Synthesis of 2,6-trans-Tetrahydropyrans Using a Palladium-Catalyzed Oxidative Heck Redox-Relay Strategy.

The C-aryl-tetrahydropyran motif is prevalent in nature in a number of natural products with biological activity; however, this challenging architecture still requires novel synthetic approaches. We demonstrate the application of a stereoselective Heck redox-relay strategy for the synthesis of functionalized 2,6-trans-tetrahydropyrans in excellent selectivity in a single step from an enantiopure dihydropyranyl alcohol, proceeding through a novel exo-cyclic migration. The strategy has also been applied to the total synthesis of a trans-epimer of the natural product centrolobine in excellent yield and stereoselectivity.

Remote area nurses' experiences of workplace safety in very remote primary health clinics: A qualitative study.

AIM: To explore Remote Area Nurses' experiences of the implementation of workplace health and safety policies and risk mitigation strategies in Australian very remote primary health clinics. DESIGN: This qualitative study used online semi-structured interviews, with participants purposively sampled to maximize variation in work location and service type. Data were analysed using a reflexive thematic analysis approach. Coding was carried out inductively, with NVivo 12 aiding data management. SETTING: The interviews were conducted from 24 Februrary 2021 to 06 March 2021 with Remote Area Nurses from very remote primary health clinics in Australia. PARTICIPANTS: Fifteen Remote Area Nurses participated in the study. RESULTS: Thematic analysis revealed varied approaches to workplace safety among the different health services and regions. While the spread of 'never alone' policies in many clinics addressed one of the significant risks faced by Remote Area Nurses, gaps remained even for hazards specifically highlighted in existing work health and safety legislation. Meaningful collaboration with staff and the community, local orientation, preparation for the role and providing quality care were protective factors for staff safety. Understaffing, unsafe infrastructure and inadequate equipment were common concerns among Remote Area Nurses. CONCLUSION: Health services need to prioritize workplace safety and take a continuous quality improvement approach to its implementation. This will include ensuring safety strategies are appropriate for the local context, improving infrastructure maintenance, and establishing sustainable second responder systems such as a pool of drivers with local knowledge. IMPLICATIONS FOR THE PROFESSION: Poor personal safety contributes to burnout and high turnover of staff. Nurses' insights into the barriers and enablers of current workplace safety strategies will aid policymakers and employers in future improvements. REPORTING METHOD: COREQ reporting guidelines were followed. PIPE STATEMENT: A panel of six Remote Area Nurses collaborated in the development of this project.

Robust and General Late-Stage Methylation of Aryl Chlorides: Application to Isotopic Labeling of Drug-like Scaffolds.

The preparation of isotopically labeled compounds for drug discovery and development presents a unique challenge. Both stable and radioactive isotopes must be incorporated into complex bioactive molecules as efficiently as possible, using precious, and often expensive, isotopically enriched reagents. Due to the ubiquity and importance of methyl groups in drug molecules, there is a requirement for a general, late-stage methylation that allows for the incorporation of both carbon and hydrogen isotopes. Herein, we report a highly efficient, robust palladium-catalyzed approach, optimized via high-throughput experimentation, for the methylation of aryl chlorides using potassium methyltrifluoroborate. A practically straightforward route to isotopically labeled methylating agents has also been developed, and the methodology applied to isotopologue synthesis, including the installation of isotopic labels in a range of drug-like scaffolds.

Student Employment Models for Undergraduate Nurses and Midwives in Australia: A Scoping Review.

