Mechanical properties, collagen and glycosaminoglycan content of equine superficial digital flexor tendons are not affected by training.

Physical activity can activate extracellular matrix (ECM) protein synthesis and influence the size and mechanical properties of tendon. In this study, we aimed to investigate whether different training histories of horses would influence the synthesis of collagen and other matrix proteins and alter the mechanical properties of tendon. Samples from superficial digital flexor tendon (SDFT) from horses that were either (a) currently race trained (n = 5), (b) previously race trained (n = 5) or (c) untrained (n = 4) were analysed for matrix protein abundance (mass spectrometry), collagen and glycosaminoglycan (GAG) content, ECM gene expression and mechanical properties. It was found that ECM synthesis by tendon fibroblasts in vitro varied depending upon the previous training history. In contrast, fascicle morphology, collagen and GAG content, mechanical properties and ECM gene expression of the tendon did not reveal any significant differences between groups. In conclusion, although we could not identify any direct impact of the physical training history on the mechanical properties or major ECM components of the tendon, it is evident that horse tendon cells are responsive to loading in vivo, and the training background may lead to a modification in the composition of newly synthesised matrix.

Insulin-like growth factor-1 infusion in preterm piglets does not affect growth parameters of skeletal muscle or tendon tissue.

Prematurity has physical consequences, such as lower birth weight, decreased muscle mass and increased risk of adult-onset metabolic disease. Insulin-like growth factor 1 (IGF-1) has therapeutic potential to improve the growth and quality of muscle and tendon in premature births, and thus attenuate some of these sequalae. We investigated the effect of IGF-1 on extensor carpi radialis muscle and biceps brachii tendon of preterm piglets. The preterm group consisted of 19-day-old preterm (10 days early) piglets, treated with either IGF-1 or vehicle. Term controls consisted of groups of 9-day-old piglets (D9) and 19-day-old piglets (D19). Muscle samples were analysed by immunofluorescence to determine the cross-sectional area (CSA) of muscle fibres, fibre type composition, satellite cell content and central nuclei-containing fibres in the muscle. Tendon samples were analysed for CSA, collagen content and maturation, and vascularization. Gene expression of the tendon was measured by RT-qPCR. Across all endpoints, we found no significant effect of IGF-1 treatment on preterm piglets. Preterm piglets had smaller muscle fibre CSA compared to D9 and D19 control group. Satellite cell content was similar across all groups. For tendon, we found an effect of age on tendon CSA, and mRNA levels of COL1A1, tenomodulin and scleraxis. Immunoreactivity for elastin and CD31, and several markers of tendon maturation, were increased in D9 compared to the preterm piglets. Collagen content was similar across groups. IGF-1 treatment of preterm-born piglets does not influence the growth and maturation of skeletal muscle and tendon.

Inequality in smoking and related risk factors for smoking in expectant mothers - a nationwide Danish register-based study.

AIMS: Foetuses exposed to smoking during pregnancy are disadvantaged due to numerous adverse obstetric outcomes. This study aimed to examine 1) inequality in maternal smoking between subgroups of pregnant women and 2) significant risk factors of maternal smoking. METHODS: Data were collected from Danish registries. Trends in maternal smoking within each study period, T1 (2000-2002) and T2 (2014-2016), were investigated by Poisson regression calculating prevalence proportion ratios, and trends between study periods were studied by adding an interaction term. The significance of risk factors for maternal smoking (low age, low education, living alone and having a moderate/severe mental health condition) were studied by interaction analysis on the additive scale. RESULTS: The prevalence of maternal smoking decreased from 21% in 2000 to 7% in 2016. Decreases were found in all subgroups of maternal age, cohabitation status, educational level and mental health condition. However, large differences in smoking prevalence between subgroups were found, and inequality in maternal smoking increased from 2000 to 2016. The probability of maternal smoking increased with the addition of risk factors, and positive additive interactions were found for almost all combinations of multiple risk factors. CONCLUSIONS: Our results provide knowledge on risk factors and increasing levels of inequality in maternal smoking which points to a need for targeted interventions in relation to maternal smoking for subgroups of pregnant women in future smoking cessation programmes and in antenatal care.

