Nitric oxide synthase:non-canonical expression patterns

Science can move ahead by questioning established or canonical views and, so it may be with the enzymes, nitric oxide synthases (NOS). Nitric oxide (NO) is generated by NOS isoforms that are often described by their tissue-specific expression patterns. NOS1 (nNOS) is abundant in neural tissue, NOS2 is upregulated in activated macrophages and known as inducible NOS (iNOS), and NOS3 (eNOS) is abundant in endothelium where it regulates vascular tone. These isoforms are described as constitutive or inducible, but in this perspective we question the broad application of these labels. Are there instances where “constitutive” NOS (NOS1 and NOS3) are inducibly expressed; conversely, are there instances where NOS2 is constitutively expressed? NOS1 and NOS3 inducibility may be linked to post-translational regulation, making their actual patterns activity much more difficult to detect. Constitutive NOS2 expression has been observed in several tissues, especially the human pulmonary epithelium where it may regulate airway tone. These data suggest that expression of the three NOS enzymes may include non-established patterns. Such information should be useful in designing strategies to modulate these important enzymes in different disease states

Whole-Person Care: Implementing Behavioral Health Integration in the Patient-Centered Medical Home

Primary Care Payment Reform (PCPR) is an alternative payment pilot program of MassHealth, with learning collaborative support from UMass Medical School, that introduces the principles of accountable care, behavioral health integration and patient-centered medical homes in primary care practices. The pilot demonstrated that behavioral health integration is a necessary component of whole-person care and a complex, but highly accomplishable task; numerous transformation strategies can support the clinical, financial and cultural challenges to integration; and alternative payment models are essential to support sustainable, expandable and successful behavioral health services in primary care

Relationship Between Sediment Morphology and PCB Contamination in the Acushnet River, New Bedford, Massachusetts

The New Bedford Harbor Superfund Site in southeastern Massachusetts includes the shallow northern reaches of the Acushnet River estuary through the commercial port of New Bedford and adjacent areas of Buzzards Bay. The sediments in the harbor are contaminated with high levels of PCBs and heavy metals from the industrial development surrounding the harbor. From the 1940s through the 1970s, electrical capacitor manufacturing plants discharged PCBs into New Bedford Harbor and its estuaries. In the mid-1970s EPA sampling identified PCBs in the river and harbor sediments greater than 100,000 mg/kg. In 1979, the Massachusetts Department of Public Health prohibited fishing and shell-fishing from the river and harbor due to the high levels of PCB contamination found in the harbor and in the seafood from the area. The site was included on the National Priorities List (NPL) in September 1983, as one of the hottest PCB sites in the United States. In September 1998, after years of study and public debate, EPA selected a cleanup remedy that involved the dredging and containment of approximately 170 acres of PCB contaminated sediment. The principal goals of the project were the reduction in health risks from consumption of PCB-contaminated local seafood and from exposure to contaminated shoreline sediments, and the improvement of water quality in the marine ecosystem. The prescribed PCB cleanup standards for the sediment ranged from 1 mg/kg shoreline areas immediately adjacent to residential properties, up to 50 mg/kg in sediment in remote salt marshes not readily accessible to the public. Removal of sediments to achieve the cleanup standards requires mechanical or hydraulic dredging of more than 800,000 cubic yards of material. Correlation of analytical data and sediment cores shows a relationship between the presence of PCB contamination and distribution of the organic layer (OL) in the river. The relationship exists because of the nature of the contamination and its affinity for organic material. Sediment cores have been collected to refine the modeled sediment removal maps and guide target depths for dredging

The prevalence of bronchiectasis in patients with alpha-1 antitrypsin deficiency: initial report of EARCO

