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# Background Resistance training with the barbell back squat (BBS) exercise is practiced in sports, recreation, and rehabilitation. Although extensively debated, it is commonly believed and recommended that maintaining a neutral lumbopelvic alignment during BBS is an important technical aspect that might reduce the risk of injury. There is limited knowledge of how objectively measurable factors affect the extent to which the lumbopelvic region moves into flexion during a BBS. # Purpose The aim of the study was to investigate the association among anthropometric measurements, range of motion in the hips and ankle joints, lumbopelvic movement control tests, and flexion of the lumbopelvic region during execution of the BBS. # Study design Observational, cross sectional. # Methods Eighteen experienced powerlifters and Olympic weightlifters were included and measurements of lumbopelvic movements were collected with inertial measurement units during BBS performed at 70 % of 1RM. Examination of anthropometric properties, range of motion in the hip and ankle joints, and lumbopelvic movement control tests were collected as independent variables. Linear regression analysis was used to investigate which independent variables were associated with lumbopelvic flexion during a BBS. # Results The linear regression showed that a higher range of motion in ankle dorsiflexion could statistically significantly explain an increased amplitude of lumbopelvic flexion during the BBS. Anthropometrics, range of motion of the hips, and performance in lumbopelvic movement control tests did not show any statistically significant associations. # Conclusions The results suggest that strength and conditioning professionals and clinicians who instruct and assess lifting technique in the BBS and/or use the BBS to assess performance or as an intervention should recognize that a higher range of motion in the ankle joints might affect lumbopelvic flexion during the BBS. In practice, the value of an individual assessment of lifting technique focusing on the goal of the movement should be emphasized. # Level of Evidence 3

Lipoprotein(a) [Lp(a)] contributes to cardiovascular disease risk. A genetically determined size polymorphism in apolipoprotein(a) [apo(a)], determined by the number of Kringle (K) repeats, inversely regulates Lp(a) levels. Nongenetic factors including dietary saturated fat influence Lp(a) levels. However, less is known about the effects of carbohydrates including dietary sugars. In this double-blind, parallel arm study among 32 overweight/obese adults, we investigated the effect of consuming glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks on Lp(a) level and assessed the role of the apo(a) size polymorphism. The mean (±SD) age of participants was 54 ± 8 years, 50% were women, and 75% were of European descent. Following the 10-week intervention, Lp(a) level was reduced by an average (±SEM) of −13.2% ± 4.3% in all participants (P = 0.005); −15.3% ± 7.8% in the 15 participants who consumed glucose (P = 0.07); and −11.3% ± 4.5% in the 17 participants who consumed fructose (P = 0.02), without any significant difference in the effect between the two sugar groups. Relative changes in Lp(a) levels were similar across subgroups of lower versus higher baseline Lp(a) level or carrier versus noncarrier of an atherogenic small (≤22K) apo(a) size. In contrast, LDL-C increased. In conclusion, in older, overweight/obese adults, consuming sugar-sweetened beverages reduced Lp(a) levels by ∼13% independently of apo(a) size variability and the type of sugar consumed. The Lp(a) response was opposite to that of LDL-C and triglyceride concentrations. These findings suggest that metabolic pathways might impact Lp(a) levels.

Abstract Background While assessment tools can increase the detection of cognitive impairment, there is currently insufficient evidence regarding clinical outcomes based on screening for cognitive impairment in older adults. Methods The study purpose was to investigate whether Timed Up and Go dual-task test (TUGdt) results, based on TUG combined with two different verbal tasks (name different animals, TUGdt-NA, and recite months in reverse order, TUGdt-MB), predicted dementia incidence over a period of five years among patients (N = 186, mean = 70.7 years; 45.7% female) diagnosed with Subjective Cognitive Impairment (SCI) and Mild Cognitive Impairment (MCI) following assessment at two memory clinics. Associations between TUG parameters and dementia incidence were examined in Cox regression models. Results During follow-up time (median (range) 3.7 (0.1–6.1) years) 98 participants converted to dementia. Novel findings indicated that the TUGdt parameter words/time, after adjustment for age, gender, and education, can be used for the prediction of conversion to dementia in participants with SCI or MCI over a period of five years. Among the TUG-related parameters investigated, words/time showed the best predictive capacity, while time scores of TUG and TUGdt as well as TUGdt cost did not produce significant predictive results. Results further showed that the step parameter step length during TUGdt predicts conversion to dementia before adjustment for age, gender, and education. Optimal TUGdt cutoffs for predicting dementia at 2- and 4-year follow-up based on words/time were calculated. The sensitivity of the TUGdt cutoffs was high at 2-year follow-up: TUGdt-NA words/time, 0.79; TUGdt-MB words/time, 0.71; reducing respectively to 0.64 and 0.65 at 4-year follow-up. Conclusions TUGdt words/time parameters have potential as cost-efficient tools for conversion-to-dementia risk assessment, useful for research and clinical purposes. These parameters may be able to bridge the gap of insufficient evidence for such clinical outcomes. Trial registration ClinicalTrials.gov Identifier: NCT05893524: https://www.clinicaltrials.gov/study/NCT05893524?id=NCT05893524&rank=1 .

Background: Stress-related biomarkers have the potential to provide objective measures of whether interventions directed at people with dementia (PWD) and their family caregivers (FCG) are successful. The use of such biomarkers has been limited by logistical barriers to sample collection. Objective: Explore saliva concentration of steroid hormones in dementia care dyads during a music intervention. Methods: Consecutive PWD attending a memory evaluation center and their FCG were allocated to either an intervention-with-music or a non-intervention control group. All were living at home. Stress biomarkers, salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) samples were collected by the PWD and their FCG, in the morning and evening, 5 days a week, for 8 consecutive weeks. Biomarker concentrations of the intervention and the control groups were compared at week 8, in an intention-to-treat approach with adjustment for baseline value. Results: Twenty-four PWD in the intervention group and 10 in the control group, and their FCG were included in the analyses. The mean number of morning saliva collections was similar in the intervention and the control groups, ranging from 4.3 to 4.9 per participant weekly during the first 7 weeks, declining to 3.3 during week 8. Median log morning cortisol (pg/mL) among caregivers was lower in the intervention group than in the control group (8.09 vs. 8.57, P = 0.0133). Conclusion: This study demonstrates that music intervention was associated with lower morning saliva cortisol concentrations for FCGs.

