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Abstract Agreement was reached with 12 acute medical and surgical wards/units at Sydney's Prince of Wales Hospital to participate in a trial of team nursing (TN). Six units employed action research principles to undertake a change to a team nursing model and six remained with the pre-existing individual patient allocation (IPA) model. Task-based teaming was widely discarded by the team nursing units in favour of allocating patients within the team and introducing more supportive and communicative processes aimed at fostering responsibility sharing. Localised team-based models of care arose in the change wards and were outlined, implemented and refined using social action research principles. A 12-month prospective experimental comparison of job satisfaction and staff retention between the TN and IPA groups indicated statistically significant job satisfaction benefits and practically important staff retention benefits associated with moving away from an IPA model of nursing care delivery towards a team-based model of care delivery. Perhaps not surprisingly, job satisfaction gains were most marked among new graduate nurses, who reported real benefits from a teaming inspired shift in model of care in the acute inpatient environment. [ABSTRACT FROM AUTHOR]

Abstract A nursing job satisfaction questionnaire was designed by a project group of nurses seeking a suitable job satisfaction measure to track as an outcome in a large Sydney hospital-wide models of nursing care project. Existing tools were rejected by the group as overly lengthy, US-biased and over-using respondent assessment of the character of the work environment as a proxy for job satisfaction, or happiness at work. A one-page, 14-item tool was developed after instrument reviewing and facilitated groupwork. The tool reduces to three measurable domains: intrinsic, extrinsic and relational job satisfaction. Exploratory factor analysis (n = 220 responses) confirmed the validity of this 'three-way' conceptualisation of nursing job satisfaction. Internal consistency analysis on a larger sample of responses (n = 459) yielded high Cronbach's Alpha values for all three domains and for the total overall, suggesting a stable and reliable measure. The NWSQ is short, one page, sensibly worded for Australian conditions and yields scoring against three validated domains. It holds significant potential utility as a standard metric for prospective ward-based or institution-wide performance trending. [ABSTRACT FROM AUTHOR]