Alpha-1 antitrypsin deficiency; Emphysema; PrevalenceDeficiència d'alfa-1 antitripsina; Emfisema; PrevalençaDeficiencia de alfa-1 antitripsina; Enfisema; PrevalenciaBackground Although bronchiectasis has been recognised as a feature of some patients with Alpha1-Antitrypsin deficiency the prevalence and characteristics are not widely known. We wished to determine the prevalence of bronchiectasis and patient characteristics. The first cohort of patients recruited to the EARCO (European Alpha1 Research Collaboration) International Registry data base by the end of 2021 was analysed for radiological evidence of both emphysema and bronchiectasis as well as baseline demographic features. Results Of the first 505 patients with the PiZZ genotype entered into the data base 418 (82.8%) had a reported CT scan. There were 77 (18.4%) with a normal scan and 38 (9.1%) with bronchiectasis alone. These 2 groups were predominantly female never smokers and had lung function in the normal range. The remaining 303 (72.5%) ZZ patients all had emphysema on the scan and 113 (27%) had additional evidence of bronchiectasis. Conclusions The data indicates the bronchiectasis alone is a feature of 9.1% of patients with the PiZZ genotype of Alpha1-antitrypsin deficiency but although emphysema is the dominant lung pathology bronchiectasis is also present in 27% of emphysema cases and may require a different treatment strategy.The International EARCO registry is funded by unrestricted grants of Grifols, CSL Behring, Kamada, pH Pharma and Takeda to the European Respiratory Society (ERS)

Evaluating the long-term storage of Cryphonectria parasitica

Isolates of the Chestnut blight pathogen, Cryphonectria parasitica, from six populations in Michigan, were stored in the late 1990s as agar plugs of mycelium in vials of sterile water held at room temperature. Approximately 29% of the fungal isolates were infected with mycoviruses at the time of storage. Each isolate was tested for revivification effectiveness by taking aliquots from vials filled with agar plugs of C. parasitica and sterile water and plating onto potato dextrose agar. Average revivification success was 70.5% across populations with a range of 33—84% within populations. In situations where vials had dried out during storage, success was low (4%), while success for vials that retained sterile water averaged 90%. Most importantly however, is the loss of mycoviruses from stored isolates; only 2 of 119 stored mycovirus infected isolates still contained mycoviruses after storage, suggesting that the double-stranded RNA mycoviruses are degraded during storage

Use of Evidence-Based Best Practices and Behavior Change Techniques in Breast Cancer Apps: Systematic Analysis

Background: Theoretically designed mobile health (mHealth) breast cancer interventions are essential for achieving positive behavior change. In the case of breast cancer, they can improve the health outcomes of millions of women by increasing prevention and care efforts. However, little is known about the theoretical underpinnings of breast cancer apps available to the general public. Objective: Given that theories may strengthen mHealth interventions, this study aimed to identify breast cancer apps designed to support behavior change, to assess the extent to which they address content along the cancer care continuum and contain behavior change techniques, and to assess the degree to which star rating is related to theory-based design. Methods: Using a criteria-based screening process, we searched 2 major app stores for breast cancer apps designed to promote behavior change. Apps were coded for content along the cancer care continuum and analyzed for behavior change techniques. The Mann-Whitney U test was used to examine the relationship between star ratings and the use of behavior change techniques in apps with star ratings compared to those without ratings. Results: The search resulted in a total of 302 apps, of which 133 were identified as containing breast cancer content. Only 9.9% (30/302) of apps supported behavior change and were further analyzed. These apps were disproportionally focused on behaviors to enhance early detection, whereas only a few apps supported care management, treatment, and posttreatment behaviors. Regarding theories, 63% (19/30) of apps customized content to users, 70% (21/30) established a health-behavior link, and 80% (24/30) provided behavior change instructions. Of the 30 apps, 15 (50%) prompted intention formation whereas less than half of the apps included goal setting (9/30, 30%) and goal reviewing (7/30, 23%). Most apps did not provide information on peer behavior (7/30, 23%) or allow for social comparison (6/30, 20%). None of the apps mobilized social norms. Only half of the apps (15/30, 50%) were user rated. The results of the Mann-Whitney U test showed that apps with star ratings contained significantly more behavior change techniques (median 6.00) than apps without ratings. The analysis of behavior change techniques used in apps revealed their shortcomings in the use of goal setting and social influence features. Conclusions: Our findings indicate that commercially available breast cancer apps have not yet fully realized their potential to promote behavior change, with only a minority of apps focusing on behavior change, and even fewer including theoretical design to support behavior change along the cancer care continuum. These shortcomings are likely limiting the effectiveness of apps and their ability to improve public health. More attention needs to be paid to the involvement of professionals in app development and adherence to theories and best practices in app design to support individuals along the cancer care continuum

