Phosphatic metabolism in dark- and light-adapted rat retinas.

This study defines retinal phosphatic metabolites and their adjustment to illumination in rat retinas under conditions that preserve retinal function. Metabolic data are measured using high-performance liquid chromatography (HPLC) and 31P nuclear magnetic resonance (31P NMR) spectroscopy after 10 min of light exposure in vivo compared with retinas from dark-adapted rats. Multiple high-energy and low-energy phosphatic metabolites of intermediary metabolism were quantified. The concentration of the high-energy phosphate adenosine triphosphate (ATP) remained unchanged from dark- to light-adaptation. Under the same conditions the concentrations of the high-energy phosphates guanosine triphosphate (GTP) and creatine phosphate increased, whereas the inorganic phosphate decreased. Comparing dark-adapted controls with retinas light-adapted either in vitro or in vivo, the evidence is consistent with a light-dependent increase in GTP and a decrease in cyclic guanosine monophosphate. Although cyclic adenosine monophosphate (cAMP) levels were lower in retinas light-adapted in vivo than in the dark-adapted controls, this did not seem to be an effect of light, as cAMP levels decreased similarly after 10 min incubation in dark or light in parallel with recovery of ATP/adenosine diphosphate ratios. This study: (1) reports on retinal metabolic changes with adjustment in illumination, (2) provides baseline measurements of retinal phosphatic metabolites in whole retinas, and (3) reports on the validity of chromatographic and spectroscopic methods used for studying retinal metabolism establishing a high correlation among measurements made using HPLC and 31P NMR.

An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase.

N-acetylgalactosaminyl-transferases (GalNAc-Ts) initiate mucin-type O-glycosylation, an abundant and complex posttranslational modification that regulates host-microbe interactions, tissue development, and metabolism. GalNAc-Ts contain a lectin domain consisting of three homologous repeats (α, ß, and γ), where α and ß can potentially interact with O-GalNAc on substrates to enhance activity toward a nearby acceptor Thr/Ser. The ubiquitous isoenzyme GalNAc-T1 modulates heart development, immunity, and SARS-CoV-2 infectivity, but its substrates are largely unknown. Here, we show that both α and ß in GalNAc-T1 uniquely orchestrate the O-glycosylation of various glycopeptide substrates. The α repeat directs O-glycosylation to acceptor sites carboxyl-terminal to an existing GalNAc, while the ß repeat directs O-glycosylation to amino-terminal sites. In addition, GalNAc-T1 incorporates α and ß into various substrate binding modes to cooperatively increase the specificity toward an acceptor site located between two existing O-glycans. Our studies highlight a unique mechanism by which dual lectin repeats expand substrate specificity and provide crucial information for identifying the biological substrates of GalNAc-T1.

Pilot evaluation of the Fiscal Mapping Process for sustainable financing of evidence-based youth mental health treatments: A comparative case study analysis.

Background: Sustained delivery of evidence-based treatments (EBTs) is essential to addressing the public health impacts of youth mental health problems, but is complicated by the limited and fragmented funding available to youth mental health service agencies. Supports are needed that can guide service agencies in accessing sustainable funding for EBTs. We conducted a pilot evaluation of the Fiscal Mapping Process, an Excel-based strategic planning tool that helps service agency leaders identify and coordinate financing strategies for their EBT programs. Method: Pilot testing of the Fiscal Mapping Process was completed with 10 youth mental health service agencies over a 12-month period, using trauma-focused cognitive-behavioral therapy or parent-child interaction therapy programs. Service agency representatives received initial training and monthly coaching in using the tool. We used case study methods to synthesize all available data (surveys, focus groups, coaching notes, document review) and contrast agency experiences to identify key findings through explanation building. Results: Key evaluation findings related to the process and outcomes of using the Fiscal Mapping Process, as well as contextual influences. Process evaluation findings helped clarify the primary use case for the tool and identified the importance-and challenges-of engaging external collaborators. Outcome evaluation findings documented the impacts of the Fiscal Mapping Process on agency-reported sustainment capacities (strategic planning, funding stability), which fully explained reported improvements in outcomes (extent and likelihood)-although these impacts were incremental. Findings on contextual factors documented the influence of environmental and organizational capacities on engagement with the tool and concerns about equitable impacts, but also the view that the process could usefully generalize to other EBTs. Conclusions: Our pilot evaluation of the Fiscal Mapping Process was promising. In future work, we plan to integrate the tool into EBT implementation initiatives and test its impact on long-term sustainment outcomes across various EBTs, while increasing attention to equity considerations.

