Analysis of mammograms using artificial intelligence to predict response to neoadjuvant chemotherapy in breast cancer patients: proof of concept.

OBJECTIVES: In this proof of concept study, a deep learning-based method for automatic analysis of digital mammograms (DM) as a tool to aid in assessment of neoadjuvant chemotherapy (NACT) treatment response in breast cancer (BC) was examined. METHODS: Baseline DM from 453 patients receiving NACT between 2005 and 2019 were included in the study cohort. A deep learning system, using the aforementioned baseline DM, was developed to predict pathological complete response (pCR) in the surgical specimen after completion of NACT. Two image patches, one extracted around the detected tumour and the other from the corresponding position in the reference image, were fed into a classification network. For training and validation, 1485 images obtained from 400 patients were used, and the model was ultimately applied to a test set consisting of 53 patients. RESULTS: A total of 95 patients (21%) achieved pCR. The median patient age was 52.5 years (interquartile range 43.7-62.1), and 255 (56%) were premenopausal. The artificial intelligence (AI) model predicted the pCR as represented by the area under the curve of 0.71 (95% confidence interval 0.53-0.90; p = 0.035). The sensitivity was 46% at a fixed specificity of 90%. CONCLUSIONS: Our study describes an AI platform using baseline DM to predict BC patients' responses to NACT. The initial AI performance indicated the potential to aid in clinical decision-making. In order to continue exploring the clinical utility of AI in predicting responses to NACT for BC, further research, including refining the methodology and a larger sample size, is warranted. KEY POINTS: • We aimed to answer the following question: Prior to initiation of neoadjuvant chemotherapy, can artificial intelligence (AI) applied to digital mammograms (DM) predict breast tumour response? • DMs contain information that AI can make use of for predicting pathological complete (pCR) response after neoadjuvant chemotherapy for breast cancer. • By developing an AI system designed to focus on relevant parts of the DM, fully automatic pCR prediction can be done well enough to potentially aid in clinical decision-making.

Effects on health and process outcomes of physiotherapist-led orthopaedic triage for patients with musculoskeletal disorders: a systematic review of comparative studies.

BACKGROUND: Physiotherapist-led (PT-led) orthopaedic triage is an evolving model of care for patients with musculoskeletal disorders. Objectives for this study were to establish the current evidence body on the impact of PT-led orthopaedic triage on health, quality, and service outcomes for patients referred for orthopaedic consultation, compared with standard (orthopaedic surgeon) care. METHODS: Medline, EMBASE, Scopus and CINAHL were searched from inception until 7 May 2018; search updated 24 April 2020. Search terms (including derivatives) included physiotherapy, advanced/extended scope, musculoskeletal/orthopaedic, triage. The search was framed as Population = patients referred for orthopaedic consultation; Intervention = PT-led orthopaedic triage; Comparison = standard care; Outcomes = health, quality and process outcomes. Only randomised controlled trials (RCTs) and prospective comparative cohort studies were eligible for inclusion. Screening, study selection, data extraction, and assessment of methodological quality were performed independently by reviewer pairs. Quality was scored with the Downs and Black checklist. Certainty of evidence was determined using GRADE. PROSPERO registration number CRD42017070950. RESULTS: We included two RCTs and eleven cohort studies (n = 1357 participants) of variable methodological quality (range 14-23 of possible 28). Certainty of evidence was low to moderate. There was no difference between PT-led orthopaedic triage and standard care for patient-reported outcomes (two RCTs). Perceived quality of care with PT-led orthopaedic triage was higher (two RCTs, four cohort studies) or equal (one cohort study) compared with standard care. PT-led orthopaedic triage had higher surgery conversion rates (one RCT, three cohort studies) (55-91% vs 22-38%), lower (two RCTs) or equal rate (two cohort studies) of referral for investigations, shorter waiting times (one RCT, one cohort study), and lower costs (one RCT). Furthermore, there was high agreement between physiotherapists' and orthopaedic surgeons' treatment approach (eight cohort studies), referral for investigation (five cohort studies), and diagnosis (nine cohort studies). Study limitations were the low number of RCTs, and variable methodological quality. CONCLUSIONS: Evidence of low to moderate certainty suggests that PT-led orthopaedic triage leads to similar diagnostic decisions as standard care, has a higher conversion-to-surgery rate, reduces waiting times, is cost effective and valued by patients, and that health outcomes are equivalent.

