GripAble: Interrater reliability and normative grip strength of UK population.

BACKGROUND: Hand grip strength is an established indicator of individual health status and is used as a biomarker for predicting mortality, disability, and disease risks. GripAble hand grip dynamometer offers a modernized approach to measuring grip strength with its digital and high-accuracy measurement system. PURPOSE: This study aimed to (1) assess the interrater reliability of maximum grip strength (MGS) measurement and (2) establish GripAble's own gender-, age group- and hand-stratified normative MGS reference values of the adult UK population. STUDY DESIGN: Cross-sectional study design. METHODS: Interrater reliability among three raters assessing 30 participants across diverse age groups was measured using the intraclass correlation. In the second study, 11 investigators gathered MGS data from 907 participants across diverse age groups and gender. The average, standard deviation, minimum, median, maximum, and percentiles of MGS were computed for each gender, age group, and hand (L/R). The relationship between MGS and age was examined using quantile regression analysis. Additionally, generalized linear model regression analysis was conducted to explore the influence of participants' demographics (gender, hand [L/R], hand length, hand circumference, age, weight, and height) on MGS. RESULTS: MGS measurements between raters showed excellent agreement (ICC(2,1) = 0.991, 95% confidence interval [0.98, 1.0]). The MGS and age relationship follows a curvilinear pattern, reaching a peak median MGS values of up to 20 kg between 30 and 49 years for females and up to 35 kg between 30 and 59 years for males. Subsequently, MGS declined as age advanced. Gender and hand (L/R) emerged as the primary factors influencing MGS, followed by hand length, hand circumference, age, weight, and height. CONCLUSIONS: The presented normative MGS reference values can be used for interpreting MGS measurements obtained from adults in the United Kingdom using GripAble. This study, along with previous studies on GripAble devices, confirms GripAble as a reliable and valid tool for measuring MGS.

Effects of Noxious Electrical Stimulation and Eccentric Exercise on Pain Sensitivity in Asymptomatic Individuals.

BACKGROUND: Achilles tendinopathy is a common overuse injury in running and jumping athletes. Currently, we do not understand why some conservative interventions (eg, noxious electrical stimulation and eccentric training) may reduce the pain associated with tendinopathy. OBJECTIVE: To determine whether noxious electrical stimulation (NES) or eccentric contractions would alter pain sensitivity around the asymptomatic Achilles tendon. DESIGN: A double-blind trial with block-randomization by gender into 3 intervention arms: NES, eccentric contractions, or low-intensity cycling. PARTICIPANTS: A total of 40 volunteers with no current pain conditions started the study, and 39 completed follow-up testing. METHODS: Participants underwent 2 baseline sessions to assess pain sensitivity response stability of pressure pain threshold (PPT), heat pain threshold (HPT), and heat temporal summation (HTS) over the Achilles tendon. Immediately after the second baseline session, participants performed 1 session of an intervention and were tested immediately postintervention and the next morning. Eccentric-only plantarflexor exercise was performed (4 sets of 15 repetitions) using full bodyweight and slow, 5-second contractions. Noxious electrical stimulation was applied to the Achilles for 20 minutes and dosed to the subjects' pain tolerance. Low-intensity cycling was dosed (60-70 W for 20 minutes) to minimize occurrence of exercise-induced hypoalgesia. The PPT was the primary outcome measure. RESULTS: For PPT, both NES (P < .001) and eccentric (P = .003) groups were less sensitive to pressure immediately posttreatment, and the eccentric group maintained this effect through the next morning (P = .043). No group differences were seen for HPT, but the NES (P = .031) and eccentric (P = .036) groups had less HTS the next morning. CONCLUSIONS: A single session of eccentric exercise and NES can produce immediate and next-day reductions in pain sensitivity in asymptomatic adults. The immediacy of these effects points toward a neurophysiologic mechanism. Future research needs to be performed in clinical populations and to assess any cumulative effects to repetitive intervention.

Loss of the extraembryonic ectoderm in Elf5 mutants leads to defects in embryonic patterning.

The extraembryonic ectoderm (ExE) is essential for mammalian placental formation and survival of the embryo in utero. We have obtained a mouse model lacking the ExE, by targeted deletion of the transcription factor Elf5. Although Elf5 mutant embryos implant and form an ectoplacental cone, no trophoblast stem (TS) cells can be derived, indicating that the absence of ExE is a result of the lack of TS cell maintenance. Embryos without ExE tissue are able to form the anterior visceral endoderm but fail to undergo gastrulation, demonstrating an essential role for the ExE in embryonic patterning during a defined window of development.

The sheep (Ovis aries) H19 gene: genomic structure and expression patterns, from the preimplantation embryo to adulthood.