Introduction: Evidence has shown that throughout their undergraduate years, many nursing and midwifery students obtain paid employment in a wide variety of clinical and non-clinical positions. Across Australia, inconsistencies exist in the models of clinical employment available to these student groups. Previous Australian studies have described the employment of undergraduate nursing and midwifery students in regulated and unregulated clinical roles. No studies have reported on the various regulated roles available to both student nurses and midwives in Australia. The purpose of this scoping review is to identify and synthesize evidence related to nursing and/or midwifery students employed in regulated and unregulated clinical roles in Australia. Methods: This scoping review utilized published recommendations for data screening, abstraction, and synthesis. One of the authors, a librarian, undertook systematic searches in CINAHL Complete (1937-present), Emcare on Ovid (1995-present), Scopus (1969-present), and Ovid MEDLINE(R) (including Epub Ahead of Print, In-Process, and In-Data-Review & Other Non-Indexed Citations, 1946-present). The initial searches were completed in April 2019 and repeated in March 2021 and May 2022 to identify any new literature. Manual searching of reference lists in the included papers was also undertaken, together with selected organizational websites. The extracted data included the lead author, date, title, study design, study sample and location, and key findings. Results: From the 53 items retrieved, 23 peer-reviewed studies met the inclusion criteria and were included in the review. All items were published between 2011 and 2022. Only four of the studies focused upon student midwives. Undergraduate nursing and midwifery students in Australia obtain paid employment in a variety of regulated and unregulated clinical roles. Conclusion: The literature reported here demonstrates that there are differing models, nomenclature, educational requirements, and pay scales in place for student employment in clinical roles across Australian states and territories.

Experimental and computational insights into the mechanism of the copper(i)-catalysed sulfonylative Suzuki-Miyaura reaction.

A mechanistic study into the copper(i)-catalysed sulfonylative Suzuki-Miyaura reaction, incorporating sulfur dioxide, is described. Utilising spectroscopic and computational techniques, an exploration into the individual components of the competing catalytic cycles is delineated, including identification of the resting state catalyst, transmetalation of arylboronic acid onto copper(i), the sulfur dioxide insertion process, and the oxidative addition of aryl halide to CuI. Studies also investigated prominent side-reactions which were uncovered, including a competing copper(ii)-catalysed mechanism. This led to an additional proposed and connected CuI/CuII/CuIII catalytic cycle to account for by-product formation.

Factors Affecting Quality of Care in Maternal and Child Health in Timor-Leste: A Scoping Review.

Timor-Leste faces many challenges implementing quality maternal, newborn and child health (MNCH) services due to resource constraints and socio-cultural factors that disproportionately affect the health of women and children. A scoping review was conducted to map the quality of MNCH services against WHO quality standards on: 1. Provision of care, 2. Experiences of care, and 3. Cross-cutting standards. The literature search identified 1058 citations, from which 28 full-text articles met the inclusion criteria. The findings highlight health workers' limited capacity to provide quality services and referrals. The major reasons for this are: a lack of essential supplies, poor infrastructure and transport, limited opportunities for ongoing learning, and gaps in health information systems. Provision of care standards and cross-cutting standards require attention at a broad systems level. Findings related to experiences of care highlight the importance of effective communication, respect, and emotional support, particularly for vulnerable women and children who have difficulty accessing services, and for those who have experienced violence. These experience-related standards could be addressed at an individual health worker and health service level, as well as at a systems level. This review provides direction to focus quality-improvement initiatives within local health facilities, as well as at municipal and national level.

Horses affected by EPM have increased sCD14 compared to healthy horses.

Equine protozoal myeloencephalitis (EPM) is a debilitating neurologic disease affecting horses across the Americas. Gaps in understanding the inflammatory immune response in EPM-affected horses create difficulties with diagnosis and treatment, subsequently negatively impacting the prognosis of affected horses. The purpose of the current study was to evaluate circulating levels of the inflammatory immune marker soluble CD14 (sCD14), in horses with EPM (n = 7) and determine if they differed from healthy neurologically normal horses (n = 6). Paired sera and cerebrospinal fluid (CSF) samples were analyzed for sCD14. Inclusion criteria for EPM horses consisted of the presence of neurologic signs consistent with EPM, Sarcocystis neurona surface antigens 2, 4/3 (SnSAG 2, 4/3) ELISA serum: CSF antibody ratio ≤ 100, and a postmortem diagnosis of EPM. Control horses were neurologically normal, healthy horses with SnSAG 2, 4/3 ELISA serum: CSF antibody ratios of > 100. Serum anti-Sarcocystis neurona antibodies indicate that healthy control horses were exposed to S. neurona but resistant to developing clinical EPM. EPM cases had significantly greater concentrations of sCD14 in CSF samples compared to control horses and increased serum sCD14 concentrations. A positive correlation between sCD14 serum and CSF concentrations was observed in EPM-affected horses but not healthy horses. Soluble CD14 is an inflammatory marker, and the study results suggest it is elevated in EPM patients. When performed in conjunction with clinical evaluation and standard antibody testing, there may be potential for sCD14 to be utilized as a correlate for EPM.

