Skeletal stem cells: phenotype, biology and environmental niches informing tissue regeneration

Advances in our knowledge of the biology of skeletal stem cells, together with an increased understanding of the regeneration of normal tissue offer exciting new therapeutic approaches in musculoskeletal repair. Skeletal stem cells from various adult tissues such as bone marrow can be identified and isolated based on their expression of a panel of markers associated with smooth muscle cells, pericytes and endothelial cells. Thus, skeletal stem cell-like populations within bone marrow may share a common perivascular stem cell niche within the microvascular network. To date, the environmental niche that nurtures and maintains the stromal stem cell at different anatomical sites remains poorly understood. However, an understanding of the osteogenic and perivascular niches will inform identification of the key growth factors, matrix constituents and physiological conditions that will enhance the ex vivo amplification and differentiation of osteogenic stem cells to mimic native tissue critical for tissue repair. This review will examine skeletal stem cell biology, the advances in our understanding of the skeletal and perivascular niche and interactions therein and the opportunities to harness that knowledge for musculoskeletal regeneration.     

Bioactive nano‐fibrous scaffold for vascularized craniofacial bone regeneration

There has been a growing demand for bone grafts for correction of bone defects in complicated fractures or tumours in the craniofacial region. Soft flexible membrane like material that could be inserted into defect by less invasive approaches; promote osteoconductivity and act as a barrier to soft tissue in growth while promoting bone formation is an attractive option for this region. Electrospinning has recently emerged as one of the most promising techniques for fabrication of extracellular matrix such as nano‐fibrous scaffolds that can serve as a template for bone formation. To overcome the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA)‐poly (ε) caprolactone (PCL)‐Hydroxyapatite based bioceramic (HAB), namely, PVA‐PCL‐HAB. The scaffold prepared by dual electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic PCL by combination with a hydrophilic PVA and the HAB can contribute to enhance osteoconductivity. We characterized the physicochemical and biocompatibility properties of the new scaffold material. Our results indicate PVA‐PCL‐HAB scaffolds support attachment and growth of stromal stem cells; [human bone marrow skeletal (mesenchymal) stem cells and dental pulp stem cells]. In addition, the scaffold supported in vitro osteogenic differentiation and in vivo vascularized bone formation. Thus, PVA‐PCL‐HAB scaffold is a suitable potential material for therapeutic bone regeneration in dentistry and orthopaedics.     

Maldistribution of pulmonary blood flow in patients after the Fontan operation is associated with worse exercise capacity

Background

Maldistribution of pulmonary artery blood flow (MPBF) is a potential complication in patients who have undergone single ventricle palliation culminating in the Fontan procedure. Cardiovascular magnetic resonance (CMR) is the best modality that can evaluate MPBF in this population. The purpose of this study is to identify the prevalence and associations of MPBF and to determine the impact of MPBF on exercise capacity after the Fontan operation.

Methods

This retrospective single-center study included all patients after Fontan operation who had maximal cardiopulmonary exercise test (CPET) and CMR with flow measurements of the branch pulmonary arteries. MPBF was defined as >?20% difference in branch pulmonary artery flow. Exercise capacity was measured as percent of predicted oxygen consumption at peak exercise (% predicted VO₂). Linear and logistic regression models were used to determine univariate and multivariable predictors of exercise capacity and correlates of MPBF, respectively.

Results

A total of 147 patients who had CMR between 1999 and 2017 were included (median age at CMR 21.8?years [interquartile range (IQR) 16.5–30.6]) and the median time between CMR and CPET was 2.8?months [IQR 0–13.8]. Fifty-three patients (36%) had MPBF (95% CI 29–45%). The mean % predicted VO₂ was 63?±?16%. Patients with MPBF had lower mean % predicted VO₂ compared to patients without MPBF (60?±?14% versus 65?±?16%, p?=?0.04). On multivariable analysis, a lower % predicted VO₂ was independently associated with longer time since Fontan, higher ventricular mass-to-volume ratio, and MPBF. On multivariable analysis, only compression of the branch pulmonary arteries by the ascending aorta or aortic root was associated with MPBF (OR 6.5, 95% CI 5.6–7.4, p?<?0.001).

Conclusion

In patients after the Fontan operation, MPBF is common and is independently associated with lower exercise capacity. MPBF was most likely to be caused by pulmonary artery compression by the aortic root or the ascending aorta. This study identifies MPBF as an important risk factor and as a potential target for therapeutic interventions in this fragile patient population.

     

Household Debt and Relation to Intimate Partner Violence and Husbands' Attitudes Toward Gender Norms: A Study Among Young Married Couples in Rural Maharashtra,India

Objective

Evidence has linked economic hardship with increased intimate partner violence (IPV) perpetration among males. However, less is known about how economic debt or gender norms related to men''s roles in relationships or the household, which often underlie IPV perpetration, intersect in or may explain these associations. We assessed the intersection of economic debt, attitudes toward gender norms, and IPV perpetration among married men in India.

Methods

Data were from the evaluation of a family planning intervention among young married couples (n=1,081) in rural Maharashtra, India. Crude and adjusted logistic regression models for dichotomous outcome variables and linear regression models for continuous outcomes were used to examine debt in relation to husbands'' attitudes toward gender-based norms (i.e., beliefs supporting IPV and beliefs regarding male dominance in relationships and the household), as well as sexual and physical IPV perpetration.

Results

Twenty percent of husbands reported debt. In adjusted linear regression models, debt was associated with husbands'' attitudes supportive of IPV (b=0.015, p=0.004) and norms supporting male dominance in relationships and the household (b=0.006, p=0.003). In logistic regression models adjusted for relevant demographics, debt was associated with perpetration of physical IPV (adjusted odds ratio [AOR] = 1.4, 95% confidence interval [CI] 1.1, 1.9) and sexual IPV (AOR=1.6, 95% CI 1.1, 2.1) from husbands. These findings related to debt and relation to IPV were slightly attenuated when further adjusted for men''s attitudes toward gender norms.

