Metabolic and behavioural risk factors for cardiovascular diseases in Southern Latin America: analysis of the Global Burden of Disease 1990-2019.

OBJECTIVES: Cardiovascular diseases (CVDs) are the leading causes of global mortality. Modifiable behavioural and metabolic risk factors significantly contribute to the burden of CVD. Given the vast socio-demographic and health outcome heterogeneity in Latin America, similar southern Latin American countries (Argentina, Chile, and Uruguay) were analysed as a distinct group to describe the CVD death rates related to metabolic and behavioural risk factors. STUDY DESIGN: An ecological study was performed using data from the Global Burden of Disease Study 2019. METHODS: Metabolic and behavioural risk factors-related CVD death were examined by analysing age-standardised rates per 100,000 individuals in the three countries between 1990 and 2019. RESULTS: While exposure to behavioural risk is decreasing, an upwards trend was observed in metabolic risks. Among the assessed risk factors, metabolic factors emerged as the primary contributors to deaths. High fasting plasma glucose exhibited a remarkable increase in relative importance across most studied contexts. Dietary risks stood out among behavioural factors due to their complexity and substantial changes observed. Although mortality rates have declined for overall CVD, peripheral artery disease mortality is rising. CONCLUSION: Modifiable behavioural and metabolic risk factors significantly influence CVD mortality in Southern Latin America. Despite the increasing exposure to metabolic risks, advancements in prevention and treatment are evidenced in the decline of mortality rates for most CVD. These findings emphasise the need for targeted interventions and comprehensive strategies to address their impact on cardiovascular health, advocating for healthy lifestyle behaviours to mitigate the progression and CVD development.

Soluble biomarkers in osteoarthritis in 2022: year in review.

OBJECTIVE: To review articles reporting on the development of soluble biomarkers in osteoarthritis (OA) over the past year. DESIGN: Two literature searches were conducted using the PubMed database for articles published between April 1, 2021 and March 31, 2022. Two searches were done, one on soluble biomarkers and another on circulating non-coding RNAs in OA. Additional articles were hand-picked to highlight emerging biomarker trends in OA. RESULTS: Of 348 publications retrieved, we included 20 articles with 3 that were hand-picked for the narrative synthesis. We review recent data on soluble biomarkers and circulating non-coding microRNAs in OA using the BIPED classification system. We highlight studies using proteomics to show that cartilage acidic protein 1 (CRTAC1) is a promising biomarker, helping diagnose and estimate severity in hand, hip, and knee OA. Subtle changes in the structure of glycosaminoglycans from the extracellular cartilage matrix were shown to discriminate OA from non-OA cartilage. C-reactive protein metabolite (CRPM) and collagen metabolites may help discriminate subsets of OA patients as well as disease progression. Additionally, physical activity may impact determination of biomarkers. We also report on circulating microRNAs, lncRNAs, and circRNAs in OA and their predictive accuracy in diagnosis and prognosis. CONCLUSIONS: Biomarkers for routine use are still an unmet need in the OA clinical scenario. Emerging data and novel classes of biomarkers (i.e., non-coding RNAs) show promise. Although still requiring validation in multiple independent cohorts, the past year brought advances towards a ready-to-use, reproducible, cost-effective biomarker, namely CRTAC1, to better manage the OA patient.

The cardiovascular disease burden attributable to particulate matter pollution in South America: analysis of the 1990-2019 global burden of disease.

OBJECTIVES: Fine particulate matter <2.5 microns (PM2.5) is the most studied air pollutant. Both short- and long-term exposure to PM2.5 have been linked to cardiovascular disease (CVD). Studies evaluating air pollution in South America are scarce. Therefore, the impact of exposure to PM2.5, household air pollution (HAP), and ambient air pollution (AAP) on CVD mortality and CVD disability-adjusted life years (DALYs) in South American countries from 1990 to 2019 was explored. STUDY DESIGN AND METHODS: The Global Burden of Disease initiative exposure-response function was used to analyze the total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and DALYs rates, per 100,000 individuals, in 12 South American countries between 1990 and 2019. The relative change in burden was also assessed by comparing the 1990-1994 to 2015-2019 periods. RESULTS: In 2019, 70,668 deaths and 1,736,414 DALYs due to CVD were attributed to total PM2.5 exposure in South America. Substantial regional heterogeneity was observed concerning the absolute change in PM2.5 concentration levels comparing 1990 to 2019. All South American countries observed a relative decline in CVD deaths and DALYs comparing the 1990-1994 to 2015-2019 periods. No country was able to reach the current World Health Organization 5 µg/m3 recommended limit in 2019. Predominantly, AAP was the greatest contributor to the CVD burden. CONCLUSION: Air pollution substantially impacted CVD in South America; however, this impact was heterogenous, and the relative reduction of HAP and AAP burden was also not uniform. Recognizing PM2.5 importance is key for developing target population and individual-level interventions, which could ultimately alleviate its burden.

