Modes and Mechanisms of Pacific Decadal-Scale Variability.

The modes of Pacific decadal-scale variability (PDV), traditionally defined as statistical patterns of variance, reflect to first order the ocean's integration (i.e., reddening) of atmospheric forcing that arises from both a shift and a change in strength of the climatological (time-mean) atmospheric circulation. While these patterns concisely describe PDV, they do not distinguish among the key dynamical processes driving the evolution of PDV anomalies, including atmospheric and ocean teleconnections and coupled feedbacks with similar spatial structures that operate on different timescales. In this review, we synthesize past analysis using an empirical dynamical model constructed from monthly ocean surface anomalies drawn from several reanalysis products, showing that the PDV modes of variance result from two fundamental low-frequency dynamical eigenmodes: the North Pacific-central Pacific (NP-CP) and Kuroshio-Oyashio Extension (KOE) modes. Both eigenmodes highlight how two-way tropical-extratropical teleconnection dynamics are the primary mechanisms energizing and synchronizing the basin-scale footprint of PDV. While the NP-CP mode captures interannual- to decadal-scale variability, the KOE mode is linked to the basin-scale expression of PDV on decadal to multidecadal timescales, including contributions from the South Pacific.

Effect of live Eimeria vaccination or salinomycin on growth and immune status in broiler chickens receiving in-feed inclusion of gelatin and vitamin E.

This experiment determined if 2% of gelatin, to improve the levels of proline and glycine in the diet, and 70 mg/kg of vitamin E supplementation would relieve the impaired performance of male Cobb broilers vaccinated for coccidiosis. Half of the chicks were vaccinated via water (live oocysts), while the other half received medication (salinomycin) in the feed until 35 d of age. The effects of coccidiosis vaccine on performance and mRNA levels of genes involved in mucin synthesis, cytokines, trefoil family factor-2 (TFF2), and metabolic processes (CD36) in the jejunum of broilers were measured. Vaccination negatively affected performance in the first 21 d; however, the inclusion of gelatin and vitamin E reduced this negative response. Additionally, supplementation with these nutrients led to an improvement in broilers receiving the coccidiostat (P < 0.05). From 21 to 35 d, birds treated with gelatin and coccidiosis vaccine experienced better body weight gain than birds without gelatin and vitamin E (P < 0.05). Vaccinated chickens had decreased body weight and decreased anti-inflammatory cytokine expression. Furthermore, they had increased inflammatory cytokine expression, mucin 2 expression, and TFF2 compared to salinomycin-fed broilers (P < 0.05). Transcripts for IL-1B, IFN-y, MUC2, TFF2 were decreased while mRNAs for IL-4 and IL-10 increased in salinomycin-fed broilers compared to vaccinated broilers (P < 0.05). In conclusion, broilers vaccinated against coccidiosis increase their pro-inflammatory immune status and mucin expression compared to broilers receiving salinomycin. These events may contribute to lower performance in vaccinated broiler chicks. Moreover, vitamin E and gelatin can minimize the vaccine's negative immune effects and promote better performance.

Protein-based HDL subspecies: Rationale and association with cardiovascular disease, diabetes, stroke, and dementia.

HDL-cholesterol is associated with reduced risk of cardiovascular disease, and is used in clinical practice for risk stratification. HDL is composed of many protein-defined subspecies that each comprises just a few percent of the total, some associated with lower and some with higher risk of CVD. HDL that contains apoC3 or apoE are subspecies that have opposing actions on HDL reverse cholesterol transport and opposing associations with risk of future CVD, apoC3 adverse and apoE beneficial. In addition to coronary heart disease, HDL that contains apoC3 is associated with risk of future type 2 diabetes and insulin resistance; ischemic stroke and cerebral infarction; dementia and the deposition of beta-amyloid in the brain. HDL that contains apoE and apoE itself are associated with lower risk of dementia. Other HDL subspecies that contain complement C3, alpha-2 macroglobulin, plasminogen, or haptoglobin are associated with higher future risk of coronary heart disease, whereas others such as HDL that contains apoC1 are associated with lower risk. At this time, these findings provide improved understanding of the multifaceted HDL system to better determine risk and targeting of therapy for the most prevalent chronic lifestyle diseases in our society.