Structure and function of Achilles and patellar tendons following moderate slow resistance training in young and old men.

The aim of this study was to investigate the effect of aging and resistance training with a moderate load on the size and mechanical properties of the patellar (PT) and Achilles tendon (AT) and their associated aponeuroses; medial gastrocnemius (MG) and vastus lateralis (VL). Young (Y55; 24.8 ± 3.8 yrs, n = 11) and old men (O55; 70.0 ± 4.6 yrs, n = 13) were assigned to undergo a training program (12 weeks; 3 times/week) of moderate slow resistance training [55% of one repetition maximum (RM)] of the triceps surae and quadriceps muscles. Tendon dimensions were assessed using 1.5 T magnetic resonance imaging before and after 12 weeks. AT and PT cross sectional area (CSA) were determined every 10% of tendon length. Mechanical properties of the free AT, MG aponeurosis, PT, and VL aponeurosis were assessed using ultrasonography (deformation) and tendon force measurements. CSA of the AT but not PT was greater in O55 compared with Y55. At baseline, mechanical properties were generally lower in O55 than Y55 for AT, MG aponeurosis and VL aponeurosis (Young's modulus) but not for PT. CSA of the AT and PT increased equally in both groups following training. Further, for a given force, stiffness and Young's modulus also increased equally for VL aponeurosis and AT, for boths groups. The present study highlights that except for the PT, older men have lower tendon (AT, MG aponeurosis, and VL aponeurosis) mechanical properties than young men and 12-weeks of moderate slow resistance training appears sufficient to improve tendon size and mechanical adaptations in both young and older men. New and Noteworthy: These novel findings suggest that short-term moderate slow resistance training induces equal improvements in tendon size and mechanics regardless of age.

Interventions, methods and outcome measures used in teaching evidence-based practice to healthcare students: an overview of systematic reviews.

BACKGROUND: To fully implement the internationally acknowledged requirements for teaching in evidence-based practice, and support the student's development of core competencies in evidence-based practice, educators at professional bachelor degree programs in healthcare need a systematic overview of evidence-based teaching and learning interventions. The purpose of this overview of systematic reviews was to summarize and synthesize the current evidence from systematic reviews on educational interventions being used by educators to teach evidence-based practice to professional bachelor-degree healthcare students and to identify the evidence-based practice-related learning outcomes used. METHODS: An overview of systematic reviews. Four databases (PubMed/Medline, CINAHL, ERIC and the Cochrane library) were searched from May 2013 to January 25th, 2024. Additional sources were checked for unpublished or ongoing systematic reviews. Eligibility criteria included systematic reviews of studies among undergraduate nursing, physiotherapist, occupational therapist, midwife, nutrition and health, and biomedical laboratory science students, evaluating educational interventions aimed at teaching evidence-based practice in classroom or clinical practice setting, or a combination. Two authors independently performed initial eligibility screening of title/abstracts. Four authors independently performed full-text screening and assessed the quality of selected systematic reviews using standardized instruments. Data was extracted and synthesized using a narrative approach. RESULTS: A total of 524 references were retrieved, and 6 systematic reviews (with a total of 39 primary studies) were included. Overlap between the systematic reviews was minimal. All the systematic reviews were of low methodological quality. Synthesis and analysis revealed a variety of teaching modalities and approaches. The outcomes were to some extent assessed in accordance with the Sicily group`s categories; "skills", "attitude" and "knowledge". Whereas "behaviors", "reaction to educational experience", "self-efficacy" and "benefits for the patient" were rarely used. CONCLUSIONS: Teaching evidence-based practice is widely used in undergraduate healthcare students and a variety of interventions are used and recognized. Not all categories of outcomes suggested by the Sicily group are used to evaluate outcomes of evidence-based practice teaching. There is a need for studies measuring the effect on outcomes in all the Sicily group categories, to enhance sustainability and transition of evidence-based practice competencies to the context of healthcare practice.