Interferon gamma protective against Sarcocystis neurona encephalitis in susceptible murine model.

Sarcocystis neurona is the predominant etiological agent of the infectious equine neurologic disease, equine protozoal myeloencephalitis (EPM), which is prevalent in the United States. A wealth of knowledge about S. neurona biology and its life cycle has accumulated over the last several decades. However, much remains unknown about the aberrant equine host's immune response to S. neurona and the relatively high prevalence of exposure to the protozoa but relatively infrequent occurrence of clinical neurologic disease. Mouse models simulating EPM are commonly used to study the disease due to numerous challenges associated with studying the disease in horses. The critical role of the cytokine, interferon gamma (IFNγ), in protection against S. neurona encephalitis has been well established as Ifnγ-/- mice are highly susceptible to S. neurona encephalitis. However, there are discrepancies in the literature regarding S. neurona disease susceptibility in lymphocyte deficient mice, lacking T-lymphocytes and their associated Ifnγ production. In the current study, we investigated S. neurona encephalitis susceptibility in 2 genetically different strains of lymphocyte null mice, C57Bl/6 (B6).scid and Balb/c.scid. The B6.scid mouse was determined to be susceptible to S. neurona encephalitis as 100 % of infected mice developed neurologic disease within 60 days post infection (DPI). The Balb/c.scid mouse was nearly disease resistant as only 10 % of mice developed neurologic disease 60 DPI. Encephalitis was histologically demonstrable and S. neurona was identified in cerebellar samples collected from B6.scid but absent in Balb/c.scid mice. To further investigate the importance of T-lymphocyte derived Ifnγ, T- lymphocytes were adoptively transferred into B6.scid mice. The adoptive transfer of Ifnγ competent T- lymphocytes offered complete protection against S. neurona encephalitis but transfer of Ifnγ deficient T- lymphocytes did not with 100 % of these recipient mice succumbing to S. neruona encephalitis. Histological analysis of collected cerebellar samples confirmed the presences of S. neurona and encephalitis in recipient mice that developed neurologic disease. These studies show that the background strain is critical in studying SCID susceptibility to S. neurona disease and suggest a protective role of Ifnγ producing T- lymphocytes in S. neurona encephalitis susceptible mice.

Antiplasmodial, antimalarial activities and toxicity of African medicinal plants: a systematic review of literature.

BACKGROUND: Malaria still constitutes a major public health menace, especially in tropical and subtropical countries. Close to half a million people mainly children in Africa, die every year from the disease. With the rising resistance to frontline drugs (artemisinin-based combinations), there is a need to accelerate the discovery and development of newer anti-malarial drugs. A systematic review was conducted to identify the African medicinal plants with significant antiplasmodial and/or anti-malarial activity, toxicity, as wells as assessing the variation in their activity between study designs (in vitro and in vivo). METHODS: Key health-related databases including Google Scholar, PubMed, PubMed Central, and Science Direct were searched for relevant literature on the antiplasmodial and anti-malarial activities of African medicinal plants. RESULTS: In total, 200 research articles were identified, a majority of which were studies conducted in Nigeria. The selected research articles constituted 722 independent experiments evaluating 502 plant species. Of the 722 studies, 81.9%, 12.4%, and 5.5% were in vitro, in vivo, and combined in vitro and in vivo, respectively. The most frequently investigated plant species were Azadirachta indica, Zanthoxylum chalybeum, Picrilima nitida, and Nauclea latifolia meanwhile Fabaceae, Euphorbiaceae, Annonaceae, Rubiaceae, Rutaceae, Meliaceae, and Lamiaceae were the most frequently investigated plant families. Overall, 248 (34.3%), 241 (33.4%), and 233 (32.3%) of the studies reported very good, good, and moderate activity, respectively. Alchornea cordifolia, Flueggea virosa, Cryptolepis sanguinolenta, Zanthoxylum chalybeum, and Maytenus senegalensis gave consistently very good activity across the different studies. In all, only 31 (4.3%) of studies involved pure compounds and these had significantly (p = 0.044) higher antiplasmodial activity relative to crude extracts. Out of the 198 plant species tested for toxicity, 52 (26.3%) demonstrated some degree of toxicity, with toxicity most frequently reported with Azadirachta indica and Vernonia amygdalina. These species were equally the most frequently inactive plants reported. The leaves were the most frequently reported toxic part of plants used. Furthermore, toxicity was observed to decrease with increasing antiplasmodial activity. CONCLUSIONS: Although there are many indigenous plants with considerable antiplasmodial and anti-malarial activity, the progress in the development of new anti-malarial drugs from African medicinal plants is still slothful, with only one clinical trial with Cochlospermum planchonii (Bixaceae) conducted to date. There is, therefore, the need to scale up anti-malarial drug discovery in the African region.

