Fat and fat-free mass of healthy Swedish children show tracking during early life, but there are differences.

AIM: Obesity may start early in life. We investigated relationships between size and body composition variables in infancy and at 4 years of age using valid estimates of body composition. The results were compared to those obtained when body mass index (BMI) was used to estimate body fatness at 4 years. METHODS: Using air displacement plethysmography, size, fat mass and fat-free mass were studied, between 2007 and 2015, in 253 full-term healthy Swedish children at 1 week, 12 weeks and 4 years of age. RESULTS: Positive associations between variables in infancy and at 4 years were found at 1 and 12 weeks for weight, height, BMI, fat-free mass and fat-free mass index (p ≤ 0.002) and for fat mass, per cent body fat and fat mass index (p ≤ 0.04) at 12 weeks. Fat mass gained during infancy correlated positively (p ≤ 0.031) with per cent fat mass, fat mass index and BMI, all at 4 years. In girls, gains in fat-free mass during infancy correlated with BMI (p = 0.0005) at 4 years. CONCLUSION: The results provide information regarding body composition trajectories during early life and demonstrate limitations of BMI as a proxy for body fatness when relating early weight gain to variables, relevant for later obesity risk.

Myocardial infarction and death findings from a 22-year follow-up of a cohort of 980 employed Swedish men.

OBJECTIVES: In this article, we present death and myocardial infarction (MI) incidences over 22 years in relation to possible risk factors and their explanatory value. STUDY DESIGN: In 1993, 980 middle-aged Swedish men in an automotive industry were surveyed at a health checkup as part of the Renault-Volvo Coeur project. The Swedish cohort was revisited in 2015. METHODS: In 2015, incident MIs were identified using postal questionnaires, hospital records, and the Swedish national MI and death registers. The statistical results were given as odds ratios (ORs) and pseudo-R2 (PR2), showing the proportion of variation in risk explained by logistic models. RESULTS: One hundred and four deaths (4.6 per 1000 person-years) and 89 first MIs (4.2 per 1000 person-years) were identified. The Framingham risk index showed the strongest association with MI (OR = 23; 95% confidence interval [CI] = 5.42, 96.9), comparing the fifth quintile with the first. The all-cause death showed an OR of 3.2 (95% CI = 1.65, 6.08), with a suggested U-shape over quintiles. The percentages of PR2 for MI and death were 8.8% and 6.6%, respectively. All risk factors together explained 22% of the variation in risk of MI. Comparing mortality in men living alone with those married yielded an OR of 3.78, which was found to be statistically significant. The corresponding OR for MI was not significant. CONCLUSIONS: Traditional risk factors were confirmed but explained a modest proportion of the risk variation.

Density-dependent positive feedbacks buffer aquatic plants from interactive effects of eutrophication and predator loss.

Self-facilitation allows populations to persist under disturbance by ameliorating experienced stress. In coastal ecosystems, eutrophication and declines of large predatory fish are two common disturbances that can synergistically impact habitat-forming plants by benefitting ephemeral algae. In theory, density-dependent intraspecific plant facilitation could weaken such effects by ameliorating the amount of experienced stress. Here, we tested whether and how shoot density of a common aquatic plant (Myriophyllum spicatum) alters the response of individual plants to eutrophication and exclusion of large predatory fish, using a 12-week cage experiment in the field. Results showed that high plant density benefitted individual plant performance, but only when the two stressors were combined. Epiphytic algal biomass per plant more than doubled in cages that excluded large predatory fish, indicative of a trophic cascade. Moreover, in this treatment, individual shoot biomass, as well as number of branches, increased with density when nutrients were added, but decreased with density at ambient nutrient levels. In contrast, in open cages that large predatory fish could access, epiphytic algal biomass was low and individual plant biomass and number of branches were unaffected by plant density and eutrophication. Plant performance generally decreased under fertilization, suggesting stressful conditions. Together, these results suggest that intraspecific plant facilitation occurred only when large fish exclusion (causing high epiphyte load) was accompanied by fertilization, and that intraspecific competition instead prevailed when no nutrients were added. As coastal ecosystems are increasingly exposed to multiple and often interacting stressors such as eutrophication and declines of large predatory fish, maintaining high plant density is important for ecosystem-based management.

Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40% in primary care- and hospital care-based outpatient clinics.

OBJECTIVE: The aim of this study is to describe patients with heart failure and an ejection fraction (EF) of more than or equal to 40%, managed in both Primary- and Hospital based outpatient clinics separately with their prognosis, comorbidities and risk factors. Further to compare the heart failure medication in the two groups. DESIGN: We used the prospective Swedish Heart Failure Registry to include 9654 out-patients who had HF and EF ≥40%, 1802 patients were registered in primary care and 7852 in hospital care. Descriptive statistical tests were used to analyze base line characteristics in the two groups and multivariate logistic regression analysis to assess mortality rate in the groups separately. SETTING: The prospective Swedish Heart Failure Registry. SUBJECTS: Patients with heart failure and an ejection fraction (EF) of more than or equal to 40%. MAIN OUTCOME MEASURES: Comorbidities, risk factors and mortality. RESULTS: Mean-age was 77.5 (primary care) and 70.3 years (hospital care) p < 0.0001, 46.7 vs. 36.3% women respectively (p < 0.0001) and EF ≥50% 26.1 vs. 13.4% (p < 0.0001). Co-morbidities were common in both groups (97.2% vs. 92.3%), the primary care group having more atrial fibrillation, hypertension, ischemic heart disease and COPD. According to the multivariate logistic regression analysis smoking, COPD and diabetes were the most important independent risk factors in the primary care group and valvular disease in the hospital care group. All-cause mortality during mean follow-up of almost 4 years was 31.5% in primary care and 27.8% in hospital care. One year-mortality rates were 7.8%, and 7.0% respectively. CONCLUSION: Any co-morbidity was noted in 97% of the HF-patients with an EF of more than or equal to 40% managed at primary care based out-patient clinics and these patients had partly other independent risk factors than those patients managed in hospital care based outpatients clinics. Our results indicate that more attention should be payed to manage COPD in the primary care group. KEY POINTS 97% of heart failure patients with an ejection fraction of more than or equal to 40% managed at primary care based out-patient clinics had any comorbidity. Patients in primary care had partly other independent risk factors than those in hospital care. All-cause mortality during mean follow-up of almost 4 years was higher in primary care compared to hospital care. In matched HF-patients RAS-antagonists, beta-blockers as well as the combination of the two drugs were more seldom prescribed when managed in primary care compared with hospital care.

A cross-scale trophic cascade from large predatory fish to algae in coastal ecosystems.

Trophic cascades occur in many ecosystems, but the factors regulating them are still elusive. We suggest that an overlooked factor is that trophic interactions (TIs) are often scale-dependent and possibly interact across spatial scales. To explore the role of spatial scale for trophic cascades, and particularly the occurrence of cross-scale interactions (CSIs), we collected and analysed food-web data from 139 stations across 32 bays in the Baltic Sea. We found evidence of a four-level trophic cascade linking TIs across two spatial scales: at bay scale, piscivores (perch and pike) controlled mesopredators (three-spined stickleback), which in turn negatively affected epifaunal grazers. At station scale (within bays), grazers on average suppressed epiphytic algae, and indirectly benefitted habitat-forming vegetation. Moreover, the direction and strength of the grazer-algae relationship at station scale depended on the piscivore biomass at bay scale, indicating a cross-scale interaction effect, potentially caused by a shift in grazer assemblage composition. In summary, the trophic cascade from piscivores to algae appears to involve TIs that occur at, but also interact across, different spatial scales. Considering scale-dependence in general, and CSIs in particular, could therefore enhance our understanding of trophic cascades.

Recovery of calf muscle endurance 3 months after an Achilles tendon rupture.