Disruption of day-to-night changes in circadian gene expression with chronic tendinopathy.

Overuse injury in tendon tissue (tendinopathy) is a frequent and costly musculoskeletal disorder and represents a major clinical problem with unsolved pathogenesis. Studies in mice have demonstrated that circadian clock-controlled genes are vital for protein homeostasis and important in the development of tendinopathy. We performed RNA sequencing, collagen content and ultrastructural analyses on human tendon biopsies obtained 12 h apart in healthy individuals to establish whether human tendon is a peripheral clock tissue and we performed RNA sequencing on patients with chronic tendinopathy to examine the expression of circadian clock genes in tendinopathic tissues. We found time-dependent expression of 280 RNAs including 11 conserved circadian clock genes in healthy tendons and markedly fewer (23) differential RNAs with chronic tendinopathy. Further, the expression of COL1A1 and COL1A2 was reduced at night but was not circadian rhythmic in synchronised human tenocyte cultures. In conclusion, day-to-night changes in gene expression in healthy human patellar tendons indicate a conserved circadian clock as well as the existence of a night reduction in collagen I expression. KEY POINTS: Tendinopathy is a major clinical problem with unsolved pathogenesis. Previous work in mice has shown that a robust circadian rhythm is required for collagen homeostasis in tendons. The use of circadian medicine in the diagnosis and treatment of tendinopathy has been stifled by the lack of studies on human tissue. Here, we establish that the expression of circadian clock genes in human tendons is time dependent, and now we have data to corroborate that circadian output is reduced in diseased tendon tissues. We consider our findings to be of significance in advancing the use of the tendon circadian clock as a therapeutic target or preclinical biomarker for tendinopathy.

Tendon properties in a mouse model of severe osteogenesis imperfecta.

PURPOSE/AIM OF THE STUDY: Osteogenesis imperfecta is a heritable bone disorder that is usually caused by mutations in collagen type I encoding genes. The impact of such mutations on tendons, a structure with high collagen type I content, remains largely unexplored. We hypothesized that tendon properties are abnormal in the context of a mutation affecting collagen type I. The main purpose of the study was to assess the anatomical, mechanical, and material tendon properties of Col1a1Jrt/+ mice, a model of severe dominant OI. MATERIALS AND METHODS: The Flexor Digitorum Longus (FDL) tendon of Col1a1Jrt/+ mice and wild-type littermates (WT) was assessed with in vitro mechanical testing. RESULTS: The results showed that width and thickness of FDL tendons were about 40% larger in WT (p < 0.01) than in Col1a1Jrt/+ mice, whereas the cross-sectional area was 138% larger (p < 0.001). The stiffness, peak- and yield-force were between 160% and 194% higher in WT vs. Col1a1Jrt/+ mice. The material properties did not show significant differences between mouse strains with differences <15% between WT and Col1a1Jrt/+ (p > 0.05). Analysis of the Achilles tendon collagen showed no difference between mice strains for the content but collagen solubility in acetic acid was 66% higher in WT than in Col1a1Jrt/+ (p < 0.001). CONCLUSIONS: This study shows that the FDL tendon of Col1a1Jrt/+ mice has reduced mechanical properties but apparently normal material properties. It remains unclear whether the tendon phenotype of Col1a1Jrt/+ mice is secondary to muscle weakness or a direct effect of the Col1a1 mutation or a combination of both.

Preserved stem cell content and innervation profile of elderly human skeletal muscle with lifelong recreational exercise.