Pilot-Testing a Tool for Planning the Sustainable Financing of Youth Mental Health Treatments that Work Plain Language Summary Youth mental health treatments that work must be consistently available to improve youth mental health in our communities, but funding for these treatments is often limited and hard to access. Youth mental health service agencies need tools that can help guide them in accessing sustainable funding for evidence-based treatments. We developed the Fiscal Mapping Process, an Excel-based strategic planning tool for planning sustainable financing of youth mental health treatment programs, and conducted a 1-year pilot-testing evaluation with 10 youth mental health service agencies. We used case study methods to compare and contrast agency experiences with using the tool, related to the process, outcomes, and contextual influences on using the Fiscal Mapping Process. Key findings included clarification of the ideal characteristics of contributors and treatment programs for using the tool; initial confirmation that the tool can improve agency-reported capacities for sustaining treatments that work and long-term sustainment outlooks, although these impacts were incremental; and documentation of the influence of environmental and organizational capacities on engagement with the tool, concerns about equitable impacts, and user views that the process could be applied to a wide range of treatment models. In summary, our pilot evaluation of the Fiscal Mapping Process showed that this tool is promising for supporting the financial sustainment of treatments that work in youth mental health services. In future research, we plan to incorporate the tool into real-world training initiatives with mental health service agencies, test its impact on long-term sustainment across a variety of treatment models, and incorporate attention to equity considerations.

Formation of Se (0) nanoparticles by Duganella sp. and Agrobacterium sp. isolated from Se-laden soil of North-East Punjab, India.

BACKGROUND: Selenium (Se) is an essential trace element, but is toxic at high concentrations. Depending upon the geological background, the land use or on anthropogenic pollution, different amounts of Se may be present in soil. Its toxicity is related to the oxyanions selenate and selenite as they are water soluble and bioavailable. Microorganisms play an important role in Se transformations in soil and its cycling in the environment by transforming water-soluble oxyanions into water insoluble, non-toxic elemental Se (0). For this study, soil samples were collected from selenium-contaminated agricultural soils of Punjab/India to enrich and isolate microbes that interacted with the Se cycle. RESULTS: A mixed microbial culture enriched from the arable soil of Punjab could reduce 230 mg/l of water soluble selenite to spherical Se (0) nanoparticles during aerobic growth as confirmed by SEM-EDX. Four pure cultures (C 1, C 4, C 6, C 7) of Gram negative, oxidase and catalase positive, aerobic bacteria were isolated from this mixed microbial consortium and identified by 16 S rDNA gene sequence alignment as two strains of Duganella sp. (C 1, C 4) and two strains of Agrobacterium sp.(C 6, C 7). SEM/TEM-EDX analyses of the culture broth of the four strains revealed excretion of uniformly round sharply contoured Se (0) nanoparticles by all cultures. Their size ranged from 140-200 nm in cultures of strains C 1 and C 4, and from 185-190 nm in cultures of strains C 6 and C 7. Both Duganella sp. revealed better selenite reduction efficiencies than the two Agrobacterium sp. CONCLUSIONS: This is the first study reporting the capability of newly isolated, aerobically growing Duganella sp. and Agrobacterium sp. from soils of Punjab/India to form spherical, regularly formed Se (0) nanoparticles from water soluble selenite. Among others, the four strains may significantly contribute to the biogeochemical cycling of Se in soil. Bioconversion of toxic selenite to non-toxic Se (0) nanoparticles under aerobic conditions in general may be useful for detoxification of agricultural soil, since elemental Se may not be taken up by the roots of plants and thus allow non-dangerous fodder and food production on Se-containing soil.

Long-term effects of antibiotics on the elimination of chemical oxygen demand, nitrification, and viable bacteria in laboratory-scale wastewater treatment plants.

