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Aims: Tailored education is recommended for cardiac patients, yet little is known about information needs in areas of the world where it is most needed. This study aims to assess (i) the measurement properties of the Information Needs in Cardiac Rehabilitation short version (INCR-S) scale and (ii) patient's information needs globally., Methods and Results: In this cross-sectional study, English, simplified Chinese, Portuguese, or Korean versions of the INCR-S were administered to in- or out-patients via Qualtrics (January 2022-November 2023). Members of the International Council of Cardiovascular Prevention and Rehabilitation community facilitated recruitment. Importance and knowledge sufficiency of 36 items were rated. Links to evidence-based lay education were provided where warranted. A total of 1601 patients from 19 middle- and high-income countries across the world participated. Structural validity was supported upon factor analysis, with five subscales extracted: symptom response/medication, heart diseases/diagnostic tests/treatments, exercise and return-to-life roles/programmes to support, risk factors, and healthy eating/psychosocial management. Cronbach's alpha was 0.97. Construct validity was supported through significantly higher knowledge sufficiency ratings for all items and information importance ratings for all subscales in cardiac rehabilitation (CR) enrolees vs. non-enrolees (all P < 0.001). All items were rated as very important-particularly regarding cardiac events, nutrition, exercise benefits, medications, symptom response, risk factor control, and CR-but more so in high-income countries in the Americas and Western Pacific. Knowledge sufficiency ranged from 30.0 to 67.4%, varying by region and income class. Ratings were highest for medications and lowest for support groups, resistance training, and alternative medicine., Conclusion: Identification of information needs using the valid and reliable INCR-S can inform educational approaches to optimize patients' health outcomes across the globe., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Mounting evidence suggests that environmentally induced epigenetic inheritance occurs in mammals and that traits in the progeny can be shaped by parental environmental experiences. Epidemiological studies link parental exposure to environmental toxicants, such as the pesticide DDT, to health phenotypes in the progeny, including low birth and increased risk of chronic diseases later in life. Here, we show that the progeny of male mice exposed to DDT in the pre-conception period are born smaller and exhibit sexual dimorphism in metabolic function, with male, but not female, offspring developing severe glucose intolerance compared to controls. These phenotypes in DDT offspring were linked to reduced fetal growth and placenta size as well as placenta-specific reduction of glycogen levels and the nutrient sensor and epigenetic regulator OGT, with more pronounced phenotypes observed in male placentas. However, placenta-specific genetic reduction of OGT only partially replicates the metabolic phenotype observed in offspring of DDT-exposed males. Our findings reveal a role for paternal pre-conception environmental experiences in shaping placenta development and in fetal growth restriction. While many questions remain, our data raise the tantalizing possibility that placenta programming could be a mediator of environmentally induced intergenerational epigenetic inheritance of phenotypes and needs to be further evaluated., (© 2024. The Author(s).)

This study examined the impact of maternal protein supplementation during mid-gestation on offspring, considering potential sex-related effects. Forty-three pregnant purebred Tabapuã beef cows (20 female and 23 male fetuses) were collectively managed in a pasture until 100 d of gestation. From 100 to 200 d of gestation, they were randomly assigned to the restricted group [(RES) - basal diet (75% corn silage + 25% sugar cane bagasse + mineral mixture); n = 24] or control group [(CON) - same basal diet + based-plant supplement [40% of crude protein, 3.5 g/kg of body weight (BW); n = 19]. From 200 d of gestation until parturition, all cows were equally fed corn silage and mineral mixture. During the cow-calf phase, cows and their calves were maintained in a pasture area. After weaning, calves were individually housed and evaluated during the backgrounding (255 to 320 d), growing 1 (321 to 381 d), and growing 2 (382 to 445 d) phases. Offspring's blood samples were collected at 210 and 445 d of age. Samples of skeletal muscle tissue were collected through biopsies at 7, 30, and 445 d of age. Muscle tissue samples were subjected to reverse-transcription quantitative polymerase chain reaction analysis. Prenatal treatment and offspring's sex (when pertinent) were considered fixed effects. The significance level was set at 5%. At mid-gestation, cows supplemented with protein reached 98% and 92% of their protein and energy requirements, while nonsupplemented cows attained only 30% and 50% of these requirements, respectively. The RES offspring were lighter at birth (27 vs. 31 kg), weaning (197 vs. 214 kg), and 445 d of age (398 vs. 429 kg) (P ≤ 0.05). The CON calves had greater (P < 0.05) morphometric measurements overall. The CON offspring had ~26% greater muscle fiber area (P ≤ 0.01). There was a trend (P = 0.06) for a greater Mechanistic target of rapamycin kinase mRNA expression in the Longissimus thoracis in the CON group at 7 d of age. The Myogenic differentiation 1 expression was greater (P = 0.02) in RES-females. Upregulation of Carnitine palmitoyltransferase 2 was observed in RES offspring at 445 d (P = 0.04). Expression of Fatty acid binding protein 4 (P < 0.001), Peroxisome proliferator-activated receptor gamma (P < 0.001), and Stearoyl-Coenzyme A desaturase (P < 0.001) was upregulated in CON-females. Therefore, protein supplementation during gestation enhances offspring growth and promotes favorable responses to lipogenesis, particularly in females., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cardiac rehabilitation (CR) programs are underutilized globally, especially by women. In this study we investigated sex differences in CR barriers across all world regions, to our knowledge for the first time, the characteristics associated with greater barriers in women, and women's greatest barriers according to enrollment status., Methods: In this cross-sectional study, the English, Simplified Chinese, Arabic, Portuguese, or Korean versions of the Cardiac Rehabilitation Barriers Scale was administered to CR-indicated patients globally via Qualtrics from October 2021 to March 2023. Members of the International Council of Cardiovascular Prevention and Rehabilitation community facilitated participant recruitment. Mitigation strategies were provided and rated., Results: Participants were 2163 patients from 16 countries across all 6 World Health Organization regions; 916 (42.3%) were women. Women did not report significantly greater total barriers overall, but did in 2 regions (Americas, Western Pacific) and men in 1 (Eastern Mediterranean; all P < 0.001). Women's barriers were greatest in the Western Pacific (2.6 ± 0.4/5) and South East Asian (2.5 ± 0.9) regions (P < 0.001), with lack of CR awareness as the greatest barrier in both. Women who were unemployed reported significantly greater barriers than those not (P < 0.001). Among nonenrolled referred women, the greatest barriers were not knowing about CR, not being contacted by the program, cost, and finding exercise tiring or painful. Among enrolled women, the greatest barriers to session adherence were distance, transportation, and family responsibilities. Mitigation strategies were rated as very helpful (4.2 ± 0.7/5)., Conclusions: CR barriers-men's and women's-vary significantly according to region, necessitating tailored approaches to mitigation. Efforts should be made to mitigate unemployed women's barriers in particular., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Dysfunctional hepatic metabolism has been linked to numerous diseases, including non-alcoholic fatty liver disease, the most common chronic liver disorder worldwide, which can progress to hepatic fibrosis, and is closely associated with insulin resistance and cardiovascular diseases. In addition, the liver secretes a wide array of metabolites, biomolecules, and microRNAs (miRNAs) and many of these secreted factors exert significant effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the involvement of liver-derived miRNAs in biological processes with an emphasis on delineating the communication between the liver and other tissues associated with metabolic disease progression. Furthermore, the review identifies the primary molecular targets by which miRNAs act. These consolidated findings from numerous studies provide insight into the underlying mechanism of various metabolic disease progression and suggest the possibility of using circulatory miRNAs as prognostic predictors and therapeutic targets for improving clinical intervention strategies.