Background Pain increases the risk for cardiovascular diseases, including myocardial infarction (MI). However, the impact of pain on mortality after MI has not yet been investigated in large studies with long‐term follow‐up periods. Thus, we aimed to examine various levels of pain severity 1 year after an MI as a potential risk for all‐cause mortality. Methods and Results We collected data from 18 376 patients, aged

Reducing dietary saturated fatty acids (SFA) intake results in a clinically significant lowering of low-density lipoprotein cholesterol (LDL-C) across ethnicities. In contrast, dietary SFA’s role in modulating emerging cardiovascular risk factors in different ethnicities remains poorly understood. Elevated levels of lipoprotein(a) [Lp(a)], an independent cardiovascular risk factor, disproportionally affect individuals of African descent. Here, we assessed the responses in Lp(a) levels to dietary SFA reduction in 166 African Americans enrolled in GET-READI (The Gene-Environment Trial on Response in African Americans to Dietary Intervention), a randomized controlled feeding trial. Participants were fed two diets in random order for 5 weeks each: 1) an average American diet (AAD) (37% total fat: 16% SFA), and 2) a diet similar to the Dietary Approaches to Stop Hypertension (DASH) diet (25% total fat: 6% SFA). The participants’ mean age was 35 years, 70% were women, the mean BMI was 28 kg/m2, and the mean LDL-C was 116 mg/dl. Compared to the AAD diet, LDL-C was reduced by the DASH-type diet (mean change: −12 mg/dl) as were total cholesterol (−16 mg/dl), HDL-C (−5 mg/dl), apoA-1 (−9 mg/dl) and apoB-100 (−5 mg/dl) (all P < 0.0001). In contrast, Lp(a) levels increased following the DASH-type diet compared with AAD (median: 58 vs. 44 mg/dl, P < 0.0001). In conclusion, in a large cohort of African Americans, reductions in SFA intake significantly increased Lp(a) levels while reducing LDL-C. Future studies are warranted to elucidate the mechanism(s) underlying the SFA reduction-induced increase in Lp(a) levels and its role in cardiovascular risk across populations.

Research on risk factors and injuries in powerlifting has so far only been studied through cross-sectional/observational studies. In other sports, training load has been prospectively investigated and shown to influence injury risk. However, no method to quantify training load in powerlifting exist. The purpose of this study was to assess the feasibility of a novel standardized method for prospective recording of training load and injuries. The study was conducted in two phases with eight powerlifters initially included in each phase respectively. In Phase 1, the powerlifters registered training load and injuries throughout four weeks and answered a feasibility questionnaire. Based on the results from the questionnaire, updates to the training and injury log were made and the powerlifters in Phase 2 used the updated version to log four weeks of training. Training load and injuries were reported consistently which made calculations on training load and injury incidence possible. The participants reported rate of perceived exertion as difficult to assess and report. However, 9/12 powerlifters stated that they could the training and injury log for a period of at least six months. In conclusion, this standardized training and injury log seems to be a feasible method to quantify training load and injuries in powerlifting. The method could be used in further prospective studies on training load and injuries in powerlifting and in clinical practice.

# Background Maintaining neutral spinal alignment is considered important when performing the barbell back squat exercise. Since male and female lifters may differ in injury location it is important to examine whether they differ in spinal alignment during the back squat. # Objectives The study aimed to quantify the spinal alignment in the upper and lower lumbar spine during the barbell back squat exercise in male and female lifters. Secondary aims were to compare alignment during the back squat to standing habitual lumbar spine alignment and determine whether male and female lifters differ in these aspects. # Study Design Observational, Cross-sectional. # Methods Competitive power- and weightlifters were recruited and performed three repetitions of the barbell back squat exercise using a load equivalent to 70% of their one-repetition maximum. Spinal alignment and range of motion were measured using inertial measurement units placed on the thoracic, lumbar and sacral spine. Data was presented descriptively and comparisons between men and women as well as spinal alignment in four different positions were done with a factorial repeated measures analysis of variance. # Results Twenty-three (14 males, 9 females) were included. During execution of the squat, spinal alignment adjustments in the lumbar spine were made in all three planes of movement, compared to the start position, in both male and female lifters. Compared to their standing habitual posture, all lifters adjusted their upper lumbar spine to a less lordotic position when in the start position of the back squat (standing upright with the barbell on their back). Only male lifters assumed a less lordotic alignment in their lower lumbar spine in the start position compared their habitual posture. # Conclusions Adjustments of spinal alignment, predominantly in the sagittal plane, are made during execution of the back squat in both male and female lifters. Further, lifters adopt a less lordotic alignment with a heavy barbell on their upper back, more so in male than female lifters. In conclusion, it seems that spinal alignment changes noticeably during the barbell back squat. # Level of Evidence 3

Owing to the hierarchical structure, easy multi-functionalization and favorable mechanical properties, wood could harvest electricity from mechanical energy through piezoelectric behavior. In this work, a scalable method to synthesize wood/ZnO composite with multilayered ZnO morphologies is reported for efficient mechanical energy conversion. The synthesis includes charged wood template fabrication, precursor infiltration, and ZnO hydrothermal growth, resulting in controlled ZnO morphologies and distributions while maintaining the hierarchical structure of the wood. Stereo-digital image correlation (stereo-DIC) investigated the relationship between deformation and piezoelectric performance, which revealed the homogeneous distribution of multilayered ZnO enhance piezoelectric performance. The output voltage of wood/ZnO was 1.5 V under periodic mechanical compression (8–10 N) for 300 cycles, while the output current was 2.91 nA. The scalable synthesis strategy and piezoelectric performance are significant for the design of advanced wood nanocomposites for sustainable and efficient energy conversion systems.