The purpose of this study was to evaluate calf muscle endurance in a seated position 3 months after an Achilles tendon rupture and to evaluate how the ability to perform standardized seated heel-rises correlated to the single-leg standing heel-rise test and to patient-reported symptoms evaluated with the Achilles tendon Total Rupture Score (ATRS) 3 and 6 months after the injury. Ninety-three patients were included from a cohort of 101 patients participating in a prospective, randomized controlled trial comparing surgical and nonsurgical treatment after Achilles tendon rupture. Forty-seven patients were treated surgically and 46 nonsurgically. Ninety-one patients out of 93 (98%) could perform the standardized seated heel-rises. At the 3-month follow-up, there was a significant difference (P < 0.001) between the injured and the healthy side performing standardized seated heel-rises. There were also significant correlations (r = 0.29-0.37, P = < 0.05) between the standardized seated heel-rises and ATRS 3 and 6 months after injury in the group who could not perform single-leg standing heel-rises. There were no significant differences between the surgical and nonsurgical treatment groups. The evaluation of standardized seated heel-rises appears to be a useful tool to quantify progress and predict future functional performance and patient-reported symptoms.

Increased mortality rate and suicide in Swedish former elite male athletes in power sports.

Physical training has been shown to reduce mortality in normal subjects, and athletes have a healthier lifestyle after their active career as compared with normal subjects. Since the 1950s, the use of anabolic androgenic steroids (AAS) has been frequent, especially in power sports. The aim of the present study was to investigate mortality, including causes of death, in former Swedish male elite athletes, active 1960-1979, in wrestling, powerlifting, Olympic lifting, and the throwing events in track and field when the suspicion of former AAS use was high. Results indicate that, during the age period of 20-50 years, there was an excess mortality of around 45%. However, when analyzing the total study period, the mortality was not increased. Mortality from suicide was increased 2-4 times among the former athletes during the period of 30-50 years of age compared with the general population of men. Mortality rate from malignancy was lower among the athletes. As the use of AAS was marked between 1960 and 1979 and was not doping-listed until 1975, it seems probable that the effect of AAS use might play a part in the observed increased mortality and suicide rate. The otherwise healthy lifestyle among the athletes might explain the low malignancy rates.

Ability to perform a single heel-rise is significantly related to patient-reported outcome after Achilles tendon rupture.

This study evaluated the short-term recovery of function after an acute Achilles tendon rupture, measured by a single-legged heel-rise test, with main emphasis on the relation to the patient-reported outcomes and fear of physical activity and movement (kinesiophobia). Eighty-one patients treated surgically or non-surgically with early active rehabilitation after Achilles tendon rupture were included in the study. Patient's ability to perform a single-legged heel-rise, physical activity level, patient-reported symptoms, general health, and kinesiophobia was evaluated 12 weeks after the injury. The heel-rise test showed that 40 out of 81 (49%) patients were unable to perform a single heel-rise 12 weeks after the injury. We found that patients who were able to perform a heel-rise were significantly younger, more often of male gender, reported a lesser degree of symptoms, and also had a higher degree of physical activity at 12 weeks. There was also a significant negative correlation between kinesiophobia and all the patient-reported outcomes and the physical activity level. The heel-rise ability appears to be an important early achievement and reflects the general level of healing, which influences patient-reported outcome and physical activity. Future treatment protocols focusing on regaining strength early after the injury therefore seem to be of great importance. Kinesiophobia needs to be addressed early during the rehabilitation process.

Cytomegalovirus-specific CD4 and CD8 T cell responses in infants and children.

Congenital cytomegalovirus (CMV) infection is the most common congenital infection causing childhood morbidity. The pathogenetic mechanisms behind long-term sequelae are unclear, but long-standing viremia as a consequence of the inability to convert the virus to a latent state has been suggested to be involved. Whereas primary CMV infection in adults is typically rapidly controlled by the immune system, children have been shown to excrete virus for years. Here, we compare T cell responses in children with congenital CMV infection, children with postnatal CMV infection and adults with symptomatic primary CMV infection. The study groups included 24 children with congenital CMV infection, 19 children with postnatal CMV infection and eight adults with primary CMV infection. Among the infants with congenital CMV infection, 13 were symptomatic. T cell responses were determined by analysis of interferon gamma production after stimulation with CMV antigen. Our results show that whereas adults display high CMV-specific CD4 T cell responses in the initial phase of the infection, children younger than 2 years have low or undetectable responses that appear to increase with time. There were no differences between groups with regard to CD8 T cell function. In conclusion, inadequate CD 4 T cell function seems to be involved in the failure to get immune control of the CMV infection in children younger than 2 years of age with congenital as well as postnatal CMV infection.