Problem: Although endometrial receptivity is a key factor in influencing implantation in both naturally conceived and assisted reproductive technology (ART) cycles, very little is known about the endometrium milieu around the time of implantation. Previous studies have demonstrated the presence of several cytokines in the endometrium that affect implantation. However, there is lacking data about the presence of immune cell subtypes within the endometrium and in the uterine cavity at the time of implantation., Method of Study: This study was approved by the Institutional Review Board (# 225589). The study was designed as a prospective observational cohort study between May 2021 and December 2022 at a single academic-based fertility center. All patients underwent at least one In Vitro Fertilization (IVF) cycle and have frozen embryos. Twenty-four participants were recruited for this study which was conducted during the frozen embryo transfer (FET) cycle regardless of the outcome of previous cycles. Two samples were acquired from each subject, denoted as lower and upper. A trial transfer catheter was introduced under ultrasound guidance into the lower uterine segment. Upon removal, the tip was rinsed in IMDM medium containing 10% FBS (lower uterus). A transfer catheter was then loaded with the embryo that was placed in the upper uterus under ultrasound guidance. The tip of the transfer catheter was rinsed in separate aliquot of the above media (upper uterus). After centrifugation, pelleted cells were stained for the following surface markers: CD45, CD3, CD19, CD4, CD8, gamma delta TCR, CD25, CD127, CD66b, CD14, CD16, CD56 and acquired on Sony SP6800 Spectral Analyzer., Results: Upon staining the pelleted cells, we were able to identify viable leukocytes from samples obtained from both, upper and lower uterus (0.125 × 10 6 cells ± SD 0.32), (0.123 × 10 6 cells ± SD 0.12), respectively. Among total viable cells, there was no significant difference in both percent and number of CD45+ cells between the upper and lower uterus (9.88% ± 6.98 SD, 13.67% ± 9.79 SD, p = .198) respectively. However, there was significantly higher expression of CD3+ (p = .006), CD19+ (p = .032) and CD14+ (p = .019) cells in samples collected from upper compared to lower uterus. Within all CD3+ cells, we found that gamma delta T cells (GDT) were the major population of T cells in both upper and lower uterus. In contrast, CD8+ T cells were significantly higher in the lower uterus when compared to the upper uterus (p = .009). There was no statistically significant difference in the expression of CD4+ T cells, T regulatory cells (CD4+CD25+CD127-), NK cells (CD56+), neutrophils (CD66b+) and FcγRIII+ cells (CD16+) between upper and lower uterus., Conclusions: We believe the immune milieu at the time of embryo transfer will affect implantation. Understanding the composition of immune cells will guide further research in identifying optimal immune milieus that favor implantation. Comprehensive analysis of endometrium is expected to lead to new diagnostic and therapeutic approaches to improve IVF outcomes., (© 2024 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Introduction: A highly efficacious and durable vaccine against malaria is an essential tool for global malaria eradication. One of the promising strategies to develop such a vaccine is to induce robust CD8+ T cell mediated immunity against malaria liver-stage parasites., Methods: Here we describe a novel malaria vaccine platform based on a secreted form of the heat shock protein, gp96-immunoglobulin, (gp96-Ig) to induce malaria antigen specific, memory CD8+ T cells. Gp96-Ig acts as an adjuvant to activate antigen presenting cells (APCs) and chaperone peptides/antigens to APCs for cross presentation to CD8+ T cells., Results: Our study shows that vaccination of mice and rhesus monkeys with HEK-293 cells transfected with gp96-Ig and two well-known Plasmodium falciparum CSP and AMA1 (PfCA) vaccine candidate antigens, induces liver-infiltrating, antigen specific, memory CD8+ T cell responses. The majority of the intrahepatic CSP and AMA1 specific CD8+ T cells expressed CD69 and CXCR3, the hallmark of tissue resident memory T cells (Trm). Also, we found intrahepatic, antigen-specific memory CD8+ T cells secreting IL-2, which is relevant for maintenance of effective memory responses in the liver., Discussion: Our novel gp96-Ig malaria vaccine strategy represents a unique approach to induce liver-homing, antigen-specific CD8+ T cells critical for Plasmodium liver-stage protection., Competing Interests: WW was a contractor employed by Camris International to perform work at the Naval Medical Research Center during the time of work presented in this article. NP, JH and HG are contractors employed by Henry M Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF) to perform work at NMRC. TR is a contractor employed by Parsons Technical Services, Inc to perform work at the Walter Reed Army Institute of Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Padula, Fisher, Wijayalath, Patterson, Huang, Ganeshan, Robinson, Bates, Hanson, Martin, Rivas, Garcia, Edgel, Sedegah, Villasante and Strbo.)

Encouraging protection results from current mRNA-based SARS-CoV-2 vaccine platforms are primarily due to the induction of SARS- CoV-2- specific B cell antibody and CD4 + T cell. Even though, current mRNA vaccine platforms are adept in inducing SARS-CoV2-specific CD8 + T cell, much less is known about CD8 T cells contribution to the overall vaccine protection. Our allogeneic cellular vaccine, based on a secreted form of the heat-shock protein gp96-Ig, achieves high frequencies of polyclonal CD8 + T cell responses to tumor and infectious antigens through antigen cross-priming in vivo . We and others have shown that gp96-Ig, in addition to antigen-specific CD8 + T cell anti-tumor and anti-pathogen immunity, primes antibody responses as well. Here, we generated a cell-based vaccine that expresses SARS-Cov-2 Spike (S) protein and simultaneously secretes gp96-Ig and OX40L-Fc fusion proteins. We show that co-secretion of gp96-Ig-S peptide complexes and the OX40L-Fc costimulatory fusion protein in allogeneic cell lines results in enhanced activation of S protein-specific IgG antibody responses. These findings were further strengthened by the observation that this vaccine platform induces T follicular helper cells (TFH) and protein-S -specific CD8 + T cells. Thus, a cell-based gp96-Ig vaccine/OX40-L fusion protein regimen provides encouraging translational data that this vaccine platform induces pathogen-specific CD8+, CD4 + T and B cell responses, and may cohesively work as a booster for FDA-approved vaccines. Our vaccine platform can be rapidly engineered and customized based on other current and future pathogen sequences., Competing Interests: NS is inventor on the patent application No 62/983,783 entitled “Immune-mediated coronavirus treatments”; NS is a member of Heat Biologics COVID-19 Advisory Board. MMS is the Vice President of Research; ED is the Executive Director of Research.; PJ is the Director of Business Development, all are employed by Heat Biologics, Inc. RJ is the CEO of Pelican Therapeutics, a subsidiary of Heat Biologics, Inc. MMS, ED, PJ, RJ, and KP hold stock options in Heat Biologics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors. Published by Elsevier Ltd.)

