Bone marrow-derived mesenchymal stem cells in repair of the injured lung

We sought to determine whether an intact bone marrow is essential to lung repair following bleomycin-induced lung injury in mice, and the mechanisms of any protective effects conferred by bone marrow-derived mesenchymal stem cell (BMDMSC) transfer. We found that myelosupression increased susceptibility to bleomycin injury and that BMDMSC transfer was protective. Protection was associated with the differentiation of engrafted BMDMSC into specific and distinct lung cell phenotypes, with an increase in circulating levels of G-CSF and GM-CSF (known for their ability to promote the mobilization of endogenous stem cells) and with a decrease in inflammatory cytokines. In vitro, cells from injured, but not from normal, mouse lung produced soluble factors that caused BMDMSC to proliferate and migrate toward the injured lung. We conclude that bone marrow stem cells are important in the repair of bleomycin-injured lung and that transfer of mesenchymal stem cells protects against the injury. BMDMSC localize to the injured lung and assume lung cell phenotypes, but protection from injury and fibrosis also involves suppression of inflammation and triggering production of reparative growth factors.     

Heterogeneity in the plasma levels of two acute-phase proteins in mice from inbred strains infected withTrypanosoma cruzi

We analyzed the variations observed in the plasma levels of both alpha-macroglobulins (AM) and serum amyloid P (SAP) in mice from three different inbred strains (C3H, Balb/C and C57black/6) acutely infected withTrypanosoma cruzi. SAP levels increased in C57black/6 and Balb/C mice but not C3H mice. AM levels increased in all C3H mice but not in C57black/6 mice and rose slightly in only 43% of the Balb/C mice. AM and SAP levels are differently modulated in patterns that may be strain-determined.     

A Systematic Review and Meta-Analysis of Risk Factors for Postpartum Depression Among Latinas

Maternal and Child Health Journal - The purpose of this article was to describe the findings from a systematic review, quality review, and meta-analysis of risk factors for postpartum depression...     

Effects of the Family Check-Up 4 Health on Parenting and Child Behavioral Health: A Randomized Clinical Trial in Primary Care

The Family Check-Up 4 Health (FCU4Health) is an adaptation of the Family Check-Up (FCU) for delivery in primary care settings. While maintaining the original FCU’s focus on parenting and child behavioral health, we added content targeting health behaviors. This study evaluated whether the adapted FCU maintained positive effects on parenting (positive behavior support, limit setting, parental warmth) and child behavioral health (self-regulation, conduct problems, emotional problems). Pediatric (6–12 years) primary care patients with a BMI?≥?85^th%ile (n?=?240) were recruited from primary care clinics in Phoenix. Children were 75% Latino, 49% female, and 73% Medicaid recipients. This type 2 effectiveness-implementation hybrid trial compared families randomized to FCU4Health (n?=?141) or usual care (n?=?99). FCU4Health was delivered over a period of 6 months. This study focuses on a priori secondary outcomes included parenting and child behavioral health targets of the original FCU, assessed at baseline and 3, 6, and 12 months. Significant improvements were found for the FCU4Health condition, compared to usual care, in parenting from baseline to the 3-month assessment [β?=?.17 (.01; .32)]. Parenting predicted improvements in child self-regulation at 6-months [β?=?.17 (.03; .30)], which in turn predicted reductions in conduct problems [β?=?? .38 (? .51; ? .23)] and emotional problems [β?=?? .24 (? .38; ? .09)] at 12 months. Ethnicity and language of delivery (English or Spanish) did not moderate these effects. The FCU4Health can improve parenting and child behavioral health outcomes when delivered in primary care.

Trial Registration Trial registration number: NCT03013309 ClinicalTrials.gov

     

Facilitators and Barriers in Cross-Country Transport of Evidence-based Preventive Interventions: a Case Study Using the Family Check-Up

Prevention Science - This study is a qualitative analysis of facilitators and barriers in the dissemination of Family Check-Up (FCU), a U.S.-developed preventive intervention in Sweden. The FCU is...     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Left ventricular mass index and ventricular contractility improvement in patients with severe obesity following rapid weight loss after bariatric surgery

BackgroundObesity is a well-known risk factor for heart disease, resulting in a broad spectrum of cardiovascular changes. Left ventricular mass (LVM) and contractility are recognized markers of cardiac function.ObjectivesTo determine the changes of LVM and contractility after bariatric surgery (BaS).SettingUniversity hospital, United StatesMethodsTo determine the cardiac changes in ventricular mass, ventricular contractility, and left ventricular shortening fraction (LVSF), we retrospectively reviewed the 2-dimensional echocardiographic parameters of patients with obesity who underwent BaS at our institution. We compared these results before and after BaS.ResultsA total of 40 patients met the inclusion criteria. The majority were females (57.5%; n = 23), with an average age of 63.5 ± 12.1. The excess body mass index (BMI) lost at 12 months was 48.9 ± 28.9%. The percent total weight loss after BaS was 16.46 ± 9.9%. The left ventricular mass was 234.9 ± 88.1 grams before and 181.5 ± 52.7 grams after BaS (P = .002). The LVM index was 101.3 ± 38.3 g/m² before versus 86.7 ± 26.6 g/m² after BaS (P = .005). The LVSF was 31% ± 8.8% before and 36.3% ± 8.2% after BaS (P = .007). We found a good correlation between the decrease in LVM index and the BMI after BaS (P = .03).ConclusionRapid weight loss results in a decrease of the LVM index, as well as improvement in the left ventricular muscle contractility. Our results suggest that there is left ventricular remodeling and an improvement of heart dynamics following bariatric surgery. Further studies are needed to better assess these findings.     

Changes in retinoblastoma gene expression during cervical cancer progression

The role of tumour suppressor genes in the development of human cancers has been studied extensively. In viral carcinogenesis, the inactivation of suppressor proteins such as retinoblastoma (pRb) and p53, and cellular oncogenes overexpression, such as c-myc, has been the subject of a number of investigations. In uterine-cervix carcinomas, where high-risk human papillomavirus (HPV) plays an important role, pRb and p53 are inactivated by E7 and E6 viral oncoproteins, respectively. However, little is known about the in situ expression of some of these proteins in pre-malignant and malignant cervical tissues. On the other hand, it has also been demonstrated that c-myc is involved in cervical carcinogenesis, and that pRb participates in the control of c-myc gene expression. By using immunostaining techniques, we investigated pRb immunodetection pattern in normal tissues, squamous intraepithelial lesions (SILs) and invasive carcinomas from the uterine cervix. Our data show low pRb detection in both normal cervical tissue and invasive lesions, but a higher expression in SILs. C-Myc protein was observed in most of the cellular nuclei of the invasive lesions, while in SILs was low. These findings indicate a heterogeneous pRb immunostaining during the different stages of cervical carcinogenesis, and suggest that this staining pattern could be a common feature implicated in the pathogenesis of uterine-cervix carcinoma.