Extracorporeal membrane oxygenation improves coagulopathy in an experimental traumatic hemorrhagic model.

PURPOSE: Hemorrhage is the most common cause of preventable death after trauma. Coagulopathy plays a central role in uncontrolled bleeding and is caused by multiple factors. Extracorporeal Membrane Oxygenation (ECMO) is an established treatment for patients with respiratory failure and has in recent years also been used in severely injured trauma patients with cardiopulmonary failure and coexisting bleeding shock. The aim of this study was to evaluate the effect of ECMO on hypothermia, acidosis, and coagulopathy in a traumatic hemorrhagic rabbit model. METHODS: After anesthesia and tracheostomy, ten New Zealand White rabbits sustained laparotomy, bilateral femur fractures and were hemorrhaged 45% of their estimated blood volume. After 90 min of hemorrhagic shock they were resuscitated with a standard transfusion protocol together with venoarterial ECMO (n = 5) or with a standard transfusion protocol only (n = 5) for 60 min. No systemic heparin was administered. RESULTS: ECMO during 60 min of resuscitation significantly increased heart rate (p = 0.01), mean arterial pressure (p = 0.01), body temperature (p = 0.01) and improved the metabolic acidosis, pH (p = 0.01), and lactate (p = 0.01). ECMO also improved the coagulation capacity measured in vitro by Rotational Thromboelastometry with a significant decrease in clot formation time (p < 0.01). This finding was confirmed in vivo with a significant reduction in the animals' ear bleeding time (p < 0.01) and cuticle bleeding time (p < 0.01); 5/5 animals survived in the ECMO group and 3/5 animals survived in the control group. CONCLUSIONS: Heparin-free ECMO stabilizes circulation, improves coagulation, and may impact short-time survival, during the first 60 min, in an experimental traumatic model with severe hemorrhagic shock.

Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia.

OBJECTIVE: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt-1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt-1, PlGF and the sFlt-1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE. METHODS: Serum sFlt-1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22-MHz) ultrasonography in 55 women at PE diagnosis and in 64 women with normal pregnancy at a similar gestational age, with reassessment at 1 year postpartum. RESULTS: During pregnancy, higher levels of sFlt-1, lower levels of PlGF, a thicker intima, a thinner media and a higher I/M ratio of the CCA were found in women with PE vs controls (all P < 0.0001). Further, sFlt-1 and the sFlt-1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all P < 0.0001). At 1 year postpartum, levels of sFlt-1 and the sFlt-1/PlGF ratio had decreased in both groups; however, their levels in the PE group were still higher than in the controls (P = 0.001 and < 0.0001, respectively). Levels of sFlt-1 and the sFlt-1/PlGF ratio remained positively correlated with intima thickness and I/M ratio at 1 year postpartum. CONCLUSIONS: Higher sFlt-1 levels and sFlt-1/PlGF ratio in women with PE were positively associated with signs of arterial aging during pregnancy. At 1 year postpartum, sFlt-1 levels and the sFlt-1/PlGF ratio were still higher in the PE group and were associated with the degree of arterial aging. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Valor prognóstico da variabilidade da frequência cardíaca e da eletrocardiografia ambulatorial em cães Boxer com cardiomiopatia arritmogênica do ventrículo direito / Prognostic value of heart rate variability and Holter monitoring in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy

A cardiomiopatia arritmogênica do ventrículo direito (CAVD) é uma importante causa de morte súbita em cães da raça Boxer. A validação de fatores prognósticos para essa doença auxiliaria na detecção de animais mais gravemente afetados e sua exclusão dos programas de reprodução. O objetivo deste estudo foi avaliar o valor prognóstico da presença de manifestações clínicas, dos índices de variabilidade de frequência cardíaca (VFC) e das arritmias supraventriculares ou ventriculares registradas à monitorização eletrocardiográfica com Holter na sobrevida de cães Boxer em diferentes estágios da CAVD. Essas variáveis foram analisadas, de forma prospectiva, em 69 cães Boxer, divididos em cinco grupos: cães Boxer controle (grupo CB, <50 VPC/24 horas, n=28), cães Boxer suspeitos (grupo SB, 50 a 300 VPC/24 horas, n=8), cães Boxer com CAVD (grupo ARVC, >300 VPC/24 horas, n=19), cães Boxer com CAVD e disfunção sistólica sem insuficiência cardíaca congestiva (grupo SDB sem ICC, n=6) e com ICC (grupo SDB com ICC, n=8). A análise estatística compreendeu teste ANOVA, correlação de Pearson e análise de riscos proporcionais de Cox. Comparando-se com o grupo CB, não foi encontrada diminuição nos índices de VFC nos grupos SB, ARVC ou SDB sem ICC; por outro lado, o grupo SDB com ICC apresentou diminuição desses índices. Não houve relação entre os índices de VFC e a morte de origem cardíaca; porém, a presença de síncopes com ou sem sinais clínicos de ICC e o número de episódios de taquicardia ventricular (TV) correlacionaram-se com a sobrevida dos animais. Estes resultados permitem concluir que a presença de sinais clínicos de ICC, a presença de síncopes e o número de TV ao Holter apresentam valor prognóstico de sobrevida em cães Boxer com CAVD.(AU)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in Boxer dogs. Validation of prognostic factors for this disease could help in detecting more severely affected animals and their exclusion from breeding programs. The aims of this study were to evaluate the prognostic significance of presence of symptoms, heart rate variability (HRV) indices and ventricular or supraventricular arrhythmias recorded by Holter monitoring on survival of Boxer dogs with ARVC at different stages. Symptoms, arrhythmias registered on Holter and five HRV indices were prospectively analyzed in 69 client-owned Boxer dogs divided into five groups: control Boxer dogs (CB group, <50 VPC/24 hours, n=28), suspicious Boxers (SB group, 50 to 300 VPC/24 hours, n=8), Boxers with ARVC (ARVC group, >300 VPC/24 hours, n=19), Boxers with ARVC and systolic dysfunction without congestive heart failure (SDB without CHF group, n=6) and with CHF (SDB with CHF group, n=8). Statistical analyses consisted of an ANOVA test, Pearson correlation and Cox's proportional hazards regression. Compared to the CB group, no decrease in HRV indices was found in SB, ARVCB or SDB without CHF groups; otherwise, SDB with CHF group had impaired indices. No relation was found between HRV indices and cardiac-related death, but the presence of syncopes with or without clinical signs of heart failure and number of ventricular tachycardia (VT), were correlated with survival. These results allow us to conclude that the presence of symptoms of heart failure, presence of syncopes and number of VT on Holter examination seem to have prognostic value in Boxer ARVC.(AU)

Cardiomiopatia arritmogênica do ventrículo direito em felino: relato de caso / Arrhythmogenic right ventricular cardiomiopathy in a feline: case report

Felino de 3,3kg, fêmea, oito anos de idade, castrada, sem definição racial, foi atendida no Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo (HOVET-USP), com histórico de dispneia, prostração, hiporexia e consequente emagrecimento progressivo, havia uma semana. Foram realizados exames de sangue: hemograma com contagem de plaquetas, função renal, função hepática e dosagens séricas de sódio e potássio, eletrocardiograma (ECG), radiografia torácica, ecoDopplercardiograma, e os resultados dos exames indicaram diagnóstico presuntivo de cardiomiopatia arritmogênica do ventrículo direito. O diagnóstico foi confirmado pela necropsia e pela constatação da presença de tecido fibroadiposo no miocárdio no exame histopatológico, possibilitando, assim, o relato do primeiro caso de cardiomiopatia arritmogênica do ventrículo direito, em gato, no Brasil.(AU)

A female 3.3kg feline, eight years-old, spayed, without racial definition, was submitted to the Veterinary Hospital of the School of Veterinary Medicine and Animal Science, São Paulo University (HOVET-USP) with dyspnea, prostration, hyporexia, and consequent progressive weight loss a week ago. Blood count with platelet count, renal and hepatic profiles, and serum sodium and potassium, chest radiography, electrocardiogram (ECG), and echocardiography were performed and diagnosis of arrhythmogenic right ventricular cardiomyopathy was assumed. The diagnosis was confirmed by necropsy findings and by the presence of fibro-fatty tissue infiltration observed in histopathology, thus featuring the first report of arrhythmogenic right ventricular cardiomyopathy in a cat in Brazil.(AU)

Scintillate: An open-source graphical viewer for time-series calcium imaging evaluation and pre-processing.

