An Unusual Etiology of Severe Right Heart Failure Deserving of Wider Recognition.

A previously healthy 31-year-old man presented with worsening shortness of breath and a petechial rash. Echocardiography showed severe right-sided heart failure with midsystolic notching of the antegrade right ventricular outflow Doppler envelope suggesting pulmonary hypertension. An extensive work-up revealed scurvy, with a dramatic resolution of symptoms shortly after vitamin C supplementation.

Abiotic factors and aging alter the physicochemical characteristics and toxicity of Phosphorus nanomaterials to zebrafish embryos.

Nanoscale phosphorus (P)-based formulations are being investigated as potentially new fertilizers to overcome the challenges of conventional bulk P fertilizers in agriculture, including low efficacy rates and high application levels. After agricultural applications, the NMs may be released into aquatic environments and transform over time (by aging) or in the presence of abiotic factors such as natural organic matter or sunlight exposure. It is, therefore, important to investigate the physicochemical changes of NMs in environmentally realistic conditions and assess their potential acute and sublethal toxic effects on aquatic organisms. To investigate this, two separate studies were conducted: 1. the effects of 3-months aged P-based NMs on zebrafish embryos, and 2. the influence of humic acid (HA), UV exposure, or a combination of both on P-based NM toxicity in zebrafish embryos. Four different types of nanohydroxyapatites (nHAPs) and a nanophosphorus (nP) were included in the study. These NMs differed in their physicochemical properties, most prominently their shape and size. Environmental transformations were observed for P-based NMs due to aging or interaction with abiotic factors. The aging of the NMs increased the hydrodynamic diameter (HDD) of rod- and needle-shaped NMs and decreased the size of the platelet and spherical NMs, whereas interactions with HA and UV decreased the NMs' HDD. It was observed that no LC50 (survival) and IC50 (hatch and heart rates) were obtained when the zebrafish embryos were exposed to the aged NMs or when NMs were added in the presence of HA and UV. Overall, these results suggest that P-based NMs cause no acute toxicity and minimal sub-lethal toxicity to zebrafish embryos in environmentally realistic experimental conditions.

Investigation into the trophic transfer and acute toxicity of phosphorus-based nano-agromaterials in Caenorhabditis elegans.

Biogenic phosphorus (P) based - nanomaterials (NMs) are currently being explored as nanofertilizers. In this study, the acute toxic effects and trophic transfer of multiple types of P-based NMs were examined on soil-dwelling nematode, Caenorhabditis elegans. The study involved four variants of nanohydroxyapatites (nHAPs) synthesized either via a biogenic or a chemical route and another NM, nanophosphorus (nP), biosynthesized from bulk rock phosphate (RP). The pristine NMs differed in their physicochemical properties with each possessing different shapes (biogenic nHAP: platelet-shaped, ˜35 nm; biogenic nP, ˜5-10 nm: dots; chemically synthesized nHAPs: spherical, ˜33 nm, rod, ˜80 nm and needle-shaped, ˜64 nm). The toxic effects of NMs' in C. elegans were assessed using survival, hatching and reproductive cycle as the key endpoints in comparison to bulk controls, calcium phosphate and RP. The interactions and potential uptake of fluorescent-tagged nHAP to E. coli OP50 and C. elegans were investigated using confocal microscopy. The transformation of NMs within the nematode gut was also explored using dynamic light scattering and electron microscopy. C. elegans exposed to all of the variants of nHAP and the nP had 88-100% survival and 82-100% hatch rates and insignificant effects on brood size as observed at the tested environmentally relevant concentrations ranging from 5 to 100 µg.mL-1. Confocal microscopy confirmed the interaction and binding of fluorescent-tagged nHAP with the surface of E. coli OP50 and their trophic transfer and internalization into C. elegans. Interestingly, there was only a small reduction in the hydrodynamic diameter of the nHAP after their uptake into C. elegans and the transformed NMs did not induce any additional toxicity as evident by healthy brood sizes after 72 h. This study provides key information about the environmental safety of agriculturally relevant P-based NMs on non-target species.

Vitamin D Deficiency, Supplementation, and Cardiovascular Health.

Vitamin D has been traditionally recognized as a vitamin quintessential for bone-mineral health. In the past 2 decades, numerous experimental and observational studies have highlighted the role of vitamin D in immunity, metabolic syndrome (obesity and diabetes), cancers, renal disease, memory, and neurological dysfunction. In this article, we review important studies that focused on the impact of vitamin D on blood pressure, myocardial infarction, peripheral arterial disease, heart failure, and statin intolerance. Amidst the current pool of ambiguous evidence, we intend to discuss the role of vitamin D in "high-value cardiovascular health care".

