Clinical Recovery and Circulating Botulinum Toxin Type F in Adult Patient

A 56-year-old woman in Helena, Montana, USA, who showed clinical signs of paralysis, received antitoxins to botulinum toxins A, B, and E within 24 hours; nevertheless, symptoms progressed to complete quadriplegia. On day 8, she began moving spontaneously, even though blood tests later showed botulinum toxin type F remained

Left Ventricular Hypertrabeculation Is Not Associated With Cardiovascular Morbity or Mortality: Insights From the Eurocmr Registry

Aim: Left ventricular non-compaction (LVNC) is perceived as a rare high-risk cardiomyopathy characterized by excess left ventricular (LV) trabeculation. However, there is increasing evidence contesting the clinical significance of LV hyper-trabeculation and the existence of LVNC as a distinct cardiomyopathy. The aim of this study is to assess the association of LV trabeculation extent with cardiovascular morbidity and all-cause mortality in patients undergoing clinical cardiac magnetic resonance (CMR) scans across 57 European centers from the EuroCMR registry. Methods and Results: We studied 822 randomly selected cases from the EuroCMR registry. Image acquisition was according to international guidelines. We manually segmented images for LV chamber quantification and measurement of LV trabeculation (as per Petersen criteria). We report the association between LV trabeculation extent and important cardiovascular morbidities (stroke, atrial fibrillation, heart failure) and all-cause mortality prospectively recorded over 404 ± 82 days of follow-up. Maximal non-compaction to compaction ratio (NC/C) was mean (standard deviation) 1.81 ± 0.67, from these, 17% were above the threshold for hyper-trabeculation (NC/C > 2.3). LV trabeculation extent was not associated with increased risk of the defined outcomes (morbidities, mortality, LV CMR indices) in the whole cohort, or in sub-analyses of individuals without ischaemic heart disease, or those with NC/C > 2.3. Conclusion: Among 882 patients undergoing clinical CMR, excess LV trabeculation was not associated with a range of important cardiovascular morbidities or all-cause mortality over ~12 months of prospective follow-up. These findings suggest that LV hyper-trabeculation alone is not an indicator for worse cardiovascular prognosis

The effects of low and high glycemic index foods on exercise performance and beta-endorphin responses

Τhe aim of this study was to examine the effects of the consumption of foods of various glycemic index values on performance, β-endorphin levels and substrate (fat and carbohydrate) utilization during prolonged exercise. Eight untrained healthy males underwent, in a randomized counterbalanced design, three experimental conditions under which they received carbohydrates (1.5 gr. kg-1 of body weight) of low glycemic index (LGI), high glycemic index (HGI) or placebo. Food was administered 30 min prior to exercise. Subjects cycled for 60 min at an intensity corresponding to 65% of VO2max, which was increased to 90% of VO2max, then they cycled until exhaustion and the time to exhaustion was recorded. Blood was collected prior to food consumption, 15 min prior to exercise, 0, 20, 40, and 60 min into exercise as well as at exhaustion. Blood was analyzed for β-endorphin, glucose, insulin, and lactate. The mean time to exhaustion did not differ between the three conditions (LGI = 3.2 ± 0.9 min; HGI = 2.9 ± 0.9 min; placebo = 2.7 ± 0.7 min). There was a significant interaction in glucose and insulin response (P < 0.05) with HGI exhibiting higher values before exercise. β-endorphin increased significantly (P < 0.05) at the end of exercise without, however, a significant interaction between the three conditions. Rate of perceived exertion, heart rate, ventilation, lactate, respiratory quotient and substrate oxidation rate did not differ between the three conditions. The present study indicates that ingestion of foods of different glycemic index 30 min prior to one hour cycling exercise does not result in significant changes in exercise performance, β-endorphin levels as well as carbohydrate and fat oxidation during exercise

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Crianças pequenas, o processo de iniciação à brincadeira. As relações sociais no berçário II