Spatiotemporal distribution of a non-haematophagous bat community and rabies virus circulation: a proposal for urban rabies surveillance in Brazil.

In Brazil, rabies surveillance is based on monitoring domestic and wild animals, although the most prevalent lineage of the rabies virus (RABV) currently diagnosed in Brazil is associated with bats, particularly non-haematophagous bats. Disease control is based on the mass vaccination of dogs and cats. We used data collected by the passive surveillance system of the city of Campinas from 2011 to 2015, to describe the temporal and geographic distributions of the bat specimens and RABV and discuss the current rabies surveillance with the advent of the declaration of canine and feline rabies-free areas in Brazil. We described the species, locations and health statuses of the collected bat specimens. Moreover, all samples were submitted for RABV diagnosis. Then, we performed a time series decomposition for each bat family. Additionally, we determined the spatiotemporal relative risk for RABV infection using the ratio of the kernel-smoothed estimates of spatiotemporal densities of RABV-positive and RABV-negative bats. From the 2537 bat specimens, the most numerous family was Molossidae (72%), followed by Vespertilionidae (14%) and Phyllostomidae (13%). The bat families behaved differently in terms of seasonal and spatial patterns. The distribution of bats varied geographically in the urban environment, with Molossidae and Phyllostomidae being observed downtown and Vespertilionidae being observed in peripheral zones. Concurrently, a significant relative risk of RABV infection was observed downtown for Vespertilionidae and in peripheral zones for Molossidae. No RABV-positive sample clusters were observed. As a result of the official declaration of RABV-free areas in southern Brazil, mass dog and cat vaccinations are expected to halt in the near future. This stoppage would make most dog and cat populations susceptible to other RABV lineages, such as those maintained by non-haematophagous bats. In this scenario, all information available on bats and RABV distribution in urban areas is essential. Currently, few studies have been conducted. Some local health authorities, such as that in Campinas, are spontaneously basing their surveillance efforts on bat rabies, which is the alternative in reality scenario of increased susceptibility to bat-associated RABV that is developing in Brazil.

Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate.

OBJECTIVES: Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) for focal-onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL. METHODS: Eslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200 mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses. RESULTS: Eslicarbazepine PK was described by a one-compartment model with linear absorption and elimination. The probability of a treatment-emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800 mg than with an initial dose of ESL 400 mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline. CONCLUSIONS: Pharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision-making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions.

Effects of adjunctive eslicarbazepine acetate on neurocognitive functioning in children with refractory focal-onset seizures.

PURPOSE: This was a phase-II, randomized, double-blind (DB), placebo-controlled study aimed to evaluate neurocognitive effects of eslicarbazepine acetate (ESL) as adjunctive therapy in pediatric patients with refractory focal-onset seizures (FOS). METHODS: Children (6-16years old) with FOS were randomized (2:1) to ESL or placebo. Treatment started at 10mg/kg/day, was up-titrated up to 30mg/kg/day (target dose), and maintained for 8weeks, followed by one-year open-label follow-up. The primary endpoint was change from baseline to the end of maintenance period in the composite Power of Attention assessed with the Cognitive Drug Research (CDR) system. Behavioral and emotional functioning and quality of life (QOL), secondary endpoints, were assessed with Child Health Questionnaire-Parent Form 50 (CHQ-PF50), Child Behavior Checklist (CBCL), and Raven's Standard Progressive Matrices (SPM). Efficacy was evaluated through changes in standardized seizure frequency (SF), responder rate, and proportion of seizure-free patients. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs). RESULTS: One hundred and twenty-three patients were randomized. A noninferiority analysis failed to reject the null hypothesis that the change from baseline in the Power of Attention score in the ESL group was at least 121ms inferior to the placebo group for all age groups. The CDR scores showed no differences between placebo and ESL in Power of Attention (1868.0 vs 1759.5), Continuity of Attention (1.136 vs -1.786), Quality of Working Memory (-0.023 vs -0.024), and Speed of Memory (-263.4 vs -249.6). Nonsignificant differences between placebo and ESL were seen for CHQ-PF50, CBCL scores, and Raven's SPM. Episodic Memory Index showed significant negative effect on ESL. Efficacy results favored the ESL group (SF least square [LS] means 1.98 vs 4.29). The TEAEs had a similar incidence between treatment groups (41.0% vs 47.5%). CONCLUSIONS: Overall ESL did not produce statistically significant effects on neurocognitive and behavioral functioning in patients with epilepsy aged 6 to 16years. Additionally, ESL was effective in reducing seizure frequency and was well-tolerated.