A retrospective 30-year follow-up study of former Swedish-elite male athletes in power sports with a past anabolic androgenic steroids use: a focus on mental health.

BACKGROUND: The knowledge concerning the long-term effect of former anabolic androgenic steroids (AAS)-use on mental health is sparse. AIM: This study aims to investigate whether previous AAS-use affects mental health, present sociodemographic data, sport activity and substance abuse in a retrospective 30-year follow-up study of former elite athletes. METHODS: Swedish male-elite power sport athletes (n=683) on the top 10 national ranking lists during any of the years 1960-1979 in wrestling, Olympic lifting, powerlifting and the throwing events in track and field answered a questionnaire. RESULTS: At least 20% of the former athletes admitted previous AAS-use. They had more often sought professional expertise for mental problems and had used illicit drugs compared to those not having used AAS. The AAS-users also differed in former sport activity pattern compared to non AAS-users. CONCLUSIONS: It is clear that a relationship exists between use of AAS and mental-health problems. Further studies need to be done in order to clarify this relationship.

Comment on "The lower Cambrian lobopodian Cardiodictyon resolves the origin of euarthropod brains".

Strausfeld et al. (Report, 24 Nov 2022, p. 905) claim that Cambrian fossilized nervous tissue supports the interpretation that the ancestral panarthropod brain was tripartite and unsegmented. We argue that this conclusion is unsupported, and developmental data from living onychophorans contradict it.

New method for time alignment and time calibration of the TOFOR time-of-flight neutron spectrometer at JET.

The TOFOR time-of-flight (TOF) neutron spectrometer at the Joint European Torus (JET) is composed of 5 start (S1) and 32 stop (S2) scintillation detectors. Recently, the data acquisition system (DAQ) of TOFOR was upgraded to equip each of the 37 detectors with its own waveform digitizer to allow for correlated time and pulse height analysis of the acquired data. Due to varying cable lengths and different pulse processing pathways in the new DAQ system, the 160 (5 · 32) different TOF pairs of start-stop detectors must be time-aligned to enable the proper construction of a summed TOF spectrum. Given the time (energy) resolution required by the entire spectrometer system to measure different plasma neutron emission components, it is of importance to align the detector pairs to each other with sub-nanosecond precision. Previously, the alignment partially depended on using fusion neutron data from Ohmic heating phases of JET experimental pulses. The dependence on fusion neutron data in the time alignment process is, however, unsatisfactory as it involves data one would wish to include in an independent analysis for physics results. In this work, we describe a method of time-aligning the detector pairs by using gamma rays. Given the known geometry and response of TOFOR to gamma rays, the time alignment of the detector pairs is found by examining gamma events interacting in coincidence in both S1-S1 and S1-S2 detector combinations. Furthermore, a technique for separating neutron and gamma events in the different detector sets is presented. Finally, the time-aligned system is used to analyze neutron data from Ohmic phases for different plasma conditions and to estimate the Ohmic fuel ion temperature.

Interleukin-4 receptor polymorphisms in asthma and allergy: relation to different disease phenotypes.

AIM: Inheritance and genetic factors are supposed to influence susceptibility to asthma and allergy. We tested if single nucleotide polymorphisms (SNPs) in the IL4R gene were associated with susceptibility to such diseases, or if they were related to the phenotypic presentation of asthma and allergic rhinoconjunctivitis (ARC). METHODS: Three hundred and nine 12- to 13-year-old children were included. Six SNPs in the IL4R were analysed in response to current allergic disease, and to presentation of specific asthma and ARC phenotypes. Questionnaires were used to determine allergic disease status, and skin prick tests to evaluate sensitization to common airborne allergens. RESULTS: Less eczema was seen in individuals with the AA-genotype of rs2057768, and less ARC among those with the AA-genotype of rs2107356, especially ARC associated with sensitization to pollen. The AA-genotype of rs2057768 and the TT genotype of rs3024632 were associated with a specific asthma phenotype. CONCLUSION: Variations within the IL4R gene are associated with allergic diseases in children, preferably with eczema and disease phenotypes of ARC and asthma.

Trisodium phosphonoformate, a new antiviral compound.

