Smart Drugs and Synthetic Androgens for Cognitive and Physical Enhancement: Revolving Doors of Cosmetic Neurology

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined.     

Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients

Cardiovascular Drugs and Therapy - The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of...     

Prevention and treatment of venous thromboembolism in the elderly patient

Venous thromboembolism (VTE) is a common complication among hospitalized patients. Pharmacological thromboprophylaxis has emerged as the cornerstone for VTE prevention. As trials on thromboprophylaxis in medical patients have proven the efficacy of both low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH), all acutely medical ill patients should be considered for pharmacological thromboprophylaxis. Unlike in the surgical setting where the risk of associated VTE attributable to surgery is well recognized, and where widespread use of pharmacological thromboprophylaxis and early mobilization has resulted in significant reductions in the risk of VTE, appropriate VTE prophylaxis is under-used in medical patients. Many reasons for this under-use have been identified, including low perceived risk of VTE in medical patients, absence of optimal tools for risk assessment, heterogeneity of patients and their diseases, and fear of bleeding complications. A consistent group among hospitalized medical patients is composed of elderly patients with impaired renal function, a condition potentially associated with bleeding. How these patients should be managed is discussed in this review. Particular attention is devoted to LMWHs and fondaparinux and to measures to improve the safety and the efficacy of their use.     

Cardiac structural and functional changes during long-term antihypertensive treatment with lacidipine and atenolol in the European Lacidipine Study on Atherosclerosis (ELSA)

OBJECTIVES: To evaluate and correlate the effects of long-term antihypertensive treatment on left ventricular (LV) mass and carotid structural changes in a large group of essential hypertensive patients, participating in the European Lacidipine Study on Atherosclerosis (ELSA). DESIGN: In four (Brescia, Glasgow, Naples and Pisa) of 23 centres participating in the ELSA study, an echocardiographic examination was performed at baseline and repeated, until the end of the 4-year study, in essential hypertensive patients, followed-up for carotid quantitative ultrasound examination of intima-media thickness (IMT), after random allocation to treatment with either lacidipine or atenolol (and added hydrochlorothiazide, as required for control of blood pressure). METHODS: M-mode, two-dimensional guided echocardiography was used to measure left ventricular (LV) wall thickness and dimensions, from which LV mass was calculated, using an anatomically validated formula (Penn Convention) and indexed to body surface area (left ventricular mass index, LVMI). The echocardiographic tracings were blindly evaluated in a single reading centre (Brescia). Bilateral IMT was measured at the site of common carotid and bifurcation far walls (CBMmax). RESULTS: At baseline, cardiac and carotid ultrasound scans were available in 278 patients (mean age 54 +/- 7 years, 57% males, 22% obese). A significant correlation was observed between baseline LVMI and CBMmax (r = 0.22, P < 0.001), independent of age. In multivariate analysis, CBMmax and mean 24-h pulse pressure were most strongly associated with baseline LVMI. A significant reduction in LVMI was observed both during lacidipine (n = 96) (-12.5% reduction) and atenolol (n = 78) (-13.9% reduction) treatments (up to 4 years) (P < 0.001 for both, without significant differences between treatments). Changes in LVMI were not related to changes in carotid wall thickness. In multivariate analysis, baseline LV mass and mean 24-h systolic blood pressure changes were significantly associated with changes in LV mass. CONCLUSIONS: In this large, long-term controlled study, antihypertensive treatment with atenolol or lacidipine was accompanied by a similar and significant decrease in LV mass. Treatment-induced changes in LV mass were related to baseline LV mass and changes in 24-h mean systolic blood pressure, without any correlation with changes in carotid structure. In the whole ELSA population, carotid IMT changes have been shown to be unrelated to blood pressure reduction, but significantly influenced by the type of antihypertensive treatment.     

Usefulness of the PARIS Score to Evaluate the Ischemic-hemorrhagic Net Benefit With Ticagrelor and Prasugrel After an Acute Coronary Syndrome

Introduction and objectives

The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry.

Nonunion fracture healing: Evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model

Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (a) develop a new large animal model for bone atrophic nonunion and (b) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a noncritical, full‐thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM + MSC) for 1 day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic, and histomorphometric analysis showed the formation of bone callus in DBM group, whereas the fracture healing appeared at an early stage in DBM + MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM + MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, whereas MSC do not improve the healing process when cultivated on DBM particles before implantation.     

Cortical Somatosensory Excitability Is Modulated in Response to Several Days of Muscle Soreness

Changes in excitability of the sensorimotor cortex have been demonstrated in clinical musculoskeletal pain, although the timing is unknown. Eccentric exercise provokes delayed-onset muscle soreness providing a model to study the temporal profile of sensorimotor cortical plasticity during progressively developing muscle soreness. Twelve healthy participants performed eccentric exercise of the wrist extensors. Likert pain scores, pressure pain thresholds at the extensor carpi radialis (ECR) muscle, somatosensory evoked potentials from electrical stimulation of the radial nerve, maximal wrist extension force, and ECR motor evoked potentials to transcranial magnetic stimulation were recorded before (baseline) and at 2 hours (2-h post), 2 days (day 2), and 6 days (day 6) after exercise. Compared with baseline, 1) the Likert pain score was increased at 2-h post and increased further at day 2 (P < .01); 2) the ECR pressure pain thresholds were decreased at day 2 (P < .001); 3) the P45 amplitude of the somatosensory evoked potential from central-parietal recording sites was increased at day 2 (P < .001); 4) maximal wrist extension force was reduced 2-h post and at day 2 (P < .002); and 5) the cortical area from which ECR motor evoked potentials could be elicited was reduced at 2-h post and at day 2 (P < .03). A decrease in the ECR pressure pain thresholds was correlated (P < .027) with an increase in the P45 amplitude at a centroparietal recording site.