The veterinarian is responsible for monitoring and inspecting rodeos, thus ensuring the welfare of the animals. Clinical follow-up is of great importance in animal athletes, and ultrasound has become an important, widely used complementary diagnostic method in the evaluation of these animals. In equine medicine and dairy cattle, there are several studies that describe tendon injuries through ultrasonography. However, in athlete bulls, there are still no studies using this tool as a diagnostic aid for these injuries. The first objective of the present study is to describe the ultrasound anatomy of the distal flexor structures of the thoracic limbs of healthy rodeo bulls and their measurements. The second objective is to report sonographic findings referring to changes found in the studied region of these animals. Forty-two bulls from a farm specialized in breeding and training high-performance animals were evaluated. Physical evaluation and measurements of external parameters were performed to verify possible correlations. For the ultrasound examination, a 10 MHz linear probe was used. Measurements were taken of the tendons of the flexor digit muscles, branch of the interosseous muscle for the tendon of the superficial digital flexor muscle and interosseous muscle. 42 animals were evaluated, but two were excluded from the statistical analysis because they had a history of lameness or excessive effort in the preceding six months, and their cases are described in this study. Based on knowledge of ultrasound and anatomy, greater reliability is obtained in the diagnosis and prognosis of these animals., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Adipose tissue constantly secretes adipokines and extracellular vesicles including exosomes to crosstalk with distinct tissues and organs for whole-body homeostasis. However, dysfunctional adipose tissue under chronic inflammatory conditions such as obesity, atherosclerosis, and diabetes shows pro-inflammatory phenotypes accompanied by oxidative stress and abnormal secretion. Nevertheless, molecular mechanisms of how adipocytes are stimulated to secrete exosomes under those conditions remain poorly understood., Methods: Mouse and human in vitro cell culture models were used for performing various cellular and molecular studies on adipocytes and macrophages. Statistical analysis was performed using Student's t-test (two-tailed, unpaired, and equal variance) for comparisons between two groups or ANOVA followed by Bonferroni's multiple comparison test for comparison among more than two groups., Results and Discussion: In this work, we report that CD36, a scavenger receptor for oxidized LDL, formed a signaling complex with another membrane signal transducer Na/K-ATPase in adipocytes. The atherogenic oxidized LDL induced a pro-inflammatory response in in vitro differentiated mouse and human adipocytes and also stimulated the cells to secrete more exosomes. This was largely blocked by either CD36 knockdown using siRNA or pNaKtide, a peptide inhibitor of Na/K-ATPase signaling. These results showed a critical role of the CD36/Na/K-ATPase signaling complex in oxidized LDL-induced adipocyte exosome secretion. Moreover, by co-incubation of adipocyte-derived exosomes with macrophages, we demonstrated that oxidized LDL-induced adipocyte-derived exosomes promoted pro-atherogenic phenotypes in macrophages, including CD36 upregulation, IL-6 secretion, metabolic switch to glycolysis, and mitochondrial ROS production. Altogether, we show here a novel mechanism through which adipocytes increase exosome secretion in response to oxidized LDL and that the secreted exosomes can crosstalk with macrophages, which may contribute to atherogenesis., Competing Interests: JIS has ownership on Xipiro, a company dedicated to the development of pNaKtide as a therapy for neovascularization disorders of the eye. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Pillai, Pereira, Zhang, Huang, Beg, Knaack, de Souza Goncalves, Sahoo, Silverstein, Shapiro, Sodhi and Chen.)

