Using qualitative behavior assessment to investigate the effect of tourist presence on the welfare in captive tigers (Panthera tigris) in three tourism facilities in Thailand.

Numerous facilities around the world offer tourists interactive experiences with captive tigers. Yet, the animal welfare implications of this practice have not been widely studied. This study aimed to investigate whether qualitative behavioral assessment (QBA) could: (i) provide a valid indicator of tiger's emotional state and (ii) be applied to assess whether unfamiliar human presence with hand-raised captive tigers had an impact on the emotional state of those tigers. To investigate this, QBA was applied to video clips of hand-raised captive tigers from three sites (two offering unfamiliar human interaction, Sites A and C, and one retirement site with no direct interactions, Site B) in Thailand. QBA allows inferences to be made about animal emotion on the basis of descriptions of behavioral expression. Analysis, using a free choice profiling methodology, was provided by observers (N = 38) split between three groups; tiger keepers and vets from the Thai venues (n = 12), UK-based animal behavior MSc and vet students (n = 16), and international tiger keepers (n = 10). Tigers (N = 35) were split between Sites A (n = 7), B (n = 18), and C (n = 10) and filmed at three time points; morning (0800-0930 h); midday, (1130-1230 h); and evening, (1630-1830h) totaling 105 clips. Using generalized procrustes analysis, a consensus profile was calculated for each observer group. Two meaningful dimensions of behavioral expression, explaining 75.0% of the variation, were observed across these groups: Dimension 1 (D1: "active"/"interested"/"agitated" to "relaxed"/"calm"/"chilled-out") and Dimension 2 (D2: "bored"/"stressed"/"frustrated" to "relaxed"/"curious"/"interested"). There was clear agreement between the three observer groups in terms of tiger emotional expression along D1. However, agreement was more variable on D2. The behavioral expression on D1 was not significantly affected by site but was significantly affected by an interaction between age and time of day. Time of day also affected scores on D2, with the Thai observer group also showing an effect of site. During the midday period, when unfamiliar humans were present, all tiger age groups showed more positive behavioral expressions on D1 (lower scores: "relaxed"/"calm"/"chilled-out") and more negative behavioral expressions on D2 (higher scores: "bored"/"stressed"/"frustrated"), which could indicate that the presence of unfamiliar humans was a stressor. However, tigers in the retirement Site C also displayed similar behavioral expressions, which could indicate a deeper welfare issue. With further development, QBA could be used as part of a valid tool for long-term measurement of behavioral expression in captive tigers.

Immunosuppressive effects of new thiophene-based KV1.3 inhibitors.

Voltage-gated potassium channel KV1.3 inhibitors have been shown to be effective in preventing T-cell proliferation and activation by affecting intracellular Ca2+ homeostasis. Here, we present the structure-activity relationship, KV1.3 inhibition, and immunosuppressive effects of new thiophene-based KV1.3 inhibitors with nanomolar potency on K+ current in T-lymphocytes and KV1.3 inhibition on Ltk- cells. The new KV1.3 inhibitor trans-18 inhibited KV1.3 -mediated current in phytohemagglutinin (PHA)-activated T-lymphocytes with an IC50 value of 26.1 nM and in mammalian Ltk- cells with an IC50 value of 230 nM. The KV1.3 inhibitor trans-18 also had nanomolar potency against KV1.3 in Xenopus laevis oocytes (IC50 = 136 nM). The novel thiophene-based KV1.3 inhibitors impaired intracellular Ca2+ signaling as well as T-cell activation, proliferation, and colony formation.

Correction: Gubic et al. Design of New Potent and Selective Thiophene-Based KV1.3 Inhibitors and Their Potential for Anticancer Activity. Cancers 2022, 14, 2595.

In the original publication [...].

IMMUNEPOTENT CRP increases intracellular calcium through ER-calcium channels, leading to ROS production and cell death in breast cancer and leukemic cell lines.

