The Association between Popular #Diets and Serum #Testosterone among Men in the United States

..Mean ± SD serum testosterone was 435.5 ± 6.7 ng/dl. Mean testosterone was lower among men with a low fat diet (410.8 ± 8.1 vs 443.5 ± 7.3, p=0.005) and a Mediterranean diet (412.9 ± 9.1 vs 443.5 ± 7.3, p=0.002). Multivariable analysis controlling for age, body mass index, activity level, diabetes, comorbidities and prostate cancer showed that men with a nonrestrictive diet had higher serum testosterone than those adhering to a low fat diet (ß –57.2, 95% CI –105.6 to –8.8, p <0.05).

Conclusions:

Men adhering to low fat diets had lower serum testosterone levels even when controlling for comorbidities, age, body mass index and activity levels. As differences in serum testosterone between the diets were modest, the avoidance of fat restrictive diets should be weighed against the potential benefits on an individual basis.

https://bit.ly/3aJzwMH

NP03, a Microdose #Lithium Formulation, Blunts Early #Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats

Epidemiological, preclinical, and clinical studies have suggested a role for microdose lithium in reducing Alzheimer’s disease (AD) risk by modulating key mechanisms associated with AD pathology. The novel microdose lithium formulation, NP03, has disease-modifying effects in the McGill-R-Thy1-APP transgenic rat model of AD-like amyloidosis at pre-plaque stages, before frank amyloid-β (Aβ) plaque deposition, during which Aβ is primarily intraneuronal..

During the early Aβ post-plaque stage, we find that NP03 rescues functional deficits in object recognition, reduces loss of cholinergic boutons in the hippocampus, reduces levels of soluble and insoluble cortical Aβ42 and reduces hippocampal Aβ plaque number. In addition, NP03 reduces markers of neuroinflammation and cellular oxidative stress. Together these results indicate that microdose lithium NP03 is effective at later stages of amyloid pathology, after appearance of Aβ plaques.

https://bit.ly/38D9icR

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Association of Low-Carbohydrate and Low-Fat #Diets With #Mortality Among US Adults

..Overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality. The multivariable-adjusted hazard ratios for total mortality per 20-percentile increase in dietary scores were 1.07 (95% CI, 1.02-1.11; P = .01 for trend) for unhealthy low-carbohydrate-diet score, 0.91 (95% CI, 0.87-0.95; P < .001 for trend) for healthy low-carbohydrate-diet score, 1.06 (95% CI, 1.01-1.12; P = .04 for trend) for unhealthy low-fat-diet score, and 0.89 (95% CI, 0.85-0.93; P < .001 for trend) for healthy low-fat-diet score. The associations remained similar in the stratification and sensitivity analyses.

Conclusions and Relevance In this study, overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality. Unhealthy low-carbohydrate-diet and low-fat-diet scores were associated with higher total mortality, whereas healthy low-carbohydrate-diet and low-fat-diet scores were associated with lower total mortality. These findings suggest that the associations of low-carbohydrate and low-fat diets with mortality may depend on the quality and food sources of macronutrients.

https://bit.ly/2vsDhWZ

#Zinc acetate lozenges for the treatment of the common #cold: a randomised controlled trial

There was no difference in the recovery rate between zinc and placebo participants during the 10-day follow-up (rate ratio for zinc vs placebo=0.68, 95% CI 0.42 to 1.08; p=0.10). The recovery rate for the two groups was similar during the 5-day intervention, but for 2 days after the end of zinc/placebo use, the zinc participants recovered significantly slower compared with the placebo participants (p=0.003). In the zinc group, 37% did not report adverse effects, the corresponding proportion being 69% in the placebo group.

Conclusions A commercially available zinc acetate lozenge was not effective in treating the common cold when instructed to be used for 5 days after the first symptoms. Taste has been a common problem in previous zinc lozenge trials, but a third of zinc participants did not complain of any adverse effects. More research is needed to evaluate the characteristics of zinc lozenges that may be clinically efficacious before zinc lozenges can be widely promoted for common cold treatment.

https://bit.ly/3aHfKSh

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Abdominal #obesity and the risk of recurrent atherosclerotic cardiovascular disease after myocardial #infarction

..Univariate and multivariable-adjusted Cox regression models were used to calculate hazard ratios and 95% confidence intervals in quintiles of waist circumference as well as three categories of body mass index including normal weight, overweight and obesity.