Burden of arrhythmias in peripartum cardiomyopathy: Analysis of 9841 hospitalizations.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is associated with significant morbidity and mortality. Arrhythmogenic causes of death have been implicated in a significant number of patients. However, there is a dearth of systematic studies evaluating the burden of arrhythmias in PPCM. METHODS: We used the Healthcare Utilization Project, Nationwide Inpatient Sample database (2007-2012) and identified 9841 hospitalizations for women aged ≥18years with a primary diagnosis of PPCM. Frequency of arrhythmias, utilization of electrophysiologic procedures, length of stay, hospitalization costs and outcomes associated with arrhythmias were determined. RESULTS: Mean age was 30.05±6.69years. Arrhythmias were present in 18.7% of hospitalized PPCM cohort. Ventricular tachycardia was the most common arrhythmia and was noted in 4.2%. Approximately 2.2% of cases experienced cardiac arrest. Electrical cardioversion was performed in 0.3%, Catheter ablation in 1.9%, PPM implantation in 3.4% and ICD in 6.8% of hospitalizations for PPCM with arrhythmias. In-hospital mortality was 3-times more frequent in arrhythmia cohort (2.1% vs. 0.7%). Hospitalization costs were significantly higher in PPCM with arrhythmias. Elixhauser comorbidity score (adjusted OR:1.10; 95%CI:1.02-1.18; p=0.016), in-hospital mortality (adjusted OR:2.35; 95%CI:1.38-4.02; p=0.002), cardiogenic shock (adjusted OR:2.61; 95%CI:1.44-4.72; p=0.002), utilization of balloon pump (adjusted OR:13.4; 95%CI: 2.55-70.53; p<0.001), Swan-Ganz catheterization (adjusted OR:3.12; 95%CI:1.21-8.06; p=0.019), and coronary angiography (adjusted OR:1.79; 95%CI:1.19-2.70; p=0.005) were significantly associated with arrhythmias in PPCM. CONCLUSIONS: Arrhythmias were present in 18.7% of PPCM related hospitalizations. Morbidity, in-hospital mortality, length of inpatient stay, hospitalization costs and cardiac procedure utilization were significantly higher in the arrhythmia cohort.

The Antileishmanial Potential of C-3 Functionalized Isobenzofuranones against Leishmania (Leishmania) Infantum Chagasi.

Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. Clinically, leishmaniases range from cutaneous to visceral forms, with estimated global incidences of 1.2 and 0.4 million cases per year, respectively. The treatment of these diseases relies on multiple parenteral injections with pentavalent antimonials or amphotericin B. However, these pharmaceuticals are either too toxic or expensive for routine use in developing countries. These facts call for safer, cheaper, and more effective new antileishmanial drugs. In this investigation, we describe the results of the assessment of the activities of a series of isobenzofuran-1(3H)-ones (phtalides) against Leishmania (Leishmania) infantum chagasi, which is the main causative agent of visceral leishmaniasis in the New World. The compounds were tested at concentrations of 100, 75, 50, 25 and 6.25 µM over 24, 48, and 72 h. After 48 h of treatment at the 100 µM concentration, compounds 7 and 8 decreased parasite viability to 4% and 6%, respectively. The concentration that gives half-maximal responses (LC50) for the antileishmanial activities of compounds 7 and 8 against promastigotes after 24 h were 60.48 and 65.93 µM, respectively. Additionally, compounds 7 and 8 significantly reduced parasite infection in macrophages.

Medicinal Plants Used by a Mbyá-Guarani Tribe Against Infections: Activity on KPC-Producing Isolates and Biofilm-Forming Bacteria.

The traditional use of medicinal plants for treatment of infectious diseases by an indigenous Mbyá-Guarani tribe from South Brazil was assessed by evaluating the antibiotic and antibiofilm activities against relevant bacterial pathogens. Aqueous extracts from 10 medicinal plants were prepared according to indigenous Mbyá-Guarani traditional uses. To evaluate antibiotic (OD600) and antibiofilm (crystal violet method) activities, Pseudomonas aeruginosa ATCC 27853, Staphylococcus epidermidis ATCC 35984 and seven multi-drug resistant Klebsiella pneumoniae carbapenemase (KPC)-producing bacterial clinical isolates were challenged with the extracts. Furthermore, the susceptibility profile of KPC-producing bacteria and the ability of these isolates to form biofilm were evaluated. The plants Campomanesia xanthocarpa, Maytenus ilicifolia, Bidens pilosa and Verbena sp. showed the best activity against bacterial growth and biofilm formation. The majority of KPC-producing isolates, which showed strong ability to form biofilm and a multidrug resistance profile, was inhibited by more than 50% by some extracts. The Enterobacter cloacae (KPC 05) clinical isolate was the only one resistant to all extracts. This study confirms the importance of indigenous traditional medicinal knowledge and describes for the first time the ability of these plants to inhibit biofilm formation and/or bacterial growth of multi-drug resistant KPC-producing isolates.

