Left atrial appendage morphology and relative contrast agent concentration in patients undergoing coronary artery CTA.

AIM: To evaluate whether certain morphological features of the left atrial appendage (LAA) would influence the LAA/ascending aorta (AA) radiodensity ratio, as a reflection of the blood flow conditions in the LAA. MATERIALS AND METHODS: Eight-hundred and eight consecutive patients undergoing computed tomography angiography (CCTA) were evaluated. Of these, 749 had no history of atrial fibrillation and none had suffered acute stroke. The LAA/AA radiodensity ratio, and the length, lobe number, and morphological classification of LAAs were assessed. RESULTS: The distribution of morphological classes for LAAs were: windsock 62.3%, cactus 18.6%, chicken wing 10.0%, and cauliflower 9.2%. The mean LAA/AA radiodensity ratio was 0.87±0.14 (range 0.22-1.44). Female gender (p=0.001), elevated body mass index (BMI; r=-0.129; p=0.003), and diabetes (p=0.03) were associated with lower LAA/AA radiodensity ratios, while heart failure (p=0.017), significant coronary artery stenosis (p=0.010), and LAAs with multiple lobes (p=0.018), exhibited higher LAA/AA radiodensity ratios. Multiple regression analysis revealed that a short one-lobed cauliflower morphology was an independent predictor (p=0.007) of a decreased LAA/AA radiodensity ratio. CONCLUSION: A decline in the LAA/AA radiodensity ratio may reflect decreased blood flow in the LAA, paralleling spontaneous echo contrast in transoesophageal echocardiography. Thus, CCTA might be of value in recognising LAA structures that predispose to decreased blood flow.

The Transpolar Drift conveys methane from the Siberian Shelf to the central Arctic Ocean.

Methane sources and sinks in the Arctic are poorly quantified. In particular, methane emissions from the Arctic Ocean and the potential sink capacity are still under debate. In this context sea ice impact on and the intense cycling of methane between sea ice and Polar surface water (PSW) becomes pivotal. We report on methane super- and under-saturation in PSW in the Eurasian Basin (EB), strongly linked to sea ice-ocean interactions. In the southern EB under-saturation in PSW is caused by both inflow of warm Atlantic water and short-time contact with sea ice. By comparison in the northern EB long-time sea ice-PSW contact triggered by freezing and melting events induces a methane excess. We reveal the Ttranspolar Drift Stream as crucial for methane transport and show that inter-annual shifts in sea ice drift patterns generate inter-annually patchy methane excess in PSW. Using backward trajectories combined with δ18O signatures of sea ice cores we determine the sea ice source regions to be in the Laptev Sea Polynyas and the off shelf regime in 2011 and 2015, respectively. We denote the Transpolar Drift regime as decisive for the fate of methane released on the Siberian shelves.

Automated image analysis detects aging in clinical-grade mesenchymal stromal cell cultures.

BACKGROUND: Senescent cells are undesirable in cell therapy products due to reduced therapeutic activity and risk of aberrant cellular effects, and methods for assessing senescence are needed. Early-passage mesenchymal stromal cells (MSCs) are known to be small and spindle-shaped but become enlarged upon cell aging. Indeed, cell morphology is routinely evaluated during MSC production using subjective methods. We have therefore explored the possibility of utilizing automated imaging-based analysis of cell morphology in clinical cell manufacturing. METHODS: An imaging system was adopted for analyzing changes in cell morphology of bone marrow-derived MSCs during long-term culture. Cells taken from the cultures at the desired passages were plated at low density for imaging, representing morphological changes observed in the clinical-grade cultures. The manifestations of aging and onset of senescence were monitored by population doubling numbers, expression of p16INK4a and p21Cip1/Waf1, ß-galactosidase activity, and telomeric terminal restriction fragment analysis. RESULTS: Cell area was the most statistically significant and practical parameter for describing morphological changes, correlating with biochemical senescence markers. MSCs from passages 1 (p1) and 3 (p3) were remarkably uniform in size, with cell areas between 1800 and 2500 µm2. At p5 the cells began to enlarge resulting in a 4.8-fold increase at p6-9 as compared to p1. The expression of p16INK4a and activity of ß-galactosidase had a strong correlation with the increase in cell area, whereas the expression of p21Cip1/Waf1 reached its maximum at the onset of growth arrest and subsequently decreased. Mean telomere length shortened at an apparently constant rate during culture, from 8.2 ± 0.3 kbp at p1, reaching 6.08 ± 0.6 kbp at senescence. CONCLUSIONS: Imaging analysis of cell morphology is a useful tool for evaluating aging in cell cultures throughout the lifespan of MSCs. Our findings suggest that imaging analysis can reproducibly detect aging-related changes in cell morphology in MSC cultures. These findings suggest that cell morphology is still a supreme measure of cell quality and may be utilized to develop new noninvasive imaging-based methods to screen and quantitate aging in clinical-grade cell cultures.