COVID-19 and HIV/AIDS in a cohort study in Sao Paulo, Brazil: outcomes and disparities by race and schooling.

Studies describing characteristics and outcomes of COVID-19 among people living with HIV are currently limited, lacking detailed evaluation of the interplay among demographics, HIV-related variables, and comorbidities on COVID-19 outcomes. This retrospective cohort study describes mortality rates overall and according to demographic characteristics and explores predictors of admission to intensive care unit and death among 255 persons living with HIV with severe acute respiratory syndrome and confirmed SARS-CoV-2 infection in the State of Sao Paulo, Brazil. We found that the overall mortality rate was 4.1/1,000 person-days, with a case-fatality of 34%. Higher rates occurred among older adults, Black/Mixed skin color/race patients, and those with lower schooling. In a multivariable analysis adjusted for age, sex, CD4 count, viral load and number of comorbidities, skin color/race, and schooling remained significantly associated with higher mortality. Although tenofovir use was more frequent among survivors in the univariable analysis, we failed to find a statistically significant association between tenofovir use and survival in the multivariable analysis. Our findings suggest that social vulnerabilities related to both HIV and COVID-19 significantly impact the risk of death, overtaking traditional risk factors such as age, sex, CD4 count, and comorbidities.

Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of Zika Virus Infection in Gestation cohort study.

OBJECTIVE: To define the prevalence of adverse outcomes of maternal infection in a large cohort of ZIKV-infected Brazilian women and their infants. DESIGN: Prospective population-based cohort study. SETTING: Ribeirão Preto's region's private and public health facilities. POPULATION: Symptomatic ZIKV-infected mothers and their infants. METHODS: Prenatal/early neonatal data were obtained for all mother-child pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing and neurological examinations and Bayley III screening tests within 3 months of age. MAIN OUTCOME MEASURES: Prevalence of pregnancy losses and anomalies detected at birth or within 3 months according to the gestational age of infection. RESULTS: Overall, 511 ZIKV-infected women were identified from a total of 1116 symptomatic women; as there were two twins, there were a total of 513 fetuses included. Of these, 13 (2.5%; 95% CI 1.5-4.3) presented with major signs of congenital Zika syndrome (CZS). Of the 511 women, there were 489 livebirths and 24 (4.7%) pregnancy losses (20 miscarriages and four stillbirths). ZIKV-related anomalies occurred in the offspring of 42/511 (8.2%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4 (25.0%) stillbirths and in 19/489 (3.9%; 95% CI 2.5-5.9) of the liveborn infants. Fetal abnormalities were 14.0 (95% CI 7.6-26.0) times more likely with gestational infection occurring in ≤11 weeks. On follow up of 280 asymptomatic infants, 2/155 (1.3%) had eye abnormalities, 1/207 (0.5%) had CNS imaging findings and 16/199 (8%) presented neurological alert signs. CONCLUSIONS: This prospective population-based study represents the largest Brazilian cohort study of ZIKV in pregnancy. Congenital anomalies potentially associated with CZS are less frequent than previously thought. There is a strong association between the gestational age of infection (≤11 weeks) and a poorer early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age. TWEETABLE ABSTRACT: ZIKV and pregnancy: adverse outcomes are less common, more prevalent for first-trimester infections, and potentially subclinical.

Plasma Concentrations of Long Chain N-3 Fatty Acids in Early and Mid-Pregnancy and Risk of Early Preterm Birth.