Key Message: The overexpression of the soybean GmEXPA1 gene reduces plant susceptibility to M. incognita by the increase of root lignification. Plant expansins are enzymes that act in a pH-dependent manner in the plant cell wall loosening and are associated with improved tolerance or resistance to abiotic or biotic stresses. Plant-parasitic nematodes (PPN) can alter the expression profile of several expansin genes in infected root cells. Studies have shown that overexpression or downregulation of particular expansin genes can reduce plant susceptibility to PPNs. Root-knot nematodes (RKN) are obligate sedentary endoparasites of the genus Meloidogyne spp. of which M. incognita is one of the most reported species. Herein, using a transcriptome dataset and real-time PCR assays were identified an expansin A gene (GmEXPA1; Glyma.02G109100) that is upregulated in the soybean nematode-resistant genotype PI595099 compared to the susceptible cultivar BRS133 during plant parasitism by M. incognita. To understand the role of the GmEXPA1 gene during the interaction between soybean plant and M. incognita were generated stable A. thaliana and N. tabacum transgenic lines. Remarkably, both A. thaliana and N. tabacum transgenic lines overexpressing the GmEXPA1 gene showed reduced susceptibility to M. incognita. Furthermore, plant growth, biomass accumulation, and seed yield were not affected in these transgenic lines. Interestingly, significant upregulation of the NtACC oxidase and NtEFE26 genes, involved in ethylene biosynthesis, and NtCCR and Nt4CL genes, involved in lignin biosynthesis, was observed in roots of the N. tabacum transgenic lines, which also showed higher lignin content. These data suggested a possible link between GmEXPA1 gene expression and increased lignification of the root cell wall. Therefore, these data support that engineering of the GmEXPA1 gene in soybean offers a powerful biotechnology tool to assist in RKN management., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

COVID-19 is renowned as a multi-organ disease having subacute and long-term effects with a broad spectrum of clinical manifestations. The evolving scientific and clinical evidence demonstrates that the frequency of cognitive impairment after COVID-19 is high and it is crucial to explore more clinical research and implement proper diagnostic and treatment strategies. Several central nervous system complications have been reported as comorbidities of COVID-19. The changes in cognitive function associated with neurodegenerative diseases develop slowly over time and are only diagnosed at an already advanced stage of molecular pathology. Hence, understanding the common links between COVID-19 and neurodegenerative diseases will broaden our knowledge and help in strategizing prognostic and therapeutic approaches. The present review focuses on the diverse neurodegenerative changes associated with COVID-19 and will highlight the importance of major circulating biomarkers and microRNAs (miRNAs) associated with the disease progression and severity. The literature analysis showed that major proteins associated with central nervous system function, such as Glial fibrillary acidic protein, neurofilament light chain, p-tau 181, Ubiquitin C-terminal hydrolase L1, S100 calcium-binding protein B, Neuron-specific enolase and various inflammatory cytokines, were significantly altered in COVID-19 patients. Furthermore, among various miRNAs that are having pivotal roles in various neurodegenerative diseases, miR-146a, miR-155, Let-7b, miR-31, miR-16 and miR-21 have shown significant dysregulation in COVID-19 patients. Thus the review consolidates the important findings from the numerous studies to unravel the underlying mechanism of neurological sequelae in COVID-19 and the possible association of circulatory biomarkers, which may serve as prognostic predictors and therapeutic targets in future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alvarez, Trent, Goncalves, Pereira, Puri, Frazier, Sodhi and Pillai.)

Cardiotoxicity is a well-known pathophysiological consequence in breast cancer patients receiving trastuzumab. Trastuzumab related cardiotoxicity typically results in an overall decline in cardiac function, primarily characterized by reduction in left ventricular ejection fraction (LVEF) and development of symptoms associated with heart failure. Current strategies for the monitoring of cardiac function, during trastuzumab therapy, includes serial echocardiography, which is cost ineffective as well as offers limited specificity, while offering limited potential in monitoring early onset of cardiotoxicity. However, biomarkers have been shown to be aberrant prior to any detectable functional or clinical deficit in cardiac function. Hence, this study aims to develop a panel of novel biomarkers and circulating miRNAs for the early screening of trastuzumab induced cardiotoxicity. Patients with clinical diagnosis of invasive ductal carcinoma were enrolled in the study, with blood specimen collected and echocardiography performed prior to trastuzumab therapy initiation at baseline, 3- and 6-months post trastuzumab therapy. Following 6-months of trastuzumab therapy, about 18% of the subjects developed cardiotoxicity, as defined by reduction in LVEF. Our results showed significant upregulation of biomarkers and circulating miRNAs, specific to cardiac injury and remodeling, at 3- and 6-months post trastuzumab therapy. These biomarkers and circulating miRNAs significantly correlated with the cardiac injury specific markers, troponin I and T. The findings in the present study demonstrates the translational applicability of the proposed biomarker panel in early preclinical diagnosis of trastuzumab induced cardiotoxicity, further allowing management of cardiac function decline and improved health outcomes for breast cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pillai, Pereira, Bonsu, Chaudhry, Puri, Lakhani, Tirona, Sodhi and Thompson.)

Background: The benefits of cardiac rehabilitation (CR) are already well established; however, such intervention has been underused, mainly in low- and middle-income countries., Aim: To compare adherence, effectiveness, and cost of a home CR with the traditional CR (TCR) in a middle-income country (MIC)., Design: Single-blind randomized control trial., Setting: A university hospital., Population: Individuals with coronary disease that were eligible were invited to participate. A randomized sample of 51 individuals was selected, where two participants were not included by not meeting inclusion criteria., Methods: The home-CR group participated in health education activities, carried out two supervised exercise sessions, and was instructed to carry out 58 sessions at home. Weekly telephone calls were made. The TCR group held 24 supervised exercise sessions and were instructed to carry out 36 sessions at home., Results: 49 individuals (42 male, 56.37±10.35years) participated in the study, 23 in the home-CR group and 26 in the TCR group. After the intervention, adherence in the home-CR and TCR groups was 94.18% and 79.08%, respectively, with no significant difference (P=0.191). Both protocols were effective for the other variables, with no differences. The cost per patient for the service was lower in the home-CR (US$ 59.31) than in the TCR group (US$ 135.05)., Conclusions: CR performed at home in an MIC demonstrated similar adherence and effectiveness compared to the TCR program, but with a lower cost for the service. The results corroborate the possibility of using home CR programs, even in MICs, after exercise risk stratification and under remote supervision., Clinical Rehabilitation Impact: Home-CR can contribute to overcome participants' barriers with compatible cost. Home-CR is effective in improving functional capacity and risk factors control. Perform risk stratification and remote supervision are essential to offer Home-CR.