Workforce safety in the remote health sector of Australia: a scoping review.

OBJECTIVES: To scope the evidence surrounding workplace health and safety risks for the remote health workforce in Australia and to collate the recommendations to address those risks. DESIGN: A five-stage scoping review framework refined by Cooper et al was used for this review. Informit Health Collection, Ovid Emcare, Medline, Web of Science Core Collection, ProQuest and the grey literature were searched in October 2020 using a combination of key words derived from the eligibility criteria. No date restriction was placed on the search. Title and abstract screening, full-text review and data extraction were performed by three reviewers. Data were analysed by the lead author using qualitative thematic analysis. ELIGIBILITY CRITERIA: Articles were eligible for inclusion if they were published research or industry reports, focused on safety for the remote health workforce in Australia, identified hazards/safety risks or recommendations to reduce risk, and were written in English. RESULTS: The search yielded 312 articles, of which 18 met the inclusion criteria. A wide range of hazards/safety risks and recommendations were identified within the literature, which related to safety culture, isolation, safe environment, and education and training. Some recommendations, such as the use of a risk management approach, good post-incident support, safer clinics and accommodation, and improved access to education and training, had been discussed in the literature for over a decade, with a high level of agreement regarding their importance. Two articles briefly evaluated the impact of some recommendations. CONCLUSION: While many recommendations have been developed to improve the safety of the remote health workforce in Australia, there is little evidence of their implementation and evaluation. As many remote health professionals report ongoing or worsening workplace safety issues, there is an urgent need for the implementation and evaluation of the workforce safety strategies recommended in the literature and required by legislation.

GAMOGONY OF SARCOCYSTIS STRIXI IN MAMMALIAN CELL CULTURES.

We are interested in the disease ecology of Sarcocystis species that infect birds of prey as definitive and intermediate hosts. The present study was done to test our hypothesis that a laboratory model can be developed for sarcocystis infection in mammals using gamma interferon gene knockout (KO) mice as a source of Sarcocystis strixi bradyzoites and mammalian cell cultures as a source of sporulated S. strixi oocysts. Sporocysts of S. strixi from a naturally infected barred owl (Strix varia) were fed to KO mice to produce sarcocysts, and the enclosed bradyzoites were obtained by acid-pepsin digestion of abdominal and thigh muscles. Bradyzoites, metrocytes, and an unusual spherical stage were seen in digest before the inoculation of host cells. The spherical stages stained dark with Giemsa stain, but no nucleus was observed, and they were seen free and associated with the concave portion of some bradyzoites. Examination of infected cell cultures demonstrated that macrogamonts and microgamonts were present at 24 hr post-inoculation. Since sporulated oocysts were not observed, we had to reject our current hypothesis.

Nurses in advanced roles as a strategy for equitable access to healthcare in the WHO Western Pacific region: a mixed methods study.

