A business approach to climate adaptation in local communities.

Climate change poses risks to the assets and operations of businesses. They can anticipate, prepare for, and adapt to the potential impacts of climate change by focusing on modifying their own internal operations. But businesses can find additional opportunities to adapt by examining their relationships with local governments. Businesses provide critical services to the communities in which they are located, and also benefit from services provided by the local governments. This symbiotic relationship is an important consideration for businesses as they work to adapt to a changing climate. By thinking broadly about how working with local governments can influence their resilience, businesses may be able to uncover additional adaptation opportunities and enhance their adaption efforts in ways they may not be able to achieve on their own. This paper includes two case studies of businesses that pursued adaptation efforts with local, state, or federal government officials to provide real-world context for the symbiotic relationships that exist between the private and public sectors in communities.

Factors associated with transfers from healthcare facilities among readmitted older adults with chronic illness.

OBJECTIVE: Because chronic illness accounts for a considerable proportion of Australian healthcare expenditure, there is a need to identify factors that may reduce hospital readmissions for patients with chronic illness. The aim of the present study was to examine a range of factors potentially associated with transfer from healthcare facilities among older adults readmitted to hospital within a large public health service in Melbourne, Australia. METHODS: Data on readmitted patients between June 2006 and June 2011 were extracted from hospital databases and medical records. Adopting a retrospective case-control study design, a sample of 51 patients transferred from private residences was matched by age and gender with 55 patients transferred from healthcare facilities (including nursing homes and acute care facilities). Univariate and multivariate logistic regression analyses were used to compare the two groups, and to determine associations between 46 variables and transfer from a healthcare facility. RESULTS: Univariate analysis indicated that patients readmitted from healthcare facilities were significantly more likely to experience relative socioeconomic advantage, disorientation on admission, dementia diagnosis, incontinence and poor skin integrity than those readmitted from a private residence. Three of these variables remained significantly associated with admission from healthcare facilities after multivariate analysis: relative socioeconomic advantage (odds ratio (OR) 11.30; 95% confidence interval (CI) 2.62-48.77), incontinence (OR 7.18; 95% CI 1.19-43.30) and poor skin integrity (OR 18.05; 95% CI 1.85-176.16). CONCLUSIONS: Older adults with chronic illness readmitted to hospital from healthcare facilities are significantly more likely to differ from those readmitted from private residences in terms of relative socioeconomic advantage, incontinence and skin integrity. The findings direct efforts towards addressing the apparent disparity in management of patients admitted from a facility as opposed to a private residence.

Antenatal Administration of Extracellular Vesicles Derived From Amniotic Fluid Stem Cells Improves Lung Function in Neonatal Rats With Congenital Diaphragmatic Hernia.

BACKGROUND: The severity of pulmonary hypoplasia is a main determinant of outcome for babies with congenital diaphragmatic hernia (CDH). Antenatal administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs) has been shown to rescue morphological features of lung development in the rat nitrofen model of CDH. Herein, we evaluated whether AFSC-EV administration to fetal rats with CDH is associated with neonatal improvement in lung function. METHODS: AFSC-EVs were isolated by ultracentrifugation and characterized by size, morphology, and canonical marker expression. At embryonic (E) day 9.5, dams were gavaged with olive oil (control) or nitrofen to induce CDH. At E18.5, fetuses received an intra-amniotic injection of either saline or AFSC-EVs. At E21.5, rats were delivered and subjected to a tracheostomy for mechanical ventilation (flexiVent system). Groups were compared for lung compliance, resistance, Newtonian resistance, tissue damping and elastance. Lungs were evaluated for branching morphogenesis and collagen quantification. RESULTS: Compared to healthy control, saline-treated pups with CDH had fewer airspaces, more collagen deposition, and functionally exhibited reduced compliance and increased airway resistance, elastance, and tissue damping. Conversely, AFSC-EV administration resulted in improvement of lung mechanics (compliance, resistance, tissue damping, elastance) as well as lung branching morphogenesis and collagen deposition. CONCLUSIONS: Our studies show that the rat nitrofen model reproduces lung function impairment similar to that of human babies with CDH. Antenatal administration of AFSC-EVs improves lung morphology and function in neonatal rats with CDH. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

Design, synthesis and inhibitory activities of naringenin derivatives on human colon cancer cells.