Meniscal transection rather than excision increases pain behavior and structural damage in experimental osteoarthritis in mice.

OBJECTIVE: To evaluate pain behavior and structural damage in mice subjected to either meniscal transection or removal. METHODS: Mice (10/group) were subjected to transection of the medial collateral and anterior cruciate ligaments (ACLT/MCLT) followed by either transection (meniscotomy) or removal (meniscectomy) of the medial meniscus. A control group was subjected only to transection of the ligaments. Pain was assessed using the electronic pressure-meter paw test. Cell influx, measured in joint exudates, and joint histopathology were assessed after 49 days. Four other groups subjected to meniscotomy received indomethacin, the inducible nitric oxide synthase (iNOS) inhibitor 1400W, morphine or the vehicles. RESULTS: Both meniscotomy and meniscectomy groups displayed persistent and significant increase in pain behavior as compared to controls, being significantly more severe in the former. Cell influx was more intense in the meniscotomy as compared to the meniscectomy group. Structural damage at the tibia, but not at the femur, was also more severe in the meniscotomy group. Indomethacin and 1400W partially but significantly reduced pain whereas morphine abrogated pain behavior in meniscotomized mice. CONCLUSION: Meniscal transection rather than resection promotes more severe pain and structural damage in mice. Administration of opioids, cyclooxygenase and nitric oxide (NO) synthase inhibitors provide analgesia in this model. Careful description of the structures damaged is crucial when reporting experimental osteoarthritis (OA).

Geochemistry, mineralogy, solid-phase fractionation and oral bioaccessibility of lead in urban soils of Lisbon.

An urban survey of Lisbon, the largest city in Portugal, was carried out to investigate its environmental burden, emphasizing metallic elements and their public health impacts. This paper examines the geochemistry of lead (Pb) and its influence on human health data. A total of 51 soil samples were collected from urban recreational areas used by children to play outdoors. The semi-quantitative analysis of Pb was carried out by inductively coupled plasma mass spectrometry after an acid digestion. X-ray diffraction was used to characterize the soil mineralogy. The solid-phase distribution of Pb in the urban soils was investigated on a subset of 7 soils, out of a total of 51 samples, using a non-specific sequential extraction method coupled with chemometric analysis. Oral bioaccessibility measurements were obtained using the Unified BARGE Method developed by the Bioaccessibility Research Group of Europe. The objectives of the study are as follows: (1) investigation of Pb solid-phase distribution; (2) interpretation of Pb oral bioaccessibility measurements; (3) integration of metal geochemistry with human health data; and (4) understanding the influence of geochemistry and mineralogy on oral bioaccessibility. The results show that the bioaccessible fraction of Pb is lower when major metal fractions are associated with less soluble soil phases such as Fe oxyhydroxides, and more increased when the metal is in the highly soluble carbonate phase. However, there is some evidence that the proportion of carbonates in the soil environment is also a key control over the oral bioaccessibility of Pb, irrespective of its solid-phase fractionation.

Metabarcoding analysis reveals an interaction among distinct groups of bacteria associated with three different varietals of grapes used for wine production in Brazil.

