Survival bias may explain the appearance of the obesity paradox in hip fracture patients.

Patients with low-energy hip fractures do not follow the obesity paradox as previously reported. In datasets where injury mechanism is not available, the use of age >50 years (as opposed to commonly used >65 years) as a surrogate for a low-energy hip fracture patients may be a more robust inclusion criterion. PURPOSE: In elderly patients with a hip fracture, limited data suggests that obese patients counterintuitively have improved survival compared to normal-weight patients. This "obesity paradox" may be the byproduct of selection bias. We hypothesized that the obesity paradox would not apply to elderly hip fracture patients. METHODS: The National Surgical Quality Improvement Project dataset identified 71,685 hip fracture patients ≥50 years-of-age with complete body mass index (BMI) data that underwent surgery. Patients were stratified into under and over 75-year-old cohorts (n=18,956 and 52,729, respectively). Within each age group, patients were stratified by BMI class and compared with respect to preoperative characteristics and 30-day mortality. Significant univariate characteristics (p<0.1) were included in multivariate analysis to determine the independent effect of obesity class on 30-day mortality (p<0.05). RESULTS: Multivariate analysis of <75-year-old patients with class-III obesity were more likely to die within 30-days than similarly aged normal-weight patients (OR 1.91, CI 1.06-3.42, p=0.030). Multivariate analysis of ≥75-year-old overweight (OR 0.69, CI 0.62-0.77, p<0.001), class-I obese (OR 0.62, CI 0.51-0.74, p<0.001), or class-II obese (OR=0.69, CI 0.50-0.95, p=0.022) patients were less likely to die within 30-days when compared to similarly aged normal-weight patients. CONCLUSIONS: Our data suggest that obesity is a risk factor for mortality in low-energy hip fracture patients, but the appearance of the "obesity paradox" in elderly hip fracture patients results from statistical bias that is only evident upon subgroup analysis.

Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.

BACKGROUND: Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. OBJECTIVES: To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. METHODS: We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. CONCLUSIONS: A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.

Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation.

BACKGROUND: Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise. OBJECTIVES: To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11 mutations. METHODS: We performed a large 4-year, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations. CONCLUSIONS: The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.

Distinctive cutaneous and systemic features associated with specific antimyositis antibodies in adults with dermatomyositis: a prospective multicentric study of 117 patients.

BACKGROUND: Identification of myositis-specific autoantibodies (MSAs) for dermatomyositis (DM) could allow the characterization of an antibody-associated clinical phenotype. OBJECTIVE: We sought to define the clinical phenotype of DM and the risk of cancer, interstitial lung disease (ILD) and calcinosis based on MSA. METHODS: A 3.5-year multicentre prospective study of adult DM patients was conducted to determine the clinical phenotype associated with MSAs and the presence of cancer, ILD and calcinosis. RESULTS: MSAs were detected in 47.1% of 117 included patients. Patients with antimelanoma differentiation-associated protein-5 antibodies (13.7%) had significantly more palmar violaceous macules/papules [odds ratio (OR) 9.9], mechanic's hands (OR 8), cutaneous necrosis (OR 3.2), articular involvement (OR 15.2) and a higher risk of ILD (OR 25.3). Patients with antitranscriptional intermediary factor-1 antibodies (11.1%), antinuclear matrix protein-2 antibodies (6.8%) and antiaminoacyl-transfer RNA synthetase (5.1%) had, respectively, significantly more poikiloderma (OR 5.9), calcinosis (OR 9.8) and articular involvement (OR 15.2). Cutaneous necrosis was the only clinical manifestation significantly associated with cancer (OR 3.1). CONCLUSION: Recognition of the adult DM phenotype associated with MSAs would allow more accurate appraisal of the risk of cancer, ILD and calcinosis.

[Massive localized lymphedema]. / Lymphœdèmes massifs localisés.

BACKGROUND: Massive localized lymphedema (MLL) is a benign soft-tissue lesion that usually presents as a large and isolated mass in morbidly obese adults. PATIENTS AND METHODS: We report the case of a 39-year-old woman presenting obesity and multiple MLL. There was a large tumor in the left groin and two smaller lesions on the backs of the thighs. DISCUSSION: MLL is a benign tumor that must be removed wherever possible because such tumors may degenerate into angiosarcomas in 13% of cases. MLL is probably secondary to a prolonged obstruction of lymphatic vessels due to marked excess of adipose tissue.

