Abdominal and hip flexor muscle activation during various training exercises

 The purpose of this study was to provide objective information on the involvement of different abdominal and hip flexor muscles during various types of common training exercises used in rehabilitation and sport. Six healthy male subjects performed altogether 38 different static and dynamic training exercises – trunk and hip flexion sit-ups, with various combinations of leg position and support, and bi- and unilateral leg lifts. Myoelectric activity was recorded with surface electrodes from the rectus abdominis, obliquus externus, obliquus internus, rectus femoris, and sartorius muscles and with indwelling fine-wire electrodes from the iliacus muscle. The mean electromyogram amplitude, normalised to the highest observed value, was compared between static and dynamic exercises separately. The hip flexors were highly activated only in exercises involving hip flexion, either lifting the whole upper body or the legs. In contrast, the abdominal muscles showed marked activation both during trunk and hip flexion sit-ups. In hip flexion sit-ups, flexed and supported legs increased hip flexor activation, whereas such modifications did not generally alter the activation level of the abdominals. Bilateral, but not unilateral, leg lifts required activation of abdominal muscles. In trunk flexion sit-ups an increased activation of the abdominal muscles was observed with increased flexion angle, whereas the opposite was true for hip flexion sit-ups. Bilateral leg lifts resulted in higher activity levels than hip flexion sit-ups for the iliacus and sartorius muscles, while the opposite was true for rectus femoris muscles. These data could serve as a basis for improving the design and specificity of test and training exercises. Accepted: 12 August 1996     

A Validated Prognostic Biomarker Score for Adult Patients with Nonmetastatic Soft Tissue Sarcomas of the Trunk and Extremities

BACKGROUND: The prognostic value of serum biomarkers in soft tissue sarcoma (STS) is limited, and its clinical applicability is compromised by a common inability to adjust for important confounders. The aim of this study was to determine the prognostic value of pretreatment biomarkers on disease-specific survival (DSS) adjusted for confounders. METHODS: The study included 818 patients with localized STS. Pretreatment levels of albumin, C-reactive protein, hemoglobin, neutrophils, and lymphocytes were tested individually and combined in prognostic scores: neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), and Aarhus Composite Biomarker Score (ACBS) which includes all five biomarkers. Patients were randomly split into a test cohort and a validation cohort. The prognostic value of biomarkers on DSS was estimated using crude and adjusted Cox proportional hazard models. The different biomarker scores were compared using Akaike's information criteria. RESULTS: In the test cohort of 403 patients, all biomarkers except lymphocyte count were significant prognostic factors for DSS also after adjusting for confounders. NLR, GPS, and ACBS were independently associated with decreased survival; however, ACBS was significantly superior to NLR (P = .02) and GPS (P = .002). These findings were validated in the randomly assigned validation cohort of 415 patients. In the pooled data of 818 patients, the ACBS performed better than GPS and NLR. ACBS 2 was independently associated with decreased DSS compared to ACBS 0, hazard ratio 2.3[95% confidence interval: 1.5-3.5], P < .001. CONCLUSION: Patients with abnormal values in more than one serum biomarkers had a significant additional risk of dying compared to patients with only one abnormal value. ACBS was validated as an independent prognostic factor that is superior to both NLR and GPS.     

Dominant negative <Emphasis Type="Italic">Bmp5</Emphasis>mutation reveals key role of BMPs in skeletal response to mechanical stimulation

Background  

Over a hundred years ago, Wolff originally observed that bone growth and remodeling are exquisitely sensitive to mechanical forces acting on the skeleton. Clinical studies have noted that the size and the strength of bone increase with weight bearing and muscular activity and decrease with bed rest and disuse. Although the processes of mechanotransduction and functional response of bone to mechanical strain have been extensively studied, the molecular signaling mechanisms that mediate the response of bone cells to mechanical stimulation remain unclear.     

The design and synthesis of potent and cell-active allosteric dual Akt 1 and 2 inhibitors devoid of hERG activity

This letter details the attenuation of hERG in a class of Akt inhibitors through heteroatom insertions into aromatic rings. The development of a cell-active dual Akt 1 and 2 inhibitors devoid of hERG activity is discussed using structure–activity relationships.     