BACKGROUND: Fish oil supplementation has been shown to delay spontaneous delivery, but the levels and clinical significance remain uncertain. We examined the association between plasma fatty acids quantified in pregnancy and subsequent risk of early preterm birth. METHODS: In a case-control design nested in the Danish National Birth Cohort, we identified 376 early preterm cases (<34 gestational weeks, excluding preeclampsia cases) and 348 random controls. Plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA% of total fatty acids), were measured twice in pregnancy, at gestation weeks 9 and 25 (medians). Odds ratios and 95% confidence intervals (CI's) for associations between EPA+DHA and early preterm risk were estimated by logistic regression, adjusted for the woman's age, height, pre-pregnancy BMI, parity, smoking, and socioeconomic factors. Hypotheses and analytical plan were defined and archived a priori. FINDINGS: Analysis using restricted cubic splines of the mean of 1st and 2nd sample measurements showed a strong and significant non-linear association (p < 0.0001) in which the risk of early preterm birth steeply increased when EPA+DHA concentrations were lower than 2% and flattened out at higher levels. Women in the lowest quintile (EPA+DHA < 1.6%) had 10.27 times (95% confidence interval 6.80-15.79, p < 0.0001) increased risk, and women in the second lowest quintile had 2.86 (95% CI 1.79-4.59, p < 0.0001) times increased risk, when compared to women in the three aggregated highest quintiles (EPA+DHA ≥ 1.8%). INTERPRETATION: Low plasma concentration of EPA and DHA during pregnancy is a strong risk factor for subsequent early preterm birth in Danish women.

Aquatic life protection index of an urban river Bacanga basin in northern Brazil, São Luís - MA / Índice de proteção da vida aquática em uma bacia urbana do rio Bacanga no norte do Brasil, São Luís - MA

Abstract Bacanga River Basin faces environmental problems related to urbanization and discharge of untreated domestic sewage, which compromise its ecosystem health. Due to the small number of studies that assessed its water quality, the present study aimed to assess the current status of this ecosystem based on the aquatic life protection index. Samples were carried out every two months, in a total of six events, in six sites along the basin, where the water samples were collected to assess physicochemical parameters and calculate the trophic state index and the index of minimum parameters for the protection of aquatic communities. The data were also compared with values determined by the resolution National Environment Council - CONAMA 357/05. Our results reveal significant changes in the water quality of Bacanga River Basin. An increase in nutrients and chlorophyll-a concentration led it to eutrophication. The surfactant values were high and put in danger the aquatic biota. Dissolved oxygen rates were below the values allowed by the resolution in most sites sampled. The current water quality is terrible for the protection of aquatic life in 61.92% of the sites sampled.

Resumo A Bacia Hidrográfica do rio Bacanga (BHRB) apresenta problemas ambientais relacionados a urbanização e lançamentos de esgoto in natura que comprometem a qualidade desse ecossistema. Devido ao reduzido número de estudos associados à avaliação da qualidade da água no local, este estudo teve como objetivo avaliar a situação atual desse ecossistema por meio do Índice de Proteção da Vida Aquática. Seis amostragens bimestrais foram realizadas em seis pontos ao longo da bacia, coletando parâmetros físico-químicos para a aplicação do Índice de Estado Trófico e Índice de Parâmetros Mínimos para a Proteção da Vida Aquática, relacionando-os com a resolução Conselho Nacional do Meio Ambiente - CONAMA/357. Os resultados revelaram alterações significativas na qualidade da água da BHRB, o aumento de nutrientes e das concentrações de clorofila-a conduziram ao um estado geral de eutrofização. Os valores de surfactantes foram altos colocando em risco a biota aquática e as taxas de oxigênio dissolvido estiveram abaixo do permitido pela resolução na maioria dos pontos amostrados. A situação atual da qualidade da água para proteção da vida aquática é péssima em 61,92% dos pontos amostrados.

Oligomerization affects the kinetics and thermodynamics of the interaction of a Bowman-Birk inhibitor with proteases.

The black-eyed pea trypsin/chymotrypsin inhibitor (BTCI) forms concentration dependent homomultimers, as previously demonstrated by Light scattering and Atomic Force Microscopy. Considering that these self-aggregates might influence their binding to cognate enzymes, we investigated the interaction of BTCI at picomolar concentrations using surface immobilized Chymotrypsin (α-CT) and Trypsin (T) by Surface Plasmon Resonance. Our results indicate that BTCI has subnanomolar affinity to both immobilized enzymes, which is approximately two orders of magnitude higher than previously reported. Moreover, we probed the influence of temperature on protein binding equilibria in order to investigate their interaction energetics. While the BTCI/T interaction concurs with the canonical entropy-driven mechanism described for BBI interactions with serine proteinases, the BTCI/α-CT interaction does not. Our measurements indicate that bimolecular BTCI/α-CT complexes form with a negative enthalpy change and a moderate entropic increase. Direct calorimetric evaluation is in accord with the van't Hoff approximation obtained by SPR. We demonstrate that as protein concentrations increase to the micromolar range, secondary endothermic events become prevalent and affect both the kinetics and thermodynamics of protein associations. Our study reinforces that BBI interactions with serine proteinases should be studied in dilute solutions to abridge often neglected secondary interactions.