A rapid manual technique does not have adequate sensitivity and specificity to reliably discriminate between neutropenic and non-neutropenic dogs prior to administration of chemotherapy.

OBJECTIVES: To develop and determine the accuracy of a rapid manual technique for the detection of pre-treatment neutropenia (<1.50 × 109/L) in dogs receiving chemotherapy. MATERIALS AND METHODS: Twenty canine blood smears with known neutrophil counts between 1.00 × 109/L and 3.00 × 109/L were reviewed by two internal medicine clinicians and linear regressions performed to determine a cut-off value for a manual neutrophil count equating to >1.50 × 109/L. Consecutive blood samples from dogs undergoing chemotherapy were processed through an automated haematology analyser (VetScan HM5, Abaxis), and prospective blinded manual review by the same two observers assessed whether the manual technique could accurately detect dogs with neutropenia. RESULTS: Linear regression analysis found a cut-off of >26 neutrophils per 10 low power fields at the monolayer to be equivalent to a neutrophil count of >1.5 × 109/L. A total of 183 blood samples from 43 dogs were reviewed. Automated techniques detected neutropenia in 16 of 183 (9%) blood samples. Using the manual cut-off technique, 13 of 16 (81%) and 11 of 16 (69%) of neutropenic samples were correctly identified by observer 1 and observer 2, respectively. Twenty-three of 167 non-neutropenic dogs (14%) were incorrectly classified as neutropenic by observer 1, and 27 (16%) by observer 2. Inter-observer agreement was 92%. Sensitivity was 81% (95% confidence interval 54% to 96%) for observer 1 and 69% (95% confidence interval 41% to 89%) for observer 2. Specificity was 86% (95% confidence interval 80% to 91%) for observer 1 and 84% (95% confidence interval 77% to 89%) for observer 2. CLINICAL SIGNIFICANCE: Manual estimation resulted in up to five of 16 (31%) neutropenic samples being incorrectly classified. A full automated differential cell count remains preferable.

Diagnostic findings in sinonasal aspergillosis in dogs in the United Kingdom: 475 cases (2011-2021).

OBJECTIVES: To describe the diagnostic tests used and their comparative performance in dogs diagnosed with sinonasal aspergillosis in the United Kingdom. A secondary objective was to describe the signalment, clinical findings and common clinicopathologic abnormalities in sinonasal aspergillosis. MATERIALS AND METHODS: A multi-centre retrospective survey was performed involving 23 referral centres in the United Kingdom to identify dogs diagnosed with sinonasal aspergillosis from January 2011 to December 2021. Dogs were included if fungal plaques were seen during rhinoscopy or if ancillary testing (via histopathology, culture, cytology, serology or PCR) was positive and other differential diagnoses were excluded. RESULTS: A total of 662 cases were entered into the database across the 23 referral centres. Four hundred and seventy-five cases met the study inclusion criteria. Of these, 419 dogs had fungal plaques and compatible clinical signs. Fungal plaques were not seen in 56 dogs with turbinate destruction that had compatible clinical signs and a positive ancillary test result. Ancillary diagnostics were performed in 312 of 419 (74%) dogs with observed fungal plaques permitting calculation of sensitivity of cytology as 67%, fungal culture 59%, histopathology 47% and PCR 71%. CLINICAL SIGNIFICANCE: The sensitivities of ancillary diagnostics in this study were lower than previously reported challenging the clinical utility of such tests in sinonasal aspergillosis. Treatment and management decisions should be based on a combination of diagnostics including imaging findings, visual inspection, and ancillary testing, rather than ancillary tests alone.

Latitudinal gradients in seed predation persist in urbanized environments.

Urbanization is creating a new global biome, in which cities and suburbs around the world often resemble each other more than the local natural areas they replaced. But while urbanization can profoundly affect ecology at local scales, we know little about whether it disrupts large-scale ecological patterns. Here we test whether urbanization disrupts a macroecological pattern central to ecological and evolutionary theory: the increase in seed predation intensity from high to low latitudes. Across 14,000 km of latitude spanning the Americas, we compared predation intensity on two species of standardized experimental seeds in urbanized and natural areas. In natural areas, predation on both seed species increased fivefold from high latitudes to the tropics, one of the strongest latitudinal gradients in species interactions documented so far. Surprisingly, latitudinal gradients in predation were equally strong in urbanized areas despite significant habitat modification. Nevertheless, urbanization did affect seed predation. Compared with natural areas, urbanization reduced overall predation and vertebrate predation, did not affect predation by invertebrates in general, and increased predation by ants. Our results show that macroecological patterns in predation intensity can persist in urbanized environments, even as urbanization alters the relative importance of predators and potentially the evolutionary trajectory of urban populations.

