Sequence variants in malignant hyperthermia genes in Iceland: classification and actionable findings in a population database.

Malignant hyperthermia (MH) susceptibility is a rare life-threatening disorder that occurs upon exposure to a triggering agent. MH is commonly due to protein-altering variants in RYR1 and CACNA1S. The American College of Medical Genetics and Genomics recommends that when pathogenic and likely pathogenic variants in RYR1 and CACNA1S are incidentally found, they should be reported to the carriers. The detection of actionable variants allows the avoidance of exposure to triggering agents during anesthesia. First, we report a 10-year-old Icelandic proband with a suspected MH event, harboring a heterozygous missense variant NM_000540.2:c.6710G>A r.(6710g>a) p.(Cys2237Tyr) in the RYR1 gene that is likely pathogenic. The variant is private to four individuals within a three-generation family and absent from 62,240 whole-genome sequenced (WGS) Icelanders. Haplotype sharing and WGS revealed that the variant occurred as a somatic mosaicism also present in germline of the proband's paternal grandmother. Second, using a set of 62,240 Icelanders with WGS, we assessed the carrier frequency of actionable pathogenic and likely pathogenic variants in RYR1 and CACNA1S. We observed 13 actionable variants in RYR1, based on ClinVar classifications, carried by 43 Icelanders, and no actionable variant in CACNA1S. One in 1450 Icelanders carries an actionable variant for MH. Extensive sequencing allows for better classification and precise dating of variants, and WGS of a large fraction of the population has led to incidental findings of actionable MH genotypes.

Evaluating the Benefits of Exercise Training in HFrEF or COPD Patients: ISO-LEVEL COMPARISON CAN ADD VALUABLE INFORMATION TO V˙o2peak.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) are relatively common conditions with similar symptoms of exercise intolerance and dyspnea. The aim of this study was to compare exercise capacity, ventilatory response, and breathing pattern in patient groups with either advanced HFrEF or COPD before and after exercise training. METHODS: An observational study was conducted with parallel groups of 25 HFrEF and 25 COPD patients who took part in 6 wk of inpatient rehabilitation with exercise training. All patients underwent cardiopulmonary exercise tests at the start and end of the training, with resting arterial blood gas measurements. RESULTS: The average peak oxygen uptake (V˙o2) was low at the start of the study but increased significantly after training in both groups, or by 2.2 ± 2.1 mL/kg/min in HFrEF patients and 1.2 ± 2.2 mL/kg/min in COPD patients. At ISO-V˙o2 (ie, same level of V˙o2 in pre- and post-exercise tests), carbon dioxide production (V˙co2) decreased after exercise training in both groups. Similarly, at ISO-V˙E (ie, same level of ventilation), breathing frequency (f) decreased and tidal volume (VT) increased, resulting in an improved breathing pattern (lower f/VT ratio) after training. CONCLUSION: The findings of this study show that exercise training in severely affected patient groups with HFrEF or COPD led to an increase in maximal exercise capacity, a more favorable breathing pattern, and a diminished V˙co2 during exercise. Therefore, comparisons of V˙co2 and breathing pattern at ISO-levels of V˙o2 or V˙E before and after training are valuable and underutilized outcome measures in treatment studies.

Self-rated health and socio-economic status among older adults in Northern Iceland.

Little is known about self-rated health (SRH) of older people living in more remote and Arctic areas. Iceland is a high-income country with one of the lowest rates of income inequality in the world, which may influence SRH. The research aim was to study factors affecting SRH, in such a population living in Northern Iceland. Stratified random sample according to the place of residency, age and gender was used and data collected via face-to-face interviews. Inclusion criteria included community-dwelling adults ≥65 years of age. Response rate was 57.9% (N = 175), average age 74.2 (sd 6.3) years, range 65-92 years and 57% were men. The average number of diagnosed diseases was 1.5 (sd 1.3) and prescribed medications 3.0 (sd 1.7). SRH ranged from 5 (excellent) to 1 (bad), with an average of 3.26 (sd 1.0) and no difference between the place of residency. Lower SRH was independently explained by depressed mood (OR = 0.88, 95% CI = 0.80-0.96), higher body mass index (OR = 0.93, 95% CI = 0.87-0.99), number of prescribed medications (OR = 0.88, 95% CI = 0.78-1.00) and perception of inadequate income (OR = 0.45, 95% CI = 0.21-0.98). The results highlight the importance of physical and mental health promotion for general health and for ageing in place and significance of economic factors as predictors of SRH.