Antibiotics and other pharmaceuticals are contaminants of the environment because of their widespread use and incomplete removal by microorganisms during wastewater treatment. The influence of a mixture of ciprofloxacin (CIP), gentamicin (GM), sulfamethoxazole (SMZ)/trimethoprim (TMP), and vancomycin (VA), up to a final concentration of 40 mg/L, on the elimination of chemical oxygen demand (COD), nitrification, and survival of bacteria, as well as the elimination of the antibiotics, was assessed in a long-term study in laboratory treatment plants (LTPs). In the presence of 30 mg/L antibiotics, nitrification of artificial sewage by activated sludge ended at nitrite. Nitrate formation was almost completely inhibited. No nitrification at all was possible in the presence of 40 mg/L antibiotics. The nitrifiers were more sensitive to antibiotics than heterotrophic bacteria. COD elimination in antibiotic-stressed LTPs was not influenced by ≤20 mg/L antibiotics. Addition of 30 mg/L antibiotic mixture decreased COD removal efficiency for a period, but the LTPs recovered. Similar results were obtained with 40 mg/L antibiotic mixture. The total viable count of bacteria was not affected negatively by the antibiotics. It ranged from 2.2 × 10(6) to 8.2 × 10(6) colony-forming units per milliliter (CFU/mL) compared with the control at 1.4 × 10(6)-6.3 × 10(6) CFU/mL. Elimination of the four antibiotics during phases of 2.4-30 mg/L from the liquid was high for GM (70-90 %), much lower for VA, TMP, and CIP (0-50 %), and highly fluctuating for SMZ (0-95 %). The antibiotics were mainly adsorbed to the sludge and not biodegraded.

Coordination of sustainable financing for evidence-based youth mental health treatments: protocol for development and evaluation of the fiscal mapping process.

BACKGROUND: Sustained delivery of evidence-based treatments (EBTs) is essential to addressing the public health and economic impacts of youth mental health problems, but is complicated by the limited and fragmented funding available to youth mental health service agencies (hereafter, "service agencies"). Strategic planning tools are needed that can guide these service agencies in their coordination of sustainable funding for EBTs. This protocol describes a mixed-methods research project designed to (1) develop and (2) evaluate our novel fiscal mapping process that guides strategic planning efforts to finance the sustainment of EBTs in youth mental health services. METHOD: Participants will be 48 expert stakeholder participants, including representatives from ten service agencies and their partners from funding agencies (various public and private sources) and intermediary organizations (which provide guidance and support on the delivery of specific EBTs). Aim 1 is to develop the fiscal mapping process: a multi-step, structured tool that guides service agencies in selecting the optimal combination of strategies for financing their EBT sustainment efforts. We will adapt the fiscal mapping process from an established intervention mapping process and will incorporate an existing compilation of 23 financing strategies. We will then engage participants in a modified Delphi exercise to achieve consensus on the fiscal mapping process steps and gather information that can inform the selection of strategies. Aim 2 is to evaluate preliminary impacts of the fiscal mapping process on service agencies' EBT sustainment capacities (i.e., structures and processes that support sustainment) and outcomes (e.g., intentions to sustain). The ten agencies will pilot test the fiscal mapping process. We will evaluate how the fiscal mapping process impacts EBT sustainment capacities and outcomes using a comparative case study approach, incorporating data from focus groups and document review. After pilot testing, the stakeholder participants will conceptualize the process and outcomes of fiscal mapping in a participatory modeling exercise to help inform future use and evaluation of the tool. DISCUSSION: This project will generate the fiscal mapping process, which will facilitate the coordination of an array of financing strategies to sustain EBTs in community youth mental health services. This tool will promote the sustainment of youth-focused EBTs.

NLM-Chem-BC7: manually annotated full-text resources for chemical entity annotation and indexing in biomedical articles.