Telopathes magna gen. nov., spec. nov. (Cnidaria: Anthozoa: Antipatharia: Schizopathidae) from deep waters off Atlantic Canada and the first molecular phylogeny of the deep-sea family Schizopathidae.

A new genus and species of deep-sea antipatharian, Telopathes magna gen. nov., spec. nov., is described from the western North Atlantic off the coast of Canada. Five additional paratypes, consisting ofjuvenile to adult forms, are reported from the New England and Corner Rise Seamounts (NW Atlantic). Preliminary sequencing of a subsection of the nuclear ribosomal cistron confirmed the phylogenetic affinity of T. magna to the order Antipatharia, and in particular the family Schizopathidae. Subsequent sequencing of three mitochondrial DNA segments from nine of the 11 currently-recognized genera within the Schizopathidae revealed a well-supported phylogenetic relationship between T. magna and Stauropathes. This is the first study to use molecular techniques to elucidate the evolutionary relationships of the Schizopathidae, a family of black corals almost exclusively found in the deep sea (depths > 200 m). Telopathes is distinguished from other genera within the family Schizopathidae by its largely pinnulated stalk, sparse branching pattern to the second degree that is not restricted to a single plane, two anterolateral rows of long, simple primary pinnules, arranged alternately to sub-opposite, and colony with an adhesive base. This record of T. magna brings the total number of nominal species of Antipatharia reported to occur off eastern Canada to 12 and represents the third new genus added to the Schizopathidae since a critical review of the family by Dennis Opresko in 2002.

Validation of the Knowledge of Genome Sequencing (KOGS) scale in cancer patients.

INTRODUCTION: The Knowledge of Genome Sequencing (KOGS) questionnaire was recently developed to measure knowledge of genomic sequencing (GS), with preliminary psychometric data supporting its reliability and validity. The aim of this study was to test the reliability and validity of the KOGS in a larger sample, and to confirm its utility in a cancer setting. METHODS: The Genetic Cancer Risk in the Young (RisC) study recruits participants with a personal history of cancer, to investigate heritable cancer causes and future cancer risk using germline GS. Participants (n = 261) in a psychosocial substudy of RisC completed a questionnaire after consent to RisC but before GS, including the KOGS, the Intolerance of Uncertainty Scale, the Chew health literacy scale and items assessing demographic and disease variables. Confirmatory factor analysis (CFA), Cronbach alpha and correlational analyses were undertaken. RESULTS: The CFA testing a single-factor model yielded a good model fit, χ2/df = 2.43, comparative fit index (CFI) = 0.97, root mean square error of approximation (RMSEA) = 0.07 and weighted mean root square (WRMR) = 1.03. Factor loadings of all items were above 0.60 and ranged between.66 and.93. The single factor score demonstrated excellent internal consistency (α = 0.82). KOGS scores were significantly associated with health literacy (r = 0.23, p < .001), having a university education [t(258) = -4.53, p < .001] and having a medical or science background [t(259) = -3.52, p < .001] but not with speaking a language other than English at home, time since diagnosis, previous genetic counselling/testing or intolerance of uncertainty. DISCUSSION: This study confirmed a single-factor structure for the KOGS, and its reliability and validity in a cancer population. Associations with measures of health literacy and education were significant and positive as expected, supporting the KOG's construct validity. Previous genetic counselling may not be sufficient to provide specific knowledge of GS.

The impact of COVID-19 on cancer patients, their carers and oncology health professionals: A qualitative study.