IMMUNEPOTENT CRP (ICRP) is an immunotherapy that induces cell death in cancer cell lines. However, the molecular mechanisms of death are not completely elucidated. Here, we evaluated the implication of intracellular Ca2+ augmentation in the cell death induced by ICRP on T-ALL and breast cancer cell lines. Cell death induction and the molecular characteristics of cell death were evaluated in T-ALL and breast cancer cell lines by assessing autophagosome formation, ROS production, loss of mitochondrial membrane potential, ER stress and intracellular Ca2+ levels. We assessed the involvement of extracellular Ca2+, and the implication of the ER-receptors, IP3R and RyR, in the cell death induced by ICRP, by using an extracellular calcium chelator and pharmacological inhibitors. Our results show that ICRP increases intracellular Ca2+ levels as the first step of the cell death mechanism that provokes ROS production and loss of mitochondrial membrane potential. In addition, blocking the IP3 and ryanodine receptors inhibited ER-Ca2+ release, ROS production and ICRP-induced cell death. Taken together our results demonstrate that ICRP triggers intracellular Ca2+-increase leading to different regulated cell death modalities in T-ALL and breast cancer cell lines. See also Figure 1(Fig. 1).

Design of New Potent and Selective Thiophene-Based KV1.3 Inhibitors and Their Potential for Anticancer Activity.

The voltage-gated potassium channel KV1.3 has been recognized as a tumor marker and represents a promising new target for the discovery of new anticancer drugs. We designed a novel structural class of KV1.3 inhibitors through structural optimization of benzamide-based hit compounds and structure-activity relationship studies. The potency and selectivity of the new KV1.3 inhibitors were investigated using whole-cell patch- and voltage-clamp experiments. 2D and 3D cell models were used to determine antiproliferative activity. Structural optimization resulted in the most potent and selective KV1.3 inhibitor 44 in the series with an IC50 value of 470 nM in oocytes and 950 nM in Ltk- cells. KV1.3 inhibitor 4 induced significant apoptosis in Colo-357 spheroids, while 14, 37, 43, and 44 significantly inhibited Panc-1 proliferation.

Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model.

Inflammatory diseases are often characterised by excessive neutrophil infiltration from the blood stream to the site of inflammation, which damages healthy tissue and prevents resolution of inflammation. Development of anti-inflammatory drugs is hindered by lack of in vitro and in vivo models which accurately represent the disease microenvironment. In this study, we used the OrganoPlate to develop a humanized 3D in vitro inflammation-on-a-chip model to recapitulate neutrophil transmigration across the endothelium and subsequent migration through the extracellular matrix (ECM). Human umbilical vein endothelial cells formed confluent vessels against collagen I and geltrex mix, a mix of basement membrane extract and collagen I. TNF-α-stimulation of vessels upregulated inflammatory cytokine expression and promoted neutrophil transmigration. Intriguingly, major differences were found depending on the composition of the ECM. Neutrophils transmigrated in higher number and further in geltrex mix than collagen I, and did not require an N-formyl-methionyl-leucyl-phenylalanine (fMLP) gradient for transmigration. Inhibition of neutrophil proteases inhibited neutrophil transmigration on geltrex mix, but not collagen I. These findings highlight the important role of the ECM in determining cell phenotype and response to inhibitors. Future work could adapt the ECM composition for individual diseases, producing accurate models for drug development.

Antisense Therapy Attenuates Phospholamban p.(Arg14del) Cardiomyopathy in Mice and Reverses Protein Aggregation.