Stevia rebaudiana (Bertoni) Bertoni is a plant of economic interest in the food and pharmaceutical industries due its steviol glycosides (SG), which are rich in metabolites that are 300 times sweeter than sucrose. In addition, S. rebaudiana plants contain phenolic compounds and flavonoids with antioxidant activity. Endophytic bacteria promote the growth and development and modulate the metabolism of the host plant. However, little is known regarding the role of endophytic bacteria in the growth; synthesis of SG, flavonoids and phenolic compounds; and the relationship between trichome development and specialized metabolites in S. rebaudiana , which was the subject of this study. The 12 bacteria tested did not increase the growth of S. rebaudiana plants; however, the content of SG increased with inoculation with the bacteria Enterobacter hormaechei H2A3 and E. hormaechei H5A2. The SG content in leaves paralleled an increase in the density of glandular, short, and large trichome. The image analysis of S. rebaudiana leaves showed the presence of SG, phenolic compounds, and flavonoids principally in glandular and short trichomes. The increase in the transcript levels of the KO , KAH , UGT74G1 , and UGT76G1 genes was related to the SG concentration in plants of S. rebaudiana inoculated with E. hormaechei H2A3 and E. hormaechei H5A2. In conclusion, inoculation with the stimulating endophytes E. hormaechei H2A3 and E. hormaechei H5A2 increased SG synthesis, flavonoid content and flavonoid accumulation in the trichomes of S. rebaudiana plants., Competing Interests: The authors declare there are no competing interests., (©2022 Oviedo-Pereira et al.)

The native marmoset of the Southeastern Atlantic Forest in Brazil is among the 25 most endangered primates of the world. Hybridization with alien species is one of its main threats registered since the early 2000s based on phenotype, so far, without genetic confirmation. Using uniparental molecular markers, we analyzed 18 putative hybrids, captured from 2004 to 2013 in different localities of the Atlantic Forest. A nine base pair deletion in the SRY gene of C. aurita was used to investigate paternal ancestry. Maternal ancestry was assessed by DNA sequencing of ca. 455 bp from the COX2 gene. Hybridization was confirmed for 16 out of the 18 marmosets since they inherited COX2 haplotypes of the alien C. penicillata or C. jacchus and the SRY deletion specific to C. aurita. Two individuals inherited both parental lineages of C. aurita, which is probably related to backcrossing or hybrid interbreeding. The direction of hybridization of females with the matrilineal lineage of invasive species with males descending from the native lineage was predominant in our sampling. This is the first time that hybridization between C. aurita and invasive species has been confirmed through genetic analysis., (© 2022. The Author(s).)

Cardiac glycosides, such as digoxin and digitoxin, are compounds that interact with Na + /K + -ATPase to induce anti-neoplastic effects; however, these cardiac glycosides have narrow therapeutic index. Thus, semi-synthetic analogs of digitoxin with modifications in the sugar moiety has been shown to be an interesting approach to obtain more selective and more effective analogs than the parent natural product. Therefore, the aim of this study was to assess the cytotoxic potential of novel digitoxigenin derivatives, digitoxigenin-α-L-rhamno-pyranoside (1) and digitoxigenin-α-L-amiceto-pyranoside (2), in cervical carcinoma cells (HeLa) and human diploid lung fibroblasts (Wi-26-VA4). In addition, we studied the anticancer mechanisms of action of these compounds by comparing its cytotoxic effects with the potential to modulate the activity of three P-type ATPases; Na + /K + -ATPase, sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA), and plasma membrane Ca 2+ -ATPase (PMCA). Briefly, the results showed that compounds 1 and 2 were more cytotoxic and selectivity for HeLa tumor cells than the nontumor cells Wi-26-VA4. While the anticancer cytotoxicity in HeLa cells involves the modulation of Na + /K + -ATPase, PMCA and SERCA, the modulation of these P-type ATPases was completely absent in Wi-26-VA4 cells, which suggest the importance of their role in the cytotoxic effect of compounds 1 and 2 in HeLa cells. Furthermore, the compound 2 inhibited directly erythrocyte ghosts PMCA and both compounds were more cytotoxic than digitoxin in HeLa cells. These results provide a better understanding of the mode of action of the synthetic cardiac glycosides and highlights 1 and 2 as potential anticancer agents., (© 2021 Wiley Periodicals LLC.)

There has been a progressive increase in the prevalence of obesity and its comorbidities such as type 2 diabetes and cardiovascular diseases worldwide. Recent studies have suggested that the crosstalk between adipose tissue and central nervous system (CNS), through cellular mediators and signaling pathways, may causally link obesity with cognitive decline and give rise to neurodegenerative disorders. Several mechanisms have been proposed in obesity, including inflammation, oxidative stress, insulin resistance, altered lipid and cholesterol homeostasis, which may result in neuroinflammation, altered brain insulin signaling, amyloid-beta (Aβ) deposition and neuronal cell death. Since obesity is associated with functional and morphological alterations in the adipose tissues, the resulting peripheral immune response augments the development and progression of cognitive decline and increases susceptibility of neurodegenerative disorders, such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). Studies have also elucidated an important role of high fat diet in the exacerbation of these clinical conditions. However, the underlying factors that propel and sustain this obesity associated cognitive decline and neurodegeneration, remains highly elusive. Moreover, the mechanisms linking these phenomena are not well-understood. The cumulative line of evidence have demonstrated an important role of microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression and transcriptional changes, as biomarkers of pathophysiological conditions. Despite the lack of utility in current clinical practices, miRNAs have been shown to be highly specific and sensitive to the clinical condition being studied. Based on these observations, this review aims to assess the role of several miRNAs and aim to elucidate underlying mechanisms that link obesity with cognitive decline and neurodegenerative disorders. Furthermore, this review will also provide evidence for the effect of dietary modulation which can potentially ameliorate cognitive decline and neurodegenerative diseases associated with obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Perdoncin, Konrad, Wyner, Lohana, Pillai, Pereira, Lakhani and Sodhi.)

