PAR 4 (1-6)

N-terminal fragment of protease-activated receptor 4 (PAR4) that acts as a PAR4 agonist (EC50 ~ 100 μM). Induces platelet aggregation and annexin V activation with no effect on clotting time. Mimics thrombin-induced increases in IL-8/CXCL8-Luc activity an

Atrial-selective K(+) channel blockers: potential antiarrhythmic drugs in atrial fibrillation?[Pubmed:28738160]

Can J Physiol Pharmacol. 2017 Nov;95(11):1313-1318.

In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K(+)) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting IKur, the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting IK,ACh, the Ca(2+)-activated K(+) channels of small conductance (SK) conducting ISK, and the two-pore domain K(+) (K2P) channels (tandem of P domains, weak inward-rectifying K(+) channels (TWIK-1), TWIK-related acid-sensitive K(+) channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents ITWIK-1, ITASK-1, and ITASK-3. Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

Functional Impairment and Risk of Venous Thrombosis in Older Adults.[Pubmed:28598535]

J Am Geriatr Soc. 2017 Sep;65(9):2003-2008.

OBJECTIVES: To determine the role of age-specific risk factors for thrombosis in older age, such as functional impairment. DESIGN: Case-control study. SETTING: The Age and Thrombosis-Acquired and Genetic risk factors in the Elderly Study, a two-center study conducted in the Netherlands and the United States from 2008 to 2011. PARTICIPANTS: Individuals aged 70 and older with a first-time deep venous thrombosis in the leg or pulmonary embolism (n = 401) and controls aged 70 and older (n = 431) without a history of thrombosis. Exclusion criteria were active malignancy and severe cognitive disorders. MEASUREMENTS: The thrombotic risk associated with functional impairment, defined as impairment in two or more activities of daily living (ADLs), impaired mobility (inability to walk outside), sedentary lifestyle (>/=20 h/d sleeping or sitting), and low handgrip strength (<15th percentile), was assessed. Odds ratios (ORs) adjusted for age, sex, and study center with 95% confidence intervals (95% CI) and population attributable risks (PAR) were calculated. RESULTS: Risk of venous thrombosis was 2.9 times greater (OR = 2.9, 95% CI = 1.6-5.3) in individuals with impairment in ADLs, three times as great (OR = 3.0, 95% CI = 1.9-4.7) in those with impaired mobility, four times as great (OR = 4.0, 95% CI = 2.5-6.3) in those with a sedentary life style, and 2.3 times as great (OR = 2.3, 95% CI = 1.5-3.4) in those with weak handgrip strength. PARs were 8% for ADL disability, 13% for inability to walk outside for 15 minutes, 29% for sedentary lifestyle, and 13% for weak hand grip strength. CONCLUSION: In individuals aged 70 and older, functional impairments are a major risk factor for venous thrombosis. These findings may help providers caring for older people be more aware of venous thrombosis risk.

Physiological responses during intermittent running exercise differ between outdoor and treadmill running.[Pubmed:28549220]

Appl Physiol Nutr Metab. 2017 Sep;42(9):973-977.

The aim of this study was to compare the physiological responses during 15 min of intermittent running consisting of 30 s of high-intensity running exercise at maximal aerobic velocity (MAV) interspersed with 30 s of passive recovery (30-30) performed outdoor versus on a motorized treadmill. Fifteen collegiate physically active males (age, 22 +/- 1 years old; body mass, 66 +/- 7 kg; stature, 176 +/- 06 cm; weekly training volume, 5 +/- 2 h.week(-1)), performed the Fitness Intermittent Test 45-15 to determine maximal oxygen uptake (VO2max) and MAV and then completed in random order 3 different training sessions consisting of a 30-s run/30-s rest on an outdoor athletic track (30-30 Track) at MAV; a 30-s run/30-s rest on a treadmill (30-30 Treadmill) at MAV; a 30-s run/30-s rest at MAV+15% (30-30 + 15% MAV Treadmill). Oxygen uptake (VO2), time above 90%VO2max (t90%VO2max), and rating of perceived exertion (RPE) were measured during each training session. We observed a statistical significant underestimation of VO2 (53.1 +/- 5.4 mL.kg(-1).min(-1) vs 49.8 +/- 6.7 mL.kg(-1).min(-1), -6.3%, P = 0.012), t90%VO2max (8.6% +/- 11.5% vs 38.7% +/- 32.5%, -77.8%, P = 0.008), RPE (11.4 +/- 1.4 vs 16.5 +/- 1.7, -31%, P < 0.0001) during the 30-30 Treadmill compared with the same training session performed on track. No statistical differences between 30-30 +15 % MAV Treadmill and 30-30 Track were observed. The present study demonstrates that a 15% increase in running velocity during a high-intensity intermittent treadmill training session is the optimal solution to reach the same physiological responses than an outdoor training session.

