Lessons from angiotensin-converting enzyme-deficient mice.

Journal ArticleMice which lack ACE have low systolic blood pressure, reduced male fertility and a renal abnormality characterized by medullary hypoplasia and the inability to concentrate urine. The diverse phenotypes caused by inactivation of a single gene emphasize the many functional roles of ACE and the renin-qngiotensin system

Mapping targetable inflammation and outcomes with cystic fibrosis biomarkers

Cystic fibrosis is characterized by an overly exuberant neutrophilic inflammatory response to pathogens and other stimuli that starts very early in disease. The overwhelming nature of this response is a primary cause of remodeling and destruction of the airways, suggesting that anti-inflammatory therapies could be beneficial in CF. However, finding therapies that can effectively reduce the inflammatory response without compromising host defenses remains elusive. New approaches towards mapping inflammatory targets promise to aid in developing novel therapeutic strategies and improve outcomes in individuals with CF

Lessons from angiotensin-converting enzyme-deficient mice

Journal ArticleSince the first description of renin by Tigerstedt and Bergman [1] in 1898, many papers have described the biochemistry and physiological roles of the reninangiotensin system [2]. A critical component of this system is angiotensin-converting enzyme (ACE), a peptidase which cleaves the inactive peptide angiotensin (Ang) I to generate the potent vasoconstrictor Ang II. This enzyme also cleaves other peptides, including bradykinin. Its activity increases blood pressure, and ACE inhibitors have become a mainstay in the treatment of hypertension and congestive heart failure. It has recently become possible to create mice which lack ACE. These mice have low systolic blood pressure, striking renal defects and reduced male fertility, phenotypes which emphasize the familiar roles of ACE and provide insight into unexpected functions of this enzyme

Continuous vancomycin in a pediatric cystic fibrosis patient

Continuous vancomycin has been previously reported to maximize antimicrobial activity while avoiding toxicities associated with dose escalation, but the efficacy of this dosing strategy has not been reported. This case report describes the successful use of continuous vancomycin, including improvement in lung function and avoidance of nephrotoxicity, demonstrated in a pediatric cystic fibrosis (CF) patient with MRSA

Dermal substitutes for full‐thickness wounds in a one‐stage grafting model

We tested different biodegradable matrix materials as dermal substitutes in a porcine wound model. Matrixes were covered with a split-skin mesh graft and protected with a microporous, semipermeable membrane, which prevents blister formation, wound infection and provides ultimate healing conditions. Evaluation parameters were as follows: epithelization, dermal reconstitution, wound contraction, and cosmetic and functional aspect. A microfibrillar matrix of nondenatured collagen gave the best result, with immediate fibroblast ingrowth and epidermal outgrowth. Slight inflammatory reaction and minimal wound contraction were observed. Application of a split-skin mesh graft, in combination with this collagen matrix, generated a thicker dermal layer than did a split-skin mesh graft directly applied on a wound bed. However, the histologic dermal architecture was less optimal than one obtained with a full-thickness punch graft method. Other matrixes caused inflammatory reactions, interfering with epithelization and dermal reconstitution. We conclude that a nondenatured collagen matrix, in combination with a split-skin mesh graft, can provide a substitute dermis in a full-thickness wound. This combination is preferable to a split-skin mesh graft directly applied on the wound bed. With our microporous semipermeable membrane, the combined use of a dermal substitute and a split-skin mesh graft can be applied in a single-stage operatio

Metabolomic biomarkers predictive of early structural lung disease in cystic fibrosis

Neutrophilic airway inflammation plays a role in early structural lung disease in cystic fibrosis (CF), but the mechanisms underlying this pathway are incompletely understood

Metabolomic analysis of bronchoalveolar lavage fluid from cystic fibrosis patients

Metabolite profiles of bronchoalveolar lavage fluid (BALF) from pediatric patients with cystic fibrosis (CF) were correlated to the degree of airway inflammation using nuclear magnetic resonance spectroscopy-based metabolomics. BALF was collected from 11 children with CF during clinically indicated bronchoscopy. The spectra from BALF with high levels of neutrophilic airway inflammation displayed signals from numerous metabolites, whereas the spectra from subjects with low levels of inflammation were very sparse. The metabolites identified in samples taken from subjects with high inflammation include known markers of inflammation such as amino acids and lactate, as well as many novel signals. Statistical analysis highlighted the most important metabolites that distinguished the high- from the low-inflammation groups. This first demonstration of metabolomics of human BALF shows that clear distinctions in the metabolic profiles can be observed between subjects experiencing high versus low inflammation and is a first step toward the goal of discovering novel biomarkers of airway inflammation