Results
The majority of patients had abdominal obesity. During a median follow-up time of 3.8 years, 1232 men (7.3%) and 469 women (7.9%) experienced a recurrent atherosclerotic cardiovascular disease event. In the univariate analysis, risk was elevated in the fifth quintile (hazard ratio 1.22, 95% confidence interval 1.07–1.39) compared with the first. In the multivariable-adjusted analysis, risk was elevated in the fourth and fifth quintiles (hazard ratio 1.21, confidence interval 1.03–1.43 and hazard ratio 1.25, confidence interval 1.04–1.50), respectively. Gender-stratified analyses showed similar associations in men, while U-shaped associations were observed in women and the body mass index analyses.

Conclusions
Abdominal obesity was common in post-myocardial infarction patients and larger waist circumference was independently associated with recurrent atherosclerotic cardiovascular disease, particularly in men. We recommend utilising waist circumference to identify patients at increased risk of recurrent atherosclerotic cardiovascular disease after myocardial infarction.

https://bit.ly/2vkx13c

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Implications of Abnormal Exercise Electrocardiography With Normal Stress Echocardiography

..After excluding submaximal tests and nondiagnostic ECG or stress imaging results, 15 077 patients (mean [SD] age, 52 [13] years; 6228 [41.3%] men) were classified by stress test results

Death occurred in 425 patients with −ECG/−Echo (4.8%), 50 patients with +ECG/−Echo (5.9%), and 70 patients with +Echo (11.2%). Myocardial infarction occurred in 195 patients with −ECG/−Echo (2.2%), 31 patients with +ECG/−Echo (3.6%), and 59 patients with +Echo (8.7%). The addition of stress ECG findings to clinical and exercise data yielded incremental prognostic value. Patients with −ECG/−Echo imaging results had the least downstream testing (2.3%), followed by +ECG/−Echo (12.8%), and +Echo (33.6%) (P < .001).

Conclusions and Relevance The presence of +ECG results with normal stress Echo imaging may identify a population of patients who are at slightly increased risk for adverse cardiac events, which was not previously recognized. Further study is needed to determine whether these patients will benefit from intensification of medical management.

https://bit.ly/2vsK1nE

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Association of Isolated Diastolic #Hypertension as Defined by the 2017 ACC/AHA Blood Pressure Guideline With Incident Cardiovascular Outcomes

..the definition of hypertension was lowered from a blood pressure (BP) of greater than or equal to 140/90 to greater than or equal to 130/80 mm Hg. The new diastolic BP threshold of 80 mm Hg was recommended based on expert opinion and changes the definition of isolated diastolic hypertension (IDH).

atherosclerotic cardiovascular disease (ASCVD)

..Compared with normotensive ARIC participants, IDH by the 2017 ACC/AHA definition was not significantly associated with incident ASCVD (n = 1386 events; median follow-up, 25.2 years; hazard ratio [HR], 1.06 [95% CI, 0.89-1.26]), HF (n = 1396 events; HR, 0.91 [95% CI, 0.76-1.09]), or CKD (n = 2433 events; HR, 0.98 [95% CI, 0.65-1.11]). Results were also null for cardiovascular mortality in the 2 external cohorts (eg, HRs of IDH by the 2017 ACC/AHA definition were 1.17 [95% CI, 0.87-1.56] in the NHANES [n = 1012 events] and 1.02 [95% CI, 0.92-1.14] in CLUE II [n = 1497 events]).

Conclusions and Relevance In this analysis of US adults, the estimated prevalence of IDH was more common when defined by the 2017 ACC/AHA BP guideline compared with the JNC7 guideline. However, IDH was not significantly associated with increased risk for cardiovascular outcomes.

https://bit.ly/2O8suYu

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Vitamin #B6 Addiction in Acute Myeloid #Leukemia

Cancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK—an enzyme that produces pyridoxal phosphate (PLP) from vitamin B6—as an acute myeloid leukemia (AML)-selective dependency..