Major electrocardiographic abnormalities and 25-hydroxy vitamin D deficiency: insights from National Health and Nutrition Examination Survey-III.

BACKGROUND: We explored the relationship between major electrocardiogram (ECG) abnormalities (mECG) and 25-hydroxy (25-OH) vitamin D deficiency (VDD) and the effect of mECG abnormalities on all-cause and cardiovascular mortality in a healthy cohort with 25-OH vitamin D insufficiency and deficiency. HYPOTHESIS: Lower levels of serum 25-OH vitamin D are associated with increased prevalence of mECG on resting ECG. METHODS: We identified 5108 individuals from the National Health and Nutrition Examination Survey-III. mECG abnormalities included: major Q-QS wave abnormalities, ST depression/elevation, negative T waves, Wolff-Parkinson-White pattern, and ventricular conduction defect. Our cohort was divided into 3 groups based on 25-OH vitamin D levels: Group 1 (referent): > 40 ng/mL; group 2 (insufficient): ≥ 20.01 to ≤ 40 ng/mL; and group 3 (deficient): ≤ 20 ng/mL. Logistic regression and Cox proportional hazards regression models were built. RESULTS: The prevalence of major ECG abnormalities across 25-OH vitamin D sufficiency, insufficiency, and deficiency was .9%, 11%, and 13 %, respectively (P = 0.01). VDD was an independent predictor of mECG abnormalities after adjusting for traditional risk factors (continuous variable odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.97-0.99, P = 0.007; categorical variable group 3 vs group 1 OR: 2.36, 95% CI: 1.1-5.12, P = 0.03). Baseline major ECG abnormalities were predictive of long-term all-cause (hazard ratio [HR]:1.52, 95% CI: 1.23-1.89), composite cardiovascular (HR: 1.7, 95% CI: 1.34-2.15), cardiovascular (HR: 1.64, 95% CI: 1.27-2.12), and ischemic heart disease mortality (HR: 1.98, 95% CI: 1.46-2.69) in individuals with 25-OH vitamin D levels ≤ 40 ng/mL. CONCLUSIONS: VDD is associated with increased prevalence of major ECG abnormalities. Well-structured trials are needed to assess progression/resolution of mECG abnormalities with vitamin D supplementation in deficient individuals.

In vitro antioxidant, anticoagulant and antimicrobial activity and in inhibition of cancer cell proliferation by xylan extracted from corn cobs.

Xylan is one of most abundant polymer after cellulose. However, its potential has yet to be completely recognized. Corn cobs contain a considerable reservoir of xylan. The aim of this work was to study some of the biological activities of xylan obtained from corn cobs after alkaline extraction enhanced by ultrasonication. Physical chemistry and infrared analyses showed 130 kDa heteroxylan containing mainly xylose:arabinose: galactose:glucose (5.0:1.5:2.0:1.2). Xylan obtained exhibited total antioxidant activity corresponding to 48.5 mg of ascorbic acid equivalent/g of xylan. Furthermore, xylan displayed high ferric chelating activity (70%) at 2 mg/mL. Xylan also showed anticoagulant activity in aPTT test. In antimicrobial assay, the polysaccharide significantly inhibited bacterial growth of Klebsiella pneumoniae. In a test with normal and tumor human cells, after 72 h, only HeLa tumor cell proliferation was inhibited (p < 0.05) in a dose-dependent manner by xylan, reaching saturation at around 2 mg/mL, whereas 3T3 normal cell proliferation was not affected. The results suggest that it has potential clinical applications as antioxidant, anticoagulant, antimicrobial and antiproliferative compounds.

Quantification of myocardial iron overload by cardiovascular magnetic resonance imaging T2* and review of the literature.

Heart failure due to myocardial iron overload remains the leading cause of death in patients with transfusion-dependent anemias. Iron overload-induced cardiomyopathy is reversible if intensive chelation therapy is instituted on time. Thus, early detection of myocardial iron deposition is imperative to prevent overt heart failure. Conventional cardiac monitoring, including physical examination, electrocardiography, echocardiography or serum ferritin levels fail to predict manifest or subclinical myocardial involvement resulting from iron overload. Cardiovascular magnetic resonance imaging T2* (cMRI-T2*, pronounced T2 star) times correlate well with myocardial iron levels. This timely review focuses on the utility of cMRI-T2*, for the preclinical detection of myocardial iron overload and monitoring of myocardial iron content during chelation therapy.