Aquatic life protection index of an urban river Bacanga basin in northern Brazil, São Luís - MA.

Bacanga River Basin faces environmental problems related to urbanization and discharge of untreated domestic sewage, which compromise its ecosystem health. Due to the small number of studies that assessed its water quality, the present study aimed to assess the current status of this ecosystem based on the aquatic life protection index. Samples were carried out every two months, in a total of six events, in six sites along the basin, where the water samples were collected to assess physicochemical parameters and calculate the trophic state index and the index of minimum parameters for the protection of aquatic communities. The data were also compared with values determined by the resolution National Environment Council - CONAMA 357/05. Our results reveal significant changes in the water quality of Bacanga River Basin. An increase in nutrients and chlorophyll-a concentration led it to eutrophication. The surfactant values were high and put in danger the aquatic biota. Dissolved oxygen rates were below the values allowed by the resolution in most sites sampled. The current water quality is terrible for the protection of aquatic life in 61.92% of the sites sampled.

Action of two phospholipases A2 purified from Bothrops alternatus snake venom on macrophages.

The in vitro effects of BaltTX-I, a catalytically inactive Lys49 variant of phospholipase A2 (PLA2), and BaltTX-II, an Asp49 catalytically active PLA2 isolated from Bothrops alternatus snake venom, on thioglycollate-elicited macrophages (TG-macrophages) were investigated. At non-cytotoxic concentrations, the secretory PLA2 BaltTX-I but not BaltTX-II stimulated complement receptor-mediated phagocytosis. Pharmacological treatment of TG-macrophages with staurosporine, a protein kinase C (PKC) inhibitor, showed that this kinase is involved in the increase of serum-opsonized zymosan phagocytosis induced by BaltTX-I but not BaltTX-II secretory PLA2, suggesting that PKC may be involved in the stimulatory effect of this toxin in serum-opsonized zymosan phagocytosis. Moreover, BaltTX-I and -II induced superoxide production by TG-macrophages. This superoxide production stimulated by both PLA2s was abolished after treatment of cells with staurosporine, indicating that PKC is an important signaling pathway for the production of this radical. Our experiments showed that, at non-cytotoxic concentrations, BaltTX-I may upregulate phagocytosis via complement receptors, and that both toxins upregulated the respiratory burst in TG-macrophages.

Effect of Bothrops alternatus snake venom on macrophage phagocytosis and superoxide production: participation of protein kinase C

Envenomations caused by different species of Bothrops snakes result in severe local tissue damage, hemorrhage, pain, myonecrosis, and inflammation with a significant leukocyte accumulation at the bite site. However, the activation state of leukocytes is still unclear. According to clinical cases and experimental work, the local effects observed in envenenomation by Bothrops alternatus are mainly the appearance of edema, hemorrhage, and necrosis. In this study we investigated the ability of Bothrops alternatus crude venom to induce macrophage activation. At 6 to 100 »g/mL, BaV is not toxic to thioglycollate-elicited macrophages; at 3 and 6 »g/mL, it did not interfere in macrophage adhesion or detachment. Moreover, at concentrations of 1.5, 3, and 6 »g/mL the venom induced an increase in phagocytosis via complement receptor one hour after incubation. Pharmacological treatment of thioglycollate-elicited macrophages with staurosporine, a protein kinase (PKC) inhibitor, abolished phagocytosis, suggesting that PKC may be involved in the increase of serum-opsonized zymosan phagocytosis induced by BaV. Moreover, BaV also induced the production of anion superoxide (O2-) by thioglycollate-elicited macrophages. This BaV stimulated superoxide production was abolished after treating the cells with staurosporine, indicating that PKC is an important signaling pathway for the production of this radical. Based on these results, we suggest that phagocytosis and reactive oxygen species are involved in the pathogenesis of local tissue damage characteristic of Bothrops spp. envenomations.