Acinetobacter baumannii is a major cause of illness in hospitalized patients and the most important and common pathogen in nosocomial outbreaks worldwide. In animals, A. baumannii has been associated with respiratory infections in a group of minks, leading to pneumonia and acute mortality. This report documents a case of aspiration bronchopneumonia in a wild European hare caused by A. baumannii . A free-ranging, adult male European hare was submitted to necropsy after acute trauma due to being hit by a car. Its lungs showed consolidation with abscess in the middle and cranial lobes. Histopathologic evaluation revealed liquefactive necrosis associated with neutrophilic infiltration, cellular debris, plant material, and bacterial myriads surrounded by moderate neutrophils, macrophages, multinucleated giant cells, lymphocytes, and plasma cell inflammation. Acinetobacter baumannii was isolated from lung tissue.

Despite the growing interest in the antitumor effect of cardiotonic steroids, combination treatments with well-established chemotherapy drugs like paclitaxel have been rarely investigated. Moreover, paclitaxel has been suggested as a Na + /K + -ATPase inhibitor. Here we investigated the effect of paclitaxel and digoxin alone or in combination on the viability of human lung (A549) and cervical cancer (HeLa) cell lines and the inhibitory effect of paclitaxel on several mammalian Na + /K + -ATPases. Although the viability of both tumor cell lines was concentration-dependently affected by digoxin treatment after 48 hours (A549 IC 50  = 31 nM and HeLa IC 50  = 151 nM), a partial effect was observed for paclitaxel, with a maximal inhibitory effect of 45% at 1000 nM with A549 and around 70% with HeLa cells (IC 50  = 1 nM). Although the two drugs were cytotoxic, their combined effect in HeLa cells was revealed to be antagonistic, as estimated by the combination index. No direct inhibitory effect of paclitaxel was detected in human, pig, rat, and mouse Na + /K + -ATPase enzymes, but high concentrations of paclitaxel decreased the Na + /K + -ATPase activity in HeLa cells after 48 hours without affecting protein expression. Our findings demonstrate that, under our conditions, paclitaxel and digoxin cotreatment produce antagonistic cytotoxic effects in HeLa cells, and the mechanism of action of paclitaxel does not involve a direct inhibition of Na + /K + -ATPase. More studies shall be designed to evaluate the consequences of the interaction of cardiotonic steroids and chemotherapy drugs., (© 2019 Wiley Periodicals, Inc.)

Cisplatin and other platinum-containing drugs have played a crucial role in anticancer treatments for over 30 years. However, treatment with cisplatin may cause serious side effects, such as myelosuppression, nausea, ototoxicity, nephrotoxicity, and cell resistance processes. In addition, cardiotonic steroids, particularly digoxin, have recently been suggested to exert potent anticancer effects. Therefore, it is possible that the combined treatment of HeLa cells with cisplatin and digoxin can ameliorate the cytotoxic effects and decrease the side effects of cisplatin. In this study, we demonstrated that the interaction between cisplatin and digoxin had a synergistic effect on cervical cancer cells and a significantly positive cytotoxic and antiproliferative effect on this cell line compared to the control and single cisplatin treatments. Although a decrease in the Na,K-ATPase α1 subunit expression was observed in total extracts, its expression remains unchanged in the membrane, as does the Na,K-ATPase activity. The antiproliferative effect of the synergistic treatment appears to depend on Src kinase activation, indicating the possible involvement of the Scr-EGFR-ERK1/2 pathway in the antitumor effect. The inhibition of ERK1/2 provoked the same synergism with 1 μM cisplatin as that observed with 1 nM digoxin plus 1 μM cisplatin but not with 1 nM digoxin. Pretreatment with PP2 during combined treatment abolished the synergistic effect on the antiproliferative activity. Cisplatin and digoxin are already used in the clinical setting; therefore, this study opens possibilities for future clinical trials of combined treatments to improve treatment outcomes with a lower incidence of toxicity and side effects., (© 2017 Wiley Periodicals, Inc.)

Some species are characterized by a high content of tannins, alkaloids, and phenols in their leaves. These secondary metabolites are released during DNA extraction and might hinder molecular studies based on PCR (polymerase chain reaction). To provide an efficient method to extract DNA, Mimosa tenuiflora, an important leguminous plant from Brazilian semiarid region used in popular medicine and as a source of fuelwood or forage, was used. Eight procedures previously reported for plants were tested and adapted from leaf tissues of M. tenuiflora stored at -20°C. The optimized procedure in this study encompassed the utilization of phenol during deproteinization, increased concentrations of cetyltrimethylammonium bromide and sodium chloride, and a shorter period and lower temperature of incubation concerning other methods. The extracted DNA did not present degradation, and amplification via PCR was successful using ISSR, trnL, ITS, and ETS primers. Besides M. tenuiflora, this procedure was also tested and proved to be efficient in genetic studies of other plant species.