Muscle fibre denervation and declining numbers of muscle stem (satellite) cells are defining characteristics of ageing skeletal muscle. The aim of this study was to investigate the potential for lifelong recreational exercise to offset muscle fibre denervation and compromised satellite cell content and function, both at rest and under challenged conditions. Sixteen elderly lifelong recreational exercisers (LLEX) were studied alongside groups of age-matched sedentary (SED) and young subjects. Lean body mass and maximal voluntary contraction were assessed, and a strength training bout was performed. From muscle biopsies, tissue and primary myogenic cell cultures were analysed by immunofluorescence and RT-qPCR to assess myofibre denervation and satellite cell quantity and function. LLEX demonstrated superior muscle function under challenged conditions. When compared with SED, the muscle of LLEX was found to contain a greater content of satellite cells associated with type II myofibres specifically, along with higher mRNA levels of the beta and gamma acetylcholine receptors (AChR). No difference was observed between LLEX and SED for the proportion of denervated fibres or satellite cell function, as assessed in vitro by myogenic cell differentiation and fusion index assays. When compared with inactive counterparts, the skeletal muscle of lifelong exercisers is characterised by greater fatigue resistance under challenged conditions in vivo, together with a more youthful tissue satellite cell and AChR profile. Our data suggest a little recreational level exercise goes a long way in protecting against the emergence of classic phenotypic traits associated with the aged muscle. KEY POINTS: The detrimental effects of ageing can be partially offset by lifelong self-organized recreational exercise, as evidence by preserved type II myofibre-associated satellite cells, a beneficial muscle innervation status and greater fatigue resistance under challenged conditions. Satellite cell function (in vitro), muscle fibre size and muscle fibre denervation determined by immunofluorescence were not affected by recreational exercise. Individuals that are recreationally active are far more abundant than master athletes, which sharply increases the translational perspective of the present study. Future studies should further investigate recreational activity in relation to muscle health, while also including female participants.

Bipolar disorder and regretted behavior in relation to use of social media and online dating.

OBJECTIVES: Individuals with bipolar disorder are prone to risk-taking behavior that is subsequently regretted. Here, we investigated whether this also occurs in relation to the use of social media and online dating. METHODS: A questionnaire-based survey focusing on the use of social media and online dating was conducted among individuals attending an outpatient clinic for bipolar disorder, and among individuals attending two general practices in the same region (controls). The association between bipolar disorder and self-reported regretted behavior on social media/online dating sites was investigated using logistic regression with adjustment for age and sex. RESULTS: A total of 124 individuals with bipolar disorder and 196 individuals without affective disorder from the general practices (controls) formed the study sample. Among the individuals with bipolar disorder who used social media, 66% reported regretted behavior as a consequence of this use, whereas only 31% of the controls reported such behavior. The corresponding numbers for individuals who used online dating were 65% for those with bipolar disorder and 31% for the controls. Following adjustment for age and sex, bipolar disorder was associated with elevated risk of regretted behavior in relation to the use of both social media (adjusted odds ratio: 3.6, 95% CI: 2.2, 5.9) and online dating (adjusted odds ratio: 4.1, 95% CI: 2.1, 8.0). CONCLUSIONS: These findings suggest that risk-taking behavior and subsequent regret among individuals with bipolar disorder extend to social media and online dating. Cautious use of these platforms may be particularly relevant for individuals with bipolar disorder.

RNA sequencing and immunofluorescence of the myotendinous junction of mature horses and humans.

The myotendinous junction (MTJ) is a specialized interface for transmitting high forces between the muscle and tendon and yet the MTJ is a common site of strain injury with a high recurrence rate. The aim of this study was to identify previously unknown MTJ components in mature animals and humans. Samples were obtained from the superficial digital flexor (SDF) muscle-tendon interface of 20 horses, and the tissue was separated through a sequential cryosectioning approach into muscle, MTJ (muscle tissue enriched in myofiber tips attached to the tendon), and tendon fractions. RT-PCR was performed for genes known to be expressed in the three tissue fractions and t-distributed stochastic neighbor embedding (t-SNE) plots were used to select the muscle, MTJ, and tendon samples from five horses for RNA sequencing. The expression of previously known and unknown genes identified through RNA sequencing was studied by immunofluorescence on human hamstring MTJ tissue. The main finding was that RNA sequencing identified the expression of a panel of 61 genes enriched at the MTJ. Of these, 48 genes were novel for the MTJ and 13 genes had been reported to be associated with the MTJ in earlier studies. The expression of known [COL22A1 (collagen XXII), NCAM (neural cell adhesion molecule), POSTN (periostin), NES (nestin), OSTN (musclin/osteocrin)] and previously undescribed [MNS1 (meiosis-specific nuclear structural protein 1), and LCT (lactase)] MTJ genes was confirmed at the protein level by immunofluorescence on tissue sections of human MTJ. In conclusion, in muscle-tendon interface tissue enriched with myofiber tips, we identified the expression of previously unknown MTJ genes representing diverse biological processes, which may be important in the maintenance of the specialized MTJ.