# Background A neutral spinal alignment is considered important during the execution of the deadlift exercise to decrease the risk of injury. Since male and female powerlifters experience pain in different parts of their backs, it is important to examine whether men and women differ in spinal alignment during the deadlift. # Objectives The purpose of this study was to quantify the spinal alignment in the upper (thoracolumbar, T11-L2) and lower (lumbopelvic, L2-S2) lumbar spine during the deadlift exercise in male and female lifters. Secondary aims were to compare lumbar spine alignment during the deadlift to standing habitual posture, and determine whether male and female lifters differ in these aspects. # Study Design Observational, Cross-sectional. # Methods Twenty-four (14 men, 10 women) lifters performed three repetitions of the deadlift exercise using 70% of their respective one-repetition maximum. Spinal alignment and spinal range of motion were measured using three inertial measurement units placed on the thoracic, lumbar and sacral spine. Data from three different positions were analyzed; habitual posture in standing, and start and stop positions of the deadlift, i.e. bottom and finish position respectively. # Results During the deadlift, spinal adjustments were evident in all three planes of movement. From standing habitual posture to the start position the lumbar lordosis decreased 13° in the upper and 20° in the lower lumbar spine. From start position to stop position the total range of motion in the sagittal plane was 11° in the upper and 22° in the lower lumbar spine. The decreased lumbar lordosis from standing habitual posture to the start position was significantly greater among men. # Conclusions Men and women adjust their spinal alignment in all three planes of movement when performing a deadlift and men seem to make greater adjustments from their standing habitual posture to start position in the sagittal plane. # Level of Evidence 3

Abstract Background Discrimination between early-stage dementia and other cognitive impairment diagnoses is central to enable appropriate interventions. Previous studies indicate that dual-task testing may be useful in such differentiation. The objective of this study was to investigate whether dual-task test outcomes discriminate between groups of individuals with dementia disorder, mild cognitive impairment, subjective cognitive impairment, and healthy controls. Methods A total of 464 individuals (mean age 71 years, 47% women) were included in the study, of which 298 were patients undergoing memory assessment and 166 were cognitively healthy controls. Patients were grouped according to the diagnosis received: dementia disorder, mild cognitive impairment, or subjective cognitive impairment. Data collection included participants’ demographic characteristics. The patients’ cognitive test results and diagnoses were collected from their medical records. Healthy controls underwent the same cognitive tests as the patients. The mobility test Timed Up-and-Go (TUG single-task) and two dual-task tests including TUG (TUGdt) were carried out: TUGdt naming animals and TUGdt months backwards. The outcomes registered were: time scores for TUG single-task and both TUGdt tests, TUGdt costs (relative time difference between TUG single-task and TUGdt), number of different animals named, number of months recited in correct order, number of animals per 10 s, and number of months per 10 s. Logistic regression models examined associations between TUG outcomes pairwise between groups. Results The TUGdt outcomes “animals/10 s” and “months/10 s” discriminated significantly (p

Transparent wood (TW), a biocomposite material demonstrating optical transparency in the visible range, has attracted much interest in recent years due to great potential for ecofriendly applications, for instance, in construction industry and functionalized organic materials. Optical properties of TW, including transparency and haze, depend on a particular structure of cellulose‐based backbone compound, (mis‐)matching of the refractive indices (RIs) between TW compounds, and the polymer matrix. Although there are data of cellulose RIs for various forms of cellulose (fibers, powder, hot‐pressed films, etc.), these values might differ from an effective RI of the TW substrate. Herein, a numerical model of light propagation in the TW, based on the real cellular structure in wood, is presented and applied to estimate an effective RI of the delignified wood reinforcement in the experimentally investigated TW material. Ray‐tracing and rigorous electromagnetic approaches are compared for modeling light propagation in the TW. Ray tracing demonstrates considerably simplified yet accurate and efficient solutions. The work brings substantial progress toward realistic and practical wood modeling for the purpose of applications, materials design, and fundamental studies.

Background Lp(a) (lipoprotein(a)) is the major lipoprotein carrier of oxidized phospholipids (OxPL) and this function mediates Lp(a) atherogenicity. However, the relationship between OxPL, Lp(a), and genetic and biological characteristics remains poorly understood. We assessed the relationship between Lp(a)‐bound OxPL, apolipoprotein(a) (apo(a)) size, age, and family structure in 2 racial groups. Methods and Results Healthy Black and White families were recruited from the general population (age: 6–74 years, n=267). OxPL and Lp(a) levels were assayed enzymatically; apo(a) isoform, LPA allele sizes, and allele‐specific Lp(a) levels were determined. Lp(a)‐OxPL levels did not differ significantly by racial and age groups. Lp(a)‐OxPL levels were associated with total plasma Lp(a) in all participants and in race‐specific analyses. Further, OxPL levels were significantly associated with allele‐specific Lp(a) levels carried by the smaller apo(a) size in all participants (β=0.33, P=0.0003) as well as separately for Black (β=0.50, P=0.0032) and White (β=0.26, P=0.0181) participants. A significant association of OxPL with allele‐specific Lp(a) levels for larger apo(a) sizes was seen only in Black participants (β=0.53, P=0.0076). In this group, Lp(a)‐OxPL levels were also heritable (h2=0.29, P=0.0235), resulting in a significant interracial difference in heritability between Black and White people (P=0.0352). Conclusions Lp(a)‐OxPL levels were associated with allele‐specific Lp(a) level carried on smaller apo(a) sizes and among Black participants also for larger apo(a) sizes. The heritability estimates for Lp(a)‐bound OxPL differed by race.

