Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Short-term variability in the activity and composition of the diazotroph community in a coastal upwelling system

Today we know that diazotrophs are common and active in nitrogen (N) replete regions, however the factors controlling their distribution remain elusive. Previous studies in upwelling regions revealed that the composition of diazotrophs responded to changes in hydrodynamic forcing over seasonal scales. Here we used high-frequency observations collected during a 3-week cruise in the upwelling region off NW Iberia to describe changes in the activity and composition of diazotrophs over shorter temporal scales. The cruise started after a strong upwelling event followed by a few days of relaxation-downwelling, and soon after another upwelling pulse. Higher N2 fixation rates (2.2 ± 0.7 µmol m-3 d-1) were measured during relaxation-downwelling, when surface nitrate concentration was low. During the fertilization associated with the upwelling, N2 fixation dramatically decreased to 0.10 ± 0.09 µmol m-3 d-1. The comparison with nitrate consumption and diffusion confirmed the minor role of N2 fixation (<1%) as a source of new N for primary production. The unicellular cyanobacterium UCYN-A2 was the dominant diazotroph during the cruise. UCYN-A2 abundance was four times higher during relaxation-downwelling (4x104 copies L-1) compared to upwelling conditions (0.2x104 copies L-1), when the unusual Epsilonproteobacteria increased their relative abundance. These results indicate that diazotrophs can respond rapidly to changes in the environment, and point out to the availability of N as a key factor controlling the activity, composition and distribution of diazotrophs in eutrophic regions

Electrical cardioversion during pregnancy: safe or not?

Two pregnant patients with a sustained symptomatic maternal supraventricular arrhythmia are presented. Both patients were treated with direct-current cardioversion. Electrical cardioversion during pregnancy is a rarely applied but highly effective procedure in the treatment of maternal cardiac arrhythmias and is assumed safe for both mother and child. However, once foetal viability is reached, monitoring of the foetal heart rate is advised and facilities for immediate caesarean section should be available

Remote monitoring and follow-up of cardiovascular implantable electronic devices in the Netherlands: An expert consensus report of the Netherlands Society of Cardiology

Remote monitoring of cardiac implanted electronic devices (CIED: pacemaker, cardiac resynchronisation therapy device and implantable cardioverter defibrillator) has been developed for technical control and follow-up using transtelephonic data transmission. In addition, automatic or patient-triggered alerts are sent to the cardiologist or allied professional who can respond if necessary with various interventions. The advantage of remote monitoring appears obvious in impending CIED failures and suspected symptoms but is less likely in routine follow-up of CIED. For this follow-up the indications, quality of care, cost-effectiveneness and patient satisfaction have to be determined before remote CIED monitoring can be applied in daily practice. Nevertheless remote CIED monitoring is expanding rapidly in the Netherlands without professional agreements about methodology, responsibilities of all the parties involved and that of the device patient, and reimbursement. The purpose of this consensus document on remote CIED monitoring and follow-up is to lay the base for a nationwide, uniform implementation in the Netherlands. This report describes the technical communication, current indications, benefits and limitations of remote CIED monitoring and follow-up, the role of the patient and device manufacturer, and costs and reimbursement. The view of cardiology experts and of other disciplines in conjunction with literature was incorporated in a preliminary series of recommendations. In addition, an overview of the questions related to remote CIED monitoring that need to be answered is given. This consensus document can be used for future guidelines for the Dutch profession

Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Several recent studies have shown that angiotensin type 1 receptor (AT1) antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ). PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions.</p> <p>Methods</p> <p>We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers) provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662.</p> <p>Results</p> <p>We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co-administration of GW9662.</p> <p>Conclusion</p> <p>The results suggest that telmisartan provides effective neuroprotection against dopaminergic cell death and that the neuroprotective effect is mediated by PPAR-γ activation. However, the results in AT1-deficient mice show that blockage of AT1, unrelated to the pharmacological properties of AT1 blockers, also protects against dopaminergic cell death and neuroinflammation. Furthermore, the results show that PPAR-γ activation is involved in the anti-inflammatory and neuroprotective effects of AT1 deletion.</p

2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

[Extract] Top 10 Take-Home Messages for the Primary Prevention of Cardiovascular Disease 1. The most important way to prevent atherosclerotic vascular disease, heart failure, and atrial fibrillation is to promote a healthy lifestyle throughout life. 2. A team-based care approach is an effective strategy for the prevention of cardiovascular disease. Clinicians should evaluate the social determinants of health that affect individuals to inform treatment decisions. 3. Adults who are 40 to 75 years of age and are being evaluated for cardiovascular disease prevention should undergo 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimation and have a clinician–patient risk discussion before starting on pharmacological therapy, such as antihypertensive therapy, a statin, or aspirin. In addition, assessing for other risk-enhancing factors can help guide decisions about preventive interventions in select individuals, as can coronary artery calcium scanning. 4. All adults should consume a healthy diet that emphasizes the intake of vegetables, fruits, nuts, whole grains, lean vegetable or animal protein, and fish and minimizes the intake of trans fats, red meat and processed red meats, refined carbohydrates, and sweetened beverages. For adults with overweight and obesity, counseling and caloric restriction are recommended for achieving and maintaining weight loss. 5. Adults should engage in at least 150 minutes per week of accumulated moderate-intensity physical activity or 75 minutes per week of vigorous-intensity physical activity. 6. For adults with type 2 diabetes mellitus, lifestyle changes, such as improving dietary habits and achieving exercise recommendations, are crucial. If medication is indicated, metformin is first-line therapy, followed by consideration of a sodium-glucose cotransporter 2 inhibitor or a glucagon-like peptide-1 receptor agonist. 7. All adults should be assessed at every healthcare visit for tobacco use, and those who use tobacco should be assisted and strongly advised to quit. 8. Aspirin should be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit. 9. Statin therapy is first-line treatment for primary prevention of ASCVD in patients with elevated low-density lipoprotein cholesterol levels (≥190 mg/dL), those with diabetes mellitus, who are 40 to 75 years of age, and those determined to be at sufficient ASCVD risk after a clinician–patient risk discussion. 10. Nonpharmacological interventions are recommended for all adults with elevated blood pressure or hypertension. For those requiring pharmacological therapy, the target blood pressure should generally be <130/80 mm Hg

Biodiversity - Confronting amphibian declines and extinctions

Stopping further global losses of amphibian populations and species requires an unprecedented conservation response