Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

Tendon Is Covered by a Basement Membrane Epithelium That Is Required for Cell Retention and the Prevention of Adhesion Formation

The ability of tendons to glide smoothly during muscle contraction is impaired after injury by fibrous adhesions that form between the damaged tendon surface and surrounding tissues. To understand how adhesions form we incubated excised tendons in fibrin gels (to mimic the homeostatic environment at the injury site) and assessed cell migration. We noticed cells exiting the tendon from only the cut ends. Furthermore, treatment of the tendon with trypsin resulted in cell extravagation from the shaft of the tendons. Electron microscopy and immunolocalisation studies showed that the tendons are covered by a novel cell layer in which a collagen type IV/laminin basement membrane (BM) overlies a keratinised epithelium. PCR and western blot analyses confirmed the expression of laminin β1 in surface cells, only. To evaluate the cell retentive properties of the BM in vivo we examined the tendons of the Col4a1+/Svc mouse that is heterozygous for a G-to-A transition in the Col4a1 gene that produces a G1064D substitution in the α1(IV) chain of collagen IV. The flexor tendons had a discontinuous BM, developed fibrous adhesions with overlying tissues, and were acellular at sites of adhesion formation. In further experiments, tenotomy of wild-type mice resulted in expression of laminin throughout the adhesion. In conclusion, we show the existence of a novel tendon BM-epithelium that is required to prevent adhesion formation. The Col4a1+/Svc mouse is an effective animal model for studying adhesion formation because of the presence of a structurally-defective collagen type IV-containing BM

Weaned age variation in the Virunga mountain gorillas (Gorilla beringei beringei)

The final publication is available at Springer via http://dx.doi.org/10.1007/s00265-016-2066-6Weaning marks an important milestone during life history in mammals indicating nutritional independence from the mother. Age at weaning is a key measure of maternal investment and care, affecting female reproductive rates, offspring survival and ultimately the viability of a population. Factors explaining weaned age variation in the endangered mountain gorilla are not yet well understood. This study investigated the impact of group size, group type (one-male versus multi-male), offspring sex, as well as maternal age, rank, and parity on weaned age variation in the Virunga mountain gorilla population. The status of nutritional independence was established in 69 offspring using long-term suckling observations. A Cox-regression with mixed effects was applied to model weaned age and its relationship with covariates. Findings indicate that offspring in one-male groups are more likely to be weaned earlier than offspring in multi-male groups, which may reflect a female reproductive strategy to reduce higher risk of infanticide in one-male groups. Inferior milk production capacity and conflicting resource allocation between their own and offspring growth may explain later weaning in primiparous mothers compared to multiparous mothers. Sex-biased weaned age related to maternal condition defined by parity, rank, and maternal age will be discussed in the light of the Trivers-Willard hypothesis. Long-term demographic records revealed no disadvantage of early weaning for mother or offspring. Population growth and two peaks in weaned age within the Virunga population encourage future studies on the potential impact of bamboo shoots as a weaning food and other environmental factors on weaning

Reproductive and Life History Parameters of Wild Female Macaca assamensis

Information on basic reproductive parameters and life-history traits is crucial for the understanding of primate evolution, ecology, social behavior, and reproductive strategies. Here, we report 4 yr of data on reproductive and life-history traits for wild female Assamese macaques (Macaca assamensis) at Phu Khieo Wildlife Sanctuary, northeastern Thailand. During 2 consecutive reproductive seasons, we investigated reproductive behavior and sexual swelling size in 16 females and collected 1832 fecal samples. Using enzyme immunoassays, we measured fecal estrogen and progesterone metabolites to assess ovarian activity and timing of ovulation and to ascertain conceptions and pregnancies. Timing of reproduction was strictly seasonal (births: April–July, 86% in April–June, 4 yr, n = 29; conceptions: October–February, 65% in December–January, 2 yr, n = 17). Females showed no cyclic ovarian activity outside the mating season and conceived in their first or second cycle (mean: 1.2 cycles to conception, n = 13). Gestation length was on average 164.2 d (range: 158–170, n = 10), and females had their first infant at an age of 5 yr (n = 4). Interbirth intervals were bimodally distributed, with females giving birth on average every 13.9 or 23.2 mo. Shorter interbirth intervals were linked to early parturition within the birth season. Most females displayed subcaudal sexual swellings which, however, did not reliably indicate female reproductive status or fertility. Overall, our results fall within the range of findings reported for other macaque species. These results thus add to the growing body of information available for wild macaques, facilitating comparative studies for a better understanding of interspecific differences in social and reproductive patterns