Heritability of LPA allele, apo(a) isoform sizes, and isoform-associated lipoprotein(a) [Lp(a)] levels was studied in 82 Caucasian and African-American families with two parents and two children (age: 6–74 years). We determined: 1) Lp(a) levels; 2) LPA allele sizes; 3) apo(a) isoform sizes; and 4) isoform-specific apo(a) levels (ISLs), the amount of Lp(a) carried by an individual apo(a) isoform. Trait heritability was estimated by mid-parent-offspring analysis. The ethnicity-adjusted heritability estimate for Lp(a) level was 0.95. Heritability for ISLs corresponding to the smaller LPA allele in a given allele-pair was higher than that corresponding to the larger LPA allele (0.91 vs. 0.59, P = 0.017). Although not statistically different, heritability for both apo(a) isoforms (0.90 vs. 0.70) and LPA alleles (0.98 vs. 0.82) was higher for the smaller versus larger sizes. Heritability was generally lower in African-Americans versus Caucasians with a 4-fold difference for the larger LPA allele (0.25 vs. 0.94, P = 0.001). In Caucasians, an overall higher heritability pattern was noted for the older (≥47 years) versus younger (

Aims: Weight loss is recommended for myocardial infarction (MI) patients with overweight or obesity. It has, however, been suggested that obese patients have better prognosis than normal-weight patients have, but also that central obesity is harmful. The aim of this study was to examine associations between repeated measures of body mass index (BMI) and waist circumference (WC), and all-cause mortality. Methods and results: A total of 14,224 MI patients aged

Olive stone is an important biomaterial waste product generated in large amount. As a lignocellulose material, olive stone could be a sustainable resource for biosorbents. In this work, olive stone powder delignification using sodium chlorite (NaClO2) was performed to enhance metal ion adsorption capacity. The influence of the treatment on olive stone powder physical-chemical properties was studied, including specific surface area, surface chemistry, morphology, etc. The white, delignified olive stone powder was applied for metal ions (Fe3+, Cu2+, and Zn2+) adsorption. Olive stone delignification not only increases the accessibility of the olive stone powder but also broadens the applications to materials design with optical functions by the generation of a white powder.

NIH offers multiple mentored career development award mechanisms. By building on the UC Davis Clinical and Translational Science Center (CTSC) from its initial NIH funding in 2006, we created an institution-wide K scholar resource. We investigated subsequent NIH funding for K scholars and to what extent CTSC research resources were used. Using NIH RePORTER, we created a database of UC Davis investigators who obtained K01, K08, K23, K25, or K99, as well as institutional KL2 or K12 awards and tracked CTSC research resource use and subsequent funding success. Overall, 94 scholars completed K training between 2007 and 2020, of which 70 participated in one of four institutional, NIH-funded K programs. An additional 103 scholars completed a mentored clinical research training program. Of 94 K awardees, 61 (65%) later achieved NIH funding, with the majority receiving a subsequent individual K award. A higher proportion (73%) of funded scholars used CTSC resources compared to unfunded (48%). Biostatistics and Biomedical Informatics were most commonly used and 55% of scholars used one or more CTSC resource. We conclude that institutional commitment to create a K scholar platform and use of CTSC research resources is associated with high NIH funding rates for early career investigators.

We previously demonstrated an association between lipoprotein (a) [Lp(a)] levels and atherosclerosis in human immunodeficiency virus (HIV)-seropositive women. The effects of antiretroviral therapy (ART) on Lp(a) levels in relation to apo(a) size polymorphism remain unclear. ART effects on allele-specific apo(a) level (ASL), an Lp(a) level associated with individual apo(a) alleles within each allele-pair, were determined in 126 HIV-seropositive women. ART effects were tested by a mixed-effects model across pre-ART and post-ART first and third visits. Data from 120 HIV-seronegative women were used. The mean age was 38 years; most were African-American (∼70%). Pre-ART ASLs associated with the larger (4.6 mg/dl vs. 8.0 mg/dl, P = 0.024) or smaller (13 mg/dl vs. 19 mg/dl, P = 0.041) apo(a) sizes were lower in the HIV-seropositive versus HIV-seronegative group, as was the prevalence of a high Lp(a) level (P = 0.013). Post-ART ASL and prevalence of high Lp(a) or apo(a) sizes and frequency of small size apo(a) (≤22 kringles) did not differ between the two groups. ART increased Lp(a) level (from 18 to 24 mg/dl, P < 0.0001) and both ASLs (P < 0.001). In conclusion, regardless of genetic control, Lp(a) can be modulated by HIV and its treatment. ART initiation abrogates HIV-induced suppression of Lp(a) levels and ASLs, contributing to promote CVD risk in HIV-seropositive individuals.