Genotoxicity and mutagenicity of iron and copper in mice

The toxicity of trace metals is still incompletely understood. We have previously shown that a single oral dose of iron or copper induces genotoxic effects in mice in vivo, as detected by single cell gel electrophoresis (comet assay). Here, we report the effect of these metals on subchronic exposure. Mice were gavaged for six consecutive days with either water, 33.2 mg/kg iron, or 8.5 mg/kg copper. On the 7th day, the neutral and alkaline comet assays in whole blood and the bone marrow micronucleus (MN) test were used as genotoxicity and mutagenicity endpoints, respectively. Particle induced X-ray emission was used to determine liver levels of the metals. Females showed a slightly lower DNA damage background, but there was no significant difference between genders for any endpoint. Iron and copper were genotoxic and mutagenic. While copper was more genotoxic in the neutral version, iron was more genotoxic in the alkaline version of the comet assay. Copper induced the highest mutagenicity as evaluated by the MN test. Iron was not mutagenic to male mice. Iron is thought to induce more oxidative lesions than copper, which are primarily detected in the alkaline comet assay. Treatment with iron, but not with copper, induced a significant increase in the hepatic level of the respective metal, reflecting different excretion strategies.     

Carbon utilization profiles of bacteria colonizing the headbox water of two paper machines in a Canadian mill

Forty-one bacterial strains isolated from the headbox water of two machines in a Canadian paper mill were associated with the genera Asticcacaulis, Acidovorax, Bacillus, Exiguobacterium, Hydrogenophaga, Pseudomonas, Pseudoxanthomonas, Staphylococcus, Stenotrophomonas based on the sequence of their 16S rRNA genes. The metabolic profile of these strains were determined using Biolog EcoPlate, and the bacteria were divided into four metabolic groups. Metabolic profiles of the bacterial communities colonizing the headbox water of two paper machines was also determined weekly over a 1 year period. The only compound that was not reduced by the bacterial community was 2-hydroxybenzoic acid. Utilization frequency of the other carbon sources in the Biolog EcoPlate ranged from 3 to 100%. The metabolic profiles of the bacterial community did not vary considerably between the two paper machines. However, the metabolic profile varied among the sampling dates.     

Thyroid receptor ligands. Part 5: novel bicyclic agonist ligands selective for the thyroid hormone receptor beta

Based on the examination of the crystal structure of rat TRbeta complexed with 3,5,3'-triiodo-l-thyronine (2) a novel TRbeta-selective indole derivative 6b was prepared and tested in vitro. This compound was found to be 14 times selective for TRbeta over TRalpha in binding and its beta-selectivity could be rationalized through the comparison of the X-ray crystallographic structures of 6b complexed with TRalpha and TRbeta.     

Risk prediction of complex diseases from family history and known susceptibility loci, with applications for cancer screening

Risk prediction based on genomic profiles has raised a lot of attention recently. However, family history is usually ignored in genetic risk prediction. In this study we proposed a statistical framework for risk prediction given an individual's genotype profile and family history. Genotype information about the relatives can also be incorporated. We allow risk prediction given the current age and follow-up period and consider competing risks of mortality. The framework allows easy extension to any family size and structure. In addition, the predicted risk at any percentile and the risk distribution graphs can be computed analytically. We applied the method to risk prediction for breast and prostate cancers by using known susceptibility loci from genome-wide association studies. For breast cancer, in the population the 10-year risk at age 50 ranged from 1.1% at the 5th percentile to 4.7% at the 95th percentile. If we consider the average 10-year risk at age 50 (2.39%) as the threshold for screening, the screening age ranged from 62 at the 20th percentile to 38 at the 95th percentile (and some never reach the threshold). For women with one affected first-degree relative, the 10-year risks ranged from 2.6% (at the 5th percentile) to 8.1% (at the 95th percentile). For prostate cancer, the corresponding 10-year risks at age 60 varied from 1.8% to 14.9% in the population and from 4.2% to 23.2% in those with an affected first-degree relative. We suggest that for some diseases genetic testing that incorporates family history can stratify people into diverse risk categories and might be useful in targeted prevention and screening.     

Vinculin activation is necessary for complete talin binding

Focal adhesions are critical to a number of cellular processes that involve mechanotransduction and mechanical interaction with the cellular environment. The growth and strengthening of these focal adhesions is dependent on the interaction between talin and vinculin. This study investigates said interaction and how vinculin activation influences it. Using molecular dynamics, the interaction between talin's vinculin binding site (VBS) and vinculin's domain 1 (D1) is simulated both before and after vinculin activation. The simulations of VBS binding to vinculin before activation suggest the proximity of the vinculin tail to D1 prevents helical movement in D1 and thus prevents binding of VBS. In contrast, interaction of VBS with activated vinculin shows the possibility of complete VBS insertion into D1. In the simulations of both activated and autoinhibited vinculin where VBS fails to fully bind, VBS demonstrates significant hydrophobic interaction with surface residues in D1. These interactions link VBS to D1 even without its proper insertion into the hydrophobic core. Together these simulations suggest VBS binds to vinculin with the following mechanism: 1), VBS links to D1 via surface hydrophobic interactions; 2), vinculin undergoes activation and D1 is moved away from the vinculin tail; 3), helices in D1 undergo conformational change to allow VBS binding; and 4), VBS inserts itself into the hydrophobic core of D1.