H19, which is one of the most abundantly expressed imprinted genes during mammalian embryonic and foetal development, has been cloned from a ruminant. The sheep (Ovis aries) gene contains five exons interspersed by four exceptionally small introns; only short stretches of the nucleotide sequence, particularly in exon 1, show good homology with the human gene. The size of the exons and introns and the sequences around the splice junctions however, are well conserved between the species. The gene encodes a approximately 2.6 kb transcript which contains several potential short open reading frames, none of which is conserved between the ovine and human or murine transcripts, supporting a previous hypothesis that the gene product is the untranslated RNA itself. H19 mRNA is highly abundant in most ovine embryonic and foetal tissues of mesodermal and endodermal origins but was not detected in tissues of ectodermal origin such as the trophectoderm and the foetal brain. Expression of H19 in the extraembryonic membranes was detected only after the ovine conceptus began attachment to the endometrium and the embryo itself had undergone early organogenesis. This may be regarded as the first step in implantation; thus, in comparison with the mouse, the initiation of H19 expression appears to be determined by the timing of implantation rather than by the stage of development of the embryo itself. In most tissues, H19 expression is temporally linked to IGF2, a major foetal growth factor. The exceptions were the elongated blastocyst, the trophectoderm and brain, where low levels of IGF2 were observed in the absence of detectable H19. The abundance of H19 mRNA was in general, directly correlated with IGF2 mRNA abundance in mesodermal and endodermal tissues, suggesting that the two ovine genes share common regulatory elements that co-ordinately regulate their expression. Though both are generally regarded as embryonic and foetal genes, their expression was still maintained at a fairly high level in the adult sheep liver, lung, skeletal muscle, adrenal gland and kidney, suggesting that these organs are significant sources of IGF II in the adult.

Elevated basal expression of liver peroxisomal beta-oxidation enzymes and CYP4A microsomal fatty acid omega-hydroxylase in STAT5b(-/-) mice: cross-talk in vivo between peroxisome proliferator-activated receptor and signal transducer and activator of transcription signaling pathways.

Long-term treatment of rodents with peroxisome proliferator chemicals, a group of structurally diverse nongenotoxic carcinogens, leads to liver cancer in a process dependent on the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPARalpha). Previous in vitro studies have shown that growth hormone (GH) can inhibit PPARalpha-dependent gene expression by down-regulation of PPARalpha expression and by a novel inhibitory cross-talk involving the GH-activated transcription factor STAT5b. Presently, we evaluate the role of STAT5b in mediating these inhibitory actions of GH on PPAR function using a STATb-deficient mouse model. Protein levels of three PPARalpha-responsive peroxisomal beta-oxidation pathway enzymes (fatty acyl-CoA oxidase, 3-ketoacyl-CoA thiolase, and L-bifunctional enzyme) were increased up to two- to threefold in STAT5b(-/-) relative to wild-type control mouse liver, as was the basal expression of two PPARalpha-regulated cytochrome P450 4A proteins. In contrast, protein levels of two PPARalpha-unresponsive peroxisomal enzymes, catalase and urate oxidase, were not affected by the loss of STAT5b. A corresponding increase in expression of fatty acyl-CoA oxidase and L-bifunctional enzyme mRNA, as well as PPARalpha mRNA, was observed in the STAT5b-deficient mice, suggesting a transcriptional mechanism for the observed increases. Although basal liver expression of PPARalpha and its target genes was thus elevated in STAT5b(-/-) mice, the clofibrate-induced level of enzyme expression was unaffected, suggesting that the inhibitory effects of STAT5b are overcome at high concentrations of PPARalpha activators. These findings support the hypothesis that GH and potentially other endogenous activators of STAT5b help to maintain liver PPARalpha function at a low basal level and may thereby moderate PPARalpha-dependent hepatocarcinogenesis and other responses stimulated by exposure to low levels of environmental chemicals of the peroxisome proliferator class.

Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b).

Mice lacking suppressor of cytokine signaling-2 (SOCS-2) exhibit accelerated postnatal growth resulting in adult mice that are 1.3 to 1.5 times the size of normal mice. In this study we examined the somatotrophic pathway to determine whether the production or actions of GH or IGF-I are altered in these mice. We demonstrated that SOCS-2(-/-) mice do not have elevated GH levels and suffer no major pituitary dysmorphogenesis, and that SOCS-2-deficient embryonic fibroblasts do not have altered IGF-I signaling. Primary hepatocytes from SOCS-2(-/-) mice, however, did have moderately prolonged signal transducer and activator of transcription 5 signaling in response to GH stimulation. Furthermore, the deletion of SOCS-2 from mice also lacking signal transducer and activator of transcription 5b had little effect on growth, suggesting that the action of SOCS-2 may be the regulation of the GH signaling pathway.