Correlates of health-related quality of life in primary caregivers of perinatally HIV infected and HIV exposed uninfected adolescents at the Kenyan Coast

Background: Mothers and other primary caregivers play a crucial role in looking after perinatally HIV infected, and HIV exposed uninfected adolescents in sub-Saharan Africa. Day- to-day caregiving in the context of limited instrumen- tal support and added biomedical risk (HIV seropositivity) may expose these caregivers to adverse states of health. Unfortunately, very few studies have examined their health-related quality of life (HRQoL). Our study documents the HRQoL profile, and associated factors in primary caregivers of perinatally HIV infected, perinatally HIV exposed but uninfected and HIV unexposed/uninfected adolescents aged 12–17 years at the Kenyan Coast. Methods: This was a cross-sectional analysis of 485 primary caregivers: 195 of perinatally HIV infected adolescents, 128 of perinatally HIV exposed but uninfected adolescents and 162 of HIV unexposed/uninfected adolescents. All car- egivers completed a self-report measure of HRQoL (having 8 subscales), depressive symptoms, and parenting stress. They also provided their sociodemographic information and that of the care recipients. We used one-way analysis of variance to assess statistical differences among the groups. Linear regression analyses were used to identify correlates of HRQoL. Results: Overall, caregivers of HIV unexposed/uninfected adolescents reported significantly higher mean HRQoL scores than the other caregivers in the overall HRQoL domain and majority of the subscales. There were no statistical differences in the overall HRQoL scores and most subscales between caregivers of HIV exposed adolescents. Linear regression analyses across the sample indicated that depressive symptoms, increasing age of caregiver, and caring for an adolescent perinatally exposed to HIV were significantly associated with reduced HRQoL at both the overall and sub-scale level. Having a professional job relative to subsistence farming was the only factor associated with improved overall HRQoL. At subscale level, higher socioeconomic status correlated positively with HRQoL while being a grand- parent, level of education, parenting stress were negatively associated with HRQoL. Conclusions: Caregivers in this sample, especially those who are ageing, at risk of mental ill-health, and taking care of adolescents perinatally exposed to HIV, appear to be vulnerable to poor quality of life. Inclusive and multi-component interventions tailored to the caregivers’ psychosocial and mental needs will potentially enhance their quality of life

Exhaled breath condensate purines correlate with lung function in infants and preschoolers

Although airway inflammation begins early in life in children with chronic respiratory diseases, current methods to assess this inflammation are invasive and entail significant risk. Measurement of exhaled breath condensate (EBC) purines and other biomarkers offer a less invasive method to assess airway inflammation; however, the feasibility and utility of EBC biomarkers in young children has not been established

Validity, reliability, and measurement invariance of an adapted short version of the HIV stigma scale among perinatally HIV infected adolescents at the Kenyan coast

Background: There is a dearth of instruments that have been developed and validated for use with children living with HIV under the age of 17 years in the Kenyan context. We examined the psychometric properties and measurement invariance of a short version of the Berger HIV stigma scale administered to perinatally HIV-infected adolescents in a rural setting on the Kenyan coast. Methods: A cross-sectional study was conducted among 201 perinatally HIV-infected adolescents aged 12-17 years between November 2017 and October 2018. A short version of the Berger HIV stigma scale (HSS-40) containing twelve items (HSS-12) covering the four dimensions of stigma was evaluated. The psychometric assessment included exploratory factor analysis, confirmatory factor analysis (CFA), and multi-group CFA. Additionally, scale reliability was evaluated as internal consistency by calculating Cronbach\u27s alpha. Results: Evaluation of the reliability and construct validity of the HSS-12 indicated insufficient reliability on three of the four subscales. Consequently, Exploratory Factor Analysis (EFA) was conducted to identify problematic items and determine ways to enhance the scale\u27s reliability. Based on the EFA results, two items were dropped. The Swahili version of this new 10-item HIV stigma scale (HSS-10) demonstrated excellent internal consistency with a Cronbach alpha of 0.86 (95% confidence interval (CI) 0.84-0.89). Confirmatory Factor Analysis indicated that a unidimensional model best fitted the data. The HSS-10 presented a good fit (overall Comparative Fit Index = 0.976, Tucker Lewis Index = 0.969, Root Mean Square Error of Approximation = 0.040, Standardised Root Mean Residual = 0.045). Additionally, multi-group CFA indicated measurement invariance across gender and age groups at the strict invariance level as ΔCFI was ≤ 0.01. Conclusion: Our findings indicate that the HSS-10 has good psychometric properties and is appropriate for evaluating HIV stigma among perinatally HIV-infected adolescents on the Kenyan coast. Further, study results support the unidimensional model and measurement invariance across gender and age groups of the HSS-10 measure