Supermarket Healthy Eating for Life (SHELf): protocol of a randomised controlled trial promoting healthy food and beverage consumption through price reduction and skill-building strategies

Background: In the context of rising food prices, there is a need for evidence on the most effective approaches for promoting healthy eating. Individually-targeted behavioural interventions for increasing food-related skills show promise, but are unlikely to be effective in the absence of structural supports. Fiscal policies have been advocated as a means of promoting healthy eating and reducing obesity and nutrition-related disease, but there is little empirical evidence of their effectiveness. This paper describes the Supermarket Healthy Eating for LiFe (SHELf) study, a randomised controlled trial to investigate effectiveness and cost-effectiveness of a tailored skill-building intervention and a price reduction intervention, separately and in combination, against a control condition for promoting purchase and consumption of healthy foods and beverages in women from high and low socioeconomic groups.Methods/design: SHELf comprises a randomised controlled trial design, with participants randomised to receive either (1) a skill-building intervention; (2) price reductions on fruits, vegetables and low-joule soft drink beverages and water; (3) a combination of skill-building and price reductions; or (4) a control condition. Five hundred women from high and low socioeconomic areas will be recruited through a store loyalty card program and local media. Randomisation will occur on receipt of informed consent and baseline questionnaire. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups.Discussion: This study will build on a pivotal partnership with a major national supermarket chain and the Heart Foundation to investigate the effectiveness of intervention strategies aimed at increasing women&rsquo;s purchasing and consumption of fruits and vegetables and decreased purchasing and consumption of sugar-sweetened beverages. It will be among the first internationally to examine the effects of two promising approaches - skill-building and price reductions - on diet amongst women.<br /

Transcriptomic analysis of the temporal host response to skin infestation with the ectoparasitic mite Psoroptes ovis

<p>Abstract</p> <p>Background</p> <p>Infestation of ovine skin with the ectoparasitic mite <it>Psoroptes ovis </it>results in a rapid cutaneous immune response, leading to the crusted skin lesions characteristic of sheep scab. Little is known regarding the mechanisms by which such a profound inflammatory response is instigated and to identify novel vaccine and drug targets a better understanding of the host-parasite relationship is essential. The main objective of this study was to perform a combined network and pathway analysis of the <it>in vivo </it>skin response to infestation with <it>P. ovis </it>to gain a clearer understanding of the mechanisms and signalling pathways involved.</p> <p>Results</p> <p>Infestation with <it>P. </it>ovis resulted in differential expression of 1,552 genes over a 24 hour time course. Clustering by peak gene expression enabled classification of genes into temporally related groupings. Network and pathway analysis of clusters identified key signalling pathways involved in the host response to infestation. The analysis implicated a number of genes with roles in allergy and inflammation, including pro-inflammatory cytokines (<it>IL1A, IL1B, IL6, IL8 </it>and <it>TNF</it>) and factors involved in immune cell activation and recruitment (<it>SELE, SELL, SELP, ICAM1, CSF2, CSF3, CCL2 </it>and <it>CXCL2</it>). The analysis also highlighted the influence of the transcription factors NF-kB and AP-1 in the early pro-inflammatory response, and demonstrated a bias towards a Th2 type immune response.</p> <p>Conclusions</p> <p>This study has provided novel insights into the signalling mechanisms leading to the development of a pro-inflammatory response in sheep scab, whilst providing crucial information regarding the nature of mite factors that may trigger this response. It has enabled the elucidation of the temporal patterns by which the immune system is regulated following exposure to <it>P. ovis</it>, providing novel insights into the mechanisms underlying lesion development. This study has improved our existing knowledge of the host response to <it>P. ovis</it>, including the identification of key parallels between sheep scab and other inflammatory skin disorders and the identification of potential targets for disease control.</p

Novel strategies in tendon and ligament tissue engineering: Advanced biomaterials and regeneration motifs

Tendon and ligaments have poor healing capacity and when injured often require surgical intervention. Tissue replacement via autografts and allografts are non-ideal strategies that can lead to future problems. As an alternative, scaffold-based tissue engineering strategies are being pursued. In this review, we describe design considerations and major recent advancements of scaffolds for tendon/ligament engineering. Specifically, we outline native tendon/ligament characteristics critical for design parameters and outcome measures, and introduce synthetic and naturally-derived biomaterials used in tendon/ligament scaffolds. We will describe applications of these biomaterials in advanced tendon/ligament engineering strategies including the utility of scaffold functionalization, cyclic strain, growth factors, and interface considerations. The goal of this review is to compile and interpret the important findings of recent tendon/ligament engineering research in an effort towards the advancement of regenerative strategies

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /