Ticagrelor and preconditioning in patients with stable coronary artery disease (TAPER-S): a randomized pilot clinical trial.

BACKGROUND: Ticagrelor is a reversibly binding, direct-acting, oral, P2Y12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction. METHODS: To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart. DISCUSSION: Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes. TRIAL REGISTRATION: EudraCT No. 2016-004746-28. No. NCT02701140.  TRIAL STATUS: Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019. TRIAL SPONSOR: Fondazione Policlinico Universitario A. Gemelli - Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.

Ultrastructural, Sensory and Functional Anatomy of the Northern Elephant Seal (Mirounga angustirostris) Facial Vibrissae.

Vibrissae (whiskers) play a key role in underwater orientation in foraging phocids through vibrotactile sensation processing. Our aim was to evaluate the structure of northern elephant seal (NES) vibrissae by means of light (LM) and transmission electron microscopy (TEM), in order to elucidate their function. Vibrissal follicles were processed using standardized laboratory methods and LM/TEM techniques. Individual follicular axonal numbers were counted and axonal diameter measured and averaged. NES have mystacial, rhinal, supraorbital and labial vibrissae. The vibrissal follicles are histologically subdivided into a ring, upper and lower cavernous sinuses (LCS). Each vibrissa is innervated by the deep vibrissal nerve. The average number of axons per large mystacial vibrissa is 1804 (±123), rhinal 985 (±241), supraorbital 1,064 (±204) and 374 (±65) in labial vibrissa. The entire vibrissal system carries an estimated 148 573 axons, and mystacial vibrissae alone have 125 323 axons. Axonal conduction velocity for each vibrissal type is 55.26 m/s for labial, 56.58 m/s for rhinal and 35.88 m/s for mystacial vibrissae. TEM and LM revealed a plethora of mechanoreceptors within the vibrissal follicles: Merkel cell-neurite complexes, lanceolate and pilo-Ruffini end organs. A vast number of sensory axons projecting from the entire vibrissal system indicate that the vibrissal sensory area takes up a large proportion of phocids' somatosensory cortex. In conclusion, NES has highly sensitive and finely tuned vibrotactile vibrissal sense organs.

When elders choose: Which factors could influence the decision-making among elderly in the selection of health tourism services?

BACKGROUND: Elderly beneficiaries (age 65+) exhibit specific characteristics that influence the distribution of health tourism market. High incidence of multiple morbidities and functional disability are hallmarks in this age group. For these reasons, elderly population requires different elements and diverse spectrum of services within health tourism, in comparison to younger beneficiaries. Thus, differences would occur within heterogeneous elderly population itself. A preliminary study that we conducted showed that the level of functional independence was one of the significant factors that guided decision-making among elderly beneficiaries when it came to their health tourism-related choices. Results suggested that beneficiaries recognized and appreciated the effect of the natural remedies and attractions available at the given destination. HYPOTHESIS: Maritime and continental health tourism are two different entities commonly selected by elderly beneficiaries for therapeutic purposes. We propose that the climate conditions, geographical location and availability of regional natural remedies are the key factors to why different services were elected by different groups of elderly. The model of Croatia, an established country in the field of health tourism was utilized for this purpose. Differences in the diagnostic categories of beneficiaries are expected due to effects of marine (sea, Mediterranean climate) and continental (thermal water, healing mud) health tourism. In addition, multitudes of mutually intertwined factors affect decision-making process among elderly regarding their health tourism choices. Such factors include the scale of preferences (with special emphasis on well-being and health), leisure opportunities, marketing influences, cost (price) and the availability/diversity of health tourism services within the particular region. Moreover, individual psychosocial and physical characteristics, disabilities and other debilitating conditions, examined in our preliminary study, significantly contributed to the decision-making scheme. We shouldn't disregard sociodemographic and cultural preferences among elderly as potential factors. CONCLUSIONS: Confirmation of our hypothesis could change the usual approach towards the group of elderly beneficiaries (65+) in the health tourism domain. This approach is often largely based on chronological age criteria exclusively. The contents of this manuscript could serve as a blueprint for the development of comprehensive and sustainable health tourism strategies worldwide.

Attitudes of adolescents towards sexual health in three cities from Croatia and Bosnia and Herzegovina.

AIM: This study aimed to determine the attitudes of adolescents towards sexual health and to assess their understanding of contraception use and knowledge about sexually transmitted infections in three ethnically different areas of Croatia and Bosnia and Herzegovina. METHODS: A total of 146 adolescent high school students between 17 and 19 years of age from three different cities were enrolled in this cross-sectional study. The participants completed two anonymous questionnaires: one that measured attitudes towards safe sex practice and another that measured contraception and general sexual health knowledge. RESULTS: Shame was identified as the main factor why adolescents did not seek information about sexual health and contraception. On average, respondents correctly answered only 35% of questions regarding sexual health. Adolescents from East Mostar, with a predominantly Bosniak population, had more positive attitudes towards safe sex and showed less contraception knowledge in comparison to their colleagues from two cities in Croatia. LIMITATIONS: Our study design might be burdened by socially desirable reporting and other biases inherent to the survey design. CONCLUSION: Adolescents from Croatia and Bosnia and Herzegovina, countries that experienced war and are still undergoing post-communist socio-economic transition, generally did not have adequate knowledge with respect to safe sex lifestyles. Respondents had major problems identifying sexually transmitted infections and their knowledge about contraception was insufficient. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Providing care for adolescent populations should address specificities in local ethnical and socio-economical circumstances. There is a need for further studies to determine social, cultural and religious factors influencing the knowledge and attitudes towards sexual health in order to provide most effective interventions for specific adolescent populations.