Inherited cardiomyopathy caused by the p.(Arg14del) pathogenic variant of the phospholamban (PLN) gene is characterized by intracardiomyocyte PLN aggregation and can lead to severe dilated cardiomyopathy. We recently reported that pre-emptive depletion of PLN attenuated heart failure (HF) in several cardiomyopathy models. Here, we investigated if administration of a Pln-targeting antisense oligonucleotide (ASO) could halt or reverse disease progression in mice with advanced PLN-R14del cardiomyopathy. To this aim, homozygous PLN-R14del (PLN-R14 Δ/Δ) mice received PLN-ASO injections starting at 5 or 6 weeks of age, in the presence of moderate or severe HF, respectively. Mice were monitored for another 4 months with echocardiographic analyses at several timepoints, after which cardiac tissues were examined for pathological remodeling. We found that vehicle-treated PLN-R14 Δ/Δ mice continued to develop severe HF, and reached a humane endpoint at 8.1 ± 0.5 weeks of age. Both early and late PLN-ASO administration halted further cardiac remodeling and dysfunction shortly after treatment start, resulting in a life span extension to at least 22 weeks of age. Earlier treatment initiation halted disease development sooner, resulting in better heart function and less remodeling at the study endpoint. PLN-ASO treatment almost completely eliminated PLN aggregates, and normalized levels of autophagic proteins. In conclusion, these findings indicate that PLN-ASO therapy may have beneficial outcomes in PLN-R14del cardiomyopathy when administered after disease onset. Although existing tissue damage was not reversed, further cardiomyopathy progression was stopped, and PLN aggregates were resolved.

Substantial Decline in Invasive Pneumococcal Disease During Coronavirus Disease 2019 Pandemic in Hong Kong.

Compared with other countries, a more substantial decrease in the incidence of invasive pneumococcal disease was observed in Hong Kong, which is most likely attributable to the proactive mass adoption of face masks by the public. Human behavioral changes, particularly mask wearing, should be considered as an additional preventive strategy against invasive pneumococcal disease.

Constitutive, Basal, and ß-Alanine-Mediated Activation of the Human Mas-Related G Protein-Coupled Receptor D Induces Release of the Inflammatory Cytokine IL-6 and Is Dependent on NF-κB Signaling.

G protein-coupled receptors (GPCRs) have emerged as key players in regulating (patho)physiological processes, including inflammation. Members of the Mas-related G protein coupled receptors (MRGPRs), a subfamily of GPCRs, are largely expressed by sensory neurons and known to modulate itch and pain. Several members of MRGPRs are also expressed in mast cells, macrophages, and in cardiovascular tissue, linking them to pseudo-allergic drug reactions and suggesting a pivotal role in the cardiovascular system. However, involvement of the human Mas-related G-protein coupled receptor D (MRGPRD) in the regulation of the inflammatory mediator interleukin 6 (IL-6) has not been demonstrated to date. By stimulating human MRGPRD-expressing HeLa cells with the agonist ß-alanine, we observed a release of IL-6. ß-alanine-induced signaling through MRGPRD was investigated further by probing downstream signaling effectors along the Gαq/Phospholipase C (PLC) pathway, which results in an IkB kinases (IKK)-mediated canonical activation of nuclear factor kappa-B (NF-κB) and stimulation of IL-6 release. This IL-6 release could be blocked by a Gαq inhibitor (YM-254890), an IKK complex inhibitor (IKK-16), and partly by a PLC inhibitor (U-73122). Additionally, we investigated the constitutive (ligand-independent) and basal activity of MRGPRD and concluded that the observed basal activity of MRGPRD is dependent on the presence of fetal bovine serum (FBS) in the culture medium. Consequently, the dynamic range for IL-6 detection as an assay for ß-alanine-mediated activation of MRGPRD is substantially increased by culturing the cells in FBS free medium before treatment. Overall, the observation that MRGPRD mediates the release of IL-6 in an in vitro system, hints at a role as an inflammatory mediator and supports the notion that IL-6 can be used as a marker for MRGPRD activation in an in vitro drug screening assay.