BACKGROUND: Calcium imaging is based on the detection of minute signal changes in an image time-series encompassing pre- and post-stimuli. Depending on the function of the elicited response, change may be pronounced, as in the case of a genetically encoded calcium-reporter protein, or subtle, as is the case in a bath-applied dye system. Large datasets are thus often acquired and appraised only during post-processing where specific Regions of Interest (ROIs) are examined. NEW METHOD: The scintillate software provides a platform allowing for near instantaneous viewing of time-sequenced tiffs within a discrete GUI environment. Whole sequences may be evaluated. In its simplest form scintillate provides change in florescence (ΔF) across the entire tiff image matrix. Evaluating image intensity level differences across the whole image allows the user to rapidly establish the value of the preparation, without a priori ROI-selection. Additionally, an implementation of Independent Component Analysis (ICA) provides additional rapid insights into areas of signal change. RESULTS: We imaged transgenic flies expressing Calcium-sensitive reporter proteins within projection neurons and moth mushroom bodies stained with a Ca2+ sensitive bath-applied dye. Instantaneous pre-stimulation background subtraction allowed us to appraise strong genetically encoded neuronal Ca2+ responses in flies and weaker, less apparent, responses within moth mushroom bodies. COMPARISON WITH EXISTING METHODS: At the time of acquisition, whole matrix ΔF analysis alongside ICA is ordinarily not performed. We found it invaluable, minimising time spent with unresponsive samples, and assisting in optimisation of subsequent acquisitions. CONCLUSIONS: We provide a multi-platform open-source system to evaluate time-series images.

Data set for diet specific differential gene expression analysis in three Spodoptera moths.

Examination of closely related species pairs is suggested for evolutionary comparisons of different degrees of polyphagy, which we did here with three taxa of lepidopteran herbivores, Spodoptera spp (S. littoralis, S. frugiperda maize (C) and rice (R) strains) for a RNAseq analysis of the midguts from the 3rd instar insect larvae for differential metabolic responses after feeding on pinto bean based artificial diet vs maize leaves. Paired-end (2×100 bp) Illumina HiSeq2500 sequencing resulted in a total of 24, 23, 24, and 21 million reads for the SF-C-Maize, SF-C-Pinto, SF-R-Maize, SF-R Pinto, and a total of 35 and 36 million reads for the SL-Maize and SL-Pinto samples, respectively. After quality control measures, a total of 62.2 million reads from SL and 71.7 million reads from SF were used for transcriptome assembly (TA). The resulting final de novo reference TA (backbone) for the SF taxa contained 37,985 contigs with a N50 contig size of 1030 bp and a maximum contig length of 17,093 bp, while for SL, 28,329 contigs were generated with a N50 contig size of 1980 bp and a maximum contig length of 18,267 bp. The data presented herein contains supporting information related to our research article Roy et al. (2016) http://dx.doi.org/10.1016/j.ibmb.2016.02.006[1].

Gliptin-mediated neuroprotection against stroke requires chronic pretreatment and is independent of glucagon-like peptide-1 receptor.

Gliptins are anti-type 2 diabetes (T2D) drugs that regulate glycaemia by preventing endogenous glucagon-like peptide-1 (GLP-1) degradation. Chronically administered gliptins before experimental stroke can also induce neuroprotection, and this effect is potentially relevant for reducing brain damage in patients with T2D and high risk of stroke. It is not known, however, whether acute gliptin treatment after stroke (mimicking a post-hospitalization treatment) is neuroprotective or whether gliptin-mediated neuroprotection occurs via GLP-1-receptor (GLP-1R) activation. To answer these two questions, wild-type and glp-1r(-/-) mice were subjected to transient middle cerebral artery occlusion (MCAO). Linagliptin was administered acutely (50 mg/kg intravenously), at MCAO time or chronically (10 mg/kg orally) for 4 weeks before and 3 weeks after MCAO. Neuroprotection was assessed by stroke volume measurement and quantification of NeuN-positive surviving neurons. Plasma/brain GLP-1 levels and dipeptidyl peptidase-4 activity were also measured. The results show that the linagliptin-mediated neuroprotection against stroke requires chronic pretreatment and does not occur via GLP-1R. The findings provide essential new knowledge with regard to the potential clinical use of gliptins against stroke, as well as a strong impetus to identify gliptin-mediated neuroprotective mechanisms.

Diet dependent metabolic responses in three generalist insect herbivores Spodoptera spp.