Divergent trends in ecosystem services under different climate-management futures in a fire-prone forest landscape

While ecosystem services and climate change are often examined independently, quantitative assessments integrating these fields are needed to inform future land management decisions. Using climate-informed state-and-transition simulations, we examined projected trends and trade-offs for a suite of ecosystem services under four climate change scenarios and two management scenarios (active management emphasizing fuel treatments and no management other than fire suppression) in a fire-prone landscape of dry and moist mixed-conifer forests in central Oregon, USA. Focal ecosystem services included fire potential (regulating service), timber volume (provisioning service), and potential wildlife habitat (supporting service). Projections without climate change suggested active management in dry mixed-conifer forests would create more open forest structures, reduce crown fire potential, and maintain timber stocks, while in moist mixed-conifer forests, active management would reduce crown fire potential but at the expense of timber stocks. When climate change was considered, however, trends in most ecosystem services changed substantially, with large increases in wildfire area predominating broad-scale trends in outputs, regardless of management approach (e.g., strong declines in timber stocks and habitat for closed-forest wildlife species). Active management still had an influence under a changing climate, but as a moderator of the strong climate-driven trends rather than being a principal driver of ecosystem service outputs. These results suggest projections of future ecosystem services that do not consider climate change may result in unrealistic expectations of benefits

A Mutational Analysis of the Endophilin-A N-BAR Domain Performed in Living Flies

BACKGROUND: Endophilin is a cytoplasmic protein with an important function in clathrin-dependent endocytosis at synapses and elsewhere. Endophilin has a BAR (Bin/Amphiphysin/Rvs-homology) domain, which is implicated in the sensing and induction of membrane curvature. Previous structure-function studies of the endophilin-A BAR domain have almost exclusively been made in reduced systems, either in vitro or ex vivo in cultured cells. To extend and complement this work, we have analyzed the role played by the structural features of the endophilin-A BAR domain in Drosophila in vivo. METHODOLOGY/PRINCIPAL FINDINGS: The study is based on genetic rescue of endophilin-A (endoA) null mutants with wild type or mutated endoA transgenes. We evaluated the viability of the rescuants, the locomotor behavior in adult flies and the neurotransmission at the larval neuromuscular junction. Whereas mutating the endophilin BAR domain clearly affected adult flies, larval endophilin function was surprisingly resistant to mutagenesis. Previous reports have stressed the importance of a central appendage on the convex BAR surface, which forms a hydrophobic ridge able to directly insert into the lipid bilayer. We found that the charge-negative substitution A66D, which targets the hydrophobic ridge and was reported to completely disrupt the ability of endophilin-BAR to tubulate liposomes in vitro, rescued viability and neurotransmission with the same efficiency as wild type endoA transgenes, even in adults. A similar discrepancy was found for the hydrophilic substitutions A63S/A66S and A63S/A66S/M70Q. The A66W mutation, which introduces a bulky hydrophobic side chain and induces massive vesiculation of liposomes in vitro, strongly impeded eye development, even in presence of the endogenous endoA gene. Substantial residual function was observed in larvae rescued with the EndoA(Arf) transgene, which encodes a form of endophilin-A that completely lacks the central appendage. Whereas a mutation (D151P) designed to increase the BAR curvature was functional, another mutation (P143A, DeltaLEN) designed to decrease the curvature was not. CONCLUSIONS/SIGNIFICANCE: Our results provide novel insight into the structure/function relationship of the endophilin-A BAR domain in vivo, especially with relation to synaptic function