Tromboprofilaxis, anticoagulación y coagulopatía en tiempos de pandemia: recomendación de la ACATA, ACMI, SCC CCV y ACMV / Thromboprophylaxis, anticoagulation and coagulopathy in times of pandemic: The ACATA, ACMI, SCC CCV and ACMV recommendation

Resumen Introducción La enfermedad por coronavirus 2019 (COVID-19) puede predisponer a tromboembolia venosa o trombosis arterial debido a una respuesta inflamatoria aumentada, hipoxia, inmovilización y coagulación intravascular diseminada; hasta en un 20 a 50% de pacientes hospitalizados con COVID-19 tienen alteraciones hematológicas relacionadas con coagulopatía (dímero D elevado, tiempo de protrombina prolongado, trombocitopenia y/o fibrinógeno bajo). Evaluaciones post mortem evidencian depósitos trombóticos microvasculares típicos, ricos en plaquetas en vasos pequeños de pulmones y otros órganos. Objetivo Brindar una aproximación práctica y actualizada en el manejo del paciente con riesgo elevado o que presentan eventos tromboembólicos en el marco de la actual pandemia por COVID-19. Material y métodos: Se realizó una revisión narrativa que incluyó estudios observacionales descriptivos. Se efectuó una búsqueda de la literatura de evidencia médica en diferentes buscadores como Science Direct y PubMed, usando las palabras claves “thromboprophylaxis”, “anticoagulation”, “thrombosis”, “anticoagulant”, “COVID-19”, “SARS-CoV-2”, “coronavirus”. Posteriormente se escribieron las recomendaciones generales referentes al tema. Conclusiones Existen diferentes formas en las que la pandemia por COVID-19 puede predisponer al desarrollo de enfermedades trombóticas o tromboembólicas, el efecto directo o indirecto de este virus relacionado con la tormenta de citocinas que precipita el inicio del síndrome de respuesta inflamatoria sistémica y predispone al desarrollo de eventos trombóticos; también las intervenciones disponibles pueden tener interacciones farmacológicas con antiagregantes y/o anticoagulantes.

Abstract Introduction Coronavirus 19 infection can predispose to VTE or arterial thrombosis due to a heightened inflammatory response, hypoxia, immobility and DIC. Up to 20-50% of hospitalized patients with COVID-19 have hematological disorders related to coagulopathies (elevated D-dimer, prolonged PT, thrombocytopenia and/or low fibrinogen). Post-mortem examinations show typical platelet-rich microvascular thrombotic deposits in the small vessels of the lungs and other organs. Objective To provide a practical, updated approach to the treatment of patients at high risk for or with ongoing thromboembolic events in the current COVID-19 pandemic setting. Material and methods A narrative review was performed including descriptive observational studies. A search of the medical evidence literature was carried out in different search engines such as ScienceDirect and PubMed, using the following key words: “thromboprophylaxis”, “anticoagulation”, “thrombosis”, “anticoagulant”, “COVID-19”, “SARS-CoV-2”, and “coronavirus”, and general recommendations on the topic were subsequently composed. Conclusions The are various ways in which the COVID-19 pandemic may predispose to the development of thrombotic or thromboembolic diseases. The virus may have a direct or indirect effect related to the cytokine storm which triggers the onset of systemic inflammatory response syndrome and predisposes to the development of thrombotic events. The available interventions may also have pharmacological interactions with antiplatelet drugs and/or anticoagulants.

Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy.

Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca2+ handling is a key feature of HF pathophysiology. Restoring the Ca2+ regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp-/-), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF.