Grapes are globally popular with wine production being one of the most well-known uses of grapes worldwide. Brazil has a growing wine industry, and the Serra Gaúcha region is a significant contributor to the country's wine production. Nonetheless, other states are increasing their relevance in this segment. Environmental factors and the soil microbiome (bacteria and fungi) heavily influence grape quality, shaping the crucial "terroir" for wines. Here, soil quality was assessed through nutrient analysis and bacteria microbial diversity, which could significantly impact grape health and final wine attributes. Soil samples from São Paulo's vineyards, focusing on Syrah, Malbec, and Cabernet Sauvignon, underwent chemical and microbial analysis via 16S rRNA metabarcoding and highlighted significant differences in soil composition between vineyards. Statistical analyses including PCA and CAP showcased region-based separation and intricate associations between microbiota, region, and grape variety. Correlation analysis pinpointed microbial genera linked to specific soil nutrients. Random Forest analysis identified abundant bacterial genera per grape variety and the Network analysis revealed varied co-occurrence patterns, with Cabernet Sauvignon exhibiting complex microbial interactions. This study unveils complex relationships between soil microbiota, nutrients, and diverse grape varieties in distinct vineyard regions. Understanding how these specific microorganisms are associated with grapes can improve vineyard management, grape quality, and wine production. It can also potentially optimize soil health, bolster grapevine resilience against pests and diseases, and contribute to the unique character of wines known as terroir.

First Report of Downy Mildew Caused by Peronospora sordida on Butterflybush (Buddleja stachyoides) in Brazil.

Butterflybush (common name in Brazil, verbasco), Buddleja stachyoides Cham. & Schltdl. (Buddlejaceae), is an erect herb or small shrub, native to Brazil, that is listed both as a folk medicinal plant and as a pasture weed (4). In March 2012, a group of B. stachyoides plants growing in a pasture in Viçosa (state of Minas Gerais, Brazil), were found bearing typical downy mildew symptoms. The only pathogen reported associated with this plant species is Podosphaera xanthii (1) and because there is no record of downy mildew on members of Buddleja in Brazil, an investigation was carried out to clarify the pathogen identity. Diseased plants had lesions on living leaves that were vein-delimited, chlorotic, coalescing, and becoming necrotic adaxially and bearing downy mildew-like colonies over diseased tissues abaxially. The samples were dried in a plant press and a representative specimen was deposited in the local herbarium at the Universidade Federal de Viçosa (Accession No. VIC 31836). Reproductive structures were scraped from leaves with a scalpel and mounted in lactophenol. Preliminary observations indicated the pathogen as belonging to Peronospora (Peronosporaceae). The pathogen had the following morphology: Sporangiophores are 288 to 641 µm long, dichotomously branching up to seven times, hyaline, smooth, 5 to 16 µm wide at the trunk, branches 63 to 202 µm long; tips subacute, in pairs or rarely single, 5 to 19 µm long; sporangia subglobose to ellipsoidal, 12 to 22 × 11 to 17 µm, pale yellowish brown, non-papillate. Only one species of Peronospora is known to infect members of Buddleja, namely Peronospora hariotii Gäum. (1). Nevertheless, the pathogen on B. stachyoides has smaller sporangia as compared to those of P. hariotii (20 to 26 × 16 to 21 µm) (2) and it was closer to P. sordida (3). DNA of the pathogen from B. stachyoides was extracted and the cytochrome c oxidase subunit II (COX2) and internal transcribed spacer (ITS) regions were sequenced. Sequences were deposited in GenBank (COX2 as JX982637; ITS as JX982638). A BLAST search yielded 99% and 100% of maximum identity with P. sordida for COX2 and ITS, respectively. A more detailed phylogenetic study is necessary to clarify the relationship between P. sordida, P. hariotii, and related species causing downy mildew on closely related hosts. To our knowledge, this is the first report of P. sordida occurring on a member of the genus Buddleja. This is also the first time that P. sordida is reported from South America. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , 19 October 2012. (2) S. M. Francis. C.M.I. Descr. Pathog. Fungi Bact. 767:1, 1983. (3) G. Hall. I.M.I. Descr. Fungi Bact. 1062:1, 1991. (4) K. G. Kissmann and D. Groth. Plantas Infestantes e Nocivas. São Paulo, BASF, 1997.

B cell-deficient mice display enhanced susceptibility to Paracoccidioides brasiliensis Infection.