Conclusion

Findings suggest the need for combined gender equity and economic promotion interventions to address high levels of debt and related IPV reported among married couples in rural India.Intimate partner violence (IPV) perpetrated by male partners or husbands occurs in high proportions globally as well as in low- to middle-income countries such as India.^1,2 One recent multi-country household study found that 37% of men in India reported having ever perpetrated physical violence against a female intimate partner in their lifetime. The health burden of IPV has been well demonstrated, with significant effects on women''s sexual and reproductive health (e.g., increased sexually transmitted infections, unintended pregnancy, and poor pregnancy outcomes),^3–5 mental health (e.g., anxiety, depression, and substance use),^6,7 as well as a multitude of other poor health outcomes among women and their children (e.g., maternal and child malnutrition and infant death).^8,9Recent research among women has identified economic hardship (e.g., financial dependence on male partners and economic instability) as increasing women''s vulnerability to IPV.^10,11 Although studies have found an association between economic stressors and reports of male IPV perpetration,^12–16 no research has examined debt in relation to these outcomes.Debt and other economic decisions in the context of marriage, particularly in rural India, are largely under the control of husbands. Taking on debt may be associated with economic hardship, heightening stress levels among men, and, in turn, IPV. Also, previous work documenting the association between economic hardship and increased IPV perpetration by males^12–15 has largely been explained by perceptions related to men''s roles financially within the family (e.g., men who do not feel that they are providing financially for their families may perceive that they are not fulfilling their roles as husbands/males, and this perception related to lack of role fulfillment may escalate into violence). Given that a decision to take on debt appears to be largely controlled by men in this context and likely tied to their perceived role of providing financially for the family, a man''s decision to take out loans may be determined, in part, by their support of masculine gender norms (e.g., a man''s role in the family and male dominance and control in the household). In addition, given previous work highlighting the association between masculine gender norms and a number of risk behaviors among boys and men (e.g., substance and tobacco use and behaviors resulting in unintentional injury),^17–21 such gender norms may also be linked to taking on risks associated with debt, as well as debt-acquiring behaviors (e.g., spending money on nonessential goods such as alcohol).Gender norms pertaining to IPV, relationships, and the household are also important driving factors in terms of understanding men''s behaviors related to IPV. Cross-cultural research has shown that societies with greater gender inequities in social norms and policies have a higher prevalence of IPV.²¹ In the context of India and elsewhere, women''s low status in families and high levels of societal tolerance and acceptance of IPV promote IPV.²²More research is needed to understand economic hardship, and debt specifically, in relation to attitudes toward gender norms and IPV perpetration. Many studies have hypothesized that stress related to economic hardship and debts increases IPV perpetration;^12–15 however, less research has sought to understand the role of attitudes supportive of men''s more traditional gender norms in relationships or households in contributing to decisions to take on debt as well as in terms of explaining its association with increased IPV perpetration. Increased understanding of the mechanisms that explain associations between economic hardship/debt and IPV is needed to inform prevention approaches, particularly given the increasing number of economic promotion interventions being implemented globally and throughout India.Thus, the primary objective of the current study was to assess household debt in relation to husbands'' support of gender-inequitable norms and norms promoting IPV as well as husbands'' use of IPV against wives. The secondary objective of this study was to assess whether or not gender-based attitudes are important factors in debt and IPV, as well as in explaining an association between debt and increased risk for IPV perpetration among husbands.     

Stability of Cefazolin in Polyisoprene Elastomeric Infusion Devices

Purpose

The aim was to investigate the stability of cefazolin in elastomeric infusion devices.

Cytotoxic Effect of (Z)-Ethylidene-4,6-Dimethoxycoumaran-3-One Isolated from Pogostemon quadrifolius (Benth.) on PC-3 and DU-145 Prostate Cancer Cells

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The study was conducted to identify the antiproliferative property and the mode of action of...     

The Effect of Commuting Patterns on HIV Care Attendance Among Men Who Have Sex With Men (MSM) in Atlanta,Georgia

Background

Travel-related barriers to human immunodeficiency virus (HIV) care, such as commute time and mode of transportation, have been reported in the United States.

Objective

The objective of the study was to investigate the association between public transportation use and HIV care attendance among a convenience sample of Atlanta-based, HIV-positive men who have sex with men (MSM), evaluate differences across regions of residence, and estimate the relationship between travel distance and time by mode of transportation taken to attend appointments.

Methods

We used Poisson regression to estimate the association between use of public transportation to attend HIV-related medical visits and frequency of care attendance over the previous 12 months. The relationship between travel distance and commute time was estimated using linear regression. Kriging was used to interpolate commute time to visually examine geographic differences in commuting patterns in relation to access to public transportation and population-based estimates of household vehicle ownership.

Results

Using public transportation was associated with lower rates of HIV care attendance compared to using private transportation, but only in south Atlanta (south: aRR: 0.75, 95% CI 0.56, 1.0, north: aRR: 0.90, 95% CI 0.71, 1.1). Participants living in south Atlanta were more likely to have longer commute times associated with attending HIV visits, have greater access to public transportation, and may live in areas with low vehicle ownership. A majority of attended HIV providers were located in north and central Atlanta, despite there being participants living all across the city. Estimated commute times per mile traveled were three times as high among public transit users compared to private transportation users.

Conclusions

Improving local public transit and implementing use of mobile clinics could help address travel-related barriers to HIV care.