Mindfulness based cognitive therapy for youth with inflammatory bowel disease and depression - Findings from a pilot randomised controlled trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising adjunctive treatment for adolescents and young adults (AYAs) with Inflammatory Bowel Disease (IBD) and comorbid depression. OBJECTIVES: This pilot randomised controlled trial (RCT) aimed to evaluate feasibility and efficacy of an adapted MBCT program for AYA, aged 16-29, with IBD. METHODS: Sixty-four AYAs were randomly allocated to MBCT (n = 33) or treatment as usual (TAU) (n = 31). Primary outcome measure was the depression score on Depression, Anxiety and Stress Scale. Secondary outcomes included anxiety, stress, IBD-related quality of life, coping, mindfulness, post-traumatic growth, medication adherence, IBD activity, inflammatory markers, microbiome characteristics and brain functional connectivity. RESULTS: Study recruitment rate was 75%, retention rate 70%, and session attendance 92%. Intention to treat analyses revealed that, compared to TAU group, MBCT group had significantly lower depression (∆ = -6.0; 95%CI = -10.8 to -1.2; P = 0.015) and stress (∆ = -5.1; 95%CI = -10.1 to -0.0; P = 0.049), higher active coping (∆ = 1.0;95%CI = 0.1-1.9; P = 0.022), and total mindfulness scores (∆ = 10.9;95%CI = 1.1-20.8; P = 0.030) at 8 weeks (post-therapy), and improved coping by positive reframing (∆ = 1.1;95%CI = 0.0-2.2; P = 0.043) and planning (∆ = 0.9;95%CI = 0.0-1.9; P = 0.045), mindful awareness (∆ = 5.2.;95%CI = 2.0-8.5; P = 0.002) and total mindfulness scores (∆ = 10.8.;95%CI = 0.4-21.1; P = 0.042) at 20 weeks. On per protocol analysis, MBCT group had significantly lower depression (∆ = -6.3; 95%CI = -11.4 to -1.2; P = 0.015), stress (∆ = -6.0; 95%CI = -11.2 to -0.5; P = 0.032), increased active coping (∆ = 0.9;95%CI = 0-1.7; P = 0.05) at 8 weeks, and mindful awareness (∆ = 5.4; 95%CI = 2.1-8.6; P = 0.001) at 20 weeks. CONCLUSION: In AYAs with IBD, MBCT is feasible and beneficial in improving depression, stress, mindfulness and adaptive coping. It holds promise as an important component of integrated IBD care. Trial registration number ACTRN12617000876392, U1111-1197-7370; Pre-results.

Mathematical Model Predicts that Acceleration of Diabetic Wound Healing is Dependent on Spatial Distribution of VEGF-A mRNA (AZD8601).

INTRODUCTION: Pharmacologic approaches for promoting angiogenesis have been utilized to accelerate healing of chronic wounds in diabetic patients with varying degrees of success. We hypothesize that the distribution of proangiogenic drugs in the wound area critically impacts the rate of closure of diabetic wounds. To evaluate this hypothesis, we developed a mathematical model that predicts how spatial distribution of VEGF-A produced by delivery of a modified mRNA (AZD8601) accelerates diabetic wound healing. METHODS: We modified a previously published model of cutaneous wound healing based on coupled partial differential equations that describe the density of sprouting capillary tips, chemoattractant concentration, and density of blood vessels in a circular wound. Key model parameters identified by a sensitivity analysis were fit to data obtained from an in vivo wound healing study performed in the dorsum of diabetic mice, and a pharmacokinetic model was used to simulate mRNA and VEGF-A distribution following injections with AZD8601. Due to the limited availability of data regarding the spatial distribution of AZD8601 in the wound bed, we performed simulations with perturbations to the location of injections and diffusion coefficient of mRNA to understand the impact of these spatial parameters on wound healing. RESULTS: When simulating injections delivered at the wound border, the model predicted that injections delivered on day 0 were more effective in accelerating wound healing than injections delivered at later time points. When the location of the injection was varied throughout the wound space, the model predicted that healing could be accelerated by delivering injections a distance of 1-2 mm inside the wound bed when compared to injections delivered on the same day at the wound border. Perturbations to the diffusivity of mRNA predicted that restricting diffusion of mRNA delayed wound healing by creating an accumulation of VEGF-A at the wound border. Alternatively, a high mRNA diffusivity had no effect on wound healing compared to a simulation with vehicle injection due to the rapid loss of mRNA at the wound border to surrounding tissue. CONCLUSIONS: These findings highlight the critical need to consider the location of drug delivery and diffusivity of the drug, parameters not typically explored in pre-clinical experiments, when designing and testing drugs for treating diabetic wounds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00678-9.