Physical fitness, injuries, and team performance in soccer.

PURPOSE: To investigate the relationship between physical fitness and team success in soccer, and to test for differences in physical fitness between different player positions. METHODS: Participants were 306 male soccer players from 17 teams in the two highest divisions in Iceland. Just before the start of the 1999 soccer season, the following variables were tested: height and weight, body composition, flexibility, leg extension power, jump height, and peak O2 uptake. Injuries and player participation in matches and training were recorded through the 4-month competitive season. Team average physical fitness was compared with team success (final league standing) using a linear regression model. Physical fitness was also compared between players in different playing positions. RESULTS: A significant relationship was found between team average jump height (countermovement jump and standing jump) and team success (P = 0.009 and P = 0.012, respectively). The same trend was also found for leg extension power (P = 0.097), body composition (% body fat, P = 0.07), and the total number of injury days per team (P = 0.09). Goalkeepers demonstrated different fitness characteristics from outfield players. They were taller and heavier, more flexible in hip extension and knee flexion, and had higher leg extension power and a lower peak O2 uptake. However, only minor differences were observed between defenders, midfield players, and attackers. CONCLUSION: Coaches and medical support teams should pay more attention to jump and power training, as well as preventive measures and adequate rehabilitation of previous injuries to increase team success.

Risk factors for injuries in football.

BACKGROUND: The injury risk in football is high, but little is known about causes of injury. PURPOSE: To identify risk factors for football injuries using a multivariate model. STUDY DESIGN: Prospective cohort study. METHODS: Participants were 306 male football players from the two highest divisions in Iceland. Before the 1999 football season started, the following factors were examined: height, weight, body composition, flexibility, leg extension power, jump height, peak O(2) uptake, joint stability, and history of previous injury. Injuries and player exposure were recorded throughout the competitive season. RESULTS: Older players were at higher risk of injury in general (odds ratio [OR] = 1.1 per year, P = 0.05). For hamstring strains, the significant risk factors were age (OR = 1.4 [1 year], P < 0.001) and previous hamstring strains (OR = 11.6, P <0.001). For groin strains, the predictor risk factors were previous groin strains (OR = 7.3, P = 0.001) and decreased range of motion in hip abduction (OR = 0.9 [1 degrees ], P = 0.05). Previous injury was also identified as a risk factor for knee (OR = 4.6) and ankle sprains (OR = 5.3). CONCLUSIONS: Age and previous injury were identified as the main risk factors for injury among elite football players from Iceland.

Dorzolamide induces vasodilatation in isolated pre-contracted bovine retinal arteries.

The effect of the carbonic anhydrase inhibitor dorzolamide on vascular smooth muscle in pre-contracted bovine retinal arteries was examined. Ring segments of retinal arteries were placed in a small vessel myograph for measurement of contractile activity. The arteries were placed in a physiological saline solution. Vasoconstriction was induced by either 124 mM KCl (0.90 +/- 0.46 mN, n=34), 10(-4) M prostaglandin F2alpha (1.72 +/- 0.84 mN, n=10) or 10(-6) M norepinephrine (0.78 +/- 0.47 mN, n=6). Both KCl and prostaglandin F2alpha caused steady repeatable contractions but norepinephrine caused a single phasic contraction. The effect of the carbonic anhydrase inhibitor, dorzolamide on the vasoconstriction was examined. Dorzolamide, if added to the bath when the vasoconstriction had reached a maximum steady level, caused a highly significant relaxation (vasodilatation) of the arteries. This action of dorzolamide occurred irrespective of which agent was used to induce vasoconstriction. Similar results were obtained in experiments were Hepes buffer was used instead of CO2/bicarbonate buffer. The vasodilatation induced by dorzolamide was stable as long as the drug remained in the bath, and was reversible. These results show that dorzolamide causes a vasodilatation of retinal arteries, pre-contracted by three different mechanisms by direct action and presumably independent of changes in extracellular pH.