Effect of vitamin supplementation on breast milk concentrations of retinol, carotenoids and tocopherols in HIV-infected Tanzanian women.

BACKGROUND/OBJECTIVE: The effect of daily prenatal and postnatal vitamin supplementation on concentrations of breast milk nutrients is not well characterized in HIV-infected women. We examined the impact of vitamin supplementation during pregnancy and lactation on breast milk concentrations of retinol, carotenoids and tocopherols during the first year postpartum among 626 HIV-infected Tanzanian women. SUBJECTS/METHODS: We conducted a randomized, double-blind, placebo-controlled trial. Women were assigned to one of four daily oral supplements: vitamin A+beta-carotene (VA+BC); multivitamins (MV; B, C and E); MV+VA+BC or placebo. Concentrations of breast milk nutrients were determined by high-performance liquid chromatography at birth and every 3 months thereafter. RESULTS: Supplementation with VA+BC increased concentrations of retinol, beta-carotene and alpha-carotene at delivery by 4799, 1791 and 84 nmol l(-1), respectively, compared to no VA+BC (all P<0.0001). MV supplementation did not increase concentrations of alpha-tocopherol or delta-tocopherol at delivery but significantly decreased concentrations of breast milk gamma-tocopherol and retinol. Although concentrations of all nutrients decreased significantly by 3 months postpartum, retinol, alpha-carotene and beta-carotene concentrations were significantly higher among those receiving VA+BC at 3, 6 and 12 months compared to no VA+BC. alpha-Tocopherol was significantly higher, while gamma-tocopherol concentrations were significantly lower, among women receiving MV compared to no MV at 3, 6 and 12 months postpartum. CONCLUSIONS: Sustained supplementation of HIV-infected breastfeeding mothers with MV could be a safe and effective intervention to improve vitamin E concentrations in breast milk. VA+BC supplementation increases concentrations of breast milk retinol but it is not recommended in HIV-infected mothers due to the elevated risk of vertical transmission.

Análise de medicamentos antiinflamatórios não esteroidais manipulados empregando espectroscopia de reflexão difusa no infravermelho com transformada de Fourier (DRIFTS) / Analysis of nonsteroidal antiinflammatory drugs in compounded medicines by diffuse-reflectance infrared Fourier transform spectroscopy (DRIFTS)

A análise de dois fármacos diferentes, mas estruturalmente semelhantes, foi realizada, empregando espectros de reflexão difusa no infravermelho médio com transformada de Fourier (DRIFTS), em associação com a técnica de análise por agrupamentos hierárquicos (AAH). Amostras de 3 diferentes farmácias de manipulação, contendo diclofenaco de sódio 50mg, diclofenaco de potássio 50mg e seus respectivos excipientes, foram analisadas em duplicata por dois analistas. Para a análise multivariada foi empregado o aplicativo Pirouette R 2.7 da Infometrix, selecionando-se o conjunto de regiões dos espectros com maior número de informações. Os dendogramas foram construídos com os dados auto-escalados e correção do espalhamento de luz (MSC), utilizando três tipos de construções: simples, flexível e incremental. Com a aplicação da AAH, constatou-se a formação de diferentes grupos obedecendo à discriminação de cada princípio ativo, indicando seus fornecedores e, em separado, outro grupo. Estes resultados demonstram que a técnica DRIFTS, em conjunto com ferramentas quimioterápicas, constitui uma excelente opção para a caracterização de fármacos, gerando uma inovadora metodologia para auxiliar no controle da qualidade de processos industriais de produção de medicamentos

Constructive genetic algorithm for clustering problems.

