INA Early Intervention for Babies at Risk

Brain and nervous system development are experience dependent. Indeed, the sequence of development is laid out genetically, but early environmental events are major contributors to the system’s development and optimal functioning. Various fetal injuries and birth trauma make babies vulnerable to developmental problems: cerebral palsy, seizures, abnormal muscle tone, delayed developmental milestones, sensory integration, and more. Our goal in the study presented here was to improve the neurodevelopmental track of babies at risk using Infant Neural Aquatic. Parent and baby dyads who met initial criteria were recruited for a 5–6 months intervention period through an open invitation, followed by a conversation and signing informed consent. In the beginning and end of intervention period, participants completed questionnaires, and developmental features of the babies were assessed using analysis of neuro-motor and vocal characteristics. Significant neurodevelopmental delta between values at the end and beginning of intervention period, comparing intervention and control, is described, and the strength of INA specific intervention tool is analyzed

Aspiration therapy for the treatment of obesity: 4-year results of a multicenter randomized controlled trial.

BackgroundThe AspireAssist is the first Food and Drug Administration-approved endoluminal device indicated for treatment of class II and III obesity.ObjectivesWe earlier reported 1-year results of the PATHWAY study. Here, we report 4-year outcomes.SettingUnited States-based, 10-center, randomized controlled trial involving 171 participants with the treatment arm receiving Aspiration Therapy (AT) plus Lifestyle Therapy and the control arm receiving Lifestyle Therapy (2:1 randomization).MethodsAT participants were permitted to continue in the study for an additional year up to a maximum of 5 years providing they maintained at least 10% total weight loss (TWL) from baseline at each year end. For AT participants who continued the study, 5 medical monitoring visits were provided at weeks 60, 68, 76, 90, and 104 and thereafter once every 13 weeks up to week 260. Exclusion criteria were a history of eating disorder or evidence of eating disorder on a validated questionnaire. Follow-up weight, quality of life, and co-morbidities were compared with the baseline levels. In addition, rates of serious adverse event, persistent fistula, withdrawal, and A-tube replacement were reported. All analyses were performed using a per-protocol analysis.ResultsOf the 82 AT participants who completed 1 year, 58 continued to this phase of the trial. Mean baseline body mass index of these 58 patients was 41.6 ± 4.5 kg/m2. At the end of first year (at the beginning of the follow-up study), these 58 patients had a body mass index of 34.1 ± 5.4 kg/m2 and had achieved an 18.3 ± 8.0% TWL. On a per protocol basis, patients experienced 14.2%, 15.3%, 16.6%, and 18.7% TWL at 1, 2, 3, and 4 years, respectively (P < .01 for all). Forty of 58 patients (69%) achieved at least 10% TWL at 4 years or at time of study withdrawal. Improvements in quality of life scores and select cardiometabolic parameters were also maintained through 4 years. There were 2 serious adverse events reported in the second through fourth years, both of which resolved with removal or replacement of the A tube. Two persistent fistulas required surgical repair, representing approximately 2% of all tube removals. There were no clinically significant metabolic or electrolytes disorders observed, nor any evidence for development of any eating disorders.ConclusionsThe results of this midterm study have shown that AT is a safe, effective, and durable weight loss alternative for people with class II and III obesity and who are willing to commit to using the therapy and adhere to adjustments in eating behavior

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

A word by any other intonation: fMRI evidence for implicit memory traces for pitch contours of spoken words in adult brains.

OBJECTIVES: Intonation may serve as a cue for facilitated recognition and processing of spoken words and it has been suggested that the pitch contour of spoken words is implicitly remembered. Thus, using the repetition suppression (RS) effect of BOLD-fMRI signals, we tested whether the same spoken words are differentially processed in language and auditory brain areas depending on whether or not they retain an arbitrary intonation pattern. EXPERIMENTAL DESIGN: Words were presented repeatedly in three blocks for passive and active listening tasks. There were three prosodic conditions in each of which a different set of words was used and specific task-irrelevant intonation changes were applied: (i) All words presented in a set flat monotonous pitch contour (ii) Each word had an arbitrary pitch contour that was set throughout the three repetitions. (iii) Each word had a different arbitrary pitch contour in each of its repetition. PRINCIPAL FINDINGS: The repeated presentations of words with a set pitch contour, resulted in robust behavioral priming effects as well as in significant RS of the BOLD signals in primary auditory cortex (BA 41), temporal areas (BA 21 22) bilaterally and in Broca's area. However, changing the intonation of the same words on each successive repetition resulted in reduced behavioral priming and the abolition of RS effects. CONCLUSIONS: Intonation patterns are retained in memory even when the intonation is task-irrelevant. Implicit memory traces for the pitch contour of spoken words were reflected in facilitated neuronal processing in auditory and language associated areas. Thus, the results lend support for the notion that prosody and specifically pitch contour is strongly associated with the memory representation of spoken words

Domestication effects on behavioural and hormonal responses to acute stress in chickens

Comparative studies have shown that alterations in physiology, morphology and behaviour have arisen due tothe domestication. A driving factor behind many of the changes could be a shift in stress responses,withmodifiedendocrine and behavioural profiles. In the present study we compared two breeds of chicken (Gallus gallus), thedomesticWhite Leghorn (WL) egg laying breed and its ancestor, the Red Junglefowl (RJF). Birds were exposed toan acute stress event, invoked by 3 or 10 min of physical restraint. Theywere then continuouslymonitored for theeffects on a wide range of behaviours during a 60 min recovery phase. Blood samples were collected from thechicken at baseline, and after 10 and 60 min following a similar restraint stress, and the samples wereanalyzed for nine endogenous steroids of the HPA and HPG axes. Concentration of the steroids was determinedusing validated liquid chromatography tandem mass spectrometry methods. In RJF, an immediate behaviouralresponse was observed after release from restraint in several behaviours, with a relatively fast return to baselinewithin 1 h. In WL, somebehaviourswere affected for a longer period of time, and others not at all. Concentrationsof corticosterone increasedmore in RJF, but returned faster to baseline compared toWL. A range of baseline levelsfor HPG-related steroids differed between the breeds, and they were generally more affected by the stress in WLthan in RJF. In conclusion, RJF reacted stronger both behaviourally and physiologically to the restraint stress, butalso recovered faster. This would appear to be adaptive under natural conditions, whereas the stress recovery ofdomesticated birds has been altered by domestication and breeding for increased reproductive output.Funders: Swedish Research Council (VR) [621-2011-4731]; Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) [221-2011-1088]; ERC (project Genewell) [322206]; Swedish Centre of Excellence in Animal Welfare; ARUP Institute for Clinical and Experimental Pathology</p