Magnetic Resonance T2 * Is Increased in Patients With Early-Stage Achilles and Patellar Tendinopathy.

BACKGROUND: T2 * mapping has proven useful in tendon research and may have the ability to detect subtle changes at an early stage of tendinopathy. PURPOSE: To investigate the difference in T2 * between patients with early tendinopathy and healthy controls, and to investigate the relationship between T2 * and clinical outcomes, tendon size, and mechanical properties. STUDY TYPE: Prospective cross-sectional. SUBJECTS: Sixty-five patients with early tendinopathy and 25 healthy controls. FIELD STRENGTH/SEQUENCE: Three Tesla, ultrashort time to echo magnetic resonance imaging. ASSESSMENT: Tendon T2 * was quantified using a monoexponential fitting algorithm. Clinical symptoms were evaluated using the Victorian Institute of Sports Assessment-Achilles/Patella (VISA-A/VISA-P). In vivo mechanical properties were measured using an ultrasound-based method that determined force and deformation simultaneously in tendons of patellar tendinopathy patients. STATISTICAL TESTS: A generalized linear model adjusted for age was applied to investigate the difference between patients and controls. In the two patient groups, linear regressions were applied to investigate the association between T2 * and tendon size, clinical outcomes, and biomechanical properties. RESULTS: There was a significant difference in T2 * between patients and healthy controls (204.8 [95% CI: 44.5-365.0] µsec, P < 0.05). There was a positive correlation between tendon size and T2 * for both Achilles (r = 0.72; P < 0.05) and patellar tendons (r = 0.53; P < 0.05). There was no significant correlation between VISA-A and T2 * (r = -0.2; P = 0.17) or VISA-P and T2 * (r = -0.5; P = 0.0504). Lastly, there was a negative correlation between modulus and T2 * (r = -0.51; P < 0.05). DATA CONCLUSIONS: T2 * mapping can detect subtle structural changes that translate to altered mechanical properties in early-phase tendinopathy. However, T2 * did not correlate with clinical scores in patients with early-phase Achilles and patellar tendinopathy. Thus, T2 * mapping may serve as a tool for early detection of structural changes in tendinopathy but does not necessarily describe the clinical severity of disease. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Early development of tendinopathy in humans: Sequence of pathological changes in structure and tissue turnover signaling.

Overloading of tendon tissue with resulting chronic pain (tendinopathy) is a common disorder in occupational-, leisure- and sports-activity, but its pathogenesis remains poorly understood. To investigate the very early phase of tendinopathy, Achilles and patellar tendons were investigated in 200 physically active patients and 50 healthy control persons. Patients were divided into three groups: symptoms for 0-1 months (T1), 1-2 months (T2) or 2-3 months (T3). Tendinopathic Achilles tendon cross-sectional area determined by ultrasonography (US) was ~25% larger than in healthy control persons. Both Achilles and patellar anterior-posterior diameter were elevated in tendinopathy, and only later in Achilles was the width increased. Increased tendon size was accompanied by an increase in hypervascularization (US Doppler flow) without any change in mRNA for angiogenic factors. From patellar biopsies taken bilaterally, mRNA for most growth factors and tendon components remained unchanged (except for TGF-beta1 and substance-P) in early tendinopathy. Tendon stiffness remained unaltered over the first three months of tendinopathy and was similar to the asymptomatic contra-lateral tendon. In conclusion, this suggests that tendinopathy pathogenesis represents a disturbed tissue homeostasis with fluid accumulation. The disturbance is likely induced by repeated mechanical overloading rather than a partial rupture of the tendon.