The automatic recognition of chemical names and their corresponding database identifiers in biomedical text is an important first step for many downstream text-mining applications. The task is even more challenging when considering the identification of these entities in the article's full text and, furthermore, the identification of candidate substances for that article's metadata [Medical Subject Heading (MeSH) article indexing]. The National Library of Medicine (NLM)-Chem track at BioCreative VII aimed to foster the development of algorithms that can predict with high quality the chemical entities in the biomedical literature and further identify the chemical substances that are candidates for article indexing. As a result of this challenge, the NLM-Chem track produced two comprehensive, manually curated corpora annotated with chemical entities and indexed with chemical substances: the chemical identification corpus and the chemical indexing corpus. The NLM-Chem BioCreative VII (NLM-Chem-BC7) Chemical Identification corpus consists of 204 full-text PubMed Central (PMC) articles, fully annotated for chemical entities by 12 NLM indexers for both span (i.e. named entity recognition) and normalization (i.e. entity linking) using MeSH. This resource was used for the training and testing of the Chemical Identification task to evaluate the accuracy of algorithms in predicting chemicals mentioned in recently published full-text articles. The NLM-Chem-BC7 Chemical Indexing corpus consists of 1333 recently published PMC articles, equipped with chemical substance indexing by manual experts at the NLM. This resource was used for the evaluation of the Chemical Indexing task, which evaluated the accuracy of algorithms in predicting the chemicals that should be indexed, i.e. appear in the listing of MeSH terms for the document. This set was further enriched after the challenge in two ways: (i) 11 NLM indexers manually verified each of the candidate terms appearing in the prediction results of the challenge participants, but not in the MeSH indexing, and the chemical indexing terms appearing in the MeSH indexing list, but not in the prediction results, and (ii) the challenge organizers algorithmically merged the chemical entity annotations in the full text for all predicted chemical entities and used a statistical approach to keep those with the highest degree of confidence. As a result, the NLM-Chem-BC7 Chemical Indexing corpus is a gold-standard corpus for chemical indexing of journal articles and a silver-standard corpus for chemical entity identification in full-text journal articles. Together, these resources are currently the most comprehensive resources for chemical entity recognition, and we demonstrate improvements in the chemical entity recognition algorithms. We detail the characteristics of these novel resources and make them available for the community. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/NLM-Chem-BC7-corpus/.

Stereotactic Vacuum-Assisted Needle Biopsy Outcomes of Non-calcified Mammographic Lesions.

RATIONALE AND OBJECTIVES: To identify the outcomes of stereotactic vacuum-assisted large bore biopsies performed on sonographically-occult non-calcified mammographic lesions (NCL). MATERIALS AND METHODS: In an IRB-approved retrospective study, we reviewed all NCL that underwent stereotactic biopsy from January 1, 2014 to December 31, 2017 at our institution, comparing patient age, lesion type, size and location with pathology outcome (benign, high-risk or malignant) using Wilcoxon-Mann-Whitney or Fisher's exact tests as appropriate. Multivariable logistic regression models were developed to decrease benign biopsies in our cohort with diagnostic performance assessed using receiver operating characteristic curve and area under the curve (AUC). RESULTS: Of 222 biopsied lesions in 213 patients, 79.3% (176/222) were benign, 5.9% (13/222) malignant, and 14.9% (33/222) high-risk. NCL were less likely to be malignant compared to calcifications biopsied in the same period [5.9% vs 19.0% (243/1279), p < 0.001]. All 42 asymmetries and 33 architectural distortions were benign, while 8.7% (4/46) of masses and 8.9% (9/101) of focal asymmetries were malignant. Cancers were associated with older age (mean 65.2 vs 52.7 years, p < 0.001), smaller size (mean 9.5 mm vs 15.5 mm, p < 0.01), and concurrent breast cancer (p < 0.01) compared to benign/high-risk lesions. Multivariable logistic regression model using patient age >50 years, lesion type, and size <15 mm had a high diagnostic performance [AUC=0.89, 95%CI (0.83, 0.94)], and yielded the highest PPV [0.24; 95%CI (0.13, 0.38)], and highest number of avoided, unnecessary biopsies (172/209, 82%). CONCLUSION: NCL biopsied under stereotactic guidance have low cancer yield (5.9%). A multivariate model integrating age, lesion size and type could potentially help avoid unwarranted biopsies in our cohort.

NLM-Chem, a new resource for chemical entity recognition in PubMed full text literature.