Based on the previous result, several naringenin derivatives modified at position 7 with bulky substituents were designed and synthesized, and their inhibitory effects on HCT116 human colon cancer cells were tested using a clonogenic assay. The half maximal inhibitory concentrations (IC(50)) of five naringenin derivatives ranged between 1.20 µM and 20.01 µM which are much better than naringenin used as a control. In addition, new structural modification at C-4 of flavanone results in improving both the anti-cancer effect and anti-oxidative effect. In vitro cyclin dependent kinase 2 (CDK2) binding assay was carried out based on the previous results. To elucidate the possible interaction between naringenin derivatives and CDK2, in silico docking study was performed. This result demonstrates the rationale for the different inhibitory activities of the naringenin derivatives. These findings could be used for designing cancer therapeutic or preventive flavanone-derived agents.

Hospital readmission among older adults with congestive heart failure.

INTRODUCTION: To examine the factors associated with unplanned readmission among older adults with congestive heart failure (CHF) within 28 days of discharge from an index admission, within a large Australian health service. METHODS: Using a comparative cohort design, a multivariate logistic regression model was used to compare readmitted patients with non-readmitted patients and identify risk factors associated with readmission. RESULTS: Significant risk factors identified were male gender, numerous diagnoses, length of stay 3 days or longer and patients being admitted from acute, subacute or aged-care facilities. CONCLUSIONS: The high risk of patients being readmitted from acute, subacute and aged-care services requires further review as these readmissions may be avoidable. It may also be useful to develop a readmission risk screening tool so that patients at risk of readmission can be identified. What is known about this topic? Older adults with CHF are likely to experience multiple readmissions to hospital. There have been several studies conducted on hospital readmissions; however, generalising the findings is problematic due to the use of variable definitions of what constitutes a readmission. What does this paper add? This paper addresses the absence of Australian research comparing groups of older patients with CHF who are readmitted to hospital with those who are not readmitted. It also adopts one of the more frequently used definitions of readmission to aid in future comparability of research. What are the implications for practice? Further work is necessary to improve discharge planning and effectively manage chronic illnesses such as CHF in patients' homes. It may be useful to develop a readmission risk screening tool for staff of inpatient medical wards so that these at-risk patients can be identified before discharge.

A Small Molecule That In Vitro Neutralizes Infection of SARS-CoV-2 and Its Most Infectious Variants, Delta, and Omicron.

The COVID-19 pandemic has underscored the urgent need to develop highly potent and safe medications that are complementary to the role of vaccines. Specifically, it has exhibited the need for orally bioavailable broad-spectrum antivirals that are able to be quickly deployed against newly emerging viral pathogens. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and its variants Delta and Omicron are still a major threat to patients of all ages. In this brief report, we describe that the small molecule CD04872SC was able to neutralize SARS-CoV2 infection with a half-maximal effective concentration (EC50) = 248 µM. Serendipitously, we also were able to observe that CD04872SC inhibited the infection of the SARS-CoV-2 variants; Delta (EC50 = 152 µM) and Omicron (EC50 = 308 µM). These properties may define CD04872SC as a potential broad-spectrum candidate lead for the development of treatments for COVID-19.

Increase in the growth inhibition of bovine pulmonary artery smooth muscle cells by an O-hexanoyl low-molecular-weight heparin derivative.

Proliferation of pulmonary artery smooth muscle cells (PASMCs) appears to play a significant role in chronic pulmonary hypertension. The proliferation of PASMCs is strongly inhibited by some commercial heparin preparations. Heparin fragments were prepared by periodate treatment, followed by sodium borohydride reduction, to enhance potency. The tributylammonium salt of this fragmented heparin was O-acylated with hexanoic anhydride. Gradient polyacrylamide gel electrophoresis showed that the major heparin fragment contained eight disaccharide units. NMR analysis showed that approximately one hexanoyl group per disaccharide residue was present. The O-hexanoyl heparin fragments were assayed for growth inhibitory effect on bovine PASMCs in culture. This derivative was found to be more effective in growth inhibition of bovine PASMCs in culture than the heparin from which it was derived. In the future, it is envisioned that this or similar derivatives may be an effective treatment for pulmonary hypertension.