Di-2-picolylamine triggers caspase-independent apoptosis by inducing oxidative stress in human liver hepatocellular carcinoma cells.

Di-2-picolylamine (DPA) is an organic compound that has been shown to possess antioxidant properties when conjugated to form a metal complex. The basis of this study was to determine the effects of DPA on the proliferation and apoptosis of human hepatocellular carcinoma cells and elucidate the possible mechanisms. The methylthiazol tetrazolium assay served to measure cell viability and generated an IC50 of 1591 µM. Luminometry was used to investigate caspase activity and ATP concentration. It was observed that the decreased cell viability was associated with reduced ATP levels. Despite increased Bax and caspase 9 activity, cell death was caspase independent as indicated by the reduction in caspase 3/7 activity. This was associated with the downregulation poly(ADP-ribose) polymerase cleavage (Western blotting). However, the Hoescht assay depicted nuclear condensation and apoptotic body formation with elevated DPA levels suggesting DNA damage in HepG2 cells. DNA damage assessed by the comet assay confirmed an increased comet tail formation. The presence of oxidative stress was investigated by quantifying reactive species (malondialdehyde and nitrates concentration) and Western blotting to confirm the expression of antioxidant proteins. The DPA increased lipid peroxidation (RNS), a marker of oxidative stress, consequently causing cell death. The accompanying upregulation of stress-associated proteins superoxide dismutase (SOD2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and Hsp70 verifies oxidative stress.

Mechanical properties and UTE-T2* in Patellar tendinopathy: The effect of load magnitude in exercise-based treatment.

Loading intervention is currently the preferred management of tendinopathy, but to what extent different loading regimes influence the mechanical response in tendons is scarcely investigated. Therefore, the purposes of the investigation were to examine the effect of exercise interventions with either high or low load magnitude applied to the tendinopathic patellar tendon and the influence on its mechanical, material, and morphological properties. Forty-four men with chronic patellar tendinopathy were randomized to 12 weeks of exercising with either; 55% of 1RM throughout the period (MSR group) or 90% of 1RM (HSR group), and with equal total exercise volume in both groups. Mechanical (stiffness), material (T2* relaxation time), and morphological (cross-sectional area (CSA)) properties were assessed at baseline and after 12 weeks of intervention. MRI with ultra-short echo times (UTE) and T2*-mapping was applied to explore if T2* relaxation time could be used as a noninvasive marker for internal material alteration and early change thereof in response to intervention. There was no effect of HSR or MSR on the mechanical (stiffness), material (T2* relaxation time) or morphological (CSA) properties, but both regimes resulted in significant strength gain. In conclusion, there were no statistically superior effect of exercising with high (90%) compared to moderate (55%) load magnitude on the mechanical, material or morphological properties.

Muscles adaptation to aging and training: architectural changes - a randomised trial.

BACKGROUND: To investigate how anatomical cross-sectional area and volume of quadriceps and triceps surae muscles were affected by ageing, and by resistance training in older and younger men, in vivo. METHODS: The old participants were randomly assigned to moderate (O55, n = 13) or high-load (O80, n = 14) resistance training intervention (12 weeks; 3 times/week) corresponding to 55% or 80% of one repetition maximum, respectively. Young men (Y55, n = 11) were assigned to the moderate-intensity strengthening exercise program. Each group received the exact same training volume on triceps surae and quadriceps group (Reps x Sets x Intensity). The fitting polynomial regression equations for each of anatomical cross-sectional area-muscle length curves were used to calculate muscle volume (contractile content) before and after 12 weeks using magnetic resonance imaging scans. RESULTS: Only Rectus femoris and medial gastrocnemius muscle showed a higher relative anatomical cross-sectional area in the young than the elderly on the proximal end. The old group displayed a higher absolute volume of non-contractile material than young men in triceps surae (+ 96%). After training, Y55, O55 and O80 showed an increase in total quadriceps (+ 4.3%; + 6.7%; 4.2% respectively) and triceps surae (+ 2.8%; + 7.5%; 4.3% respectively) volume. O55 demonstrated a greater increase on average gains compared to Y55, while no difference between O55 and O80 was observed. CONCLUSIONS: Muscle loss with aging is region-specific for some muscles and uniform for others. Equivalent strength training volume at moderate or high intensities increased muscle volume with no differences in muscle volume gains for old men. These data suggest that physical exercise at moderate intensity (55 to 60% of one repetition maximum) can reverse the aging related loss of muscle mass. TRIAL REGISTRATION: NCT03079180 in ClinicalTrials.gov . Registration date: March 14, 2017.