Background: Despite improved treatment of myocardial infarction (MI), real-world patients still suffer substantial risk for subsequent cardiovascular events. Little is known about coagulation activity shortly after MI and whether coagulation activity markers may identify patients at increased risk despite contemporary treatment. Objective: To evaluate D-dimer concentration and thrombin generation potential shortly after discharge after MI and evaluate if these markers could predict the risk of future cardiovascular and bleeding events. Methods: Unselected MI patients (n = 421) were included in the observational REBUS study (NCT01102933) and followed for two years. D-dimer concentrations, thrombin peak, and endogenous thrombin potential (ETP) were analyzed at inclusion (3–5 days after MI) and at early follow-up (after 2–3 weeks). Results: Seventy-five patients (17.8%) experienced the composite endpoint (all-cause death, MI, congestive heart failure, or all-cause stroke), and 31 patients (7.4%) experienced a clinically relevant bleeding event. D-dimer concentrations at early follow-up were associated with the composite endpoint (HR [per SD increase] 1.51 [95% CI 1.22–1.87]) and with clinically relevant bleeding (HR [per SD increase] 1.80 [95% CI 1.32–2.44]). Thrombin generation potential was not significantly associated with either the composite endpoint or with clinically relevant bleeding. Higher thrombin peak and ETP at early follow-up were both inversely associated with stroke (HR [per SD increase] 0.50 [95% CI 0.30–0.81] and 0.43 [95% CI 0.22–0.83], respectively). Conclusion: In unselected MI patients treated according to contemporary guidelines, D-dimer measurements may identify patients at increased risk of new cardiovascular and bleeding events. The inverse association of thrombin generation potential and risk of stroke has to be further investigated.

An elevated level of lipoprotein (a) [Lp(a)] is a risk factor for CVD. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is reported to reduce Lp(a) levels. The relationship of Lp(a) reduction with apo(a) size polymorphism, phenotype, and dominance pattern and LDL cholesterol (LDL-C) reduction was evaluated in a pooled analysis of 155 hypercholesterolemic patients (75 with heterozygous familial hypercholesterolemia) from two clinical trials. Alirocumab significantly reduced total Lp(a) (pooled median: −21%, P = 0.0001) and allele-specific apo(a), an Lp(a) level carried by the smaller (median: −18%, P = 0.002) or the larger (median: −37%, P = 0.0005) apo(a) isoform, at week 8 versus baseline. The percent reduction in Lp(a) level with alirocumab was similar across apo(a) phenotypes (single vs. double bands) and carriers and noncarriers of a small size apo(a) (≤22 kringles). The percent reduction in LDL-C correlated significantly with the percent reduction in Lp(a) level (r = 0.407, P < 0.0001) and allele-specific apo(a) level associated with the smaller (r = 0.390, P < 0.0001) or larger (r = 0.270, P = 0.0183) apo(a) sizes. In conclusion, alirocumab-induced Lp(a) reduction was independent of apo(a) phenotypes and the presence or absence of a small size apo(a).

Levels of lipoprotein (a) [Lp(a)], a complex between an LDL-like lipid moiety containing one copy of apoB, and apo(a), a plasminogen-derived carbohydrate-rich hydrophilic protein, are primarily genetically regulated. Although stable intra-individually, Lp(a) levels have a skewed distribution inter-individually and are strongly impacted by a size polymorphism of the LPA gene, resulting in a variable number of kringle IV (KIV) units, a key motif of apo(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels resulting in stable plasma levels across the lifespan. Studies have demonstrated pronounced differences across ethnicities with regard to Lp(a) levels and some of this difference, but not all of it, can be explained by genetic variations across ethnic groups. Increasing evidence suggests that age, sex, and hormonal impact may have a modest modulatory influence on Lp(a) levels. Among clinical conditions, Lp(a) levels are reported to be affected by kidney and liver diseases.

Lipoprotein(a) [Lp(a)] is an independent, causal, genetically determined risk factor for cardiovascular disease (CVD). We provide an overview of current knowledge on Lp(a) and CVD risk, and the effect of pharmacological agents on Lp(a). Since evidence is accumulating that diet modulates Lp(a), the focus of this paper is on the effect of dietary intervention on Lp(a). We identified seven trials with 15 comparisons of the effect of saturated fat (SFA) replacement on Lp(a). While replacement of SFA with carbohydrate, monounsaturated fat (MUFA), or polyunsaturated fat (PUFA) consistently lowered low-density lipoprotein cholesterol (LDL-C), heterogeneity in the Lp(a) response was observed. In two trials, Lp(a) increased with carbohydrate replacement; one trial showed no effect and another showed Lp(a) lowering. MUFA replacement increased Lp(a) in three trials; three trials showed no effect and one showed lowering. PUFA or PUFA + MUFA inconsistently affected Lp(a) in four trials. Seven trials of diets with differing macronutrient compositions showed similar divergence in the effect on LDL-C and Lp(a). The identified clinical trials show diet modestly affects Lp(a) and often in the opposing direction to LDL-C. Further research is needed to understand how diet affects Lp(a) and its properties, and the lack of concordance between diet-induced LDL-C and Lp(a) changes.

The article describes the practices of acquisition of music behind the üben Collection. Music was copied into manuscripts from prints, but was also obtained in the form of groups of manuscripts from different regions of Europe. Close personal contacts and networks seem to have been more important than traditional trade routes.

A marked increase in the frequency of obesity at the population level has resulted in an increasing number of obese women entering pregnancy. The increasing realization of the importance of the fetal environment in relation to chronic disease across the lifespan has focused attention on the role of maternal obesity in fetal development. Previous studies have demonstrated that obesity during adolescence and adulthood can be traced back to fetal and early childhood exposures. This review focuses on factors that contribute to early developmental events, such as epigenetic modifications, the potential for an increase in inflammatory burden, early developmental programming changes such as the variable development of white versus brown adipose tissue, and alterations in organ ontogeny. We hypothesize that these mechanisms promote an unfavorable fetal environment and can have a long-standing impact, with early manifestations of chronic disease that can result in an increased demand for future health care. In order to identify appropriate preventive measures, attention needs to be placed both on reducing maternal obesity as well as understanding the molecular, cellular, and epigenetic mechanisms that may be responsible for the prenatal onset of chronic disease.