BACKGROUND: The Western Pacific region constitutes one-quarter of the world's population and has diverse health needs. While dialogue on and promotion of advanced practice nurses are ongoing, this study investigated the current responsibilities of nurses in advanced roles, future healthcare needs, and the implications of these components for nurses' professional development within the Western Pacific region. METHODS: This study employed three phases, a descriptive survey on the current status of nurses in advanced roles in the Western Pacific region, followed by a Delphi survey, and exploratory interviews. A total of 55 national experts with clinical, academic, and/or government-related backgrounds from 18 countries participated from December 2017 - December 2018. The descriptive survey via email to identify the status of nurses in advanced roles and a working definition was developed. This formed the basis for the Delphi survey, which identified key barriers and challenges for enhancing the development of nurses in advanced roles within the country (round 1) and for the region (rounds 2 and 3). Lastly, semi-structured individual interviews were conducted to identify strategies for establishing nurses in advanced roles to improve equitable access to healthcare. RESULTS: Thirty-seven roles and characteristics were identified and categorized for nurses performing advanced roles. Emergency care, critical care, elderly health, child health, and rural/remote communities were identified as fields with particular need for nurses in advanced roles in the Western Pacific region. Providing effective services, influencing government leadership, and advocating for health system sustainability were deemed necessary to improve equitable healthcare access. We found that nurses in advanced roles are not limited to clinical tasks within the hospital but are poised for active participation in primary healthcare, education/teaching, professional leadership, quality management, and research. CONCLUSIONS: Demand for nurses in advanced roles is high in the Western Pacific region and 15 items were identified across five core strategic areas to enhance development of nurses in advanced roles. Governmental-level recommendations include establishing legislative protection, improving systems for remuneration, strengthening supportive channels, and conducting national needs assessments.

Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection.

Congenital athymia can present with severe T cell lymphopenia (TCL) in the newborn period, which can be detected by decreased T cell receptor excision circles (TRECs) on newborn screening (NBS). The most common thymic stromal defect causing selective TCL is 22q11.2 deletion syndrome (22q11.2DS). T-box transcription factor 1 (TBX1), present on chromosome 22, is responsible for thymic epithelial development. Single variants in TBX1 causing haploinsufficiency cause a clinical syndrome that mimics 22q11.2DS. Definitive therapy for congenital athymia is allogeneic thymic transplantation. However, universal availability of such therapy is limited. We present a patient with early diagnosis of congenital athymia due to TBX1 haploinsufficiency. While evaluating for thymic transplantation, she developed Omenn Syndrome (OS) and life-threatening adenoviremia. Despite treatment with anti-virals and cytotoxic T lymphocytes (CTLs), life threatening adenoviremia persisted. Given the imminent need for rapid establishment of T cell immunity and viral clearance, the patient underwent an unmanipulated matched sibling donor (MSD) hematopoietic cell transplant (HCT), ultimately achieving post-thymic donor-derived engraftment, viral clearance, and immune reconstitution. This case illustrates that because of the slower immune recovery that occurs following thymus transplantation and the restricted availability of thymus transplantation globally, clinicians may consider CTL therapy and HCT to treat congenital athymia patients with severe infections.

Effect of Bariatric Surgery on Cardiovascular Function and Heart Failure Outcomes.

In this article, we explore the influence of obesity on cardiovascular health and the role of bariatric surgery in reducing cardiovascular comorbidities, preventing the onset of heart failure and improving mortality and quality of life in those with cardiac dysfunction. We highlight the mechanisms by which obesity leads to cardiovascular remodeling, diastolic dysfunction, and eventual heart failure. These mechanisms include systemic inflammation, local lipotoxicity by way of ectopic fat deposition, and hemodynamic alterations that have significant effects on cardiac structure and function. Bariatric surgery has been shown to reverse these mechanisms, thereby leading to the reversal of adverse cardiac remodeling, improved diastolic function, and in some cases, improved systolic function in patients with systolic heart failure. Most importantly, bariatric surgery leads to significant improvements in cardiovascular outcomes, including the risks of myocardial infarction and stroke, heart failure incidence, and mortality. In patients with heart failure, bariatric surgery has been shown to decrease heart failure exacerbations and admissions and improve quality of life. Furthermore, in advanced heart failure patients, including those requiring mechanical circulatory support, bariatric surgery has been successfully and safely used for weight loss, as a bridge to cardiac transplantation. Therefore, bariatric surgery should be considered as a treatment for conditions ranging from subclinical cardiac dysfunction to symptomatic, advanced heart failure.

Stereoselective Remote Functionalization via Palladium-Catalyzed Redox-Relay Heck Methodologies.