Paracoccidioidomycosis (PCM) is a chronic granulomatous disease caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. T helper 1 (Th1)-mediated immunity is primarily responsible for acquired resistance during P. brasiliensis infection. On the contrary, the susceptibility is associated with occurrence of type-2 immunity (Th2), which is characterized by IL-4 release, B cell activation, and production of antibodies. Although antibodies are frequently associated with severe PCM, it is not clear whether they contribute to susceptibility or merely constitute a marker of infection stage. Here, we assessed the function of B cells during experimental P. brasiliensis infection in mice, and our results showed that B cell-knockout (B(KO)) mice are more susceptible than their wild-type littermate controls (C57BL/6, WT). The B(KO) mice showed higher mortality rate, increased number of colony-forming units in the lungs, and larger granulomas than WT mice. In the absence of B cells, we observed high levels of IL-10, whereas IFN-γ, TNF-α, and IL-4 levels were similar between both groups. Finally, we showed that transference of WT immune serum to B(KO) mice resulted in diminished infiltration of inflammatory cells and better organization of the pulmonary granulomas. Taken together, these data suggest that B cells are effectively involved in the control of P. brasiliensis growth and organization of the granulomatous lesions observed during the experimental PCM.

Reproductive biology of the guitarfish Rhinobatos percellens (Chondrichthyes, Rhinobatidae) from the São Paulo Coast, Brazil, western South Atlantic Ocean.

The reproductive biology of the guitarfish Rhinobatos percellens was studied from 751 specimens caught by bottom pair trawlers off the coast of São Paulo, Brazil, between c. 24° 00' S; 45° 15' W and c. 25° 10' S; 47° 52' W, from September 2007 to August 2009. The total length (L(T)) and total mass (M(T)) relationship for males and females combined was M(T) = 1·29E-06 L(T) (3·15) (r = 0·99, n = 751). The mean L(T) of sexually mature specimens was 548 mm for males and 583 mm for females. Clasper growth was allometric and showed three distinct phases. Most claspers were calcified in specimens of c. 550 mm L(T). The mean diameter of the largest oocyte was 29·8 mm, the mean ovarian fecundity was seven oocytes and ovulation occurred between August and November. Uterine fecundity ranged from two to 13 embryos (mean of five embryos). Larger females had higher litter sizes and larger embryos; the size-at-birth was c. 200 mm L(T). The hepato-somatic index oscillated seasonally for males and females; the gonado-somatic index had little variation in males, but varied seasonally in females. The presence of many non-pregnant adult females and of encapsulated eggs during two consecutive seasons suggests a resting period between gestations and the possibility of diapause.

Skyrmion transport and annihilation in funnel geometries.

Using atomistic simulations, we have investigated the transport and annihilation of skyrmions interacting with a funnel array under a current applied perpendicular to the funnel axis. We find that transport without annihilation is possible at low currents, when the motion is dominated by skyrmion-skyrmion interactions and skyrmions push each other through the funnel opening. Skyrmion annihilation occurs for higher currents when skyrmions in the upper half of the sample exert pressure on skyrmions in the bottom half of the sample due to the external current. Upon interacting with the funnel wall, the skyrmions undergo a size reduction that makes it easier for them to pass through the funnel opening. We find five phases as a function of the applied current and the size of the funnel opening: (i) pinned, (ii) transport without annihilation, (iii) transport with annihilation, (iv) complete annihilation, and (v) a reentrant pinning phase that only occurs for very narrow openings. Our findings provide insight into how to control skyrmion transport using funnel arrays by delineating regimes in which transport of skyrmions is possible as well as the conditions under which annihilation occurs.

Residential combustion of coal: Effect of the fuel and combustion stage on emissions.

Worldwide coal is still used for household heating purposes not only because it is available and cheap but also due to behavioural issues. Regional variability in fuels and combustion appliances make accurate emission estimates from this source hard to achieve. In the present study, gaseous (CO, VOCs, SO2 and NOX) and particulate matter (TSP) emission factors (EFs) were determined for Spanish household coal combustion covering three commercial coals and distinct combustion stages and mimicking usage patterns in real households. TSP samples were analysed to determine water-soluble inorganic ions, metal(loid)s, and organic and elemental carbon (OC and EC). Additionally, the morphology of the emitted particles was also characterised. CO (3.43-169 g kg-1), NOX (1.29-6.00 g kg-1) and SO2 (8.96-22.3 g kg-1) EFs showed no trend regarding the combustion stage or coal type tested. On the other hand, VOC, TSP and EC EFs were higher for the ignition/devolatilisation combustion stage, regardless of the fuel tested. TSP EFs (0.085-1.08 g kg-1) increased with increasing coal volatile matter while the opposite trend was recorded for VOC emissions (0.045-3.39 gC kg-1). TSP carbonaceous matter was dominated by EC while OC represented a small fraction of the particulate mass emitted (less than 8 %wt.). Inorganic compounds composed an important fraction of the TSP samples. Sulphate particulate mass fractions (8.66-22.9 %wt.) appeared to increase with coal S-content. Coal combustion released particles with diverse morphologies, including silicate-rich particles, ferro- and glassy-spheres. This study provides novel emission factors to update emission inventories of residential coal combustion. Additionally, detailed chemical profiles were obtained for source apportionment.