PDXK kinase activity is required for PLP production and AML cell proliferation, and pharmacological blockade of the vitamin B6 pathway at both PDXK and PLP levels recapitulated PDXK disruption effects. PDXK disruption reduced intracellular concentrations of key metabolites needed for cell division. Furthermore, disruption of PLP-dependent enzymes ODC1 or GOT2 selectively inhibited AML cell proliferation and their downstream products partially rescued PDXK disruption induced proliferation blockage. Our work identifies the vitamin B6 pathway as a pharmacologically actionable dependency in AML.

https://bit.ly/36x2bBl

Temporal Changes in Resting #Heart Rate, Left Ventricular Dysfunction, Heart #Failure and Cardiovascular Disease: CARDIA Study

..Higher alcohol consumption (β=0.03, p<0.001), lower physical activity (β=0.002,p=001), smoking (β=1.58, p<0.001), men (p<0.001), African-Americans (p<0.001), impaired left ventricular relaxation (e´,β=-0.13, p=0.002), and worse diastolic function (E/e´,β=0.1, p=0.01) were associated with longitudinal increases in resting heart rate. We observed 268 cardiovascular disease and 74 heart failure events over a median of 26 years. In Cox models, baseline and temporal changes in resting heart rate were associated with higher risk of heart failure (hazard ratio (HR)=1.37 95% confidence interval (CI) [1.05-1.79] and HR=1.38 95%CI [1.02-1.86]) and a higher risk cardiovascular disease (HR=1.23 95%CI [1.07-1.42] and HR=1.23 95%CI [1.05-1.44]).

Conclusions

Baseline and temporal changes in resting heart rate in young adults were associated with incident heart failure and cardiovascular disease by mid-life. Contributory factors were associations between temporal increases in resting heart rate and early adult risk factors and subsequent cardiac dysfunction.

https://bit.ly/2tZIXXY

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Five-Year Outcomes of Transcatheter or Surgical #Aortic-Valve Replacement

..At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P=0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery.

CONCLUSIONS
Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement.

https://bit.ly/3aWZ4Gf

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Effects of #Caffeine and Acute Aerobic #Exercise on Working Memory and Caffeine Withdrawal

Studies show that a single bout of exercise confers cognitive benefits. However, many individuals use psychoactive substances such as caffeine to enhance cognitive performance..

The objectives of this study were to compare the effects of acute moderate intensity aerobic exercise to caffeine on working memory (WM) and caffeine withdrawal symptoms (CWS). In Phase I, non-caffeine (n = 29) and caffeine consumers (n = 30) completed a WM assessment, followed by acute exercise and caffeine.

In Phase II, caffeine consumers (n = 25) from Phase I underwent the WM assessment and reported CWS following a 12-hour deprivation period. Acute moderate intensity aerobic exercise and caffeine (1.2 mg/kg) significantly improved WM accuracy and reduced CWS comparably. WM performance was not reduced following caffeine deprivation..

https://go.nature.com/37KcXpg

Behavioral effects of multiple-dose #oxytocin treatment in #autism: a randomized, placebo-controlled trial with long-term follow-up

Intranasal administration of the “prosocial” neuropeptide oxytocin is increasingly explored as a potential treatment for targeting the core characteristics of autism spectrum disorder (ASD)..

..Among the secondary outcome measures, treatment-specific improvements were identified in the Repetitive Behavior Scale and State Adult Attachment Measure, indicating reductions in self-reported repetitive behaviors (p = .04) and reduced feelings of avoidance toward others (p = .03) in the oxytocin group compared to the placebo group, up to 1 month and even 1 year post-treatment. Treatment-specific effects were also revealed in screenings of mood states (Profile of Mood States), indicating higher reports of “vigor” (feeling energetic, active, lively) in the oxytocin, compared to the placebo group (p = .03).

Conclusions

While no treatment-specific improvements were evident in terms of core social symptoms, the current observations of long-term beneficial effects on repetitive behaviors and feelings of avoidance are promising and suggestive of a therapeutic potential of oxytocin treatment for ASD. However, given the exploratory nature of this pilot study, future studies are warranted to evaluate the long-term effects of OT administration further

https://bit.ly/2GCndUA

HDAC inhibition improves cardiopulmonary function in a feline model of #diastolic dysfunction

Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on cardiopulmonary structure, function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysfunction common to human HFpEF..

..Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, n = 8), a Food and Drug Administration–approved pan-HDAC inhibitor, or vehicle (b + veh, n = 8) for 2 months. 

..Left ventricular (LV) end-diastolic pressure and mean pulmonary arterial pressure were significantly reduced in b + SAHA (P < 0.01) versus b + veh. SAHA increased myofibril relaxation ex vivo, which correlated with in vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, compliance, blood oxygenation, and reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar capillary stress failure. Acetylation proteomics revealed that SAHA altered lysine acetylation of mitochondrial metabolic enzymes. These results suggest that acetylation defects in hypertrophic stress can be reversed by HDAC inhibitors, with implications for improving cardiac structure and function in patients

https://bit.ly/2vDN9NB

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High-#protein diets increase #cardiovascular risk by activating macrophage mTOR to suppress mitophagy

High-protein diets are commonly utilized for weight loss, yet they have been reported to raise cardiovascular risk. The mechanisms underlying this risk are unknown. Here, we show that dietary protein drives atherosclerosis and lesion complexity. Protein ingestion acutely elevates amino acid levels in blood and atherosclerotic plaques, stimulating macrophage mammalian target of rapamycin (mTOR) signalling. This is causal in plaque progression, because the effects of dietary protein are abrogated in macrophage-specific Raptor-null mice.

Mechanistically, we find amino acids exacerbate macrophage apoptosis induced by atherogenic lipids, a process that involves mammalian target of rapamycin complex 1 (mTORC1)-dependent inhibition of mitochondrial autophagy (mitophagy), accumulation of dysfunctional mitochondria and mitochondrial apoptosis. Using macrophage-specific mTORC1- and autophagy-deficient mice, we confirm this amino acid–mTORC1–autophagy signalling axis in vivo.

Our data provide insights into the deleterious impact of excessive protein ingestion on macrophages and atherosclerotic progression. Incorporation of these concepts in clinical studies is important to define the vascular effects of protein-based weight loss regimens.

https://go.nature.com/31gUheg

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#Eating Jet Lag: A Marker of the Variability in Meal Timing and Its Association with #Body Mass Index

The timing of food intake has been associated with obesity and adverse metabolic outcomes, independently of the amount or content of food intake and activity level. However, the impact of the variability in the timing of food intake between weekends and weekdays on BMI (body mass index) remains unexplored. To address that, we propose to study a marker of the variability of meal timing on weekends versus weekdays (denominated as ‘eating jet lag’) that could be associated with increments in BMI..

Our results revealed a positive association between eating jet lag and BMI (p = 0.008), which was independent of the chronotype and social jet lag. Further analysis revealed the threshold of eating jet lag was of 3.5 h or more, from which the BMI could significantly increase. These results provided evidence of the suitability of the eating jet lag, as a marker of the variability in meal timing between weekends and weekdays, for the study of the influence of meal timing on obesity. In a long run, the reduction of the variability between meal timing on weekends versus weekdays could be included as part of food timing guidelines for the prevention of obesity among general population.

https://bit.ly/2ubXP5C

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How #odor cues help to optimize #learning during sleep in a real life-setting

Effortless learning during sleep is everybody’s dream. Several studies found that presenting odor cues during learning and selectively during slow wave sleep increases learning success..

..We (1) performed a field study of vocabulary-learning in a regular school setting, (2) stimulated with odor cues during the whole night without sleep monitoring, and (3) applied the odor additionally as retrieval cue in a subsequent test..

..Our results replicate previous findings and provide important extensions: First, the odor effect also works outside the lab. Second, continuous cueing at night produces similar effect sizes as a study with selective cueing in specific sleep stages. Whether odor cueing during memory recall further increases memory performance hast to be shown in future studies. Overall, our results extend the knowledge on odor cueing effects and provide a realistic practical perspective on it.

https://go.nature.com/37Jtmua

Long-term effects of #bouldering psychotherapy on #depression: benefits can be maintained across a 12-month follow-up

Bouldering psychotherapy (BPT), an intervention that combines a unique style of rock climbing with psychotherapy

Previous studies have identified positive effects of Bouldering Psychotherapy (BPT) on symptoms of depression. The aim of the present study was to investigate the short- and long-term effects of BPT on 97 participants with depression..

