Prevalence of peripheral arterial disease in patients with heart failure with preserved ejection fraction

OBJECTIVES: To describe the prevalence of the reduced ankle-brachial index (ABI) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) attended at a HF clinic in the metropolitan region of Porto Alegre, and to compar the patients to those with reduced ejection fraction (HFrEF). METHODS: A descriptive observational study, included patients referred to the heart failure clinic in HU-Ulbra with HFpEF or HFrEF and diastolic dysfunction, and measurements of ABIs using vascular Doppler equipment were performed in both groups. RESULTS: The sample consisted of 106 patients with HF, 53.9% of the patients had HFpEF, and 19.4% had a diagnosis of peripheral arterial disease (PAD) (ABI less than 0.9). PAD was identified in 24.1% of the patients with HFpEF, while15.8% of patients in the HFrEF group were diagnosed with PAD. CONCLUSION: Our results did not identify a significantly different prevalence of altered and compatible PAD values in patients with HFpEF. However, we showed a prevalence of 19.4%, a high value if we consider similar populations

Unravelling Ariadne’s Thread: Exploring the Threats of Decentralised DNS

The current landscape of the core Internet technologies shows considerable centralisation with the big tech companies controlling the vast majority of traffic and services. This situation has sparked a wide range of decentralisation initiatives with blockchain technology being among the most prominent and successful innovations. At the same time, over the past years there have been considerable attempts to address the security and privacy issues affecting the Domain Name System (DNS). To this end, it is claimed that Blockchain-based DNS may solve many of the limitations of traditional DNS. However, such an alternative comes with its own security concerns and issues, as any introduction and adoption of a new technology typically does - let alone a disruptive one. In this work we present the emerging threat landscape of blockchain-based DNS and we empirically validate the threats with real-world data. Specifically, we explore a part of the blockchain DNS ecosystem in terms of the browser extensions using such technologies, the chain itself (Namecoin and Emercoin), the domains, and users who have been registered in these platforms. Our findings reveal several potential domain extortion attempts and possible phishing schemes. Finally, we suggest countermeasures to address the identified threats, and we identify emerging research themes

Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles

Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model.</p

Skin Cornification Proteins Provide Global Link between ROS Detoxification and Cell Migration during Wound Healing

Wound healing is a complex dynamic process characterised by a uniform flow of events in nearly all types of tissue damage, from a small skin scratch to myocardial infarction. Reactive oxygen species (ROS) are essential during the healing process at multiple stages, ranging from the initial signal that instigates the immune response, to the triggering of intracellular redox-dependent signalling pathways and the defence against invading bacteria. Excessive ROS in the wound milieu nevertheless impedes new tissue formation. Here we identify small proline-rich (SPRR) proteins as essential players in this latter process, as they directly link ROS detoxification with cell migration. A literature-based meta-analysis revealed their up-regulation in various forms of tissue injury, ranging from heart infarction and commensal-induced gut responses to nerve regeneration and burn injury. Apparently, SPRR proteins have a far more widespread role in wound healing and tissue remodelling than their established function in skin cornification. It is inferred that SPRR proteins provide injured tissue with an efficient, finely tuneable antioxidant barrier specifically adapted to the tissue involved and the damage inflicted. Their recognition as novel cell protective proteins combining ROS detoxification with cell migration will provide new venues to study and manage tissue repair and wound healing at a molecular level

Re‐evaluation of stannous chloride (E 512) as food additive

The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of stannous chloride and stannous chloride dihydrate (E 512) as food additives. The Panel considered that adequate exposure and toxicity data were available. Stannous chloride is only permitted as food additives in one food category and no reply on the actual use level of stannous chloride (E 512) as a food additive and on its concentration in food was provided by any interested party. According to the Mintel's Global New Products Database (GNPD), stannous chloride was not labelled on any products in the EU nor in Norway. The regulatory maximum level exposure assessment scenario is based on the maximum permitted levels (MPLs) for stannous chloride (E 512), which is 25 mg Sn/kg. The mean exposure to stannous chloride (E 512) from its use as a food additive was below 1.3 μg Sn/kg body weight (bw) per day for all age groups. The 95th percentile of exposure to stannous chloride (E 512) ranged from 0.0 μg Sn/kg bw per day in all groups to 11.2 μg Sn/kg bw per day in adults. Absorption of stannous chloride from the gastrointestinal tract is low there is no concern with respect to carcinogenicity and genotoxicity. Gastrointestinal irritation was reported in humans after ingestion of a bolus dose of 40 mg Sn. The Panel concluded that stannous chloride (E 512) is of no safety concern in this current authorised use and use levels

Fatores preditores de óbito em Unidade de Terapia Intensiva: contribuição para a abordagem paliativista