The Effect of Platelet-Rich Plasma on Endothelial Progenitor Cell Functionality.

Platelets mediate circulating endothelial progenitor cell (EPC) recruitment and maturation, participating in vascular repair, however the underlying mechanism(s) remain unclear. We investigated the effect of platelet-rich plasma (PRP) on the functionality of CD34+-derived late-outgrowth endothelial cells (OECs) in culture. Confluent OECs were coincubated with PRP under platelet aggregation (with adenosine diphosphate; ADP) and nonaggregation conditions, in the presence/absence of the reversible P2Y12 platelet receptor antagonist ticagrelor. Outgrowth endothelial cell activation was evaluated by determining prostacyclin (PGI2) and monocyte chemoattractant protein-1 (MCP-1) release and intercellular adhesion molecule-1 (ICAM-1) membrane expression. Similar experiments were performed using human umbilical vein endothelial cells (HUVECs). Platelet-rich plasma increased ICAM-1 expression and PGI2 and MCP-1 secretion compared with autologous platelet-poor plasma, whereas ADP-aggregated platelets in PRP did not exhibit any effect. Platelet-rich plasma pretreated with ticagrelor prior to activation with ADP increased all markers to a similar extent as PRP. Similar results were obtained using HUVECs. In conclusion, PRP induces OEC activation, a phenomenon not observed when platelets are aggregated with ADP. Platelet inhibition with ticagrelor restores the PRP capability to activate OECs. Since EPC activation is important for endothelial regeneration and angiogenesis, we suggest that agents inhibiting platelet aggregation, such as ticagrelor, may promote platelet-EPC interaction and EPC function.

Hydrophobic Drug/Toxin Binding Sites in Voltage-Dependent K+ and Na+ Channels.

In the Nav channel family the lipophilic drugs/toxins binding sites and the presence of fenestrations in the channel pore wall are well defined and categorized. No such classification exists in the much larger Kv channel family, although certain lipophilic compounds seem to deviate from binding to well-known hydrophilic binding sites. By mapping different compound binding sites onto 3D structures of Kv channels, there appear to be three distinct lipid-exposed binding sites preserved in Kv channels: the front and back side of the pore domain, and S2-S3/S3-S4 clefts. One or a combination of these sites is most likely the orthologous equivalent of neurotoxin site 5 in Nav channels. This review describes the different lipophilic binding sites and location of pore wall fenestrations within the Kv channel family and compares it to the knowledge of Nav channels.

Incorporating subject-specific geometry to compare metatarsal stress during running with different foot strike patterns.

Stress fracture of the second metatarsal is a common and problematic injury for runners. The choice of foot strike pattern is known to affect external kinetics and kinematics but its effect on internal loading of the metatarsals is not well understood. Subject-specific models of the second metatarsal can be used to investigate internal loading in a non-invasive manner. This study aimed to compare second metatarsal stress between habitual rearfoot and non-rearfoot strikers during barefoot running, using a novel subject-specific mathematical model, including accurate metatarsal geometry. Synchronised force and kinematic data were collected during barefoot overground running from 20 participants (12 rearfoot strikers). Stresses were calculated at the plantar and dorsal periphery of the midshaft of the metatarsal using a subject-specific beam theory model. Non-rearfoot strikers demonstrated greater external loading, bending moments and compressive forces than rearfoot strikers, but there were no differences in peak stresses between groups. Statistical parametric analysis revealed that non-rearfoot strikers had greater second metatarsal stresses during early stance but that there was no difference in peak stresses. This emphasises the importance of bone geometry when estimating bone stress and supports the suggestion that external forces should not be assumed to be representative of internal loading.