Feasibility assessment of shear wave elastography to lumbar back muscles: A Radioanatomic Study.[Pubmed:28509432]

Clin Anat. 2017 Sep;30(6):774-780.

Low back pain is often associated with tensional changes in the paraspinal muscles detected by palpatory procedures. Shear wave elastography (SWE), recently introduced, allows the stiffness of muscles to be assessed noninvasively. The aim of this work was to study the feasibility of using SWE on the three main lumbar back muscles (multifidus, longissimus, and iliocostalis) in vivo after analyzing their muscular architecture ex vivo. We determined the orientation of fibers in the multifidus, longissimus, and iliocotalis muscles in seven fresh cadavers using gross anatomy and B-Mode ultrasound imaging. We then quantified the stiffness of these three muscles at the L3 level ex vivo and in 16 healthy young adults. Little pennation was observed in the longissimus and iliocostalis, in which the direction of fibers was almost parallel to the line of spinous processes. The multifidus appeared as a multiceps and multipennate muscle. Given the random layering of millimetric fascicles, tendons, and fatty spaces, the multifidus had multiple fiber orientations. Muscular fascicles and fibers were oriented from 9 degrees to 22 degrees to the line of spinous processes. The shear moduli related to stiffness were 6.9 +/- 2.7 kPa for the longissimus, 4.9 +/- 1.4 kPa for the iliocostalis, and 5.4 +/- 1.6 kPa for the multifidus. SWE is a feasible method for quantifying the stiffness of the lumbar back muscles. Clin. Anat. 30:774-780, 2017. (c) 2017Wiley Periodicals, Inc.

Long-term (>/=15 years) post-treatment changes and outcome quality after Class II:1 treatment in comparison to untreated Class I controls.[Pubmed:29016736]

Eur J Orthod. 2018 Apr 6;40(2):206-213.

Aim: To investigate the long-term (>/=15 years) post-treatment (Tx) occlusal changes and outcome quality after Class II:1 Tx. Subjects and Methods: Herbst-MBA Tx had been performed at age 12.8 +/- 2.7 years in 119 patients. A recall was conducted and study models from before and after active Tx, after retention as well as after recall were evaluated using standard occlusal variables and the PAR index. These data were compared to 31 untreated Class I controls. Results: 52 out of 119 patients could be located and participated at 33.6 +/- 3.1 years. Compared to the 67 patients who did not participate in the recall, the pre- and post-Tx occlusal data of the participants did not differ systematically; however, the PAR scores were higher by 3.0-4.7 points at all times. Pre-Tx, the mean values of the 52 participants were: PAR = 27.2 +/- 7.6, Class II molar relationship (MR) = 0.7 cusp widths (cw), overjet = 8.2 mm, overbite = 4.1 mm. After Tx, the PAR score was 3.4 +/- 2.2. A Class I MR (0.0 +/- 0.1 cw) with normal overjet (2.3 +/- 0.7 mm) and overbite (1.3 +/- 0.7 mm) existed. At recall, a mild PAR score increase to 8.2 +/- 5.5 points had occurred; this was mainly due to increased overjet and overbite values (3.6 +/- 1.1 and 2.8 +/- 1.6 mm) while the MR was stable (0.0 +/- 0.2 cw). For all these variables, similar findings were made in the untreated controls. Conclusion: The occlusal outcome of Class II:1 Tx showed very good long-term stability. While mild changes occur post-Tx, the long-term result is similar to untreated Class I controls.