Adaption to dietary changes is critical in the evolution of host plant ranges in polyphagous insects. We compared three taxa of lepidopteran herbivores from the predominantly generalist genus Spodoptera showing different degrees of polyphagy: Spodoptera littoralis, with a broad host range including both mono- and dicotyledonous plants, and two Spodoptera frugiperda strains [Corn (i.e. maize) (C) and Rice (R)] adapted primarily to different grass species. When feeding on maize we show a lower performance in the broad generalist taxon compared to the grass adapted taxa. Among these taxa, the maize adapted S. frugiperda C-strain generally performed better than the R-strain on maize leaves. On artificial pinto diet, all taxa performed well. Our RNA-Seq analysis of midgut transcriptomes from 3rd instar larvae feeding on maize showed broader transcriptional readjustments in the generalist S. littoralis compared to grass adapted S. frugiperda strains. Substantial alteration in the expression levels of midgut physiological function related transcripts, such as digestive and detoxifying enzymes, transporters, immunity, and peritrophic membrane associated transcripts, existed in all taxa. We found high background expression of UDP-glucosyl transferases, which are known to neutralize maize leaf toxins, in the maize adapted S. frugiperda C-strain, contributing to its fitness on maize compared to the R-strain. Our findings provide evidence for divergent diet specific response of digestive physiology within these Spodoptera taxa. Unexpectedly, the C- and R-strains of S. frugiperda fed on the same diet showed large differences in expression patterns between these two closely related taxa.

Effectiveness of implant therapy analyzed in a Swedish population: early and late implant loss.

Treatment outcomes in implant dentistry have been mainly assessed as implant survival rates in small, selected patient groups of specialist or university clinical settings. This study reports on loss of dental implants assessed in a large and randomly selected patient sample. The results were aimed at representing evaluation of effectiveness of implant dentistry. Using the national data register of the Swedish Social Insurance Agency, 4,716 patients were randomly selected. All had been provided with implant-supported restorative therapy in 2003. Patient files of 2,765 patients (11,311 implants) were collected from more than 800 clinicians. Information on patients, treatment procedures, and outcomes related to the implant-supported restorative therapy was extracted from the files. In total, 596 of the 2,765 subjects, provided with 2,367 implants, attended a clinical examination 9 y after therapy. Implant loss that occurred prior to connection of the supraconstruction was scored as an early implant loss, while later occurring loss was considered late implant loss. Early implant loss occurred in 4.4% of patients (1.4% of implants), while 4.2% of the patients who were examined 9 y after therapy presented with late implant loss (2.0% of implants). Overall, 7.6% of the patients had lost at least 1 implant. Multilevel analysis revealed higher odds ratios for early implant loss among smokers and patients with an initial diagnosis of periodontitis. Implants shorter than 10 mm and representing certain brands also showed higher odds ratios for early implant loss. Implant brand also influenced late implant loss. Implant loss is not an uncommon event, and patient and implant characteristics influence outcomes (ClinicalTrials.gov NCT01825772).

Intra- and extracellular activities of trimethoprim-sulfamethoxazole against susceptible and multidrug-resistant Mycobacterium tuberculosis.

We investigated the activity of trimethoprim-sulfamethoxazole (SXT) against Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB). The MIC distribution of SXT was 0.125/2.4 to 2/38 mg/liter for the 100 isolates tested, including multi- and extensively drug-resistant isolates (MDR/XDR-TB), whereas the intracellular MIC90 of sulfamethoxazole (SMX) for the pansusceptible strain H37Rv was 76 mg/liter. In an exploratory analysis using a ratio of the unbound area under the concentration-time curve from 0 to 24 h over MIC (fAUC0-24/MIC) using ≥ 25 as a potential target, the cumulative fraction response was ≥ 90% at doses of ≥ 2,400 mg of SMX. SXT is a potential treatment option for MDR/XDR-TB.

Time-domain signal-averaged electrocardiogram in healthy German Shepherd and Boxer dogs / Eletrocardiograma de alta resolução (ECGAR) no domínio do tempo em cães sadios das raças Pastor Alemão e Boxer

Signal-averaged electrocardiogram (SAECG) identifies ventricular late potentials (LP), low-amplitude electrical signals that are markers of slow cardiac conduction in fibrous myocardium, consisting in a predictive factor for sudden death in dogs at risk of sustained ventricular tachycardia. The aim of this study was to establish reference values of SAECG for German Shepherd and Boxer dogs. SAECG was performed in 19 German Shepherd and 28 Boxer client-owned dogs, and parameters analyzed were QRSd (duration of filtered QRS), LAS<40μV (duration of low-amplitude signals in terminal portion of filtered QRS) and RMS40 (root square of mean voltage over the last 40 milliseconds of filtered QRS), with two different filters (25-250 Hz and 40-250 Hz). Statistical analyses was achieved by T Student test (p<0.05) to identify differences between the two groups and between the values obtained with the two filters. No statistical difference was found in SAECG variables between the two breeds with the two different filters (p>0.05). Achieving normal values of SAECG in German Shepherd and Boxer dogs is important to further research late potentials in animals of these breeds with hereditary ventricular tachycardia or arrhythmogenic cardiomyopathy and identification of individuals at high risk of cardiac-related sudden death...