Objetivo Factores predictivos de defunción en la Unidad de Cuidados Intensivos y relacionar a pacientes elegibles para cuidados paliativos preferentes. Método Cohorte prospectivo que evaluó a pacientes hospitalizados por más de 24 horas, subdivididos en G1 (pacientes que fallecieron) y G2 (pacientes con alta hospitalaria). Para la identificación de los factores predictivos para el resultado defunción, se hizo al médico intensivista la “pregunta sorpresa” y fueron recogidos datos clínico-demográficos de los pacientes. Los datos fueron analizados por estadística descriptiva/inferencial (significante pObjetivo Identificar preditores de óbito na Unidade de Terapia Intensiva e relacionar pacientes elegíveis para cuidados paliativos preferenciais. Método Coorte prospectivo que avaliou pacientes internados por mais de 24 horas, subdivididos em G1 (pacientes que morreram) e G2 (pacientes com alta hospitalar). Para a identificação dos fatores preditores para o desfecho óbito, foi feita ao médico intensivista a “pergunta-surpresa” e foram coletados dados clínico-demográficos dos pacientes. Os dados foram analisados por estatística descritiva/inferencial (significante pObjective To identify predictors of death in the Intensive Care Unit and relate eligible patients to preferential palliative care. Method A prospective cohort study that evaluated patients hospitalized for more than 24 hours, subdivided into G1 (patients who died) and G2 (patients who were discharged from hospital). For identifying the predictors for death outcome, the intensivist physician was asked the “surprise question” and clinical-demographic data were collected from the patients. Data were analyzed by descriptive/inferential statistics (

Virus-Like Particle (VLP) Plus Microcrystalline Tyrosine (MCT) Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei/vivax

Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT) is a well described depot used in licensed allergy immunotherapy products and in clinical development. However, its proof of concept in prophylactic vaccines has only recently been explored. MCT has never been used in combination with virus-like particles (VLPs), which are considered to be one of the most potent inducers of cellular and humoral immune responses in mice and humans. In the current study we assessed the potential of MCT to serve as an adjuvant in the development of a vaccine against malaria either alone or combined with VLP using Plasmodium vivax thrombospondin-related adhesive protein (TRAP) as a target antigen. We chemically coupled PvTRAP to VLPs derived from the cucumber mosaic virus fused to a universal T-cell epitope of the tetanus toxin (CMVtt), formulated with MCT and compared the induced immune responses to PvTRAP formulated in PBS or Alum. The protective capacity of the various formulations was assessed using Plasmodium berghei expressing PvTRAP. All vaccine formulations using adjuvants and/or VLP increased humoral immunogenicity for PvTRAP compared to the antigen alone. The most proficient responder was the group of mice immunized with the vaccine formulated with PvTRAP-VLP + MCT. The VLP-based vaccine formulated in MCT also induced the strongest T cell response and conferred best protection against challenge with recombinant Plasmodium berghei. Thus, the combination of VLP with MCT may take advantage of the properties of each component and appears to be an alternative biodegradable depot adjuvant for development of novel prophylactic vaccines

Structural studies of Schiff-base [2 + 2] macrocycles derived from 2,2′-oxydianiline and the ROP capability of their organoaluminium complexes

The molecular structures of a number of solvates of the [2 + 2] Schiff-base macrocycles {[2-(OH)-5-(R)-C6H2-1,3-(CH)2][O(2-C6H4N)2]}2 (R = Me L1H2, tBu L2H2, Cl L3H2), formed by reacting 2,6-dicarboxy-4-R-phenol with 2,2′-oxydianiline (2-aminophenylether), (2-NH2C6H4)2O, have been determined. Reaction of LnH2 with two equivalents of AlR′3 (R′ = Me, Et) afforded dinuclear alkylaluminium complexes [(AlR′2)2L1–3] (R = R′ = Me (1), R = tBu, R′ = Me (2), R = Cl, R′ = Me (3), R = Me, R′ = Et (4), R = tBu, R′ = Et (5), R = Cl, R′ = Et (6)). For comparative studies, reactions of two equivalents of AlR′3 (R′ = Me, Et) with the macrocycle derived from 2,2′-ethylenedianiline and 2,6-dicarboxy-R-phenols (R = Me L4H2, tBu L5H2) were conducted; the complexes [(AlMe)(AlMe2)L5]·2¼MeCN (7·2¼MeCN) and [(AlEt2)2L4] (8) were isolated. Use of limited AlEt3 with L3H2 or L5H2 afforded mononuclear bis(macrocyclic) complexes [Al(L3)(L3H)]·4toluene (9·4toluene) and [Al(L5)(L5H)]·5MeCN (10·5MeCN), respectively. Use of four equivalents of AlR′3 led to transfer of alkyl groups and isolation of the complexes [(AlR′2)4L1′–3′] (R = L2′, R′ = Me (11); L3′, R′ = Me (12); L1′, R′ = Et (13); L2′, R′ = Et (14); L3′, R′ = Et (15)), where L1′–3′ is the macrocycle resulting from double alkyl transfer to imine, namely {[2-(O)-5-(R)C6H2-1-(CH)-3-C(R′)H][(O)(2-(N)-2′-C6H4N)2]}2. Molecular structures of complexes 7·2¼MeCN, 8, 9·4toluene, 10·5MeCN and 11·1¾toluene·1¼hexane are reported. These complexes act as catalysts for the ring opening polymerisation (ROP) of ε-caprolactone and rac-lactide; high conversions were achieved over 30 min at 80 °C for ε-caprolactone, and 110 °C over 12 h for rac-lactide