Frailty in Chile: Development of a Frailty Index Score Using the Chilean National Health Survey 2016-2017.

BACKGROUND: The Frailty Index (FI) is used to quantify and summarize vulnerability status in people. In Chile, no development and assessment of a FI have been explored. OBJECTIVE: To develop and evaluate a FI using representative data from Chilean adults aged 40 years and older stratified by sex. DESIGN: Cross-sectional study. SETTING: National representative data from the Chilean National Health Survey 2016-2017 (CNHS 2016-2017). PARTICIPANTS: 3,036 participants older than 40 years with complete data for all variables. MEASUREMENTS: A 49-item FI was developed and evaluated. This FI included deficits from comorbidities, functional limitations, mental health status, physical activity, anthropometry, medications, and falls. A score between 0 and 1 was calculated for each person. Descriptive statistics and linear regression models were employed to evaluate the FI's performance in the population. Comparative analyses were carried out to evaluate the FI score by age (1<60 and ≥ 60 years). RESULTS: The mean FI score was 0.15 (SD:0.09), with a 99% upper limit of 0.46. Scores were greater in women than men (0.17 [SD:0.09]) vs. 0.12 [0.08]); in people older than 80 years (0.22 [0.11]), and in people with ≤8 years of education (0.18 [0.10]) compared with those with >12 years (0.12 [0.08]). The average age-related increase in the FI was 2.3%. When a cut-off point ≥ 0.25 was applied, the prevalence of frail individuals was 11.8% (95% CI: 10.0 to 13.8) in the general population. The prevalence was higher in women 15.9% [95% CI: 13.3 to 18.9] than men 7.4% [95% CI: 5.3 to 10.1]. In a comparative analysis by age, higher FI mean scores and prevalence of frail were observed in people ≥ 60 than younger than 60. CONCLUSIONS: The mean FI score and frailty prevalence were higher in women than men, in people with fewer years of formal education, and incremented markedly with age. This FI can be used for early detection of frailty status focusing on women and middle-aged people as a strategy to delay or prevent frailty-related consequences.

Protein-losing enteropathy as initial manifestation of systemic lupus erythematosus.

Protein-losing enteropathy is a rare manifestation of systemic lupus erythematosus. We report the case of an 18-year-old woman that presented initially with diarrhoea and anasarca. During evaluation, there was low serum albumin of 1.6 g/dl (3.5-5.2 g/dl) and a positive antinuclear antibody test (1:2560). Anti-Sm antibodies (ELISA) were positive in addition to low serum C3 of 35 mg/dl. A scintigraphy using 99mTc-labelled albumin was positive for abdominal protein loss. A diagnosis of systemic lupus erythematosus related protein-losing enteropathy was made. She was started on prednisolone 40 mg/day without amelioration; a month later, azathioprine (100 mg/day) was added, leading to normalization of serum albumin and resolution of symptoms within 4 months. After 1.5 years, the patient developed a 2.9 g 24-h proteinuria while still in remission of the protein-losing enteropathy, receiving 5 mg prednisone and 100 mg azathioprine daily.

Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients.

OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.

Association between Poor Oral Health and Frailty in Middle-Aged and Older Individuals: A Cross-Sectional National Study.

OBJECTIVES: Older adults with poor oral health may be at higher risk of being pre-frail or frail. However, very few studies have examined this association in Latin American countries and middle-aged individuals. Therefore, we aimed to investigate the association between oral health and frailty status among Chilean adults ≥40 years. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We included 3,036 participants ≥40 years from the Chilean National Health Survey 2016-2017. METHODS: Frailty status was assessed with a 49-item frailty index, while the number of teeth, self-reported oral health, tooth decay, use of prostheses, and oral pain were the oral health conditions included. To assess the association between oral health conditions and frailty, we used multinomial logistic regression models status adjusted for sociodemographic and lifestyle variables. RESULTS: Overall, 40.6% and 11.8% of individuals were classified as pre-frail and frail, respectively. After adjusting for confounders, individuals with ≤20 teeth had a higher likelihood of being frail (odds ratio (OR): 1.94 [95% CI: 1.18-3.20]) than people with >20 teeth. Moreover, people with bad or very bad oral health, as well as oral pain, had a higher likelihood of being pre-frail (OR: 2.04 [95% CI: 1.40-2.97] and OR: 2.92 [95% CI: 1.58-5.39], respectively). Middle-aged individuals with fewer teeth and poor self-reported oral health had a higher likelihood of being pre-frail and frail than people ≥60. CONCLUSIONS AND IMPLICATIONS: Individuals with poor global oral health were more likely to be pre-frail or frail. This association seems to be stronger in people <60 years old. Our results are consistent with previously published reports.