Individuals with type 2 diabetes mellitus (DM) characteristically have elevated fasting and postprandial (PP) plasma triglycerides (TG). Previous case-control studies indicated that PPTG levels predict the presence of coronary artery disease (CAD) in people without DM; however, the data for patients with DM are conflicting. Therefore, we conducted a case-control study in DM individuals, 84 with (+) and 80 without (−) CAD. Our hypothesis was that DM individuals with or without CAD would have similar PPTG levels, but CAD+ individuals would have more small d

Apolipoproteins (apo) E and C-I are components of triglyceride (TG)-rich lipoproteins and impact their metabolism. Functional polymorphisms have been established in apoE but not in apoC-I. We studied the relationship between apoE and apoC-I gene polymorphisms and plasma lipoproteins and coronary artery disease (CAD) in 211 African Americans and 306 Caucasians. In African Americans but not in Caucasians, apoC-I H2-carriers had significantly lower total and LDL cholesterol and apoB levels, and higher glucose, insulin, and HOMA-IR levels compared with H1 homozygotes. Differences across CAD phenotypes were seen for the apoC-I polymorphism. African-American H2-carriers without CAD had significantly lower total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and apoB (P < 0.001) levels compared with H1 homozygotes, whereas no differences were found across apoC-I genotypes for African Americans with CAD. Among African-American apoC-I H1 homozygotes, subjects with CAD had a profile similar to the metabolic syndrome (i.e., higher triglyceride, glucose, and insulin) compared with subjects without CAD. For African-American H2-carriers, subjects with CAD had a pro-atherogenic lipid pattern (i.e., higher LDL cholesterol and apoB levels), compared with subjects without CAD. ApoC-I genotypes showed an ethnically distinct phenotype relationship with regard to CAD and CAD risk factors.

The genetic variability of apolipoprotein E (apoE) influences plasma lipoprotein levels, and allele frequencies differ between African Americans and Caucasians. As African Americans have higher lipoprotein [a] (Lp[a]) levels than Caucasians, we investigated the effects of the apoE gene on allele-specific apolipoprotein [a] (apo[a]) levels across ethnicity. We determined apo[a] sizes, allele-specific apo[a] levels (i.e., levels associated with alleles defined by size), and the apoE gene polymorphism in 231 African Americans and 336 Caucasians. African Americans, but not Caucasians, with the apo E2 genotype had lower levels of Lp[a] compared with those with the apo E4 genotype (9.6 vs. 11.2 nmol/l; P = 0.034, expressed as square root levels). Distribution of apo[a] alleles across apoE genotypes were similar between African Americans and Caucasians. Among African Americans with large apo[a], the allele-specific apo[a] level was significantly lower among ε2 carriers compared with ε3 or ε4 carriers (5.4 vs. 6.6 and 7.4 nmol/l, respectively; P < 0.005, expressed as square root levels). In contrast, there was no significant difference in allele-specific apo[a] levels across apoE genotypes among Caucasians. For large apo[a] sizes, apoE genotype contributed to the observed African American-Caucasian differences in allele-specific apo[a] levels.

We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for ϵ2, ϵ3, and ϵ4, respectively, in African Americans and 0.08, 0.78, and 0.14 for ϵ2, ϵ3, and ϵ4, respectively, in Caucasians. Among African Americans, CAD was present in 9 of 34 ϵ2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 ϵ3 carriers and 43 of 92 ϵ4 carriers (48% and 47%, respectively), suggesting a protective effect of the ϵ2 allele. No such difference was seen in Caucasians. In African Americans but not Caucasians, LDL cholesterol was lower in ϵ2 carriers than in ϵ3 and ϵ4 carriers (106 vs. 127 and 134 mg/dl, respectively; P < 0.005). After adjusting for lipid levels, the association between apoE2 and CAD was no longer significant. Thus, the protective effect of apoE2 seen in African Americans could be explained by a favorable lipid profile in ϵ2 carriers, whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 on the lipid profile.

Apolipoprotein [a] (apo[a]) gene size is a major predictor of lipoprotein [a] level. To determine genetic predictors of allele-specific apo[a] levels beyond gene size, we evaluated the upstream C/T and pentanucleotide repeat (PNR) polymorphisms. We determined apo[a] sizes, allele-specific apo[a] levels, and C/T and PNR in 215 Caucasians and 139 African Americans. For Caucasians, apo[a] size affected allele-specific levels substantially greater in subjects with apo[a] < 24 K4; for African Americans, the size effect was smaller than in Caucasians, 8. In a multiple regression model, apo[a] allele size and size and expression of the other apo[a] allele (and PNR > 8 for Caucasians) significantly predicted allele-specific apo[a] levels. For a common PNR 8 allele, predicted values were similar in the two ethnicities for small size apo[a]. Allele-specific apo[a] levels were influenced by the other allele size and expression. Observed differences between Caucasians and African Americans in allele-specific apo[a] levels were explained for small apo[a] sizes by the other allele size and PNR; the ethnicity differences remain unexplained for larger sizes.

HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, crossover design trial to determine the effects of simvastatin, 80 mg/day, on plasma lipid and lipoprotein levels and on the metabolism of apolipoprotein B (apoB) in VLDL, intermediate density lipoprotein (IDL), and LDL and of triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol, and apoB significantly in VLDL, IDL, and LDL. These effects were associated with reduced production of LDL-apoB, mainly as a result of reduced secretion of apoB-lipoproteins directly into the LDL density range. Statin therapy also reduced hepatic production of VLDL-TG. There were no effects of simvastatin on the fractional catabolic rates of VLDL-apoB or -TG or LDL-apoB. The basis for decreased VLDL-TG secretion during simvastatin treatment is not clear, but recent studies suggest that statins may activate peroxisomal proliferator-activated receptor α (PPARα).Activation of PPARα could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.