Exploration of novel, three-dimensional chemical space is of growing interest in the drug discovery community and with this comes the challenge for synthetic chemists to devise new stereoselective methods to introduce chirality in a rapid and efficient manner. This Minireview provides a timely summary of the development of palladium-catalyzed asymmetric redox-relay Heck-type processes. These reactions represent an important class of transformation for the selective introduction of remote stereocenters, and have risen to prominence over the past decade. Within this Minireview, the vast scope of these transformations will be showcased, alongside applications to pharmaceutically relevant chiral building blocks and drug substances. To complement this overview, a mechanistic summary and discussion of the current limitations of the transformation are presented, followed by an outlook on future areas of investigation.

Bullying in nursing: How has it changed over 4 decades?

AIM: This study sought to explore how bullying in the nursing profession in Australia has changed over four decades, and why it continues to persist. BACKGROUND: Bullying in nursing is recognized as a pervasive problem. While much attention has been given to demonstrating the existence and impact of bullying in the nursing profession, little is understood about the evolution of this phenomenon and factors that contribute to its persistence. METHODS: This study employed an historical methodology using the testimony method of data collection. Testimonies were collected online and via interview from seventy registered nurses across Australia. Data were analysed using a three-dimensional analysis to produce a chronological historiography. RESULTS: This study found that the antecedents, manifestations, responses to and impacts of bullying in the nursing profession changed according to context and over time. The findings shed light on the role of nurse managers in the prevention and appropriate management of bullying in the workplace. CONCLUSION: Prevention and intervention approaches must be developed to combat the complex and changing factors that allow bullying to persist. IMPLICATIONS FOR NURSING MANAGEMENT: This study shows the role that management plays in tackling the problem of bullying in nursing. It can no longer be acceptable for culture to be used as an excuse for unacceptable behaviour, nor for power to be abused to protect perpetrators of workplace bullying. The findings discussed in this paper reveal that inexperienced nurse managers are often ill-equipped to identify and manage bullying. Nurses in management positions must recognize and acknowledge this deficit if the problem of bullying is to be effectively tackled.

Neosporosis, Toxoplasmosis, and Sarcocystosis in Ruminants: An Update.

Neospora caninum, Toxoplasma gondii, and Sarcocystis spp. are related Apicomplexan parasites that have 2 hosts in their life cycles. The definitive hosts excrete unsporulated (Neospora caninum, T gondii) or sporulated (Sarcocystis spp.) oocysts in their feces after ingesting tissue cysts from the tissues of ruminant intermediate hosts. These coccidians can cause abortion and neonatal mortality in ruminants. T gondii and Sarcocystis hominis (from cattle) are zoonotic. This article reviews information on the etiology, life cycle, diagnosis, control and prevention of these parasites and the diseases they cause in ruminants.

Synthesis of [3 H] and [14 C]genipin.

[3 H]Genipin was synthesized in a single step by Ir(I) catalyzed hydrogen isotope exchange. Conditions for selective exchange of the sp2 CH bond ortho to the methyl ester functionality were developed through deuterium modeling studies through a catalyst screen. Optimized conditions so obtained were then utilized with tritium gas to generate [3 H]genipin at a specific activity of 18.5 Ci/mmol. Racemic [14 C]genipin was prepared in eight steps in overall 5.4% radiochemical yield from potassium [14 C]cyanide.

Bullying in Nursing: Is it in the Eye of the Beholder?

The nursing profession is presented with numerous definitions of workplace bullying. This study provides an in-depth analysis of the concept of bullying in the nursing profession in Australia through a scoping review of definitions presented in literature published up until 2018. The research questions used to guide the search were as follows: How has the definition of bullying in nursing in Australia been conceptualized in the literature? How do these definitions of bullying differ? How has the definition of bullying, as used in the literature, evolved over time? The review was informed by the approach of Arksey and O'Malley, containing explicit definitions of bullying in nursing literature. The findings reveal that the literature does not reflect a shared and integrated vision of the exact nature of bullying in the nursing profession. The conceptualization of bullying in the nursing profession has become more dynamic over time. The myriad ways in which bullying in nursing is defined in Australia has important implications for research, practice, education, and policy.