Tumor necrosis factor-alpha inhibits expression of pulmonary surfactant protein.

Tumor necrosis factor-alpha (TNF-alpha) decreased the expression of pulmonary surfactant proteins SP-A and SP-B in human pulmonary adenocarcinoma cell lines. The effect of TNF alpha on SP-A content and mRNA in the pulmonary adenocarcinoma cell line, H441-4, was concentration and time dependent. TNF alpha decreased the cellular content of SP-A to less than 10% of control 48 h after addition. TNF alpha decreased de novo synthesis of SP-A and decreased the accumulation of SP-A in media. SP-A mRNA was decreased within 12 h of addition of TNF alpha, with nearly complete loss of SP-A mRNA observed after 24 h. Inhibitory effects of TNF alpha on SP-A mRNA were dose-related with nearly complete inhibition of SP-A mRNA caused by 25 ng/ml TNF alpha. The effects of TNF alpha on SP-A were distinct from the effects of interferon gamma which increased SP-A content approximately twofold in H441-4 cells. TNF alpha also decreased the content of SP-B mRNA. In contrast to the inhibitory effect of TNF alpha on SP-A and SP-B mRNA, TNF alpha increased mRNA encoding human manganese superoxide dismutase (Mn-SOD). TNF alpha did not inhibit growth, alter cell viability or beta-actin mRNA in either cell line. These in vitro studies demonstrate the marked pretranslational inhibitory effects of the cytokine, TNF alpha, on the expression of pulmonary surfactant proteins, SP-A and SP-B. The results support the concept that macrophage-derived cytokines may control surfactant protein expression.     

Thermotropic liquid crystals from biomacromolecules

Complexation of biomacromolecules (e.g., nucleic acids, proteins, or viruses) with surfactants containing flexible alkyl tails, followed by dehydration, is shown to be a simple generic method for the production of thermotropic liquid crystals. The anhydrous smectic phases that result exhibit biomacromolecular sublayers intercalated between aliphatic hydrocarbon sublayers at or near room temperature. Both this and low transition temperatures to other phases enable the study and application of thermotropic liquid crystal phase behavior without thermal degradation of the biomolecular components.Liquid crystals (LCs) play an important role in biology because their essential characteristic, the combination of order and mobility, is a basic requirement for self-organization and structure formation in living systems (1–3). Thus, it is not surprising that the study of LCs emerged as a scientific discipline in part from biology and from the study of myelin figures, lipids, and cell membranes (4). These and the LC phases formed from many other biomolecules, including nucleic acids (5, 6), proteins (7, 8), and viruses (9, 10), are classified as lyotropic, the general term applied to LC structures formed in water and stabilized by the distinctly biological theme of amphiphilic partitioning of hydrophilic and hydrophobic molecular components into separate domains. However, the principal thrust and achievement of the study of LCs has been in the science and application of thermotropic materials, structures, and phases in which molecules that are only weakly amphiphilic exhibit LC ordering by virtue of their steric molecular shape, flexibility, and/or weak intermolecular interactions [e.g., van der Waals and dipolar forces (11)]. These characteristics enable thermotropic LCs (TLCs) to adopt a wide variety of exotic phases and to exhibit dramatic and useful responses to external forces, including, for example, the electro-optic effects that have led to LC displays and the portable computing revolution. This general distinction between lyotropic LCs and TLCs suggests there may be interesting possibilities in the development of biomolecular or bioinspired LC systems in which the importance of amphiphilicity is reduced and the LC phases obtained are more thermotropic in nature. Such biological TLC materials are very appealing for several reasons. Most biomacromolecules were extensively characterized in aqueous environments, but in TLC phases, their solvent-free properties and functions could be investigated in a state in which no or only traces of water are present. Water exhibits a high dielectric constant and has the ability to form hydrogen bonds, greatly influencing the structure and functions of biomacromolecules or compromising electronic properties such as charge transport (12–15). Indeed, anhydrous TLC systems containing glycolipids (16–19), ferritin (20), and polylysine have been reported (21–23). However, a general approach to fabricating TLCs based on nucleic acids, polypeptides, proteins, and protein assemblies of large molecular weights such as virus particles remains elusive.Here we propose that the combination of biomaterials with suitably chosen surfactants, followed by dehydration, can be effectively applied as a simple generic scheme for producing biomacromolecular-based TLCs. We demonstrate that biological TLCs can be made from a remarkable range of biomolecules and bio-inspired molecules, including nucleic acids, polypeptides, fusion proteins, and viruses. TLC materials typically combine rigid or semirigid anisometric units, which introduce orientational anisotropy, with flexible alkyl chains, which suppress crystallization (24). In the present experiments, negatively charged biomolecules and bio-inspired molecules act as rigid parts, and cationic surfactants make up the flexible units to produce TLC phases with remarkably low LC-isotropic clearing temperatures, which is another TLC signature. Electrostatic interactions couple these rigid and flexible components into hybrid assemblies, which then order into lamellar phases of alternating rigid and flexible layers (Fig. 1) stabilized by the tendency in TLCs for rigid and flexible to spatially segregate (25).Open in a separate windowFig. 1.Proposed structures of TLCs formed by the biological building blocks complexed with surfactants, showing sketches of various lamellar phases and the corresponding phase transition temperatures (°C). The lamellar bilayer structures are made of, alternately, a sublayer of the biomacromolecules and an interdigitated sublayer of the surfactants, where the negatively charged parts of the biomolecules (e.g., phosphate groups of ssDNA and ssRNA, glutamate residues of supercharged ELPs, and N-terminal glutamate and aspartate residues of pVIII protein in phages) electrostatically interact with the cationic head groups of the surfactants. For the ssDNA–DOAB and ssRNA–DOAB smectic TLCs, the oligonucleotides are randomly orientated in the DNA (RNA) sublayers. For the ELP–DDAB complexes, in addition to the bilayer smectic phase, a modulated smectic (Sm_mod) phase is observed at lower temperature. For the phage–DOAB–DDAB lamellar structures, rodlike virus particles are embedded in a sublayer between interdigitated surfactants with additional in-plane orientational order.     