OBJECTIVE: Cancer patients, carers and oncology health professionals have been impacted by the COVID-19 pandemic in many ways, but their experiences and psychosocial responses to the pandemic are still being explored. This study aimed to document the experience of Australians living with cancer, family carers, and Oncology health professionals (HPs) when COVID-19 first emerged. METHODS: In this qualitative study, participants (cancer patients currently receiving treatment, family carers and HPs) completed a semi-structured interview exploring their experiences of COVID-19 and the impact it had on cancer care. Participants also completed the Hospital Anxiety and Depression Scale (patients) and the Depression, Anxiety and Stress Scale (carers and HPs) to assess emotional morbidity. Thematic analysis was undertaken on qualitative data. RESULTS: 32 patients, 16 carers and 29 HPs participated. Qualitative analysis yielded three shared themes: fear and death anxiety, isolation, and uncertainty. For HPs, uncertainty incorporated the potential for moral distress and work-stress. Patients and carers scoring high on anxiety/depression measures were more likely to have advanced disease, expressed greater death anxiety, talked about taking more extreme precautionary measures, and felt more impacted by isolation. CONCLUSION: Cancer and COVID-19 can have compounding psychological impacts on all those receiving or giving care. PRACTICE IMPLICATIONS: Screening for distress in patients, and burnout in HPs, is recommended. Increased compassionate access and provision of creative alternatives to face-to-face support are warrented.

Quaternary raised coral-reef terraces on sumba island, indonesia.

A spectacular sequence of coral-reef terraces (six steps broader than 500 meters and many minor substeps) is developed near Cape Laundi, Sumba Island, between an ancient patch reef 475 meters high and sea level. Several raised reefs have been dated with the electron spin resonance and the uranium-series dating methods. The uplift trend deduced from these reefs is 0.5 millimeter per year; most terraces, although polycyclic in origin, appear to correspond to specific interglacial stages, with the oldest terrace formed 1 million years ago. This puts them among the longest and most complete mid-Quaternary terrace sequences.

[Stance toward psychosomatic rehabilitation: development of a patient-questionnaire]. / Einstellung zur psychosomatischen Rehabilitation: Entwicklung eines Patienten-Fragebogens.

BACKGROUND: The transition from home to psychosomatic rehabilitation is problematic for many patients. They show little treatment motivation because of insufficient information and fear of stigmatization. Pre-treatment seeks to reduce these problems. The patient-questionnaire for stance toward psychosomatic rehabilitation was developed and tested for performance criteria. METHODS: A German statutory pension insurance scheme sample of psychosomatic rehabilitation patients (n=317) were recruited for testing psychosometric attributes and were questioned before and after pre-treatment. To determine whether the questionnaire can show clinically relevant changes, 124 patients with pre-information were compared with 88 patients without intervention. Additionally, clinically relevant changes for patients without knowledge of psychosomatic rehabilitation (n=70) were analyzed. RESULTS AND CONCLUSIONS: Factor analysis shows a three factor solution with ten items. The discriminatory power was good. High reliability was found for two factors and lower reliability for one factor. The patient-questionnaire for stance toward psychosomatic rehabilitation contains three scales: "knowledge", "confidence", and "motivation", and can be characterized as a reliable and economic instrument. After pre-treatment a general improvement was observed regarding patients' stance toward psychosomatic rehabilitation. The analyses result in significantly higher mean for patients with pre-treatment. Patients without previous information showed less "confidence" and "motivation". Pre-treatment can have a positive impact on the stance toward psychosomatic rehabilitation.

[Psychosomatic rehabilitation: effects of pre-treatment counselling under the statutory pension insurance scheme]. / Psychosomatische Rehabilitation: Effekte einer prästationären Beratung durch die Rentenversicherung.

BACKGROUND: Currently, little is known about the influence of pre-treatment in rehabilitation outcomes of patients with psychosomatic symptoms. This study examines whether there are differences in therapy motivation and impairment between patients with and those without pre-treatment measures. Additionally, the outcome for patients with prior knowledge of psychosomatic rehabilitation is analyzed. METHODS: As part of a randomized controlled pre-post design the Patients' questionnaire of therapy motivation (PAREMO) and the Brief Symptom Inventory (BSI) were distributed to 166 patients in psychosomatic rehabilitation. The selection of patients with prior knowledge of psychosomatic rehabilitation was made according to the scale "knowledge" of the patients' questionnaire. Changes were tested by analysis of variance at two treatment points. RESULTS: Although there were positive effects of rehabilitation, no interaction was found between measurement points and groups. The analyses of patients without prior knowledge of psychosomatic rehabilitation showed different outcomes for males and females. Higher rehabilitation outcomes for females than for males were found on the BSI scales "somatisation", "phobic anxiety", and "psychoticism". CONCLUSIONS: The findings show that pre-treatment facilitates the patients' approach to psychosomatic rehabilitation. Apart from receiving information patients should be motivated more strongly and their confidence in psychosomatic rehabilitation strengthened.