Plasma lipoprotein [a] (Lp[a]) concentrations are inversely associated with, and largely determined by, apolipoprotein [a] (apo[a]) gene size, a highly polymorphic trait. We studied if, within an individual, the smaller apo[a] isoform always dominated, whether there was interaction between the two alleles, and whether these features differed between Caucasians and African Americans. We determined apo[a] gene sizes, apo[a] protein sizes and relative amounts, and plasma Lp[a] levels in 430 individuals (263 Caucasians and 167 African Americans). Of the 397 heterozygotes with at least one detectable apo[a] isoform (238 Caucasians and 159 African Americans), the larger allele dominated in 28% of Caucasians and 23% of African Americans, while the smaller allele dominated in 56% of Caucasians and 45% of African Americans. In Caucasians, dominance of the smaller allele increased with Lp[a] levels, from 44% at Lp[a] ≤30 nM to 81% at Lp[a] >100 nM (P < 0.0001). Dominance by the smaller allele increased with increasing size of the larger allele in both groups but with the smaller allele only in African Americans. There was no interaction between apo[a] alleles within genotypes; one apo[a] isoform level was not associated with the other isoform level, and isoform levels were not affected by the difference in size. More of the dominance pattern was explained by Lp[a] level and apo[a] genotype in African Americans than in Caucasians (29% vs. 13%). Thus, genotype influences isoform-specific Lp[a] levels and dominance patterns differently in African Americans and in Caucasians.—Rubin, J., F. Paultre, C. H. Tuck, S. Holleran, R. G. Reed, T. A. Pearson, C. M. Thomas, R. Ramakrishnan, and L. Berglund. Apolipoprotein [a] genotype influences isoform dominance pattern differently in African Americans and Caucasians.

Previous studies have revealed the presence of transthyretin (TTR) on lipoproteins. To further address this issue, we fractionated plasma lipoproteins from 9 normal individuals, 10 familial amyloidotic polyneuropathy (FAP) patients, and 19 hyperlipidemic subjects using gel filtration. In the majority of the subjects, as well as in 9 of the 10 FAP patients and 14 of the 19 patients with hyperlipidemia, TTR was detected by ELISA in the high density lipoprotein (HDL) fraction. The presence of TTR in HDL was confirmed by direct sequencing and by immunoblotting; using non-reducing conditions, TTR was found by immunoblotting in a high molecular weight complex, which reacted also for apolipoprotein A-I (apoA-I). The amount of TTR present in HDL (HDL-TTR), as quantified by ELISA corresponded to 1–2% of total plasma TTR. However, no detectable TTR levels were found in HDL fraction from 6 of the hyperlipidemic subjects. No correlation was found between the lack of TTR in HDL and plasma levels of total, LDL-, or HDL-associated cholesterol as well as levels of apoA-I and total plasma TTR. Ligand binding experiments showed that radiolabeled TTR binds to the HDL fraction of individuals with HDL-TTR but not to the corresponding fractions of individuals devoid of HDL-TTR, suggesting that HDL composition may interfere with TTR binding. The component(s) to which TTR binds in the HDL fraction were investigated. Polyclonal antibody against apoA-I was able to block the interaction of TTR with HDL, suggesting that the interaction of TTR with the HDL particle occurs via apoA-I. This hypothesis was further demonstrated by showing the formation of a complex of TTR with HDL and apoA-I by crosslinking experiments. Furthermore, anti-apoA-I immunoblot under native conditions suggested the existence of differences in HDL particle properties and/or stability between individuals with and without HDL-TTR. —Sousa, M. M., L. Berglund, and M. J. Saraiva. Transthyretin in high density lipoproteins: association with apolipoprotein A-I.

Apolipoprotein (apo) C-I is a constituent of triglyceride-rich lipoproteins (TGRL) that interferes with their hepatic clearance. Functional polymorphism in the apoC-I gene has not been established. We determined that an Hpa I site variably present at −317 relative to the apoC-I gene is produced by a 4-bp CGTT insertion. The apoC-I Hpa I alleles showed an ethnically distinct pattern of linkage disequilibrium with the alleles of the adjacent apoE gene. The frequency of apoC-I Hpa I-positive (H2) with apoE ε2 was 0.98, without significant ethnic difference. In contrast, the frequency of H2 with apoE ε4 was 0.85 in European-Americans but only 0.55 in African-Americans (P < 0.001). The frequency of H2 with apoE ε3 was 0.02 in European-Americans and 0.08 in African-Americans (P < 0.001). African-American apoE ε3/ε3 carriers of apoC-I H2 had 19% lower fasting triglyceride levels than H1 homozygotes (P = 0.03) along with 18% higher HDL-cholesterol levels (P = 0.02). ApoB levels were 21% lower (P = 0.002). H2-allelic reporter-gene constructions showed 50% higher expression in transient transfection studies. We localized the source of this difference in expression to the CGTT insertion itself. Deletion studies of the H1 allele showed a negative transcriptional effect of the polymorphic region. An H1 oligodeoxynucleotide showed specific binding of a hepatomacell nuclear protein not evident with an H2 oligodeoxynucleotide. The H2 sequence may decrease the binding of a negatively acting transcription factor, leading to overexpression of apoC-I. This may produce a functional effect on lipoprotein levels but confirmation is needed in other populations.—Xu, Y., L. Berglund, R. Ramakrishnan, R. Mayeux, C. Ngai, S. Holleran, B. Tycko, T. Leff, and N. S. Shachter. A common Hpa I RFLP of apolipoprotein C-I increases gene transcription and exhibits an ethnically distinct pattern of linkage disequilibrium with the alleles of apolipoprotein E. J. Lipid Res. 1999. 40: 50–58.