BPT took place once a week over a period of 8 weeks. In a waitlist control group design, participants were assessed at baseline and after 8 weeks (end of BPT for the intervention group; start of BPT for the waitlist group), 16 weeks, and 12 months.

Depression scores dropped by 7.21 on the BDI-II during the first intervention period with a Cohen's d of 0.59. A regression analysis at t1 showed that group allocation (p < .001) was the only significant predictor besides the baseline depression score (p < .001). A 12-month (after t0) follow-up measurement showed that the decrease in depression severity remained stable during that time, with values of d = 0.37 for the intervention group and d = 0.43 for the waitlist group.

Limitations of the study are the assessment of symptoms via only self-report, the lack of a control group during follow-up, and different durations of the follow-up period in the two groups.

Our results augment the findings of previous studies regarding the short-term effects of BPT and provide initial evidence that the positive effects of BPT on depression severity can be maintained across a period of 12 months.

https://bit.ly/37RkV02

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#Marijuana Use in Patients With #Cardiovascular Disease: JACC Review Topic of the Week

Marijuana use is increasing as more states are legalizing cannabis for both medicinal and recreational purposes. National survey data estimate that >2 million Americans with established cardiovascular diseases currently use or have used marijuana in its variety of forms, including inhalation and vaping. Cannabinoid receptors are distributed in multiple tissue beds and cells, including platelets, adipose tissue, and myocytes. Observational data suggest associations between marijuana and a broad range of adverse cardiovascular risks. Marijuana is becoming increasingly potent, and smoking marijuana carries many of the same cardiovascular health hazards as smoking tobacco. Synthetic cannabinoids have been linked to more sustained and deleterious pharmacodynamic effects. Marijuana is classified as a Schedule I substance, thus limiting its rigorous study for cardiovascular health effects.

This review summarizes cardiovascular considerations related to marijuana use, pharmacological interactions, and future steps to provide clearer guidance regarding its cardiovascular safety. Screening for marijuana use is encouraged, especially in young patients presenting with cardiovascular disease.

https://bit.ly/2SbNiiR

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Plight of the distracted #pedestrian: a research synthesis and meta-analysis of mobile #phone use on crossing behaviour

Pedestrians are commonly involved in vehicle collisions that result in injuries and fatalities. Pedestrian distraction has become an emerging safety issue as more pedestrians use their mobile phones while walking and crossing the street.

..Fourteen experimental studies were ultimately included in an N-weighted meta-analysis (k=81 effect sizes), and eight observational studies were included in a qualitative overview. Both mobile phone conversation and text messaging increased rates of hits and close calls. Texting decreased rates of looking left and right prior to and/or during street crossing. As might be expected, text messaging was generally found to have the most detrimental effect on multiple behavioural measures.

Limitations A variety of study quality issues limit the interpretation and generalisation of the results, which are described, as are future study measurement and methods improvements.

https://bit.ly/2OqwAex

#Pet Ownership and #Cardiovascular Health in the US general population

The 2013 American Heart Association Scientific Statement on pet ownership and cardiovascular risk suggested that dog ownership is probably associated with decreased cardiovascular risk. Several studies have been shown that pet ownership, particularly of dogs, is associated with increased physical activity levels, social support, and improved outcomes after a major cardiovascular event..

Pet owners were older, less likely to be women or widowed, and more likely to be white, more educated, tobacco users, and work more than 35 hours per week than non-owners (all p-values < 0.05). Pet owners had a higher hemoglobin, lower LDL cholesterol, and a lower prevalence of DM, SH, and stroke (all p-values < 0.05). After adjusting for potential confounders, pet ownership (either cat or dog ownership) was independently associated with a lower prevalence of SH (OR: 0.67; 95% CI: 0.49 - 0.89; p = 0.01), but not HF, CAD, DM, or stroke, compared with non-owners. In conclusions, using a large national database, we found that pet ownership is associated with a decreased prevalence of SH. Further longitudinal studies are needed to draw a conclusion on the protective effect of pet ownership in patients with cardiovascular disease.

https://bit.ly/2OmMIxD