Automatically identifying chemical and drug names in scientific publications advances information access for this important class of entities in a variety of biomedical disciplines by enabling improved retrieval and linkage to related concepts. While current methods for tagging chemical entities were developed for the article title and abstract, their performance in the full article text is substantially lower. However, the full text frequently contains more detailed chemical information, such as the properties of chemical compounds, their biological effects and interactions with diseases, genes and other chemicals. We therefore present the NLM-Chem corpus, a full-text resource to support the development and evaluation of automated chemical entity taggers. The NLM-Chem corpus consists of 150 full-text articles, doubly annotated by ten expert NLM indexers, with ~5000 unique chemical name annotations, mapped to ~2000 MeSH identifiers. We also describe a substantially improved chemical entity tagger, with automated annotations for all of PubMed and PMC freely accessible through the PubTator web-based interface and API. The NLM-Chem corpus is freely available.

IL-21 mediates apoptosis through up-regulation of the BH3 family member BIM and enhances both direct and antibody-dependent cellular cytotoxicity in primary chronic lymphocytic leukemia cells in vitro.

Interleukin-21 (IL-21) is a recently identified gamma-chain receptor cytokine family member that promotes B-cell apoptosis as well as activation of innate immune system. Based on this, we hypothesized that IL-21 might enhance the apoptosis induced by fludarabine and rituximab and also play a role in augmenting immune-mediated clearance of the chronic lymphocytic leukemia (CLL) cells. Our studies demonstrate that the majority of CLL patients have surface IL-21 receptor-alpha, and its expression correlates with apoptosis, tyrosine phosphorylation of STAT1, and up-regulation of the proapoptotic BH3 domain protein BIM. IL-21-induced BIM up-regulation is critical for apoptosis because inhibition of BIM expression using small interfering RNA prevented IL-21-induced apoptosis. IL-21 treatment of CLL cells but not normal T cells with fludarabine or rituximab additively enhanced the direct cytotoxic effect of these therapies. In addition to its proapoptotic effect, IL-21 promoted STAT1 and STAT5 phosphorylation in natural killer cells with concurrent enhanced antibody-dependent cellular cytotoxicity against rituximab-coated CLL cells in vitro. These data provide justification for combination studies of IL-21 with fludarabine and rituximab in CLL and suggest that BIM up-regulation might serve as relevant pharmacodynamic end point to measure biologic effect of this cytokine in vivo.

Second-degree prelicensure master's graduates and their transition to practice.

OBJECTIVE: The purpose of this study was to gain an understanding of the transition-to-practice experience of second-degree prelicensure master's graduates. BACKGROUND: Second-degree graduates are increasingly joining the nursing workforce. Scant empirical literature exists regarding this group. METHODS: Using a qualitative design, second-degree prelicensure master's graduates were interviewed 3 times through a 10-month period regarding their transition to practice. RESULTS: Participants chose nursing positions based on their perceived ability to grow. Two strengths of the participants included their ability to think critically and to establish relationships. Participants expressed typical novice nurse concerns. Residency and intern programs enhanced their transition to practice. Participants perceived their interactions with the health team as positive, and graduates urged administrators to use their knowledge gained from previous degrees. CONCLUSIONS: Findings enhance understanding of how second-degree prelicensure master's graduates transition to practice. Understanding their transition is imperative if these graduates are to be recruited and used at their fullest potential. Such insights can also help nurse administrators better support these new hires during the transition process.

Honoring children, mending the circle: cultural adaptation of trauma-focused cognitive-behavioral therapy for American Indian and Alaska native children.

American Indians and Alaska Natives are vulnerable populations with significant levels of trauma exposure. The Indian Country Child Trauma Center developed an American Indian and Alaska Native (AI/AN) adaptation of the evidence-based child trauma treatment, trauma-focused cognitive-behavioral therapy. Honoring Children, Mending the Circle (HC-MC) guides the therapeutic process through a blending of AI/AN traditional teachings with cognitive-behavioral methods. The authors introduced the HC-MC treatment and illustrated its therapeutic tools by way of a case illustration.

A scoping review of strategies for financing the implementation of evidence-based practices in behavioral health systems: State of the literature and future directions.