To differentiate effects of lovastatin on low density lipoprotein (LDL) receptor activity from effects on LDL metabolic properties, LDL apolipoprotein B (apoB) turnover was studied in eight hyperlipidemic subjects during baseline and lovastatin treatment, in the latter case with LDL tracers isolated during both baseline (C-LDL) and drug treatment (Rx-LDL) conditions. Lovastatin (40 mg/day) significantly lowered total plasma and LDL cholesterol levels (27% and 25%, respectively) as well as plasma triglyceride levels (30%). Using contemporaneous tracers (C-LDL before and Rx-LDL during treatment), lovastatin caused a modest increase in LDL fractional catabolic rate (FCR) (0.410 ± 0.113 vs. 0.339 ± 0.108 pools/day, P < 0.04 by paired t). The increase in LDL tracer FCR was higher when C-LDL tracer isolated during the untreated period was injected during lovastatin treatment (0.496 ± 0.177 vs. 0.339 ± 0.108 pools/day, P < 0.02). These in vivo studies in humans were confirmed by injecting LDL tracers from two patients into five guinea pigs. The C-LDL tracer was cleared consistently faster than the Rx-LDL tracer (0.082 ± 0.018 vs. 0.057 ± 0.015 pools/h, P < 0.001). The results demonstrate three important outcomes of lovastatin treatment in these subjects: LDL receptor activity increased by 49% (P < 0.02); LDL apoB production rate decreased by 17% (P < 0.03), and LDL particle in vivo affinity for the LDL receptor decreased by 15% (P < 0.01). The decrease in LDL particle affinity partially negated the expected effect of increased LDL receptors on LDL clearance. The present study provides an explanation for earlier observations by several investigators using contemporaneous tracers that treatment with HMG-CoA reductase inhibitors resulted in only modest increases in low density lipoprotein functional catabolic rate.—Berglund, L., J. L. Witztum, N. F. Galeano, A. S. Khouw, H. N. Ginsberg, and R. Ramakrishnan. Three-fold effect of lovastatin treatment on low density lipoprotein metabolism in subjects with hyperlipidemia: increase in receptor activity, decrease in apoB production, and decrease in particle affinity for the receptor. Results from a novel triple-tracer approach. J. Lipid Res. 1998. 39: 913–924.

The objective was to evaluate the hypothesis that growth-differentiation factor 15 (GDF-15) is an independent marker of the long-term risk for both cardiovascular disease and cancer morbidity beyond clinical and biochemical risk factors. Plasma obtained at age 71 was available from 940 subjects in the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort. Complete mortality and morbidity data were obtained from public registries. At baseline there were independent associations between GDF-15 and current smoking, diabetes mellitus, biomarkers of cardiac (high-sensitivity troponin-T, NT-proBNP) and renal dysfunction (cystatin-C) and inflammatory activity (C-reactive protein), and previous cardiovascular disease (CVD). During 10 years follow-up there occurred 265 and 131 deaths, 115 and 46 cardiovascular deaths, and 185 and 86 events with coronary heart disease mortality or morbidity in the respective total cohort (n=940) and non-CVD (n=561) cohort. After adjustment for conventional cardiovascular risk factors, one SD increase in log GDF-15 were, in the respective total and non-CVD populations, associated with 48% (95%CI 26 to 73%, p

The formation of hybrids of nanofibrillated cellulose and titania nanoparticles in aqueous media has been studied. Their transparency and mechanical behavior have been assessed by spectrophotometry and nanoindentation. The results show that limiting the titania nanoparticle concentration below 16 vol% yields homogeneous hybrids with a very high Young's modulus and hardness, of up to 44 GPa and 3.4 GPa, respectively, and an optical transmittance above 80%. Electron microscopy shows that higher nanoparticle contents result in agglomeration and an inhomogeneous hybrid nanostructure with a concomitant reduction of hardness and optical transmittance. Infrared spectroscopy suggests that the nanostructure of the hybrids is controlled by electrostatic adsorption of the titania nanoparticles on the negatively charged nanocellulose surfaces.

Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays.Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81-89), intermediate for RIA (70 nmol/L, 95% CI 66-74) and lowest with CLIA (60 nmol/L, 95% CI 56-64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p

This article is a synthesis of four investigations made by students at the special educational program at Malmö University. It describes how headmasters experience the professional role of the special needs pedagogue in schools. Research questions concerning the relationship between higher education and school practice are elucidated in the article. The responses are analyzed and problematized with the help of von Wright’s Action theory as well as of Dahllöf’s frame factor theory. In the interviews headmasters describe the special educational activities and the special pedagogue profession as multifaceted and complex. This is a situation which impedes good functioning and effective use of competence resources. Moreover, headmasters are frequently caught between the visions of policy instruments and school practice, not least concerning situational acting, and the question of short or long term planning and acting.

BackgroundData from previous studies are inconsistent, and it is therefore uncertain whether, to what extent, and at what level leisure physical activity influences the risk of osteoporotic fractures in men.Methods and findingsA cohort of 2,205 men, 49-51 y of age, was enrolled in a longitudinal, population-based study. Leisure physical activity and other lifestyle habits were established at baseline and at ages 60, 70, 77, and 82 y. During 35 y of follow-up, 482 men had at least one fracture. Cox's proportional hazards regression was used to determine hazard ratios (HRs) of fracture associated with time-dependent physical activity habits and covariates. Men with a sedentary lifestyle (HR 2.56, 95% confidence interval 1.55-4.24) or men who walked or bicycled only for pleasure (HR 1.61, 95% confidence interval 1.10-2.36) had an increased adjusted risk of hip fracture compared with men who participated in regular sports activities for at least 3 h/wk. At the end of follow-up, 8.4% of the men with a high physical activity, 13.3% of the men with a medium physical activity, and 20.5% of the men with a low physical activity had suffered a hip fracture. According to the estimation of population-attributable risk, one third of all hip fractures could be prevented by participation in regular sports activities. High activity also conferred a reduced overall fracture risk.ConclusionsOur data indicate that regular sports activities can reduce the risk of fractures in older men.