Design of the standardizing care to improve outcomes in pediatric end stage renal disease collaborative

The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a North American multi-center quality transformation effort whose primary aim is to minimize exit-site infection and peritonitis rates among pediatric chronic peritoneal dialysis patients. The project, developed by the quality improvement faculty and staff at the Children’s Hospital Association’s Quality Transformation Network (QTN) and content experts in pediatric nephrology and pediatric infectious diseases, is modeled after the QTN’s highly successful Pediatric Intensive Care Unit and Hematology-Oncology central line-associated blood-stream infection (CLABSI) Collaboratives. Like the Association’s other QTN efforts, the SCOPE Collaborative is part of a broader effort to assist pediatric nephrology teams in learning about and using quality improvement methods to develop and implement evidence-based practices. In addition, the design of this project allows for targeted research that builds on high-quality, ongoing data collection. Finally, the project, while focused on reducing peritoneal dialysis catheter-associated infections, will also serve as a model for future pediatric nephrology projects that could further improve the quality of care provided to children with end stage renal disease.     

Treatment status and risk factors for incidence and persistence of urinary incontinence in women

Introduction and hypothesis

The objective of this analysis was to describe urinary incontinence (UI) incidence and persistence over 5 years in association with treatment status, sociodemographic, medical, and lifestyle factors, in a racially/ethnically diverse population-based female sample.

Methods

The Boston Area Community Health Survey enrolled 3,201 women aged 30-79 years of black, Hispanic, and white race/ethnicity. Five-year follow-up was completed by 2,534 women (conditional response rate 83.4 %), allowing population-weighted estimates of UI incidence and persistence rates. Predictors of UI were determined using multivariate logistic regression models.

Results

Incidence of UI at least monthly was 14.1 % and weekly 8.9 %. Waist circumference at baseline and increasing waist circumference over 5-year follow-up were the most robust predictors of UI incidence in multivariate models (P?≤?0.01). Among 475 women with UI at baseline, persistence was associated with depression symptoms [monthly UI, odds ratio (OR)?=?2.39, 95 % confidence interval (CI) 1.14–5.02] and alcohol consumption (weekly UI, OR?=?3.51, 95 % CI 1.11–11.1). Among women with weekly UI at baseline, 41.7 % continued to report weekly UI at follow-up, 14.1 % reported monthly UI, and 44.2 % had complete remission. Persistence of UI was not significantly higher (58.2 % vs. 48.0 %, chi-square P?=?0.3) among untreated women. Surgical or drug treatment for UI had little impact on estimates for other risk factors or for overall population rates of persistence or remission.

Conclusions

Women with higher gains in waist circumference over time were more likely to develop UI, but waist circumference was not predictive of UI persistence. UI treatments did not affect associations for other risk factors. Additional research on the role of alcohol intake in UI persistence is warranted.     

Outcomes of Single‐Stage Compared to Two‐Stage Basilic Vein Transposition Fistulae

Basilic vein transposition (BVT) fistulae are increasing in prevalence in the United States. We examined outcomes of BVT fistulae created in a single stage compared to those created in two stages. Prospective QA databases identified a consecutive cohort of 144 patients with BVT fistulae. Of these, 42% were created in one stage and 58% in two stages. Fistula maturation rates, mean time to fistula use and intensity of percutaneous interventions were compared; patency rates were compared from time of first intervention. Maturation rates (including assisted maturation) were 90% among 1‐stage and 75% among 2‐stage BVT (p = 0.02). Mean time to initiation of fistula use was 142 days (1‐stage) and 146 days (2‐stage) (p = 0.92). Intensity of percutaneous interventions was 1.84/patient‐year of dialysis (PYD) (1‐stage) and 2.15/PYD (2‐stage) (p = 0.57). Secondary patency at 1, 2, 3, and 4 years for 1‐stage BVT was 86%, 75%, 69%, and 57%; secondary patency at 1, 2, 3, and 4 years for 2‐stage BVT was 76%, 71%, 49%, and 25%, respectively (p = 0.12). BVT creation in two stages confers only a modest reduction in maturation rates and secondary patency and therefore should be considered over a synthetic graft in patients with basilic veins deemed inadequate for 1‐stage BVT.     

Tandem hemodialysis and plasma exchange

The combination of hemodialysis and plasma exchange as one tandem procedure was first described in 1999 by Siami et al. (ASAIO J 45:229–233), but larger pediatric case series were not described until 2012. Even in adults, there are only limited case series. If performed in sequence, up to 8 h of treatment time may be required. With the use of the tandem procedure in stable patients, the same procedures can be completed during the same time as a routine hemodialysis, which is more convenient for patients and may reduce healthcare costs. Little is known about the utilization of the combination of hemodialysis and plasma exchange in children. The purpose of this review is to summarize the adult and scarce pediatric experience. The results of a survey carried out by the authors using the Internet listserver “PedNeph” to obtain an overview of the current practice patterns of pediatric nephrologists are also presented.