzed are significant for detecting users at risk, and their combination outperforms the results provided by generic, exclusively text-based baseline models. After evaluating the contribution of image-based predictive models, we believe that our results can be improved by enhancing the models based on textual and relational features. These methods can be extended and applied to different use cases related to other mental disorders.

Influence of skeletal muscle mass and fat mass on the metabolic and inflammatory profile in sarcopenic and non-sarcopenic overfat elderly.

BACKGROUND: Sarcopenic elderly present low muscle mass and strength, however, it is not clear if the inflammatory and metabolic profile is more related to low lean mass or high fat mass in sarcopenic and non-sarcopenic overfat elderly. AIM: To verify the difference in inflammatory and metabolic responses in sarcopenic and non-sarcopenic overfat elderly and the relationship between these markers, body composition, and strength in this population. METHODS: Fifty-seven elderly were divided into two groups: sarcopenic (n = 30) and non-sarcopenic (n = 27). Body composition was evaluated with octopolar bioimpedance. Total cholesterol, high-density lipoprotein cholesterol, triacylglycerol, glucose, cortisol, leptin, adiponectin, Plasminogen activator inhibitor-1 (PAI-1), TNF-α, IL-6, IL-8, and IL-10 were assessed. The handgrip test was used to evaluate strength. RESULTS: When comparing the inflammatory profile, sarcopenic individuals showed greater adiponectin concentration (p = 0.019), adiponectin/fat mass ratio (p < 0.001), adiponectin/visceral fat (p < 0.001), and higher PAI-1 (p = 0.019) than non-sarcopenic overfat elderly. After adjusting the inflammatory profile by skeletal muscle mass the significant differences between groups were maintained (p < 0.05) but no significant differences between groups were observed when adjusting by fat mass, despite a tendency to a significant difference for adiponectin concentration (p = 0.06). In addition, after adjusting leptin by fat mass there was a statistically significant lower concentration in the sarcopenic compared to non-sarcopenic overfat elderly. CONCLUSION: Non-sarcopenic overfat elderly presented lower anti-inflammatory and anti-atherogenic responses than sarcopenic elderly. Furthermore, fat mass but not skeletal muscle mass seem to change these responses.

Severity of COPD and its relationship with IL-10.

BACKGROUND: The present study was designed to compare inflammatory and metabolic responses according to severity of airflow among patients with COPD and to verify the relationship between pulmonary function, body composition, metabolic and inflammatory profile. METHODS: Fifty-one patients with mild to very severe COPD were recruited and divided according lung function in Mild-moderate (GOLD 1-2) n= 21; Severe (GOLD 3) n=25 and Very severe (GOLD 4) n=5. Patients were submitted to assessments of lung function (spirometry), functional exercise capacity (6-min walk test), body composition (Octopolar bioelectrical impedance), metabolic profile (glucose, triglycerides, total cholesterol, HDL-cholesterol and albumin (colorimetric assay)) and inflammatory profile (cytokines: IL-6, IL-10, TNF-α and IL-15 (ELISA)). RESULTS: We found that patients in GOLD 3 group had lower levels of IL-10, triglycerides, visceral fat area, and higher IL-6 and IL-6/IL-10 ratio when compared to GOLD 1-2 patients. Additionally, GOLD 1-2 group presented negative correlation between TNF-α and HDL cholesterol (p= .01) and positive correlation between IL-15 and FEV1/FVC (p=.01), while GOLD 3 group showed positive correlation between IL-6 and IL-10 (p< .01), IL-6 and total cholesterol (p<.01) and negative correlation between IL-10 and HDL-cholesterol (p=.01). CONCLUSION: Our findings suggest that patients with severe COPD can exhibit compromised "inflammatory status", characterized by higher IL6, IL-6/IL-10 ratio and lower IL-10 concentration. Furthermore, IL-10 seems to be an interesting cytokine to be investigated in this kind of patients.

Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies.

α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of α-synuclein, reducing membrane binding, impaired the clearance of α-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of α-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions.

Analysis of Autonomic Modulation in Response to a Session of Aerobic Exercise at Different Intensities in Patients With Moderate and Severe COPD.