Neste trabalho são apresentadas algumas reflexões a respeito do processo de iniciação ao brincar, oriundas da experiência de estágio realizada junto a um grupo do Berçário II, durante o primeiro semestre de 2014, em uma instituição de educação infantil pública pertencente à rede municipal de educação de Chapecó, estado de Santa Catarina. Para esse estudo elencou-se como objetivo geral compreender como se configuram as relações sociais das crianças pequenas no berçário partindo da experiência de estágio supervisionado na Educação Infantil. Para aprofundar a reflexão sobre o que foi proposto definiu-se os seguintes objetivos específicos que nortearam este estudo: identificar nos registros, situações na quais estão presentes aspectos da brincadeira de faz-de-conta; analisar a relação entre a organização dos espaços e materiais e a ampliação das relações sociais entre as crianças pequenas no contexto do Berçário, e também sobre o papel do professor nesse processo; refletir sobre as relações sociais existentes no Berçário e sobre as suas contribuições para a constituição das crianças pequenas como sujeitos sociais ativos. As contribuições teóricas de alguns autores importantes como Vigotski, Brougère, entre outros, fundamentaram as análises realizadas. Pode-se afirmar que a aprendizagem social do brincar se faz presente no espaço do berçário. Cabe ao professor proporcionar o tempo e o espaço para que a brincadeira se constitua e se consolide entre as crianças. É fundamental que discussões e reflexões direcionadas à Educação Infantil sejam realizadas para que se proporcione às crianças contextos e ações que favoreçam a ampliação de seus processos criativos e imaginários, bem como a aprendizagem de múltiplas linguagens, desta forma será possível o desenvolvimento e constituição das crianças pequenas como sujeitos históricos e sociais, cujos direitos sejam respeitados e assegurados

Cost/benefit analysis of group and solitary resting in the cowtail stingray, Pastinachus sephen

Unless a safe refuge is found where predation threats are negligible, resting poses risks for many animals, necessitating risk management strategies. The adult cowtail stingray (Pastinachus sephen) of Shark Bay, Western Australia, is a solitarily foraging animal that facultatively groups when resting on shallow, inshore sand flats. We hypothesized that environmental conditions influence the propensity of cowtails to group due to the limited ability to detect predators visually in certain conditions. We then explored the possible benefits of grouping, such as bodily protection, early warning, and predator confusion, in conjunction with potential grouping costs, such as increased interference when initiating flight and decreased escape speeds. Our study revealed that in poor underwater visibility (due to turbidity and/or low ambient light levels), cowtails primarily rest in small groups (three rays). Tests of flight initiation distance to a mock predator demonstrated that solitary cowtail escape distances are significantly shorter in poor than in good underwater visibility conditions. As to grouping benefits, filmed boat transects revealed that cowtails most often arrange themselves in a rosette position, possibly as a means to protect their bodies and expose their tails. The first cowtail in a group initiates flight to a mock predator at a significantly greater distance than a solitary cowtail, and grouped cowtails escape an approaching boat in a significantly more cohesive manner than a simulated group of escaping individual rays. Grouped cowtails exhibit behaviors that would impede immediate flight after detection. As a result, grouped rays escape a boat at significantly slower speeds than solitary cowtails. Results from this study demonstrate that the interplay between costs and benefits of grouped and solitary resting under differing environmental conditions is driven by differences in perceived predation risk and ultimately reflected in the facultative grouping behavior of this species

Anti-Predator Benefits of Mixed-Species Groups of Cowtail Stingrays (Pastinachus sephen) and Whiprays (Himantura uarnak) at Rest

Heterospecific grouping can sometimes provide greater antipredator benefits to individuals than grouping with conspecifics. We explored the potential benefits of mixed-species group resting in the cowtail stingray, Pastinachus sephen, and the reticulate whipray, Himantura uarnak, in Shark Bay, Western Australia. From focal follow data on individual resting choice, we first ascertained that cowtails preferred to rest with heterospecifics, as they chose to settle next to whiprays more often than to pass them (with the opposite trend observed for conspecifics). In addition, we determined from filmed boat transects that cowtails formed larger hetero- than monospecific groups despite the low density of whiprays. Possible benefits accrued by the cowtail were investigated in terms of predator protection. Whiprays responded earlier than cowtails to a mock predator (boat), and were most frequently the first to respond when in a mixed group. Thus, cowtails may benefit from grouping with heterospecifics by receiving earlier warning of a predator\u27s approach. A decoy experiment using model whiprays demonstrated that cowtails were more willing to rest with models with relatively longer tails (controlled for body size). Ray tails, which are equipped with a mechanoreceptor capable of detecting predators, may constitute an important secondary means of predator detection aside from early warning. This contention is supported by the observation that stingrays mainly form resting groups when their visual ability is likely to be impaired by environmental conditions, and that tail length is negatively allometric with body size, suggesting its importance in vulnerable early life stages. If the efficacy of the mechanoreceptor increases with tail length, then cowtails may have further improved their likelihood of detecting predators by grouping with longer-tailed heterospecifics