Background: Increased availability of evidence-based practices (EBPs) is essential to alleviating the negative public health and societal effects of behavioral health problems. A major challenge to implementing and sustaining EBPs broadly is the limited and fragmented nature of available funding. Method: We conducted a scoping review that assessed the current state of evidence on EBP financing strategies for behavioral health based on recent literature (i.e., post-Affordable Care Act). We defined financing strategies as techniques that secure and direct financial resources to support EBP implementation. This article introduces a conceptualization of financing strategies and then presents a compilation of identified strategies, following established reporting guidelines for the implementation strategies. We also describe the reported level of use for each financing strategy in the research literature. Results: Of 23 financing strategies, 13 were reported as being used within behavioral health services, 4 had potential for use, 5 had conceptual use only, and 1 was potentially contraindicated. Examples of strategies reported being used include increased fee-for-service reimbursement, grants, cost sharing, and pay-for-success contracts. No strategies had been evaluated in ways that allowed for strong conclusions about their impact on EBP implementation outcomes. Conclusion: The existing literature on EBP financing strategies in behavioral health raises far more questions than answers. Therefore, we propose a research agenda that will help better understand these financing strategies. We also discuss the implications of our findings for behavioral health professionals, system leaders, and policymakers who want to develop robust, sustainable financing for EBP implementation in behavioral health systems. Plain language abstract: Organizations that treat behavioral health problems (mental health and substance use) often seek to adopt and use evidence-based practices (EBPs). A challenge to adopting EBPs broadly is the limited funding available, often from various sources that are poorly coordinated with one another. To help organizations plan effectively to adopt EBPs, we conducted a review of recent evidence (i.e., since the passage of the 2010 Affordable Care Act) on strategies for financing EBP adoption in behavioral health systems. We present definitions of 23 identified strategies and describe each strategy's reported (in the research literature) level of use to fund EBP adoption in behavioral health services. Of the 23 financing strategies, 13 strategies had evidence of use, 4 had potential for use, 5 had conceptual use only, and 1 was potentially contraindicated. Examples of strategies with evidence of use include increased fee-for-service reimbursement, grants, cost sharing, and pay-for-success contracts. This comprehensive list of EBP financing strategies may help guide decision-making by behavioral health professionals, system leaders, and policymakers. The article also presents a research agenda for building on the current research literature by (1) advancing methods to evaluate financing strategies' effects, (2) partnering with stakeholders and decision-makers to examine promising financing strategies, (3) focusing on strategies and service systems with the greatest needs, (4) improving methods to guide the selection of financing strategies, and (5) paying greater attention to sustainable long-term financing of EBPs.

Primary care validation of a single-question alcohol screening test.

BACKGROUND: Unhealthy alcohol use is prevalent but under-diagnosed in primary care settings. OBJECTIVE: To validate, in primary care, a single-item screening test for unhealthy alcohol use recommended by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). DESIGN: Cross-sectional study. PARTICIPANTS: Adult English-speaking patients recruited from primary care waiting rooms. MEASUREMENTS: Participants were asked the single screening question, "How many times in the past year have you had X or more drinks in a day?", where X is 5 for men and 4 for women, and a response of 1 or greater [corrected] is considered positive. Unhealthy alcohol use was defined as the presence of an alcohol use disorder, as determined by a standardized diagnostic interview, or risky consumption, as determined using a validated 30-day calendar method. MAIN RESULTS: Of 394 eligible primary care patients, 286 (73%) completed the interview. The single-question screen was 81.8% sensitive (95% confidence interval (CI) 72.5% to 88.5%) and 79.3% specific (95% CI 73.1% to 84.4%) for the detection of unhealthy alcohol use. It was slightly more sensitive (87.9%, 95% CI 72.7% to 95.2%) but was less specific (66.8%, 95% CI 60.8% to 72.3%) for the detection of a current alcohol use disorder. Test characteristics were similar to that of a commonly used three-item screen, and were affected very little by subject demographic characteristics. CONCLUSIONS: The single screening question recommended by the NIAAA accurately identified unhealthy alcohol use in this sample of primary care patients. These findings support the use of this brief screen in primary care.

A novel transglutaminase substrate from Streptomyces mobaraensis triggers autolysis of neutral metalloproteases.

