Although these studies are invaluable in revealing the basic principles of mechanotransduction mechanisms, their physiological relevance is often uncertain. This review examines the recent progress of an alternative, "top-down" approach, in which the TME is treated as a holistic biological entity. This approach is made possible by recent advances in systems biology and fabrication technologies that enable the isolation, characterisation and reconstitution of TME. It is hoped that these new techniques will elucidate the nature of niche signals so that they can be extracted, replicated and controlled. This review summarises these emerging techniques and how the data they generated are changing our view on TME.Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition associated with ventricular arrhythmias and myocardial dysfunction; however, limited data exist on identifying patients at highest risk. The purpose of the study was to determine whether measures of right ventricular (RV) dysfunction on echocardiogram including RV strain were predictive of structural disease progression in ARVC. Methods and Results A retrospective analysis of serial echocardiograms from 40 patients fulfilling 2010 task force criteria for ARVC was performed to assess structural progression defined by an increase in proximal RV outflow tract dimensions (parasternal short or long axis) or decrease in RV fractional area change. Echocardiograms were analyzed for RV free-wall peak longitudinal systolic strain using 2-dimensional speckle tracking. Risk of structural progression and 5-year change in RV outflow tract measurements were compared with baseline RV strain. Of the 40 ARVC patients, 61% had structural progression with an increase in the mean parasternal short-axis RV outflow tract dimension from 36.2 to 38.5 mm (P=0.022) and 68% by increase in parasternal long-axis RV outflow tract dimension from 36.1 to 39.2 mm (P=0.001). RV fractional area change remained stable over time. Baseline RV strain was significantly associated with the risk of structural progression and 5-year rate of change. Patients with an RV strain more positive than -20% had a higher risk (odds ratio 18.4; 95% CI, 2.7-125.8; P=0.003) of structural progression. Conclusions RV free wall strain is associated with the rate of structural progression in patients with ARVC. It may be a useful marker in determining which patients require closer follow-up and treatment.Osteoporosis often leads to fragility fractures of the hip resulting in impaired quality of life and increased mortality. Augmenting the proximal femur could be an attractive option for prevention of fracture or fixation device failure. We describe a tissue engineering based strategy to enhance long-term bone formation in the femoral neck of osteoporotic rats by locally delivering bioactive molecules; bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) using a calcium sulphate/hydroxyapatite (CaS/HA) biomaterial. A defect was created by reaming the femoral neck canal of osteoporotic (OVX) rats and they were treated as follows G1. Empty, G2. CaS/HA, G3. CaS/HA + Systemic ZA, G4. CaS/HA + Local ZA and G5. CaS/HA + Local ZA + rhBMP-2. Bone formation was evaluated 6 months after treatment. Furthermore, radioactively labelled 14C-ZA was used to study the bioavailability of ZA at the defect location, which was determined using scintillation counting. Micro-CT indicated significantly higher bone volume (BV) in groups G4 and G5 compared to the other treatment groups. This was confirmed qualitatively by histological assessment. Addition of rhBMP-2 gave no additional benefit in this model. Local delivery of ZA performed better than systemic administration of ZA. Mechanical testing showed no differences between the groups, likely reflecting that the addition of bioactive molecules had limited effect on cortical bone or the choice of mechanical testing setup was not optimal. Scintillation counting revealed higher amounts of 14C-ZA present in the treated leg of G4 compared to its contralateral control and compared to G3 indicating that local ZA delivery can be used to achieve high local concentrations without causing a systemic effect. This long-term study shows that local delivery of ZA using a CaS/HA carrier can regenerate cancellous bone in the femoral neck canal and has clear implications for enhancing implant integration and fixation in fragile bone.Volitional sex is central to the sexual health and well-being of women and girls globally. To date, few studies have examined women's empowerment and its application to sexual health outcomes, including volitional sex. The aim of this study was to explore the relevance of a sexual and reproductive empowerment framework to volitional sex across four geographically and culturally diverse contexts in sub-Saharan Africa. Qualitative data were collected between July and August 2017 in four sites Ethiopia, Nigeria (Anambra and Kano states) and Uganda. BGB-8035 molecular weight A total of 352 women aged 15-49 and 88 men aged 18 and older were interviewed through 120 in-depth interviews and 38 focus group discussions (n = 440 total participants). Results describe the substantial barriers restraining women's sexual choices, particularly norms that stigmatise women's requests for sex, even within marriage. Results further highlight women's internal sexual motivations, particularly related to the enjoyment of sex and the role of sex in strengthening partner relationships. Future empowerment research and measurement should focus not only on sexual constraints, but also integrate internal motivations, in order to fully understand the factors that shape women's sexual health outcomes.Introduction Human papillomavirus (HPV) are the causative agent of mucosal neoplasia. Both cervical, anal and oropharyngeal cancers incidence is constantly increasing, making the HPV infection, a significant worldwide concern. Together, the CD8+ T cytotoxic cell-mediated response and the HPV-specific antibody response control most of the HPV infections before the development of cancers.Areas covered We searched the MEDLINE and EMBASE databases and identified 228 eligible studies from 1987 to 2019 which examines both naturally acquired and vaccine induced humoral immunity against HPV infection in female and male subjects from worldwide origin. Herein, we synthesize current knowledge on the features of systemic and mucosal humoral immunity against HPV. We discuss the issues of the balance between the viral clearance or the escape to the host immune response, the differences between natural and vaccine-induced HPV-specific antibodies and their neutralizing capability. We also discuss the protection afforded after natural infection or following prophylactic vaccination.