Confirmed case of Pneumocystis pneumonia in a Maltese Terrier × Papillon dog being treated with toceranib phosphate.

CASE REPORT: A 7-year-old female-neutered Maltese Terrier × Papillon dog was presented with tachypnoea and weight loss following 12 months of therapy with toceranib phosphate for a metastatic, histologically-low-grade mast cell tumour. The dog was diagnosed with Pneumocystis canis based on PCR with supportive clinical, radiographic and cytological findings. No other clinical evidence of immunocompromise was identified through assessment of haematology and immunoglobulin quantification. Clinical signs completely resolved with a short course of potentiated sulfonamides and discontinuation of the toceranib. CONCLUSION: To the authors' knowledge this represents the first case of Pneumocystis in a dog secondary to immunomodulatory drug therapy. It is also the first case of opportunist infection secondary to a tyrosine kinase inhibitor in dogs.

Protestant Christian attitudes to ART.

STUDY QUESTION: How do Christian religious beliefs affect attitudes to ART? SUMMARY ANSWER: Attitudes to ART depend on the religiosity of the respondent, and although the majority of those that had successfully used ART were positive or moderately positive in their views, the acceptability of procedures fell when damage to the marriage relationship or the embryo was a potential outcome. WHAT IS KNOWN ALREADY: Religion can impact views on ART. Sanctity of marriage and sanctity of the embryo are major concerns for some Christians, but details are unclear. METHODS: A cross-sectional online survey was used to collect data from 1587 participants over a 3-month period in 2013, of which 1334 were of the Christian faith and included in this study. Descriptive statistics were reported for individual ARTs, and a general score of all ART approval was calculated. A multivariable linear and logistic regression was conducted on general approval for ART to identify predictors of ART approval. MAIN RESULTS AND THE ROLE OF CHANCE: Indicators of religiosity (religious meeting attendance and Bible reading frequency) showed that this was a highly religious sample. We found that in this cohort of English-speaking, well-educated, practising and mainly Protestant Christians 164 (12.3%) of those had personal experience of ART. Most participants that had successfully used ART were positive or moderately positive in their views. Throughout the cohort, procedures were less acceptable if there was a perception that the marriage relationship or the life of the embryo was threatened: including donated gametes (28.7-29.1% approval), surrogacy (22.7-33.1% approval), and PGD (1.0-23.8% approval). A multivariable analysis of the ART approval score found that it was higher among those with Protestant compared with Catholic/Orthodox faith (P < 0.001; mean score difference, 5.06; 95% CI 4.36-5.81) and those who believe life begins after fertilisation (P < 0.001; mean score difference, 4.86; 95% CI 4.14-5.57). Approval was also higher, but to a lesser extent, in women than men (P = 0.008; mean score difference, 0.73; 95% CI 0.18-1.28), and those with lower religiosity (P < 0.001). The area raising most indecision for this cohort was disposal of excess embryos. LIMITATIONS REASONS FOR CAUTION: This sample includes an uneven geographical spread of respondents and restriction to English-speaking participants. Different views may be expressed by a different religious cohort. Use of an online survey platform means that a bias towards those with computers (consistent with education levels of this cohort) could exist. Use of this platform also makes it impossible to know the response rate, and the veracity of responses cannot be verified. However, despite these limitations we believe this survey gives us insight into the reservations held among a certain population of Christians regarding the use of reproductive technology. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the need for ART clinicians to consider the influence of patient spiritual beliefs on therapeutic options and provide detailed information that will allow them to be accommodated. Practices such as widening the options for collecting semen and limiting the number of embryos created through IVF so as to reduce or eliminate excess embryos may be helpful for these patients. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a grant from The Center for Bioethics & Human Dignity in Deerfield, Illinois, USA. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

A hand-held surface plasmon resonance biosensor for the detection of ricin and other biological agents.

There is an ongoing need for field-deployable biosensor devices. We have constructed a fully self-contained, hand-held biosensor, based on the surface plasmon resonance technique. The dimensions of the sensor unit are 15 x 8 cm, the weight is 600 g and it is powered by a 9 V battery. We have characterised the responsiveness of the sensor using calibrated sucrose solutions and were able to measure changes as small as 3.3 x 10(-6) refractive index units. To demonstrate functionality of the sensor, we have prepared surfaces with an antibody fragment specific for the biological toxin ricin. We were able to detect ricin at 200 ng/mL in 10 min, which is approximately 2500 times less than the minimum lethal dose. We were also able to verify positive binding within a second 10 min window. This sensor demonstrates important steps required for the development of fully integrated, hand-held sensor devices and will form the basis of a multi-analyte system, to be developed in the near future. It also represents the first completely hand-held SPR device, not requiring external power or a computer connection to operate.