The licuri palm Syagrus coronata plays a key role in the ecology and economy of Brazilian semiarid region. Nonetheless, genetic data about populations of this species are absent even though the intensive and uncontrolled exploitation since colonial periods has threatened the sustainability and viability of licuri populations. Therefore, we attempted to test the efficacy of transferability of microsatellite loci isolated from three palm tree species to S. coronata to analyze the population of this species throughout their range. A set of 19 heterologous microsatellite loci was tested in three native populations of S. coronata from the State of Bahia, northeastern Brazil, which amplified using distinct annealing temperatures (50°-60°C). Based on the 10 most polymorphic loci, the selected populations exhibited a mean number of alleles per locus of 9.8, and high genetic diversity values since the expected heterozygosity ranged from 0.573 to 0.754, while the observed heterozygosity varied from 0.785 to 1.000. In conclusion, the tested loci are transferrable and highly efficient to population studies in S. coronata, thus minimizing the lack of species-specific loci to the genetic monitoring of licuri populations.

Maytenus truncata (Celastraceae) is a plant species widely used in the treatment of ulcers and tumors. Despite the intensive harvest of native specimens in the State of Bahia, northeastern Brazil, there is no information about the genetic variability or structure of this species. Therefore, the goal of this study was to estimate the genetic diversity and population structure of M. truncata based on inter simple sequence repeat (ISSR) molecular markers. The samples comprised specimens from Jequié, Contendas do Sincorá, Boa Nova, and Boa Vista do Tupim in the State of Bahia. After selection of eight ISSR primers, the percentage of polymorphic loci was equal to 96.2% and genetic diversity was 0.3581. The Mantel test revealed positive correlation among genetic and geographic distances (r = 0.5462), but it was not significant (r ≥ 0, P = 0.8365). Even though AMOVA revealed that most variation was found within populations (68%), a high structuring was detected among them (ΦST = 0.31, P < 0.001). Both UPGMA and Bayesian analyses indicated that gene flow was higher between Jequié and Contendas do Sincorá, whereas samples from Boa Nova and Boa Vista do Tupim were more isolated. This result is likely because of the population decrease and restriction to gene flow associated with intensive extractivism of populations of this species.

Food webs include complex ecological interactions that define the flow of matter and energy, and are fundamental in understanding the functioning of an ecosystem. Temporal variations in the densities of communities belonging to the planktonic food web (i.e., microbial: bacteria, flagellate, and ciliate; and grazing: zooplankton and phytoplankton) were investigated, aiming to clarify the interactions between these organisms and the dynamics of the planktonic food web in a floodplain lake. We hypothesized that hydrological pulse determines the path of matter and energy flow through the planktonic food web of this floodplain lake. Data were collected monthly from March 2007 to February 2008 at three different sites in Guaraná Lake (Mato Grosso do Sul State, Brazil). The path analysis provided evidence that the dynamics of the planktonic food web was strongly influenced by the hydrological pulse. The high-water period favored interactions among the organisms of the microbial loop, rather than their relationships with zooplankton and phytoplankton. Therefore, in this period, the strong interaction among the organisms of the grazing food chain suggests that the microbial loop functions as a sink of matter and energy. In turn, in the low-water period, higher primary productivity appeared to favor different interactions between the components of the grazing food chain and microorganisms, which would function as a link to the higher trophic levels.

Background and Objectives: Low back pain (LBP) is a complaint of great importance among the elderly due to its significant impact on function. LBP could contribute to changes in the regulatory process of inflammatory mediators observed in elders. The aim of this study was to compare plasma levels of interleukin(IL)-6, soluble tumor necrosis factor receptor 1(sTNF-R1), and functionality among 3 groups of elderly women: GI, with LBP; GII, without LBP but reports of other pain; and GIII, without any reported pain., Material and Method: This was an observational study of a subsample of the international Back Complaints in the Elders cohort study. IL-6 and sTNF-R1 were measured using the enzyme-linked immunosorbent assay. Functionality was assessed using the Timed Up and Go, gait speed and Roland Morris Disability Questionnaire; and pain, using the numerical pain scale., Results: Two hundred and thirteen women aged 71.35 ± 4.76 years were included. GI presented the highest sTNF-R1 levels (p=0.016), worst TUG performance (p< 0.001) and slowest gait speed (p< 0.01) compared to GII and GIII, which were similar (p > 0.05). No difference was found between the IL-6 plasma levels in any of the groups., Conclusion: Elderly women with LBP had the highest sTNF-R1 plasma levels and the worst functional performance compared to elderly women with reports of other pain (not LBP) or no pain.

Background: The Duke Activity Status Index (DASI) assesses the functional capacity of patients with cardiovascular disease (CVD), but there is no Portuguese version validated for CVD., Objectives: To translate and adapt cross-culturally the DASI for the Portuguese-Brazil language, and to verify its psychometric properties in the assessment of functional capacity of patients with CVD., Methods: The DASI was translated into Portuguese, then checked by back-translation into English and evaluated by an expert committee. The pre-test version was first evaluated in 30 subjects. The psychometric properties and correlation with exercise testing was performed in a second group of 67 subjects. An exploratory factor analyses was performed in all 97 subjects to verify the construct validity of the DASI., Results: The intraclass correlation coefficient for test-retest reliability was 0.87 and for the inter-rater reliability was 0.84. Cronbach's α for internal consistency was 0.93. The concurrent validity was verified by significant positive correlations of DASI scores with the VO2max (r = 0.51, p < 0.001). The factor analysis yielded two factors, which explained 54% of the total variance, with factor 1 accounting for 40% of the variance. Application of the DASI required between one and three and a half minutes per patient., Conclusions: The Brazilian version of the DASI appears to be a valid, reliable, fast and easy to administer tool to assess functional capacity among patients with CVD.