O eletrocardiograma de alta resolução (ECGAR) identifica os potenciais tardios (PT), sinais elétricos de baixa amplitude considerados marcadores de condução cardíaca lenta de áreas fibrosadas do miocárdio, cuja presença consiste em fator preditivo de morte súbita em cães com taquicardia ventricular sustentada. O objetivo deste estudo foi o estabelecimento de valores de referência para o ECGAR de cães Boxer (n=28) e Pastor Alemão (n=19). Os seguintes parâmetros do ECGAR foram analisados: dQRS (duração do QRS filtrado), LAS<40μV (duração dos sinais de baixa amplitude no final do QRS filtrado) e RMS40 (raiz quadrada da voltagem média do final do QRS filtrado), com dois tipos diferentes de filtro (25-250 Hz e 40-250 Hz). Análise estatística foi realizada por meio do teste T de Student (p<0,05) para identificar diferenças entre os dois grupos e entre os valores obtidos com os dois filtros. Não foram encontradas diferenças significativas entre as variáveis de ECGAR nas duas raças estudadas com os dois diferentes filtros (p>0,05). A obtenção dos valores de normalidade de ECGAR em cães dessas raças auxiliará na realização de futuras pesquisas de potenciais tardios em animais com taquicardia ventricular hereditária ou cardiomiopatia arritmogênica, bem como na identificação dos indivíduos com alto risco de morte súbita de origem cardíaca...

Activity of the HMGB1-derived immunostimulatory peptide Hp91 resides in the helical C-terminal portion and is enhanced by dimerization.

We have previously shown that an 18 amino acid long peptide, named Hp91, whose sequence corresponds to a region within the endogenous protein HMGB1, activates dendritic cells (DCs) and acts as adjuvant in vivo by potentiating Th1-type antigen-specific immune responses. We analyzed the structure-function relationship of the Hp91 peptide to investigate the amino acids and structure responsible for immune responses. We found that the cysteine at position 16 of Hp91 enabled formation of reversible peptide dimmers, monomer and dimmer were compared for DC binding and activation. Stable monomers and dimers were generated using a maleimide conjugation reaction. The dimer showed enhanced ability to bind to and activate DCs. Furthermore, the C-terminal 9 amino acids of Hp91, named UC1018 were sufficient for DC binding and Circular dichroism showed that UC1018 assumes an alpha-helical structure. The ninemer peptide UC1018 induced more potent antigen-specific CTL responses in vivo as compared to Hp91 and it protected mice from tumor development when used in a prophylactic vaccine setting. We have identified a short alpha helical peptide that acts as potent adjuvant inducing protective immune responses in vivo.

Introducing reproductive life plan-based information in contraceptive counselling: an RCT.