Impact of opioid maintenance treatment during pregnancy on neonatal birth weight and head circumference.

BACKGROUND: Pregnant mothers with opioid dependency commonly receive maintenance treatment of opioid (OMT), either as buprenorphine (BMT) or methadone maintenance treatment (MMT). We investigated, whether OMT adversely affects standardized neonatal anthropometric outcomes and whether BMT is potentially safer than MMT in this regard. METHODS: Retrospective chart review of mother infant dyad, with and without OMT. Infant's absolute and standardized (z-score) anthropometric outcomes at birth were first compared, between OMT and control group (negative meconium drug screen), and then between BMT and MMT group. These outcomes were also compared between infants who did or did not require treatment after birth for neonatal abstinence syndrome (NAS). RESULT: A total of 1479 participants with MDS were included [Control = 1251; OMT = 228 (MMT = 181; BMT = 47)]. Both the z-scores of birth weight (BW) and head circumference (HC) was lower in OMT group (p < 0.001). Among the OMT group, GA at delivery was slightly higher in the BMT group (p = 0.05). There was an inverse correlation between maternal dose at the time of delivery and anthropometric z-scores in the BMT group, mainly in female infants (BW: p = 0.006; HC: p = 0.003). Furthermore, In BMT group, infants with lower HC were more likely to require treatment for NAS (p = 0.01). CONCLUSION: HC and BW when comparing Z-scores were not different between MMT and BMT. High maternal dosing of buprenorphine is associated with lower BW and HC Z-scores but dose effect is not seen with methadone. In addition, there seems to be an association between NAS severity and HC, especially in the BMT group.

In vitro and in silico assessment of antitumor properties and biomolecular binding studies for two new complexes based on NiII bearing k2N,S-donor ligands.

This work deals with two new molecule-based materials, namely NiII-complexes of general formulae [Ni(L1)2] (Ni1) and [Ni(L2)2] (Ni2), where L1 = trans-cinnamaldehyde-N(4)-methyl thiosemicarbazone and L2 = trans-cinnamaldehyde-N(4)-ethyl thiosemicarbazone, as potential antitumor agents. Both compounds were characterized by elemental analysis, molar conductivity and spectroscopic techniques (FTIR and NMR). Their molecular structures were obtained by single-crystal X-ray diffraction analysis. Each one crystallizes in a monoclinic space group P 21/c, also the asymmetric unit comprises of one NiII ion located on an inversion centre and one anionic ligand, which acts as a κ2N,S-donor affording a five-membered metallaring. The compounds were screened against two selected tumour cell lines (MCF-7 and A549) and non-tumour fibroblasts cell line (MRC-5) via MTT assays. In both tumour cells, all compounds exhibited higher cytotoxicity than the control drug (cisplatin). The IC50 values ranges of 3.70 - 41.37 µM and 1.06 - 14.91 µM were found for MCF-7 and A549, respectively. Importantly, all of them were less toxicity than cisplatin in MRC-5 with SI values ranged at 11.80 - 86.60. The red blood cell (RBC) assay revealed Ni2 as non-toxic due to its reduced haemolytic effect (0--9% at 1--10 µM). The DNA binding was investigated through a combination of spectrophotometric absorption and emission titrations, electrophoresis, and circular dichroism experiments. As a result, these metal complexes were not able to strongly binding to DNA (Kb values ~104 mol L--1) but suggesting groove-binding interactions. The scavenging ability of them towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical was also evaluated in this work, but no important antioxidant behaviour was detected. Further, the interaction of Ni1 and Ni2 to human serum albumin (HSA) was explored by quenching of tryptophan emission, warfarin competitive assay, and molecular docking protocols. The HSA binding analyses indicated good affinity of both complexes to Sudlow site I (Kb values ⁓103 mol L-1).