Nurse Informaticians Report Low Satisfaction and Multi-level Concerns with Electronic Health Records: Results from an International Survey.

This study presents a qualitative content analysis of nurses' satisfaction and issues with current electronic health record (EHR) systems, as reflected in one of the largest international surveys of nursing informatics. Study participants from 45 countries (n=469) ranked their satisfaction with the current state of nursing functionality in EHRs as relatively low. Two-thirds of the participants (n=283) provided disconcerting comments when explaining their low satisfaction rankings. More than one half of the comments identified issues at the system level (e.g., poor system usability; non-integrated systems and poor interoperability; lack of standards; and limited functionality/missing components), followed by user-task issues (e.g., failure of systems to meet nursing clinical needs; non nursing-specific systems) and environment issues (e.g., low prevalence of EHRs; lack of user training). The study results call for the attention of international stakeholders (educators, managers, policy makers) to improve the current issues with EHRs from a nursing perspective.

Advancing Nursing Informatics in the Next Decade: Recommendations from an International Survey.

In the summer of 2015, the International Medical Informatics Association Nursing Informatics Special Interest Group (IMIA NISIG) Student Working Group developed and distributed an international survey of current and future trends in nursing informatics. The survey was developed based on current literature on nursing informatics trends and translated into six languages. Respondents were from 31 different countries in Asia, Africa, North and Central America, South America, Europe, and Australia. This paper presents the results of responses to the survey question: "What should be done (at a country or organizational level) to advance nursing informatics in the next 5-10 years?" (n responders = 272). Using thematic qualitative analysis, responses were grouped into five key themes: 1) Education and training; 2) Research; 3) Practice; 4) Visibility; and 5) Collaboration and integration. We also provide actionable recommendations for advancing nursing informatics in the next decade.

Nursing Informatics Research Priorities for the Future: Recommendations from an International Survey.

We present one part of the results of an international survey exploring current and future nursing informatics (NI) research trends. The study was conducted by the International Medical Informatics Association Nursing Informatics Special Interest Group (IMIA-NISIG) Student Working Group. Based on findings from this cross-sectional study, we identified future NI research priorities. We used snowball sampling technique to reach respondents from academia and practice. Data were collected between August and September 2015. Altogether, 373 responses from 44 countries were analyzed. The identified top ten NI trends were big data science, standardized terminologies (clinical evaluation/implementation), education and competencies, clinical decision support, mobile health, usability, patient safety, data exchange and interoperability, patient engagement, and clinical quality measures. Acknowledging these research priorities can enhance successful future development of NI to better support clinicians and promote health internationally.

Current Trends in Nursing Informatics: Results of an International Survey.

Nursing informatics (NI) can help provide effective and safe healthcare. This study aimed to describe current research trends in NI. In the summer 2015, the IMIA-NI Students Working Group created and distributed an online international survey of the current NI trends. A total of 402 responses were submitted from 44 countries. We identified a top five NI research areas: standardized terminologies, mobile health, clinical decision support, patient safety and big data research. NI research funding was considered to be difficult to acquire by the respondents. Overall, current NI research on education, clinical practice, administration and theory is still scarce, with theory being the least common. Further research is needed to explain the impact of these trends and the needs from clinical practice.

Sulfation patterns in heparin and heparan sulfate: effects on the proliferation of bovine pulmonary artery smooth muscle cells.