Tsukamurella asaccharolytica sp. nov., Tsukamurella conjunctivitidis sp. nov. and Tsukamurella sputi sp. nov., isolated from patients with bacteraemia, conjunctivitis and respiratory infection in Hong Kong.

Three bacterial strains, HKU70T, HKU71T and HKU72T, were isolated from the conjunctival swab, blood and sputum samples of three patients with conjunctivitis, bacteraemia and respiratory infection, respectively, in Hong Kong. The three strains were aerobic, Gram-stain positive, catalase-positive, non-sporulating and non-motile bacilli and exhibited unique biochemical profiles distinguishable from currently recognized Tsukamurella species. 16S rRNA, secA, rpoB and groEL gene sequence analyses revealed that the three strains shared 99.6-99.9, 94.5-96.8, 95.7-97.8 and 97.7-98.9 % nucleotide identities with their corresponding closest Tsukamurella species respectively. DNA-DNA hybridization confirmed that they were distinct from other known species of the genus Tsukamurella (26.2±2.4 to 36.8±1.2 % DNA-DNA relatedness), in line with results of in silico genome-to-genome comparison (32.2-40.9 % Genome-to-Genome Distance Calculator and 86.3-88.9 % average nucleotide identity values]. Fatty acids, mycolic acids, cell-wall sugars and peptidoglycan analyses showed that they were typical of members of Tsukamurella. The G+C content determined based on the genome sequence of strains HKU70T, HKU71T and HKU72T were 69.9, 70.2 and 70.5 mol%, respectively. Taken together, our results supported the proposition and description of three new species, i.e. Tsukamurella sputi HKU70T (=JCM 33387T=DSM 109106T) sp. nov., Tsukamurella asaccharolytica HKU71T (=JCM 33388T=DSM 109107T) sp. nov. and Tsukamurella conjunctivitidis HKU72T (=JCM 33389T=DSM 109108T) sp. nov.

Epidemiology of Hematologic Malignancies in Real-World Settings: Findings From the Hemato-Oncology Latin America Observational Registry Study.

PURPOSE: Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL. METHODS: This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4). RESULTS: Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION: The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.

Public acceptability of nudging and taxing to reduce consumption of alcohol, tobacco, and food: A population-based survey experiment.

There is growing evidence for the effectiveness of choice architecture or 'nudge' interventions to change a range of behaviours including the consumption of alcohol, tobacco and food. Public acceptability is key to implementing these and other interventions. However, few studies have assessed public acceptability of these interventions, including the extent to which acceptability varies with the type of intervention, the target behaviour and with evidence of intervention effectiveness. These were assessed in an online study using a between-participants full factorial design with three factors: Policy (availability vs size vs labelling vs tax) x Behaviour (alcohol consumption vs tobacco use vs high-calorie snack food consumption) x Evidence communication (no message vs assertion of policy effectiveness vs assertion and quantification of policy effectiveness [e.g., a 10% change in behaviour]). Participants (N = 7058) were randomly allocated to one of the 36 groups. The primary outcome was acceptability of the policy. Acceptability differed across policy, behaviour and evidence communication (all ps < .001). Labelling was the most acceptable policy (supported by 78%) and Availability the least (47%). Tobacco use was the most acceptable behaviour to be targeted by policies (73%) compared with policies targeting Alcohol (55%) and Food (54%). Relative to the control group (60%), asserting evidence of effectiveness increased acceptability (63%); adding a quantification to this assertion did not significantly increase this further (65%). Public acceptability for nudges and taxes to improve population health varies with the behaviour targeted and the type of intervention but is generally favourable. Communicating that these policies are effective can increase support by a small but significant amount, suggesting that highlighting effectiveness could contribute to mobilising public demand for policies. While uncertainty remains about the strength of public support needed, this may help overcome political inertia and enable action on behaviours that damage population and planetary health.