Trisodium phosphonoformate selectively inhibits cell-free DNA polymerase activity induced by herpesvirus. The new inhibitor has an antiviral effect on herpes simplex virus types 1 and 2, pseudorables virus, and infectious bovine rhinotracheitis virus in cell culture. It has a good therapeutic activity against cutaneous herpes simplex virus infection in guinea pigs.

Safety assessment of new antithrombotic agents: lessons from the EXTEND study on ximelagatran.

BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.

Patients with hyperhidrosis have changed grip force, coefficient of friction and safety margin.

OBJECTIVE: To evaluate whether subjects with palmar hyperhidrosis have functional problems with the handgrip caused by the wet slippery surface of palm and fingertips. We used two different dosages of botulinum toxin to explore its impact on sweating and on muscle strength in the hand. METHOD: Using an object equipped with force sensors we measured the muscle strength and calculated the coefficients of friction and safety margin (SM) in the precision grip before and 2, 4, 6, 8 10-12 weeks and 6 months after treatment of 13 patients with two different doses of botulinum toxin. Sweat evaporation was measured simultaneously. RESULTS: A significant decrease in evaporation and a parallel reduction of grip force in the dominant hand of the patients were observed. The SM used by the patients was significantly lower after the treatment, and increased gradually when sweating reappeared. CONCLUSION: These measurements showed, for the first time, that hyperhidrosis of the palms may cause an objective perturbation of the hand function which may be partially corrected by botulinum toxin treatment.

Field fertility of frozen-thawed boar sperm at low doses using non-surgical, deep uterine insemination.

The lowest dose of frozen-thawed boar sperm used for deep uterine artificial insemination (DUI) of sows has been 100x10(6). A three stage field study was performed to establish to what level the dose of frozen-thawed sperm used for DUI could be reduced without adversely affecting the fertility of the sow. In stage 1, 15 sows were inseminated twice with 1000x10(6) fresh or frozen-thawed sperm at 24 and 36 h post-detection of oestrus. In stage 2, 262 sows were inseminated with 62.5, 250 or 1000x10(6) fresh or frozen-thawed sperm at 24, 36, or 24 and 36 h after detection of oestrus. Stage 3 involved post mortem investigation of the uterine lining to assess damage caused by insertion of the insemination catheter. All sows inseminated in stage 1 of the study farrowed. In stage 2, the non-return (NRR) and farrowing rates of each group were compared to a control double cervical insemination of 3250x10(6) fresh sperm. As few as 62.5x10(6) fresh sperm could be deposited at a single insemination without reduction in NRR or farrowing rates compared with the control group. A double DUI with 250x10(6) frozen-thawed sperm was required before fertility was equivalent to the controls. Investigation of the uterine lining after insertion of the DUI catheter revealed evidence of bleeding, warranting further investigation of the viability of widespread use of the Firflex catheter, despite the promising fertility achieved here with low doses of spermatozoa.

Major joint replacement. A model for antithrombotic drug development: from proof-of-concept to clinical use.

AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations.

Early posthypoglycemic insulin resistance in man is mainly an effect of beta-adrenergic stimulation.

The insulin effect following hypoglycemia was studied with the euglycemic clamp technique in seven healthy subjects. Following an initial euglycemic clamp hypoglycemia was induced and after glucose recovery a second clamp was performed. Glucose production (Ra) and utilization (Rd) were studied with [3-3H]glucose. Each subject was studied four times; during infusion of placebo, propranolol, somatostatin, and a control study where hypoglycemia was prevented. Hypoglycemia induced an insulin resistance with a lower steady state glucose infusion rate following the hypoglycemia during placebo as compared to the control study (2.5 +/- 0.5 and 4.8 +/- 1.0 mg/kg min, respectively, P less than 0.05). The insulin resistance was due to an attenuated insulin effect on both inhibition of Ra (impaired by 37%) and stimulation of Rd (impaired by 61%). The insulin-antagonistic effect was completely prevented by propranolol but only partly by somatostatin. Thus, early posthypoglycemic insulin resistance (2.5-3.5 h after hypoglycemia) is a sustained effect mainly due to beta-adrenergic stimulation.