UTE T2* mapping of tendinopathic patellar tendons: an MRI reproducibility study.

BACKGROUND: There is currently a lack of imaging modalities that can be used as a sensitive measure in tendinopathy. Recent findings suggest the applicability of ultra-short echo time (UTE) magnetic resonance imaging (MRI) T2* mapping in tendons, but the reproducibility remains unknown. PURPOSE: To evaluate test-retest reproducibility of UTE MRI T2* mapping of tendinopathic patellar tendons and to evaluate the intra- and inter-observer reproducibility of the measurement. MATERIAL AND METHODS: Fifteen patients with chronic patellar tendinopathy were evaluated with UTE MRI twice in a 3.0-T scanner on the same day. Manual segmentation of the patellar tendon was performed by two blinded investigators and automated T2*map reconstruction was performed in custom-made software. RESULTS: There was a significant and numerically small difference in test-retest T2* values (T2*meandiff = 0.06 ± 0.07 ms ≈ 3.7%; P = 0.006) with an ICC = 0.91 (95% confidence interval [CI] 0.58-0.98; typical error of 3.0%). The intra- and inter-observer reproducibility showed no significant bias (P = 0.493 and P = 0.052), and generally substantial reproducibility was demonstrated for T2* (intra-observer ICC = 0.99; 95% CI 0.98-1.00 and inter-observer ICC = 0.99; 95% CI 0.96-1.00, and typical error 1.3% and 1.3%, respectively). CONCLUSION: These data demonstrate a small bias between repeated measurements for UTE T2*, but with a very low associated mean difference (3.7%) between the two tests. The high ICC values and low typical error % demonstrate reproducibility of repeated T2*-mapping sessions. Further, the method showed substantial intra- and inter-observer reproducibility for T2* values proving feasibility for use of UTE T2* mapping in research and clinical practice.

Toxicogenicity and mechanistic pathways of aflatoxin B1 induced renal injury.

The study investigated the toxicogenic effects, molecular mechanisms and proteomic assessment of aflatoxin B1 (AFB1 ) on human renal cells. Hek293 cells were exposed to AFB1 (0-100 µM) for 24 h. The effect on cell viability was assessed using the methylthiazol tetrazolium (MTT) assay, which also produced the half maximal inhibitory concentration (IC50 ) used in subsequent assays. Free radical production was evaluated by quantifying malondialdehyde (MDA) and nitrate concentration, while DNA fragmentation was determined using the single cell gel electrophoresis (SCGE) assay and DNA gel electrophoresis. Damage to cell membranes was ascertained using the lactate dehydrogenase (LDH) assay. The concentration of ATP, reduced glutathione (GSH), necrosis, annexin V and caspase activity was measured by luminometry. Western blotting and quantitative PCR was used to assess the expression of proteins and genes associated with apoptosis and oxidative stress. The MTT assay revealed a reduction in cell viability of Hek293 cells as the AFB1 concentration was increased, with a half maximum inhibitory concentration (IC50 ) of 32.60 µM. The decreased viability corresponded to decreased ATP concentration. The upregulation of Hsp70 indicated that oxidative stress was induced in the AFB1 -treated cells. While this implies an increased production of free radicals, the accompanying upregulation of the antioxidant system indicates the activation of defense mechanisms to prevent cellular damage. Thus, membrane damage associated with increased radical formation was prevented as indicated by the reduced LDH release and necrosis. In addition, cytotoxic effects were evident as AFB1 activated the intrinsic pathway of apoptosis with corresponding increased DNA fragmentation, p53 and Bax upregulation and increased caspase activity, but externalization of phosphatidylserine (PS), a major hallmark of apoptosis, did not occur in AFB1 treated renal cells. The results suggest that AFB1 induced oxidative stress leading to cell death by the intrinsic pathway of apoptosis in renal cells.

