Physical activity and sedentary behavior thresholds for identifying childhood hypertension and its phenotypes: The Healthy Growth Study

Hypertension phenotypes may represent differential pathophysiologic mechanisms and clinical impact, yet they have been poorly investigated. The study aimed to examine the associations of physical activity and sedentary behavior with hypertension phenotypes in a large group of Greek children and to identify thresholds regarding risk of hypertension. This was a cross-sectional study with a regionally representative sample of 2473 schoolchildren aged 9–13 years, with full data on physical activity and sedentary behavior indices, as well as arterial blood pressure measurements, physical examination, and anthropometry. Hypertensive children of both sexes had lower levels of physical activity (steps/d). Hypertensive girls had lower moderate-to-vigorous physical activity (MVPA), whereas hypertensive boys with isolated systolic hypertension (ISH) had more screen time than their normotensive counterparts. Increased levels of physical activity was associated with 33%–54% lower risk of all hypertension phenotypes in both sexes, whereas increased MVPA was associated with 41%–65% lower risk of all phenotypes in girls and with ISH and systolic and diastolic hypertension (SDH) in boys. In boys, higher sedentary time was associated with 11%–13% higher risk for SDH and ISH. Cutoff points of 12,378 steps/d, 47.3 min/d of MVPA, and 2.9 h/d of sedentary behavior were determined for identifying children at increased risk of hypertension. Physical activity is inversely associated with all hypertension phenotypes, whereas sedentary behavior is positively associated with ISH and SDH in boys. More studies should confirm the hypertension-specific cutoff values identified to be used in future prevention programs for childhood hypertension.     

Nerve echogenicity and intranerve CSA variability in high-resolution nerve ultrasound (HRUS) in chronic inflammatory demyelinating polyneuropathy (CIDP)

Journal of Neurology - HRUS is increasingly being used in the diagnosis and evaluation of autoimmune neuropathies such as CIDP. Recently, studies focused not only on changes of nerves size, but...     

Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes

Objectives

Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues.

Methods

Pediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed.

Results

Nineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9 years. All patients alive at the time of data registration at a median age of 6 years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe—except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3 mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients.

Conclusion

Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.

     

Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine

Rationale

The serotonin 5-HT_2A and 5-HT_2C receptors, which are found in abundance in the mesolimbocortical dopaminergic system, appear to modulate the behavioral effects of cocaine.

Objectives

The present series of studies set out to investigate the role of 5-HT_2A and 5-HT_2C receptors on brain reward and on the reward-facilitating effect of cocaine and localize the neural substrates within the mesolimbocortical dopaminergic system that are responsible for these effects.

Methods

Male Sprague-Dawley rats were implanted with stimulating electrodes and bilateral cannulae for the experiments involving microinjections and were trained to respond to electrical stimulation. In the first study, we examined the effects of systemic administration of selective 5-HT_2A and 5-HT_2C receptor agonists (TCB-2 and WAY-161503) and antagonists (R-96544 and SB-242084) on intracranial self-stimulation (ICSS). In the second study, we examined the effectiveness of TCB-2, WAY-161503, R-96544, and SB-242084 in blocking the reward-facilitating effect of cocaine. In the third study, we examined the effects of intra-medial prefrontal cortex (mPFC), intra-nucleus accumbens (NAC), and intra-ventral tegmental area (VTA) injection of WAY-161503 on the reward-facilitating effect of cocaine.

Results

Acute systemic administration of TCB-2 and WAY-161503 increased ICSS threshold. Systemic WAY-161503 attenuated the reward-facilitating effect of cocaine. This effect was reversed by pretreatment with SB-242084. Intracranial microinjections of WAY-161503 into the mPFC and the NAC shell/core, but not the VTA, attenuated the reward-facilitating effect of cocaine.

Conclusion

These data indicate that 5-HT_2C receptors within the mPFC and the NAC modulate the reinforcing effects of cocaine and provide evidence that 5-HT_2C receptor agonists could be a possible drug discovery target for the treatment of psychostimulant addiction.     

The role of the fat mass and obesity associated gene (<Emphasis Type="Italic">FTO</Emphasis>) in breast cancer risk

Background  

Obesity has been shown to increase breast cancer risk. FTO is a novel gene which has been identified through genome wide association studies (GWAS) to be related to obesity. Our objective was to evaluate tissue expression of FTO in breast and the role of FTO SNPs in predicting breast cancer risk.     

Effect of manufacturing method on the in vitro drug release and adhesive performance of drug-in-adhesive films containing binary mixtures of ibuprofen with poloxamer 188

Drug-in-adhesive acrylic films, containing binary mixtures of ibuprofen:poloxamer 188 in 30:70, 40:60, 50:50, and 60:40 ratios, were prepared by incorporation either as physical mixture (PM), molten mixture (MM), or solid dispersion (SD). Dissolution testing showed that films prepared by MM had higher drug release compared to films prepared by PM, SD, and films containing ibuprofen alone. The MM 50:50 ratio showed the highest drug release (p < 0.05). Examination of the films by differential scanning calorimetry showed melting endotherms from the binary crystalline mixture but not from ibuprofen crystals regardless of the preparation method. Rheological measurements showed that MM films had lower elastic moduli compared to the neat adhesive, due to the plasticizing effect of the dissolved binary mixture. Fourier transfer infrared analysis confirmed the absence of ibuprofen crystal dimers in all films. It was therefore concluded that the MM method provided better mixing of the components providing crystal-free supersaturated films of high thermodynamic activity.