Early maladaptive schemas and suicidal ideation in depressed patients

Background and objectives: Suicidal ideation is a key risk factor for suicidal behaviour among depressed individuals. To explore underlying cognitive patterns associated with suicidal ideation, the present study compared early maladaptive schemas (EMSs) among psychiatric outpatients in treatment for major depressive disorder with and without current suicidal ideation. Methods: The sample consisted of 79 depressed patients who responded to the background questionnaire and completed the Young Schema Questionnaire short form-extended, 21-item Beck Depression Inventory and Beck Hopelessness Scale. Results: Patients with suicidal ideation were more maladaptive in respect to the majority of EMSs compared to those without. After controlling for the concurrent depressive symptom severity and hopelessness ‘Vulnerability to Harm or Illness’ EMS, which concerns catastrophising beliefs, remained a predictor for suicidal ideation. Conclusion: EMSs may contribute to suicidal ideation among depressed individuals regardless of their mood and future orientation. These results offer implications for the assessment and treatment of suicidality

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Effects of a 20-week high-intensity strength and sprint training program on tibial bone structure and strength in middle-aged and older male sprint athletes: a randomized controlled trial.

This randomized, controlled, high-intensity strength and sprint training trial in middle-aged and older male sprint athletes showed significant improvements in mid-tibial structure and strength. The study reveals the adaptability of aging bone, suggesting that through a novel, intensive training stimulus it is possible to strengthen bones during aging. INTRODUCTION: High-load, high-speed and impact-type exercise may be an efficient way of improving bone strength even in old age. We evaluated the effects of combined strength and sprint training on indices of bone health in competitive masters athletes, who serve as a group of older people who are likely to be able to participate in vigorous exercise of this kind. METHODS: Seventy-two men (age 40-85) were randomized into an experimental (EX, n = 40) and a control (CTRL, n = 32) group. EX participated in a 20-week program combining heavy and explosive strength exercises with sprint training. CTRL maintained their usual, run-based sprint training schedules. Bone structural, strength and densitometric parameters were assessed by peripheral QCT at the distal tibia and tibial midshaft. RESULTS: The intervention had no effects on distal tibia bone traits. At the mid-tibia, the mean difference in the change in cortical thickness (ThCO) in EX compared to CTRL was 2.0% (p = 0.007). The changes in structure and strength were more pronounced in the most compliant athletes (training adherence >75%). Compared to CTRL, total and cortical cross-sectional area, ThCO, and the area and density-weighted moments of inertia for the direction of the smallest flexural rigidity (I minA , I minD ) increased in EX by 1.6-3.2% (p = 0.023-0.006). Polar mass distribution analysis revealed increased BMC at the anteromedial site, whereas vBMD decreased (p = 0.035-0.043). CONCLUSIONS: Intensive strength and sprint training improves mid-tibia structure and strength in middle-aged and older male sprint athletes, suggesting that in the presence of high-intensity loading exercise, the adaptability of the bone structure is maintained during aging.

Whole body frontal plane mechanics across walking, running, and sprinting in young and older adults.