Objective: To evaluate the elderly persons' functionality, based on the International Classification of Functionality., Methods: a cross-sectional, descriptive study; a stratified random sample of 903 elderly persons; a confidence level of 95%; and a margin of error of 2.5%. Questionnaire based on the International Classification of Functionality; data was collected based on structured interviews undertaken by health professionals in the health centers in the Alentejo region of Portugal., Results: 30.7% of the elderly persons stated that they were illiterate, and 22.9% lived alone. Feeding/dietary (18.7%), housing (19.2%) and health needs (26.0%) were not met. Orientation functions were maintained in 83.4%; 58% of the elderly persons referred to pain so intense that it required care; 73.3% of the elderly persons did not have functional dentition. Levels of performance were superior to 80% in the participation activities: washing oneself (82.6%), toileting (92.2%), dressing, eating, and drinking (89%)., Conclusion: although a progressive decline in functionality is observed as age advances, the majority of dimensions are preserved until around 75 years of age.

Melanoxylon brauna (Fabaceae - Caesalpinioideae) is an endemic and valuable hardwood tree species in the Brazilian Atlantic rainforest; it is comparable to African ebony wood. We tested three protocols of DNA extraction based on the citrimonium bromide (CTAB) method and evaluated the quantity, purity and integrity of the DNA. We also determined whether these procedures interfere with PCR amplification in order to develop a protocol for M. brauna. We found that the quality and integrity of DNA were improved with the use of proteinase K in the extraction buffer and by modifications in the centrifugation speed. The lowest concentration of DNA was obtained with Doyle and Doyle's protocol (5.42 ng/μL). Ferreira and Grattapaglia's protocol modified for M. brauna provided the most DNA (36.89 ng/μL) and the highest quality DNA (purity ratio of 1.80 nm). The original Ferreira and Grattapaglia protocol provided 13.42 ng/μL DNA; however, the purity ratio (1.44 nm) indicates protein contamination. PCR results showed that Ferreira and Grattapaglia's protocol modified for M. brauna gave satisfactory quantity and purity of DNA for molecular studies.

Byrsonima verbascifolia, popularly known in Brazil as murici, is a medicinal plant widely used in the treatment of bacterial and viral infections, Chagas's disease, diarrhea, bronchitis, cough and fever, as well as for protection of the intestinal mucosa. Since chemotherapy and radiotherapy, broadly employed in the treatment of cancer, can have undesirable side effects, such as inducing DNA damage in normal cells, it would be useful to investigate compounds that inhibit or reduce these effects. A lyophilized water extract of murici, used at three different concentrations (25, 50, and 100 mg/mL), was tested to determine if it could reduce damage induced by the antineoplastic compound doxorubicin in somatic cells of Drosophila melanogaster, analyzed by SMART/wing. The frequency of mutant spots in descendants from standard and high bioactivation crosses was significantly reduced by treatment with murici extract. Further studies are needed using other experimental models, to determine if murici has the potential to be employed by cancer patients receiving chemotherapy.

Objective: The purpose of this study was to compare the maximum exposure and extent of bioavailability of two lithium carbonate (CAS 554-13-2) containing 300 mg tablet formulations (test and reference) for oral administration., Method: This bioequivalence study was conducted in a 2-period crossover design with a washout phase of 7 days. Plasma samples were obtained by blood sampling over 72 h in each period. Twenty-four healthy volunteers of both genders participated in the trial. Samples were analyzed by a flame atomic absorption spectrometer. Resulting Li+ concentrations were used for determination of the pharmacokinetic parameters AUC(last), AUC(inf) and C(max)., Results: 90 % confidence intervals for AUC(last), AUC(inf) and C(max) were 96.81-107.44%, 98.44-109.54% and 98.60-111.33%, respectively., Conclusion: All 90% and 95% confidence intervals were inside the limits defined by the FDA Guidance for Industry (80%-125%) and thus stated that test and reference formulation may be accepted as bioequivalent, with regard to both, maximum exposure and extent of bioavailability.

The cis and trans isomers (either E or Z isomers) of the unsubstituted and bromo-2-propen-1-amine derivatives were evaluated in vitro on Trypanosoma cruzi. The results showed that cis is the most active isomeric form against trypomastigote forms of T. cruzi, indicating that it may contribute most to the trypanocidal effect. All mice which received 5 mg kg(-1) daily for 9 consecutive days, or 200 mg kg(-1) in a single dose of the bromo derivative of 2-propen-1-amine, survived after an infection with 10(4) trypomastigotes/ml of the Y-strain of T. cruzi. They also had a significantly lower parasitemia than the controls. However, with 100 mg kg(-1) of benznidazol for 9 consecutive days, 25% of the animals died by the end of the evaluation 40 days after infection. The involvement of the biosynthesis of ergosterol in the trypanocidal effect of the unsubstituted 2-propen-1-amine derivative was investigated on proliferative epimastigote forms of the parasite. The chromatographic analyses of the lipid extracts obtained from parasites treated with 2-propen-1-amine derivatives and controls (not treated) revealed that growth inhibition is correlated with the accumulation of squalene and the decrease of ergosterol levels. These results suggest that inhibition of the biosynthesis of ergosterol is an important target for the action of the 2-propen-1-amine derivative on T. cruzi through the inhibition of the enzyme squalene epoxidase.

Growth kinetics and red pigment production of Monascus purpureus CCT 3802 was studied. A reproducible inoculum with extremely dispersed hyphae for bioreactor runs was obtained through a two-step cultivation in a shaker. First, the spores were cultivated in a complex medium rendering a suspension of vegetative cells. In the second step these cells were grown in a semisynthetic medium. Two types of media were employed in the bioreactor runs: a semisynthetic (glucose, salts, and yeast extract), and a synthetic, without yeast extract. The inclusion of yeast extract, caused an increase in cell yield on glucose (Yx/s) as high as 40%. Also, yeast extract probably yielded a higher proportion of red pigment associated with the cell, relative to the synthetic medium. On the other hand, cells grown on the synthetic medium were slightly higher producers of red soluble pigments.