Characterization of Leg Push Forces and Their Relationship to Velocity in On-Water Sprint Kayaking.

The purpose of this work was to describe the leg-muscle-generated push force characteristics in sprint kayak paddlers for females and males on water. Additionally, the relationship between leg pushing force characteristics and velocity was investigated. Twenty-eight paddlers participated in the study. The participants had five minutes of self-chosen warm-up and were asked to paddle at three different velocities, including maximal effort. Left- and right-side leg extension force were collected together with velocity. Linear regression analyses were performed with leg extension force characteristics as independent variables and velocity as the dependent variable. A second linear regression analysis investigated the effect of paddling velocity on different leg extension force characteristics with an explanatory model. The results showed that the leg pushing force elicits a sinus-like pattern, increasing and decreasing throughout the stroke cycle. Impulse over 10 s showed the highest correlation to maximum velocity (r = 0.827, p < 0.01), while a strong co-correlation was observed between the impulse per stroke cycle and mean force (r = 0.910, p < 0.01). The explanatory model results revealed that an increase in paddling velocity is, among other factors, driven by increased leg force. Maximal velocity could predict 68% of the paddlers' velocity within 1 km/h with peak leg force, impulse over 10 s, and stroke rate (p-value < 0.001, adjusted R-squared = 0.8). Sprint kayak paddlers elicit a strong positive relationship between leg pushing forces and velocity. The results confirm that sprint kayakers' cyclic leg movement is a key part of the kayaking technique.

How Precisely Can Easily Accessible Variables Predict Achilles and Patellar Tendon Forces during Running?

Patellar and Achilles tendinopathy commonly affect runners. Developing algorithms to predict cumulative force in these structures may help prevent these injuries. Importantly, such algorithms should be fueled with data that are easily accessible while completing a running session outside a biomechanical laboratory. Therefore, the main objective of this study was to investigate whether algorithms can be developed for predicting patellar and Achilles tendon force and impulse during running using measures that can be easily collected by runners using commercially available devices. A secondary objective was to evaluate the predictive performance of the algorithms against the commonly used running distance. Trials of 24 recreational runners were collected with an Xsens suit and a Garmin Forerunner 735XT at three different intended running speeds. Data were analyzed using a mixed-effects multiple regression model, which was used to model the association between the estimated forces in anatomical structures and the training load variables during the fixed running speeds. This provides twelve algorithms for predicting patellar or Achilles tendon peak force and impulse per stride. The algorithms developed in the current study were always superior to the running distance algorithm.

Influenza Viruses: Harnessing the Crucial Role of the M2 Ion-Channel and Neuraminidase toward Inhibitor Design.

As a member of the Orthomyxoviridae family of viruses, influenza viruses (IVs) are known causative agents of respiratory infection in vertebrates. They remain a major global threat responsible for the most virulent diseases and global pandemics in humans. The virulence of IVs and the consequential high morbidity and mortality of IV infections are primarily attributed to the high mutation rates in the IVs' genome coupled with the numerous genomic segments, which give rise to antiviral resistant and vaccine evading strains. Current therapeutic options include vaccines and small molecule inhibitors, which therapeutically target various catalytic processes in IVs. However, the periodic emergence of new IV strains necessitates the continuous development of novel anti-influenza therapeutic options. The crux of this review highlights the recent studies on the biology of influenza viruses, focusing on the structure, function, and mechanism of action of the M2 channel and neuraminidase as therapeutic targets. We further provide an update on the development of new M2 channel and neuraminidase inhibitors as an alternative to existing anti-influenza therapy. We conclude by highlighting therapeutic strategies that could be explored further towards the design of novel anti-influenza inhibitors with the ability to inhibit resistant strains.