This study investigated the whole body frontal plane mechanics among young (26 ± 6 years), early old (61 ± 5 years), and old (78 ± 4 years) adults during walking, running, and sprinting. The age-groups had similar walking (1.6 m/s) and running (4.0 m/s) speeds, but different maximal sprinting speed (young 9.3 m/s, early old 7.9 m/s, and old 6.6 m/s). Surprisingly, although the old group exerted much lower vertical ground reaction force during running and sprinting, the hip frontal plane moment did not differ between the age-groups. Kinematic analysis demonstrated increased hip adduction and pelvis drop, as well as reduced trunk lateral flexion among old adults, especially during sprinting. These alterations in the hip and pelvis motions may reflect insufficient force production of hip abductors to stabilize the pelvis during single-limb support, while limited trunk lateral flexion may enhance control of the mediolateral balance. On the other hand, larger trunk side-to-side movement among the young and early old adults may provide a mechanism to prevent the increase of the hip frontal moment despite greater vertical ground reaction force. This, in turn, can assist hip abductors to maintain stability of the pelvis during sprinting while allowing powerful force generation by a large adductor muscle group.

Medical surveillance for occupational asthma-how are cases detected?

BACKGROUND: In Finland, medical surveillance, including spirometry, is periodically performed for workers who are exposed to agents capable of causing occupational asthma (OA). Although it has been shown that surveillance can detect OA at an early stage, few studies have assessed its benefits or the role of surveillance spirometry. AIMS: To assess the role of surveillance and spirometry in detecting OA and to evaluate the quality of spirometry. METHODS: We retrospectively reviewed the medical files of patients in health surveillance programmes who were diagnosed with sensitizer-induced OA at the Finnish Institute of Occupational Health in 2012‒14. We collected information on work exposure, respiratory symptoms, healthcare visits that initiated the diagnostic process, first spirometry and other diagnostic tests. RESULTS: Sixty files were reviewed. Medical surveillance detected 11 cases (18%) and 49 cases (82%) were detected at doctors' appointments that were not related to surveillance. The median delay from the onset of asthma symptoms to diagnosis was 2.2 years. Delay did not differ between these groups. No cases were detected on the basis of abnormal spirometry without respiratory symptoms. However, five patients (8%) initially reported solely work-related rhinitis symptoms. Spirometry was normal in half of the cases and quality criteria were fulfilled in 86% of the tests. CONCLUSIONS: Fewer than one in five OA cases were detected through medical surveillance. Investigations were initiated by respiratory symptoms. No asymptomatic worker was referred because of abnormal spirometry. Our results highlight the importance of work-related nasal symptoms in detecting OA.

Antidepressant use and work-related injuries.

BACKGROUND: Adverse effects of antidepressants are most common at the beginning of the treatment, but possible also later. We examined the association between antidepressant use and work-related injuries taking into account the duration of antidepressant use. METHOD: Antidepressant use and work-related injuries between 2000 and 2011 were measured among 66 238 employees (mean age 43.8 years, 80% female) using linkage to national records (the Finnish Public Sector study). We analysed data using time-dependent modelling with individuals as their own controls (self-controlled case-series design). RESULTS: In 2238 individuals who had used antidepressants and had a work-related injury during a mean follow-up of 7.8 years, no increase in the risk of injury was observed in the beginning of antidepressant treatment. However, an increased injury risk was seen after 3 months of treatment (rate ratio, compared with no recent antidepressant use, 1.27, 95% confidence interval 1.10-1.48). This was also the case among those who had used only selective serotonin reuptake inhibitors (n = 714; rate ratio 1.41, 95% confidence interval 1.08-1.83). CONCLUSIONS: Antidepressant use was not associated with an increased risk of work-related injury at the beginning of treatment. Post-hoc analyses of antidepressant trials are needed to determine whether long-term use of antidepressants increases the risk of work-related injury.

Impact of age, performance and athletic event on injury rates in master athletics - first results from an ongoing prospective study.

OBJECTIVES: Recent studies have identified rates of injuries in young elite athletes during major athletic events. However, no such data exist on master athletes. The aim of this study was to assess incidence and types of injuries during the 2012 European Veteran Athletics Championships as a function of age, performance and athletic discipline. METHODS: Report forms were used to identify injured athletes and injury types. Analysis included age (grouped in five-year bands beginning at age 35 years), athletic event, and age-graded performance. RESULTS: Of the 3154 athletes (53.2 years (SD 12.3)) that participated in the championships (1004 (31.8%) women, 2150 (68.2%) men), 76 were registered as injured; 2.8% of the female (29), 2.2% of the male (47) athletes. There were no fractures. One injury required operative treatment (Achilles tendon rupture). Injury rates were significantly higher in the sprint/middle distance/jumps than the throws, long distance and decathlon/heptathlon groups (X(2) (3)=16.187, P=0.001). There was no significant interrelationship with age (X(2) (12)=6.495, P=0.889) or age-graded performance (X(2) (3)=3.563, P=0.313). CONCLUSIONS: The results suggest that healthy master athletes have a low risk of injury that does not increase with age or performance.