Transglutaminase (TGase) from Streptomyces mobaraensis is a Ca(2+) independent enzyme that cross-links proteins to high molecular weight aggregates. A dispase autolysis inducing protein (DAIP) was identified as an intrinsic TGase substrate exhibiting accessible glutamine and lysine residues. DAIP modification during culture by TGase resulted in deamidation of reactive glutamines, formation of glutamic/lysine residue pairs, and failure of cross-linking. The reactivity of modified DAIP can be restored to some extent by N-lauroylamido-3-N',N'-dimethylpropyl amine, thus exposing concertedly buried glutamines and lysines. The novel TGase substrate differs considerably from the well known Streptomyces subtilisin inhibitors in higher molecular mass (37 kDa), lower pI (7.1-7.2), moderate thermo-stability, and the mode of erasing dispase activity. Our experiments suggested that DAIP induces autolysis without removal of essential metals, such as Ca(2+) and Zn(2+). Among other endoproteases, only thermolysin was similarly affected, but at considerably higher DAIP concentrations, due to simultaneous degradation of DAIP.

The transglutaminase activating metalloprotease inhibitor from Streptomyces mobaraensis is a glutamine and lysine donor substrate of the intrinsic transglutaminase.

Transglutaminase (TGase) from Streptomyces mobaraensis is an extra-cellular enzyme that cross-links proteins to high molecular weight aggregates. Screening for intrinsic substrates now revealed the dual Streptomyces subtilisin inhibitor-like inhibitor Streptomyces subtilisin and transglutaminase activating metalloprotease (TAMEP) inhibitor (SSTI), equally directed against subtilisin and the TGase activating metalloprotease TAMEP, is both a glutamine and a lysine donor protein. Reactivity of glutamines is lost during culture, most likely by TGase mediated deamidation, and, accordingly, cross-linking only occurred if SSTI from early cultures was used. Interestingly, release of buried endo-glutamines by the lipoamino acid N-lauroylsarcosine could restore SSTI reactivity. Formation of lipoamino acids by Streptomycetes suggests such compounds could also modulate in vivo TGase mediated SSTI cross-linking.

Perspectives of caregivers of stroke survivors: implications for nursing.

The majority of stroke survivors receive home care. To offer better support, home caregivers and nurses must understand the caregiving experience. This knowledge will enable nurses to help home care givers provide more effective care and conserve their own resources.

A collaborative effort between nurse leaders to address the hospital nursing shortage.

The current nursing shortage is not a routine swinging of the supply pendulum. Indeed, this shortage is determined to be quantitatively and qualitatively different from those of the past (Kimball & O'Neil, 2002). In Cincinnati, Ohio, nurse leaders decided that the uniqueness of this shortage necessitated new strategies. Hospital nurse executives proposed the creation of a community leadership group, and other Cincinnati nurse leaders enthusiastically embraced the idea. A collaborative effort was initiated in the spring of 2000 between a representative group of hospital chief nursing officers, school of nursing deans and faculty, staff nurses, hospital nurse recruiters, and professional nursing organizations to address concerns related to the nursing shortage. This article describes the process and outcomes of this collaborative effort with a focus on the retention of hospital nurses.

Teaching by example: educating medical students through a weight management experience.

BACKGROUND AND OBJECTIVES: Surgeons General, the Institute of Medicine, and others have called for physicians to be role models for meeting the obesity epidemic. There are few published reports describing undergraduate medical education obesity curriculum elements. Physician experiences, knowledge, and attitudes have been shown to affect patient counseling behavior of physicians. METHODS: Required and extra credit obesity educational interventions were designed for third-year family medicine clerkship. For extra credit, students completed a personal weight management experience that spanned at least 4 weeks, included calculations of body mass index (BMI), waist circumference, caloric needs, description of eating and physical activity and monitoring plan, and a final report and reflection. RESULTS: During 2011--2012, 72% of the students completed this extra credit activity with almost all losing or maintaining their weight. Most reflected gratitude for this opportunity and their increased empathy for patients as they struggle with weight issues. CONCLUSIONS: Medical students completing a weight management experience during their third-year clerkship can see the effects on their own health while developing empathy for and understanding of the weight management struggles of their patients. Minimal faculty time commitment is required.