Diarylpropenamine derivatives are a class of compounds which have been evaluated as potential drug candidates. Here a specific and reproducible HPLC method for the determination of cis- and trans-isomers of the unsubstituted derivative, 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl-N,N-dimethyl-2-propen -1-amine (I, where X=H) in feces is described. The analyte I and internal standard, nitro derivative (II, where X=NO2), were isolated from the basified biological matrix using a liquid-liquid extraction with ethyl acetate followed by a solid-phase procedure performed on a silica cartridge. The organic phase was evaporated to dryness, the residue was reconstituted in mobile phase and injected into the HPLC system. The analytes were eluted with ethyl acetate-hexane-triethylamine (59:40:1) in HPLC column (silica) and detected by UV spectrophotometry at 272 nm. Linearity, precision and accuracy data for feces standards after extraction were acceptable. The method has been applied to analyses of feces samples from rats dosed with I, in which it could be anticipated that fecal excretion is quantitatively the major route for I elimination.

A case of massive rectal bleeding due to colonic tuberculosis in advanced pregnancy with intrauterine foetal death is reported. Patient was treated with resection of the left colon and left transverse end colostomy with closure of the rectal stump. Hysterotomy for the removal of the dead foetus was performed. The patient improved in health with antitubercular treatment. The colorectal anastomosis was performed after 4 months. Massive rectal bleeding in intestinal tuberculosis, though rare should be kept in mind.

Propenamine derivatives 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl)-N,N-dimethyl-2-prope n-1-amine (where X = H or Br) were tested in experimentally infected mice with Trypanosoma cruzi (Y strain). When a daily dose of 20 mg kg-1 of the bromo (X = Br) derivative for 9 consecutive days was used, no parasite by optical microscopy was found. Significant parasitemic decrease was also observed with a single dose (100 mg kg-1) of this compound. Moreover, both treatment schemes displayed a strong protective effect characterized by decreased of mortality. On the other hand, similar treatment schedules using the unsubstituted (X = H) derivative led to parasitemic and mortality curves similar to the control group. These results indicate that the bromo derivative has a remarkable activity against T. cruzi infection. Due to the potentiality of this derivative, further investigation of this class of compounds as chemotherapeutic agents for Chagas' disease is of prime importance.

Opiates have been implicated in learned helplessness (LH), a phenomenon known to be related to opiate stress-induced analgesia (SIA). In the present study, we investigated the role of opiates in the induction of LH and SIA under different conditions. Adult female Wistar rats were trained either by receiving 60 inescapable 1-mA footshocks (IS group, N = 114) or by confinement in the shock box (control or NS group, N = 92). The pain threshold of some of the animals was immediately evaluated in a tail-flick test while the rest were used 24 h later in a shuttle box experiment to examine their escape performance. The opiate antagonist naltrexone (0 or 8 mg/kg, ip) and the previous induction of cross-tolerance to morphine by the chronic administration of morphine (0 or 10 mg/kg, sc, for 13 days) were used to identify opiate involvement. Analysis of variance revealed that only animals in the IS group demonstrated antinociception and an escape deficit, both of which were resistant to the procedures applied before the training session. However, the escape deficit could be reversed if the treatments were given before the test session. We conclude that, under our conditions, induction of the LH deficit in escape performance is not opiate-mediated although its expression is opiate-modulated.

The effect of lithium administration on the learned helplessness model of depression was investigated. Female Wistar rats (190-210 g) received either tap water alone (N = 156) or 20 mM LiCL provided chronically (30 days; N = 127) or acutely (5 days; N = 22) in the drinking water. Three days before the end of treatment, each group was divided into two subgroups which received either inescapable shock (IS) or no shock (NS) treatment in shuttle boxes. All groups were subsequently submitted to an escape test on the following day and then sacrificed one day after the escape test, when blood samples were taken to measure serum Li+, Na+ and K+ concentrations by flame photometry. There were no significant differences in serum Na+ amongst the 4 groups. Chronically treated NS and IS rats both presented an increase in serum K+ compared to the control rats. The IS and not the NS chronically treated rats presented increased serum Li+ levels which cannot be accounted for in terms of differences in Li+ intake. The IS group treated chronically with lithium had a better escape performance than the IS group receiving either tap water or acute Li+ administration. We conclude that chronic but not acute Li+ treatment at a serum level within the prophylactic range (0.5 mEq/l) is able to prevent learned helplessness in the rat. These results agree with the data obtained in clinical practice indicating that Li+ is only effective after chronic administration and that Li(+)-induced hyperkalemia is a side effect.

We have investigated the effect of chronic lithium (Li+) treatment on stress-induced hypoalgesia, a phenomenon known to be dependent on the activation and sensitization of the central opioid system. Adult female Wistar rats received either 20 mM LiCl in the drinking water (serum level of 0.5 mEq/l, N = 110) or tap water (controls, N = 113) for 28 days. The rats were divided into three subgroups and were trained either by receiving 60 inescapable 1-mA footshocks (IS) while yoked to an escapable (ES) group, or by confinement (NS) to the shock box. As a control for the activation of the opioid system, we included rats injected with 0.9% saline (N = 24) or morphine (4 mg/kg, sc, N = 20) before confinement. Twenty-four hours later, the rats (N = 187) were either submitted to five inescapable (1 s, 0.6 mA) footshocks (shock reexposure) or received no shocks over the same period (N = 80). The pain threshold was estimated using a tail-flick apparatus after the training session and immediately after the shock reexposure. ANOVA followed by Duncan's test indicated that hypoalgesia was produced soon after the training session in the morphine and shocked groups and persisted in the Li(+)-IS group for up to three days. Hypoalgesia was reinstated in the control IS and morphine groups by reexposure to the shocks, but was not modified in the Li(+)-IS groups. We conclude that Li+ treatment prolongs the hypoalgesia induced by inescapable shocks.