Towards a global system of vigilance and surveillance in unrelated donors of haematopoietic progenitor cells for transplantation.

Safety of living donors is critical to the success of blood, tissue and organ transplantation. Structured and robust vigilance and surveillance systems exist as part of some national entities, but historically no global systems are in place to ensure conformity, harmonisation and the recognition of rare adverse events (AEs). The World Health Assembly has recently resolved to require AE/reaction (AE/R) reporting both nationally and globally. The World Marrow Donor Association (WMDA) is an international organisation promoting the safety of unrelated donors and progenitor cell products for use in haematopoietic progenitor cell (HPC) transplantation. To address this issue, we established a system for collecting, collating, analysing, distributing and reacting to serious adverse events and reactions (SAE/R) in unrelated HPC donors. The WMDA successfully instituted this reporting system with 203 SAE/R reported in 2011. The committee generated two rapid reports, reacting to specific SAE/R, resulting in practice changing policies. The system has a robust governance structure, formal feedback to the WMDA membership and transparent information flows to other agencies, specialist physicians and transplant programs and the general public.

Diffusion capacity of the lung in young and old endurance athletes.

Lung diffusion capacity (D LCO) declines with age. A significant proportion of older endurance athletes develop exercise-induced hypoxemia (SaO2<95%). We hypothesised that master endurance athletes have a lower D LCO than age-matched non-athletes. We recruited 33 control (16 young; 17 old) and 29 male endurance athletes (13 young; 16 old) during the World Masters Athletics Indoor Championships, 2012 (Jyväskylä, Finland). To measure D LCO the participant exhaled to residual volume and then quickly inhaled to ≥ 90% total lung capacity from a gas source with 0.3% carbon monoxide. The D LCO and transfer coefficient (K CO) were corrected for the actual haemoglobin concentration. Spirometric function was similar in athletes and age-matched controls. D LCO and K CO were 33% and 25% lower in old and young controls, respectively (P<0.001). Although predicted D LCO and K CO were 11%-points higher in athletes than age-matched controls (P<0.001), they were 23% and 16% lower in old athletes than young controls, respectively (P<0.001). D LCO did not correlate with age-graded performance or weekly training hours. The better lung diffusion capacity in male endurance athletes than age-matched controls might be an adaptation to training, self-selection and/or attrition bias. However, the diffusion capacity of the older athlete is lower than that of the young non-athlete.

Collection, processing and testing of bone, corneas, umbilical cord blood and haematopoietic stem cells by European Blood Alliance members.

BACKGROUND AND OBJECTIVES: A questionnaire study was carried out in collaboration with the European Blood Alliance (EBA) Tissues and Cells (T&C) working group. The aim was to assess the level of involvement and commonality of processes on the procurement, testing and storage of bone, corneas, umbilical cord blood (UCB) and haematopoietic stem cells (HSC) in order to identify different practices and to explore whether recommendations can be made for harmonization. MATERIALS AND METHODS: An online questionnaire was used for data collection in 2011, and 43 replies were received covering 71 product answers from 13 countries. RESULTS AND CONCLUSIONS: Estimated percentages of tissue and cell banking covered by EBA member blood banks as a proportion of all collections of each individual country varied markedly. There were also major differences in the amounts of products collected and discarded and in proportions tissues provided for grafting. However, discarding of certain collections also reflects the practice of increasing the likelihood of the very best units being used for transplantation. Harmonization of possible practices should focus on matching supply with demand and on identifying the most efficient operators. This could allow for the development of practices for minimizing unnecessary collections.

The Nordic prescription databases as a resource for pharmacoepidemiological research--a literature review.