Despite the many benefits of performing physical exercise in patients with chronic obstructive pulmonary disease (COPD), information on the response of acute cardiac autonomic modulation in subjects with moderate and severe COPD during and after an aerobic exercise session at different intensities is unknown. The aim of this study was to evaluate the response of cardiac autonomic modulation in patients with moderate and severe COPD during and after an aerobic exercise session at different intensities. Twenty-seven patients with COPD, divided into: Moderate Group and Severe Group, underwent an aerobic exercise sessions with intensities equivalent to 60% and 90% of velocity corresponding to peak oxygen consumption. The heart rate variability (HRV) indices were analyzed in the time and frequency domains at the following times: at rest, during exercise, immediately after, and 5, 10, and 15 minutes after exercise. In the comparison analysis between the two groups, no differences were observed in any of the HRV indices at different intensities applied. However, it was observed that the exercise caused autonomic changes when the groups were analyzed separately. Sessions of aerobic exercise influence the autonomic modulation in patients with COPD. However, COPD severity did not influence the autonomic nervous system response to exercise and recovery moments; and there was no difference between the exercise intensities.

Novel Multi-isotope Tracer Approach To Test ZnO Nanoparticle and Soluble Zn Bioavailability in Joint Soil Exposures.

Here we use two enriched stable isotopes, 68Znen and 64Znen (>99%), to prepare 68ZnO nanoparticles (NPs) and soluble 64ZnCl2. The standard LUFA 2.2 test soil was dosed with 68ZnO NPs and soluble 64ZnCl2 to 5 mg kg-1 each, plus between 0 and 95 mg kg-1 of soluble ZnCl2 with a natural isotope composition. After 0, 1, 3, 6, and 12 months of soil incubation, earthworms (Eisenia andrei) were introduced for 72 h exposures. Analyses of soils, pore waters, and earthworm tissues using multiple collector inductively coupled plasma mass spectrometry allowed the simultaneous measurement of the diagnostic 68Zn/66Zn, 64Zn/66Zn, and 68Zn/64Zn ratios, from which the three different isotopic forms of Zn were quantified. Eisenia andrei was able to regulate Zn body concentrations with no difference observed between the different total dosing concentrations. The accumulation of labeled Zn by the earthworms showed a direct relationship with the proportion of labeled to total Zn in the pore water, which increased with longer soil incubation times and decreasing soil pH. The 68Znen/64Znen ratios determined for earthworms (1.09 ± 0.04), soils (1.09 ± 0.02), and pore waters (1.08 ± 0.02) indicate indistinguishable environmental distribution and uptake of the Zn forms, most likely due to rapid dissolution of the ZnO NPs.

The role of fibrinogen glycation in ATTR: evidence for chaperone activity loss in disease.

Transthyretin amyloidosis (ATTR) belongs to a class of disorders caused by protein misfolding and aggregation. ATTR is a disabling disorder of autosomal dominant trait, where transthyretin (TTR) forms amyloid deposits in different organs, causing dysfunction of the peripheral nervous system. We previously discovered that amyloid fibrils from ATTR patients are glycated by methylglyoxal. Even though no consensus has been reached about the actual role of methylglyoxal-derived advanced glycation end-products in amyloid diseases, evidence collected so far points to a role for protein glycation in conformational abnormalities, being ubiquitously found in amyloid deposits in Alzheimer's disease, dialysis-related amyloidosis and Parkinson's diseases. Human fibrinogen, an extracellular chaperone, was reported to specifically interact with a wide spectrum of stressed proteins and suppress their aggregation, being an interacting protein with TTR. Fibrinogen is differentially glycated in ATTR, leading to its chaperone activity loss. Here we show the existence of a proteostasis imbalance in ATTR linked to fibrinogen glycation by methylglyoxal.

Molecular typing of environmental Cryptococcus neoformans/C. gattii species complex isolates from Manaus, Amazonas, Brazil.