Effects of clove oil on the stress response of matrinxã (Brycon cephalus) subjected to transport

O transporte de peixes vivos é certamente um dos principais estímulos adversos à homeostase dos peixes nas condições de criação em cativeiro. O presente trabalho mensurou o estresse do matrinxã (Brycon cephalus), quando submetido ao transporte em sacos plásticos, bem como avaliou os efeitos do uso do anestésico óleo de cravo nessa etapa do manejo. Foram testadas as concentrações de 0, 1, 5 e 10 mg/L de óleo de cravo em bolsas plásticas preenchidas com água e oxigênio, de acordo com as práticas comumente utilizadas no Brasil. O óleo de cravo reduziu algumas das principais respostas ao estresse (cortisol, glicose plasmática e íons) mensuradas. O alto gasto de energia para o matrinxã tolerar o transporte foi evidenciado pela diminuição dos valores de glicogênio hepático. Os resultados sugerem que o óleo de cravo em concentração de 5 mg/L pode atenuar as principais respostas de estresse do matrinxã durante o transporte.

Are hsps suitable for indicating stressed states in fish?

In response to most stressors, fish will elicit a generalized physiological stress response, which involves the activation of the hypothalamic-pituitary-interrenal axis (HPI). As in other vertebrates, this generalized stress response comprises physiological responses that are common to a wide range of environmental, physical and biological stressors. Recently, several families of heat shock proteins (hsps) have been proposed as indicators of a generalized stress response at the cellular level. Recent findings that hsp levels, in various fish tissues, respond to a wide range of stressors have supported the use of these proteins as indicators of stressed states in fish. However, the cellular stress response can vary, for example, according to tissue, hsp family and type of stressor. This brief overview of these responses in fish asks the question of whether changes in levels and families of hsps can be used as a suitable indicator of stressed states in fish. By casting this question in the context of the well-established generalized physiological stress response in fish, we argue that the use of hsps as indicators of stressed states in fish in general is premature.

Clinical failure of vancomycin treatment of Staphylococcus aureus infection in a tertiary care hospital in southern Brazil.

We describe a case of clinical failure of vancomycin treatment of Staphylococcus aureus infection and the laboratory characteristics of the organism in a tertiary referral university hospital in southern Brazil. An 11-month-old male patient presented with pneumonia and S. aureus was isolated from his respiratory tract. Initial treatment with oxacillin and gentamicin was ineffective. Vancomycin was added to the regimen as the patient worsened, but after the 30(th) day of vancomycin treatment S. aureus was isolated from the blood. This isolate had a minimum inhibitory concentration (MIC) for vancomycin of 4 mg/mL. After pre-incubation with vancomycin the isolate displayed an increase in the expression of vancomycin resistance and colonies grew in the presence of up to 12 mg/mL vancomycin. Based on these results, and considering that the patient had not responded to vancomycin, the isolate was considered to be S. aureus heteroresistant to vancomycin (SAHV). The SAHV proved to be similar, based on DNA macrorestriction analysis, to methicillin resistant S. aureus (MRSA) isolates from other patients in the hospital who had responded to vancomycin treatment. Our findings underline the need to improve methods in the clinical laboratory to detect the emergence of S. aureus clinically resistant to vancomycin. The fact that the isolate emerged in the blood 30 days after vancomycin treatment was initiated suggests that the organism was originally an MRSA that had acquired the ability to circumvent the mechanism of action of vancomycin.

Clinical failure of vancomycin treatment of Staphylococcus aureus infection in a tertiary care hospital in southern Brazil

We describe a case of clinical failure of vancomycin treatment of Staphylococcus aureus infection and the laboratory characteristics of the organism in a tertiary referral university hospital in southern Brazil. An 11-month-old male patient presented with pneumonia and S. aureus was isolated from his respiratory tract. Initial treatment with oxacillin and gentamicin was ineffective. Vancomycin was added to the regimen as the patient worsened, but after the 30th day of vancomycin treatment S. aureus was isolated from the blood. This isolate had a minimum inhibitory concentration (MIC) for vancomycin of 4 æg/mL. After pre-incubation with vancomycin the isolate displayed an increase in the expression of vancomycin resistance and colonies grew in the presence of up to 12 æg/mL vancomycin. Based on these results, and considering that the patient had not responded to vancomycin, the isolate was considered to be S. aureus heteroresistant to vancomycin (SAHV). The SAHV proved to be similar, based on DNA macrorestriction analysis, to methicillin resistant S. aureus (MRSA) isolates from other patients in the hospital who had responded to vancomycin treatment. Our findings underline the need to improve methods in the clinical laboratory to detect the emergence of S. aureus clinically resistant to vancomycin . The fact that the isolate emerged in the blood 30 days after vancomycin treatment was initiated suggests that the organism was originally an MRSA that had acquired the ability to circumvent the mechanism of action of vancomycin