PURPOSE: All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases. METHODS: The study consists of a Medline-based structured literature review of scientific papers published during 2005-2010 using data from the prescription databases in Denmark, Finland, Iceland, Norway, and Sweden, covering 25 million inhabitants. Relevant studies were analyzed in terms of pharmacological group, study population, outcomes examined, type of study (drug utilization vs. effect of drug therapy), country of origin, and extent of cross-national collaboration. RESULTS: A total of 515 studies were identified. Of these, 262 were conducted in Denmark, 97 in Finland, 4 in Iceland, 87 in Norway, and 61 in Sweden. Four studies used data from more than one Nordic country. The most commonly studied drugs were those acting on the nervous system, followed by cardiovascular drugs and gastrointestinal/endocrine drugs. A total of 228 studies examined drug utilization and 263 focused on the effects and safety of drug therapy. Pregnant women were the most commonly studied population in safety studies, whereas prescribers' adherence to guidelines was the most frequent topic of drug utilization studies. CONCLUSIONS: The Nordic prescription databases, with their possibility of record-linkage, represent an outstanding resource for assessing the beneficial and adverse effects of drug use in large populations, under routine care conditions, and with the potential for long-term follow-up.

Assessing the impact of dabigatran and warfarin on health-related quality of life: results from an RE-LY sub-study.

BACKGROUND: Anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent strokes. Vitamin K antagonists, such as warfarin, are associated with numerous practical limitations--frequent anticoagulation monitoring, lifestyle and dietary restrictions--that complicate patient management and may impact health-related quality of life (HRQoL). This study derived HRQoL estimates for AF patients receiving warfarin or dabigatran etexilate (dabigatran), a new oral anticoagulant not requiring anticoagulation monitoring, during one year of stable treatment, i.e. in the absence of outcome events, such as strokes or major bleedings. METHODS: Changes in HRQoL over time and between treatments were assessed using the EQ-5D (utility and Visual Analogue Scale (VAS) scores) at baseline, 3 and 12 months in a sub-group of 1435 patients participating in the RE-LY trial. RE-LY was a phase III study that compared the safety and efficacy of warfarin, dabigatran 150 mg bid and dabigatran 110 mg bid for stroke prevention in patients with AF. RESULTS: Utilities ranged from 0.805 (dabigatran 150 mg bid) to 0.811 (dabigatran 110 mg bid) at baseline, and did not change over the one year observation period. No differences between the dabigatran groups and warfarin were statistically significant except for the dabigatran 150 mg bid group at 3 months. Similarly, none of the within-group or between-group differences in VAS scores were statistically significant. CONCLUSIONS: Over the course of one year, all anticoagulated patients without outcome events (e.g. strokes or major bleedings) had stable HRQoL. Scores between dabigatran and warfarin were comparable, which was unexpected given the known complexities of warfarin treatment.

Predictors of failure of endovascular revascularization for critical limb ischemia.

BACKGROUND AND AIMS: To characterize predictors of failure when treating critical limb ischemia (CLI) patients with an endovascular intervention as the first-line strategy. PATIENTS AND METHODS: This retrospective, registry-based study included 217 consecutive patients with 240 chronic critically ischemic limbs treated with infrainguinal percutaneous trans-luminal angioplasty (PTA) during 2006-2007 at Helsinki University Central Hospital, Finland. The primary outcome measures were death, major (above-ankle) amputation, and the need for surgical re-intervention within 6 months after the primary procedure. The secondary out-come measures were overall major amputation and survival rates as well as the overall need for surgical or any other (surgical or endovascular) type of re-intervention. Predictors of outcome endpoints were identified with a univariate screen, and a Cox regression model was used in the multivariate analysis. RESULTS: Compared to ulcer, gangrene was significantly more strongly associated with amputation within 6 months post-procedurally as well as during the whole follow-up period (p ≤ 0.028). The patient's inability to walk upon hospital arrival was a significant predictor of death, amputation and surgical re-intervention. Mediasclerotic ankle-brachial index (ABI) was an independent predictor of amputation as well as endovascular re-interventions. CONCLUSIONS: The strong predictors of poor outcome after endovascular revascularization for patients with CLI are cardiac morbidity, the inability to ambulate upon hospital arrival, and gangrene as a manifestation of CLI. The risk of amputation seems to be significantly higher for gangrene than for ulcer and this matter should be taken into account in the clinical classifications for CLI.