Cryptococcus neoformans and Cryptococcus gattii are the main causative agents of cryptococcosis, a systemic fungal disease that affects internal organs and skin, and which is acquired by inhalation of spores or encapsulated yeasts. It is currently known that the C. neoformans/C. gattii species complex has a worldwide distribution, however, some molecular types seem to prevail in certain regions. Few environmental studies of Cryptococcus have been conducted in the Brazilian Amazon. This is the first ecological study of the pathogenic fungi C. neoformans/C. gattii species complex in the urban area of Manaus, Amazonas, Brazil. A total of 506 samples from pigeon droppings (n = 191), captive bird droppings (n = 60) and tree hollows (n = 255) were collected from June 2012 to January 2014 at schools and public buildings, squares, pet shops, households, the zoo and the bus station. Samples were plated on niger seed agar (NSA) medium supplemented with chloramphenicol and incubated at 25°C for 5 days. Dark-brown colonies were isolated and tested for thermotolerance at 37°C, cycloheximide resistance and growth on canavanine-glycine-bromothymol blue agar. Molecular typing was done by PCR-RFLP. Susceptibility to the antifungal drugs amphotericin B, fluconazole, itraconazole and ketoconazole was tested using Etest(®) strips. In total, 13 positive samples were obtained: one tree hollow (C. gattiiVGII), nine pigeon droppings (C. neoformansVNI) and three captive bird droppings (C. neoformansVNI). The environmental cryptococcal isolates found in this study were of the same molecular types as those responsible for infections in Manaus.

Correlation between heart rate variability indexes and aerobic physiological variables in patients with COPD.

BACKGROUND AND OBJECTIVE: Previous studies have shown a relationship between the level of physical fitness and autonomic variables. However, these relationships have not been investigated in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to correlate the resting heart rate variability (HRV) indexes with aerobic physiological variables obtained at a maximal exercise test in patients with COPD. METHODS: Thirty-seven patients with COPD (63 (59-70) years; 46 (35.4-63.7) forced expiratory volume in 1 s (FEV1)%) underwent assessment of autonomic modulation at rest for 20 min to determine the HRV indexes in time and frequency domains. Soon after that, the patients performed an incremental exercise test to determine the anaerobic threshold (GET), the peak oxygen uptake (VO 2PEAK) and the velocity corresponding to VO 2PEAK (vVO 2PEAK). RESULTS: The indexes that express parasympathetic component as RMSSD (11.4 [7.5-23.8], HF (ms(2)) (35 [17-195] and SD1 (8.1 [5.3-16.8]), correlated with GET (r = 0.39; r = 0.43; r = 0.39 respectively). The indexes that represent the overall variability, SDNN (19.5 [13.9-28.8]), LF (ms(2)) (111 [38-229]), and SD2 (26.8 [18.6-35.4]) correlated with vVO 2PEAK (r = 0.37; r = 0.38; r = 0.37; r = 0.44; r = 0.43; r = 0.46 respectively). Likewise, the indexes LF (ms(2)), LF (nu) (63.2 [46-77,9]), HF (nu) (36.8 [22.1-54]), and LF/HF (1.7 [0.9-3.5]) correlated with VO 2PEAK (r = 0.35; r = 0.35; r = -0.35; r = 0.40 respectively). CONCLUSIONS: This study demonstrated that HRV indexes at rest may become a predictive tool for aerobic capacity in COPD patients after the development of more consistent methods.

Modulation of CD14 and TLR4·MD-2 activities by a synthetic lipid A mimetic.

Monosaccharide lipid A mimetics based on a glucosamine core linked to two fatty acid chains and bearing one or two phosphate groups have been synthesized. Compounds 1 and 2, each with one phosphate group, were practically inactive in inhibiting LPS-induced TLR4 signaling and cytokine production in HEK-blue cells and murine macrophages, but compound 3, with two phosphate groups, was found to be active in efficiently inhibiting TLR4 signal in both cell types. The direct interaction between compound 3 and the MD-2 coreceptor was investigated by NMR spectroscopy and molecular modeling/docking analysis. This compound also interacts directly with the CD14 receptor, stimulating its internalization by endocytosis. Experiments on macrophages show that the effect on CD14 reinforces the activity on MD-2·TLR4 because compound 3's activity is higher when CD14 is important for TLR4 signaling (i.e., at low LPS concentration). The dual targeting of MD-2 and CD14, accompanied by good solubility in water and lack of toxicity, suggests the use of monosaccharide 3 as a lead compound for the development of drugs directed against TLR4-related syndromes.