STUDY QUESTION: Can reproductive life plan (RLP)-based information in contraceptive counselling before pregnancy increase women's knowledge of reproduction, and of the importance of folic acid intake in particular? SUMMARY ANSWER: The RLP-based information increased women's knowledge of reproduction including knowledge of folic acid intake. WHAT IS KNOWN ALREADY: Many women have insufficient knowledge of reproduction, including a health-promoting lifestyle prior to conception, and highly educated women in particular postpone childbearing until an age when their fertile capacity has started to decrease. STUDY DESIGN, SIZE, DURATION: The study was an randomized controlled trial with one intervention group (IG) and two control groups (CG1, CG2). A sample size calculation indicated that 82 women per group would be adequate. Recruitment took place during 3 months in 2012 and 299 women were included. The women were randomized in blocks of three. All groups received standard care (contraceptive counselling, Chlamydia testing, cervical screening). In addition, women in the IG were given oral and written RLP-based information about reproduction. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 299 out of 338 (88%) Swedish-speaking women visiting a Student Health Centre were included (mean age 23 years); response rate was 88%. Before the counselling, women in the IG and the CG1 completed a baseline questionnaire, including questions about lifestyle changes in connection to pregnancy planning, family planning intentions and knowledge of reproduction (e.g. the fecundity of an ovum). At follow-up 2 months after inclusion, a structured telephone interview was performed in all groups (n = 262, 88% participation rate). MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference between the groups regarding the mean knowledge score at baseline. The IG scored higher at follow-up than at baseline (P < 0.001); the mean increased from 6.4 to 9.0 out of a maximum 20 points. The women in the CG1 scored no differently at follow-up than at baseline. The difference in the knowledge score between the IG and the two CGs was significant (P < 0.001), whereas no difference was shown between the two CGs. There was no difference between the groups at baseline regarding how many women could mention folic acid intake among the things to do when planning to get pregnant. At follow-up, 22% in the IG, 3% in CG1 and 1% in CG2 mentioned folic acid intake (P < 0.001). At follow-up, more women in the IG also wished to have their last child earlier in life (P < 0.001) than at baseline, while there was no difference in the CG1. LIMITATIONS, REASONS FOR CAUTION: As the study sample consisted of university students, it is possible that the effect of the intervention was connected to a high level of education and conclusions for all women of reproductive age should be drawn with caution. WIDER IMPLICATIONS OF THE FINDINGS: The provision of RLP-based information seems to be a feasible tool for promoting reproductive health. STUDY FUNDING/COMPETING INTEREST(S): Study funding was received from the Faculty of Medicine, Uppsala University, Sweden. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov Identifier NCT01739101.

Avaliação ecocardiográfica do átrio esquerdo de cães sadios por meio do modo-M convencional e do modo bidimensional / Echocardiographic evaluation of the left atrium of healthy dogs using the conventional M-mode and the bidimensional mode

Avaliaram-se o átrio esquerdo (AE) utilizando-se o método bidimensional (2-B) (corte transverso) e a relação átrio esquerdo:aorta (AE:Ao), em um grupo de 40 cães adultos e sadios, entre um, cinco e sete anos de idade e com pesos corpóreos de 3,2kg a 38,3kg, e compararam-se esses valores aos do modo-M convencional. Observou-se diferença entre AE e Ao nos dois métodos e entre os seus respectivos índices. A correlação foi positiva alta entre peso e superfície corpórea e entre AE no modo 2-B (AEB) e AE no modo-M (AEM). Não se observou correlação entre os índices, nos dois métodos, com o peso e a superfície corpórea, isto é, os índices são independentes do peso ou da superfície corpórea. Concluiu-se que o AEB é maior do que o AEM, o índice médio para o AEB:AoB é de 1,379, e o intervalo de confiança de 1,337 a 1,422. O índice no método 2-B é, portanto, superior ao índice no modo-M.

The left atrium (LA) was evaluated through the bidimensional method (2-D) (short axis) and the relation left atrium:aorta (LA:Ao) in a group of 40 healthy adult dogs between 1.5 and 7 years of age and weights ranging from 3.2 to 38.3kg, and these values were compared to those in the conventional M-mode. Comparing the variable LA and Ao with the two methods and their respective indexes, significant statistical difference was observed (P<0,001), high positive correlation between the weight and LA-2D and LAM, between body surface and LA-2D and LAM. A difference between LA and Ao in both methods and these respective indicators were observed. The association was higly positive between weight and body surface area (BSA) and between M- mode LA (LAM) and 2-D mode LA (LA-2D). No correlation was observed between these indicators and weight and BSA, in both methods, so these indicators are weight and BSA-independent. Conclusions: LA-2D is bigger than LAM, the LA-2D:Ao-2D average index is 1,379 and the confidence interval is 1,337 to 1,422. The index in the 2-D method is, therefore, superior to the index in the M-mode.

Health-related quality of life in advanced non-small cell lung cancer: correlates and comparisons to normative data.

The aim was to describe self-reported health-related quality of life (HRQoL) in patients with advanced non-small cell lung cancer and to investigate the associations to stage of disease, age, gender, weight loss and performance status. Further, the study aimed to compare patients' HRQoL with that of the Swedish general population. Data on HRQoL were collected within a multi-centre randomised controlled trial. A total of 334 patients were included between 1998 and 2001. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Lung Cancer Questionnaire (EORTC QLQ-LC13) were used to assess HRQoL. HRQoL data for comparison with the Swedish population were derived from a random sample of the Swedish population. Patients reported a markedly impaired HRQoL compared to the normal population. There were statistically and clinically significant differences with regard to almost all QLQ-C30 functional and symptom scales. Global health status, physical functioning, role functioning and emotional functioning were markedly deteriorated. The most prominent symptoms were dyspnoea, fatigue, coughing, insomnia, appetite loss and pain. A low performance status, younger age, female gender and a more advanced disease were independently associated with a worse HRQoL. Additional studies are required to gain increased insight into this seriously ill group of patients and their need of supportive care.