Repeated infusions of levosimendan: well tolerated and improves functional capacity in decompensated heart failure - a single-centre experience.

BACKGROUND: Levosimendan is a novel agent used in the treatment of patients with decompensated heart failure to enhance cardiac contractility. Recent clinical studies have demonstrated that single doses of levosimendan have positive symptomatic and haemodynamic benefits, few have explored the efficacy and safety of intermittent repeated doses of levosimendan. AIMS: In this prospective study we document our single-centre experience of repeated administration of levosimendan to patients with decompensated heart failure. METHODS: Prospective data were collected and analysed with respect to New York Heart Association (NYHA) class, mean arterial pressure (MAP), brain natriuretic peptide levels (BNP) and adverse events. RESULTS: Forty-four consecutive patients with decompensated heart failure received repeated doses of levosimendan. The mean dosing interval was 66.2 (12) days. All patients had documented evidence of impaired left ventricular function, with a mean ejection fraction (EF) of 23.7% (2.2). Fifty-eight percent were NYHA class IV, mean age 50 (2.4), 82% were male. A significant drop in BNP levels and improvement in NYHA class was seen post-infusion. In general, levosimendan was well tolerated with 130 (83.5%) infusions completed without an adverse event. Twenty-five percent of patients were bridged to cardiac transplant or left ventricular assist device (LVAD) insertion. Four patients received 12 infusions, in total in the community. CONCLUSION: The majority of repeated levosimendan infusions were well tolerated, reduced BNP and improved NYHA functional class. In selected patients it can be administered in the community. Further investigation is required to assess the efficacy and safety of this approach.

Impact of Escherichia coli K12 and O18:K1 on human platelets: Differential effects on platelet activation, RNAs and proteins.

Blood platelets can interact with bacteria, possibly leading to platelet activation, cytokine and microparticle release and immune signalling. Besides, bacteria can also affect the platelet RNA content. We investigated the impact of non-pathogenic K12 and pathogenic O18:K1 Escherichia (E.) coli strains on platelet activation, RNA expression patterns, and selected proteins. Depending on bacteria concentration, contact of platelets with E. coli K12 lead to an increase of P-selectin (24-51.3%), CD63 (15.9-24.3%), PAC-1 (3.8-14.9%) and bound fibrinogen (22.4-39%) on the surface. E. coli O18:K1 did not affect these markers. Sequencing analysis of total RNA showed that E. coli K12 caused a significant concentration change of 103 spliced mRNAs, of which 74 decreased. For the RNAs of HMBS (logFC = +5.73), ATP2C1 (logFC = -3.13) and LRCH4 (logFC = -4.07) changes were detectable by thromboSeq and Tuxedo pipelines. By Western blot we observed the conversion of HMBS protein from a 47 kDA to 40 kDa product by E. coli K12, O18:K1 and by purified lipopolysaccharide. While ATP2C1 protein was released from platelets, E. coli either reduced the secretion or broke down the released protein making it undetectable by antibodies. Our results demonstrate that different E. coli strains influence activation, RNA and protein levels differently which may affect platelet-bacteria crosstalk.

Dissolved oxygen as a physico-chemical supporting element in the Water Framework Directive.

For transitional and coastal waters the Water Framework Directive identifies 5 "General chemical and physiochemical elements supporting the biological elements". The five elements are transparency, thermal conditions, oxygenation conditions, salinity and nutrient conditions. "Supporting" in the context of the directive means that the values of the physicochemical quality elements are such as to support a biological community of a certain ecological status, recognising the fact that biological communities are products of their physical and chemical environment. Physicochemical and hydromophological aspects fundamentally determine the type of water body and habitat, and hence the type specific biological community. The directive does not intended that these supporting elements should be used as surrogates for the biological elements in monitoring. The monitoring and assessment of the physical and physicochemical quality elements will support the interpretation, assessment and classification of the results arising from the monitoring of the biological quality elements. This paper considers the challenges involved in the development of oxygen standards for the directive, their relationship to the biological elements and normative conditions of the directive and to regulatory requirements.