Heparin's (HP's) antiproliferative effect on smooth muscle cells is potentially important in defining new approaches to treat pulmonary hypertension. The commercially available HP and heparan sulfate (HS) are structurally heterogenous polymers. In order to examine which sulfonate groups are required for endogenous antiproliferative activity, we prepared the following six chemically modified porcine mucosal HP and HS, which fell into three groups. One group consisted of fully O-sulfonated-N-acetylated, the second group consisted of de-N-sulfonated and re-N-acetylated, and the third group consisted of 6-O-desulfonated HP and HS derivatives. These six preparations were assayed for their antiproliferative potency on bovine pulmonary artery smooth muscle cells. The results of this assay show that (a) over-O-sulfonation of both HP and HS increases antiproliferative activity, (b) substitution of hexosamine with N-acetyl diminishes antiproliferative activity in both HP and HS, and (c) 6-O-desulfonation of HP and HS diminishes antiproliferative potency. Surprisingly, the type of uronic acid residue present at a given level of sulfation is unimportant for antiproliferative potency. In conclusion, only the level of O- and N-sulfo group substitution correlates well with HP and HS antiproliferative activity.

Sulfo-protected hexosamine monosaccharides: potentially versatile building blocks for glycosaminoglycan synthesis.

2,2,2-Trifluorodiazoethane was investigated as a reagent for sulfo group protection on hexosamine monosaccharides. The synthesis of glucosamine and galactosamine building blocks fully differentiated for glycosaminoglycan synthesis and the synthesis of glycosyl donors are described. The compatibility of trifluoroethylsulfonate under a variety of reaction conditions has also been investigated. [structure: see text]

Further evidence that periodate cleavage of heparin occurs primarily through the antithrombin binding site.

Porcine mucosal heparin was fragmented into low-molecular-weight (LMW) heparin by treatment of periodate-oxidized heparin with sodium hydroxide, followed by reduction with sodium borohydride and acid hydrolysis. Gradient polyacrylamide gel electrophoresis analysis showed a mixture of heparin fragments with an average size of eight disaccharide units. 1D 1H NMR showed two-thirds of the N-acetyl groups were lost on periodate cleavage, suggesting cleavage had occurred at the glucopyranosyluronic acid (GlcpA) and idopyranosyluronic acid (IdopA) residues located within and adjacent to the antithrombin III (ATIII) binding site. The N-acetyl glucopyranose (GlcpNAc) residue was lost on workup. The GlcpA residue, within the ATIII binding site, is on the non-reducing side of the N-sulfo, 3, 6-O-sulfo glycopyranosylamine (GlcpNS3S6S) residue. Thus, periodate cleaved heparin should be enriched in GlcpNS3S6S residues. Two-dimensional correlation spectroscopy (2D COSY) confirmed that LMW heparin prepared through periodate cleavage contained GlcpNS3S6S at its non-reducing end. As expected, this LMW heparin also showed reduced ATIII mediated anti-factor IIa and anti-factor Xa activities.

High resolution q-space imaging studies of water in elastin.

We report on the direct measurement of the molecular diffusion coefficients of water confined to purified bovine nuchal ligament elastin by high resolution q-space NMR imaging. The experimental data indicate that water trapped within an elastin fiber has two distinguishable molecular diffusion coefficients. The component with the slowest mobility has a diffusion coefficient on the order of 10(-6) cm(2)/s that varies inversely with the diffusion time and is seen to reduce near 37 degrees C. The component with higher mobility has a diffusion coefficient reminiscent of free water but is observed to also behave similarly at 37 degrees C. From our experimental data we extract the surface-to-volume ratio of pores within elastin and associated changes as a function of temperature.

Unsaturated N-acetyl- D-glucosaminuronic acid glycosides as inhibitors of influenza virus sialidase.

The threat of pandemic influenza is a significant concern of governments worldwide. There is a very limited and relatively expensive armament to tackle such a pandemic should it occur. This fact provides much impetus to the scientific community for the discovery of new and less expensive anti-influenza drugs. Our longstanding interest in the inhibition of influenza virus sialidase, coupled with the development of simple carbohydrates that mimic an unsaturated derivative of the enzyme's naturally-occurring ligand, N-acetylneuraminic acid, has led us to investigate the development of influenza virus sialidase inhibitors based on these mimetics. We have successfully prepared a range of these compounds, in good yield, from the relatively inexpensive carbohydrate N-acetylglucosamine utilising a short synthetic procedure. We have employed a sialidase inhibition assay for biological evaluation of the target compounds and to our delight these mimetics have displayed significant inhibition of influenza virus sialidase.