Genetic algorithms (GAs) have recently been accepted as powerful approaches to solving optimization problems. It is also well-accepted that building block construction (schemata formation and conservation) has a positive influence on GA behavior. Schemata are usually indirectly evaluated through a derived structure. We introduce a new approach called the Constructive Genetic Algorithm (CGA), which allows for schemata evaluation and the provision of other new features to the GA. Problems are modeled as bi-objective optimization problems that consider the evaluation of two fitness functions. This double fitness process, called fg-fitness, evaluates schemata and structures in a common basis. Evolution is conducted considering an adaptive rejection threshold that contemplates both objectives and attributes a rank to each individual in population. The population is dynamic in size and composed of schemata and structures. Recombination preserves good schemata, and mutation is applied to structures to get population diversification. The CGA is applied to two clustering problems in graphs. Representation of schemata and structures use a binary digit alphabet and are based on assignment (greedy) heuristics that provide a clearly distinguished representation for the problems. The clustering problems studied are the classical p-median and the capacitated p-median. Good results are shown for problem instances taken from the literature.

[Lesions of the central nervous system in Adams-Oliver's syndrome]. / Lesões do sistema nervoso central na síndroma de Adams-Oliver.

The authors report two cases of Adams-Oliver syndrome in 2-year-old children characterized by aplasia cutis congenita and terminal congenital abnormalities of the limbs. The diagnosis was made at birth and the aplasia cutis was associated with extensive skull defects, exposing the dural sinuses. The differences between the two patients were essentially the extension and the severity of the scalp and limb osteo-cutaneous lesions, associated malformations of the central nervous system and complications. In one child we found focal hemimegalencephaly of the right hemisphere and in the other one the syndrome was complicated by encephaloclastic cerebral lesions and encephalic herniation. Both children have survived, but the diagnosis of central nervous system malformations and the encephaloclastic lesions associated modified the initial prognosis and the future outcome conspicuously.

Dopamine-glutamate interactions in the striatum: behaviourally relevant modification of excitotoxicity by dopamine receptor-mediated mechanisms.

The two most important afferent projections to the striatum contain glutamate and dopamine, respectively. Excitotoxic damage resulting from excessive stimulation of the N-methyl-D-aspartate subtype of glutamate receptor has been implicated in pathophysiology of ischaemic stroke, hypoglycaemic brain damage and Huntington's disease. We studied the ability of the dopamine system to modify the anatomical, neurochemical and behavioural consequences of glutamatergic toxicity in the striatum. In a first set of experiments, the specific N-methyl-D-aspartate receptor agonist quinolinate was injected unilaterally into the striatum of rats pretreated with one of (i) intraperitoneal (i.p.) saline (controls); (ii) i.p. haloperidol, a D2 dopamine receptor agonist; or (iii) 6-hydroxydopamine lesion of the ipsilateral nigrostriatal tract. Quinolinate-induced striatal damage, as assessed by morphometric and neurochemical criteria, was significantly attenuated in the animals with 6-hydroxydopamine lesions and in those pretreated with haloperidol, compared with saline-pretreated controls. There were no significant differences between the 6-OHDA and haloperidol groups. In a second set of experiments, animals received (i) bilateral intrastriatal quinolinate plus perioperative i.p. saline; (ii) bilateral intrastriatal quinolinate plus i.p. haloperidol; or (iii) bilateral intrastriatal saline. Again, the quinolinate-lesioned animals treated with perioperative haloperidol had significantly less striatal damage than the bilateral quinolinate rats. Behavioural assessment in the Morris Water Maze showed the bilateral quinolinate+haloperidol group to be significantly less impaired on a spatial acquisition task than the bilateral quinolinate animals. Measures of spontaneous daytime motor activity showed significant differences in average speed and rest time between the bilateral quinolinate+haloperidol rats and the bilateral quinolinate group. The performance of the bilateral quinolinate+haloperidol group was not significantly different from that of controls on any of the behavioural tasks. These results indicate an important role for D2 dopamine receptor-mediated mechanisms in striatal excitotoxicity. Since the excitotoxic process involves the same fundamental signalling mechanism that is involved in normal glutamatergic transmission, these findings imply an ability of D2 receptor blockade to modify glutamate signalling in the striatum. These results may have implications for treatment strategies in ischaemic stroke, hypoglycaemic brain damage and schizophrenia.