Dosagem sérica de troponina I em cães com desnível do segmento ST utilizando quimioluminescência / Serum determination of troponin I in dogs with ST deviation by chemiluminescent

Com o intuito de verificar algum dano nas células do miocárdio, utilizaram-se 38 cães, 20 com traçado eletrocardiográfico normal, grupo 1, e 18 com desníveis do segmento ST, grupo 2, em registro na derivação II, velocidade de 50mm/s e sensibilidade N (1mV=1cm). No grupo 1, a dosagem sérica da troponina I (cTnI) destinou-se à obtenção dos valores referenciais (ng/mL) que seriam confrontados com os obtidos no grupo 2. A média e o desvio-padrão foram, respectivamente, 0,16ng/mL e 0,11ng/mL e 0,20ng/mL e 0,11ng/mL, nos grupos 1 e 2. A cTnI não apresentou evidências de associação com idade, massa corpórea, creatinafosfoquinase total e potássio nos dois grupos. Não houve diferenças significativas nos valores de cTnI entre os grupos. Conclui-se que é possível a utilização do kit de ensaio imunométrico quimioluminescente humano para a espécie canina e que a hipóxia-isquemia, revelada pelo desnível do segmento ST não acarreta dano miocárdico ou este é mínimo e indetectável.

In order to investigate myocardial cells injury, 38 dogs were evaluated, being 20 with a normal electrocardiogram (group 1) and 18 with ST segment elevation or depression (group 2), recorded in lead II, at paper speed of 50 mm/sec and N sensibility (1 mV = 1cm). Serum measurement of troponin I (cTnI) in group 1 was determined to obtain reference values (ng/mL). These values were compared to those obtained in dogs from group 2, to confirm or not myocardial injury. Mean cTnI values in groups 1 and 2 were 0.16ng/mL (SD±0.11ng/mL) and 0.20ng/mL (SD±0.11ng/mL), respectively. Three cTnI null values were found in group 1. cTnI was not related to age, mass, CK-T or serum potassium concentration in both animal groups, for each level varied in the group. There was no difference in cTnI values between groups 1 and 2. In conclusion, it is possible to use the human chemiluminescent immunometric assay kit in canine species and hypoxia/ischemia revealed by ST segment deviation does not mean significant myocardium injury.

PVC--as flooring material--and its association with incident asthma in a Swedish child cohort study.

UNLABELLED: The Dampness in Buildings and Health study (DBH) started in the year 2000 in Värmland, Sweden, with a baseline questionnaire sent to all children (n = 14,077) aged 1-6. Five years later, a follow-up questionnaire was sent to the children who were 1-3 years at baseline. A total of 4779 children participated in both the baseline and the follow-up studies and constitute the study population in this cohort study. The aim of this study was to examine the association between exposure to PVC-flooring in the child's and parent's bedroom in homes of children aged 1-3 and the incidence of asthma, rhinitis, and eczema during the following 5-year period. Adjusted analyses showed that the incidence of asthma among children was associated with PVC-flooring in the child's bedroom (AOR 1.52; 95% CI 0.99-2.35) and in the parent's bedroom (1.46; 0.96-2.23). The found risks were on borderline of significance and should therefore be interpreted with caution. There was further a positive relationship between the number of rooms with PVC-flooring and the cumulative incidence of asthma. PVC-flooring was found to be a stronger risk factor for incident asthma in multifamily homes when compared with single-family houses and in smoking families compared with non-smoking families and in women. PRACTICAL IMPLICATIONS: These longitudinal data from the DBH study found an association between the presence of PVC-flooring in the home and incident asthma in children. However, earlier results from the DBH study have shown that PVC-flooring is one important source for phthalates in indoor dust, and exposure to such phthalates was found to be associated with asthma and allergy among children. This emphasizes the need for prospective studies that focus on the importance of prenatal and neonatal exposure to phthalates in the development of asthma and allergy in children.