Objectives: To characterize perceived proficiency in immediate postpartum long-acting reversible contraception (LARC) provision among resident physicians in obstetrics and gynecology and family medicine in Wisconsin., Study Design: We queried 254 Wisconsin obstetrics and gynecology or family medicine residents about competency and attitudes regarding family planning services via a confidential electronic survey. We used logistic regression to identify factors associated with the primary outcome of self-reported proficiency in immediate postpartum LARC., Results: We recruited participants from 3 of 3 (100%) obstetrics and gynecology and 9 of 15 (60%) family medicine residency programs, achieving a 74% response rate among trainees (187/254 individuals). Seven of 12 programs (58%) offered immediate postpartum LARC training [100% (3/3) obstetrics and gynecology; 44% (4/9) family medicine]. Forty-eight percent of residents [68% (27/40) obstetrics and gynecology and 60/141 (43%) family medicine, p < 0.01)] reported immediate postpartum LARC proficiency (subdermal implant placement: 48%; immediate postpartum intrauterine device (IUD) placement: 16%). Residents (versus interns), who were younger, training in a program without religious affiliation, and who hoped to provide immediate postpartum LARC provision in practice, were more likely to report subdermal implant proficiency. Interns and family medicine trainees were less likely to report immediate postpartum IUD proficiency., Conclusions: Only 44% of participating family medicine programs provide immediate postpartum LARC training. Two-thirds of obstetrics and gynecology residents report proficiency in immediate postpartum LARC, compared to fewer than half of family medicine residents. Given that many Wisconsin counties do not have a practicing obstetrician/gynecologist, improving immediate postpartum LARC training among family medicine residents is paramount., Implications: STATEMENT: Family medicine physicians provide a significant portion of obstetric care, especially in rural areas. Family medicine residency programs should be supported to ensure that all trainees are proficient in placing subdermal implants and family physicians planning to provide obstetric care are trained in postpartum IUD placement., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To summarize the best available international scientific evidence on the effectiveness of interventions to reduce motor vehicle collisions and their consequences among the working and general populations., Methods: A broad and systematic review was conducted of the literature available in biomedical databases and grey literature. At least two investigators working in parallel performed data extraction, synthesis, and risk of bias analysis., Results: Forty-one studies with low to moderate risk of bias were included. Of these, 18 had an ecological design (time series), 10 were quasi-experimental, one was a population survey, one was a randomized clinical trial, and 11 were systematic reviews., Conclusions: The interventions that most consistently show a positive effect on incidence, morbidity, and mortality due to motor vehicle collisions are national policies or programs that: regulate, enforce, and penalize driving under the influence of alcohol; improve driving safety and driver conditions; improve road infrastructure with the purpose of preventing collisions; and educate and penalize drivers with a history of road violations., Competing Interests: Conflict of interests: None declared.

Objective: To assess, in two separate groups of baboons, uterine viability after ligation of the uterine veins and uterine viability after ligation of both the uterine arteries and veins, respectively., Design: Prospective, observational study., Setting: Baboon breeding colony., Animal(s): Six naïve female Papio hamadryas baboons with indicators of normal reproductive function., Intervention(s): Three baboons underwent surgical interruption of the uterine veins bilaterally, and three baboons underwent surgical interruption of the uterine arteries and the uterine veins bilaterally. All baboons also underwent colpotomy, cervico-vaginal reanastomosis, and intraoperative near-infrared fluorescence imaging after vessel ligation. In the postoperative period, transabdominal sonography, vaginoscopy, and endocervical biopsy were performed on all animals., Main Outcome Measure(s): Postoperative uterine and ovarian viability., Result(s): Near-infrared imaging confirmed intraoperative perfusion of the uterus and cervico-vaginal anastomosis in all cases. In all subjects, sonography revealed normal uteri, and vaginoscopy revealed well-healed anastomoses. Endocervical biopsies (five of six) demonstrated pathologically normal endocervical tissue without evidence of necrosis. Cyclical sex skin turgescence and menstruation were unanimously observed., Conclusion(s): Disruption of bilateral uterine vessels does not affect uterine or ovarian viability in the baboon. Bilateral uterine artery and vein ligation furthers development of a minimally invasive approach to donor hysterectomy., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Cryptosporidium is recognized as one of the main causes of childhood diarrhea worldwide. However, the current treatment for cryptosporidiosis is suboptimal. Calcium flux is essential for entry in apicomplexan parasites. Calcium-dependent protein kinases (CDPKs) are distinct from protein kinases of mammals, and the CDPK1 of the apicomplexan Cryptosporidium lack side chains that typically block a hydrophobic pocket in protein kinases. We exploited this to develop bumped kinase inhibitors (BKIs) that selectively target CDPK1. We have shown that several BKIs of Cryptosporidium CDPK1 potently reduce enzymatic activity and decrease parasite numbers when tested in vitro. In the present work, we studied the anticryptosporidial activity of BKI-1517, a novel BKI. The half maximal effective concentration for Cryptosporidium parvum in HCT-8 cells was determined to be approximately 50 nM. Silencing experiments of CDPK1 suggest that BKI-1517 acts on CDPK1 as its primary target. In a mouse model of chronic infection, 5 of 6 SCID/beige mice (83.3%) were cured after treatment with a single daily dose of 120 mg/kg BKI-1517. No side effects were observed. These data support advancing BKI-1517 as a lead compound for drug development for cryptosporidiosis., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: An international NGO, with financial and managerial support from "partner" communities, established Casas Maternas (birthing facilities) in 3 municipalities in the isolated northwestern highlands of the department of Huehuetenango in Guatemala-an area with high maternal mortality ratio (338 maternal deaths per 100,000 live births). Traditional birth attendants are encouraged to bring patients for delivery at the Casas Maternas, where trained staff are present and access to referral care is facilitated., Methods: We conducted a mixed-methods study in San Sebastian Coatán municipality to assess the contribution of 2 Casas Maternas to health facility deliveries among partner and non-partner communities, with particular emphasis on equity in access. We surveyed all women who delivered in the study area between April 2013 and March 2014, the first full year in which both Casas Maternas in the study area were operating. In addition, using purposive sampling, we conducted in-depth interviews with 22 women who delivered and 6 focus group discussions with 42 community leaders, traditional birth attendants, and Casas Maternas staff members. We analyzed the quantitative data using descriptive statstics and the qualitative data with descriptive content analysis., Results: Of the 321 women eligible for inclusion in the study, we surveyed 275 women (14.3% could not be located or refused to participate). Between April 2013 and March 2014, 70% of women living in partner communities delivered in a health facility (54% in a Casa Materna) compared with 30% of women living in non-partner communities (17% in a Casa Materna). There was no statistically significant difference in uptake of the Casa Materna by maternal education and only a weak effect by household wealth. In contrast, distance from the Casa Materna had a pronounced effect. Traditional birth attendants were strong advocates for utilization of the Casa Materna and played an important role in the decision regarding where the birth would take place. In addition, the program's outreach component, in which peer volunteers visit homes to promote healthy behaviors and appropriate use of health facilities, was identified as a key factor in encouraging mothers to deliver in facilities., Discussion: The Casa Materna approach to strengthening maternity care as developed by Curamericas has potential to increase health facility utilization in isolated mountainous areas inhabited by an indigenous population where access to government services is limited and where maternal mortality is high. The approach shows promise for broader application in Guatemala and beyond., (© Stollak et al.)

We previously discovered compounds based on a 5-aminopyrazole-4-carboxamide scaffold to be potent and selective inhibitors of CDPK1 from T. gondii . The current work, through structure-activity relationship studies, led to the discovery of compounds ( 34 and 35 ) with improved characteristics over the starting inhibitor 1 in terms of solubility, plasma exposure after oral administration in mice, or efficacy on parasite growth inhibition. Compounds 34 and 35 were further demonstrated to be more effective than 1 in a mouse infection model and markedly reduced the amount of T. gondii in the brain, spleen, and peritoneal fluid, and 35 given at 20 mg/kg eliminated T. gondii from the peritoneal fluid.

This paper describes the development and outcomes from 'joint working' between Prince of Wales Hospital and BD (Becton, Dickinson and Company) in Australia. 'Joint working' is a term used within the English National Health Service to describe health system and industry partners working together to create novel service models which benefit patients. The joint working process broadened the perspective of both parties through learning from each other and so enhanced the range of tools they each bring to their work.

5-Aminopyrazole-4-carboxamide was used as an alternative scaffold to substitute for the pyrazolopyrimidine of a known "bumped kinase inhibitor" to create selective inhibitors of calcium-dependent protein kinase-1 from both Toxoplasma gondii and Cryptosporidium parvum . Compounds with low nanomolar inhibitory potencies against the target enzymes were obtained. The most selective inhibitors also exhibited submicromolar activities in T. gondii cell proliferation assays and were shown to be non-toxic to mammalian cells.

Cryptosporidium parasites infect intestinal cells, causing cryptosporidiosis. Despite its high morbidity and association with stunting in the developing world, current therapies for cryptosporidiosis have limited efficacy. Calcium-dependent protein kinases (CDPKs) are essential enzymes in the biology of protozoan parasites. CDPK1 was cloned from the genome of Cryptosporidium parvum, and potent and specific inhibitors have been developed based on structural studies. In this study, we evaluated the anti-Cryptosporidium activity of a novel CDPK1 inhibitor, 1294, and demonstrated that 1294 significantly reduces parasite infection in vitro, with a half maximal effective concentration of 100 nM. Pharmacokinetic studies revealed that 1294 is well absorbed, with a half-life supporting daily administration. Oral therapy with 1294 eliminated Cryptosporidium parasites from 6 of 7 infected severe combined immunodeficiency-beige mice, and the parasites did not recur in these immunosuppressed mice. Mice treated with 1294 had less epithelial damage, corresponding to less apoptosis. Thus, 1294 is an important lead for the development of drugs for treatment of cryptosporidiosis.

Objective: Synthesize and assess the available scientific evidence from the period 2008-2012 on interventions of demonstrated efficacy in the treatment and rehabilitation of adolescents and adults engaged in the problematic use of alcohol and other substances., Methods: A systematic review was undertaken with search and analysis of national and international literature on the subject in Spanish and English in the main international databases: PubMed/MEDLINE, LILACS, Embase, PsycINFO, SciELO, the databases of the York University Centre for Reviews and Dissemination (DARE, ETS Database), the Cochrane Library, and other sources of gray literature. The search criteria included randomized clinical trials and systematic reviews but excluded observational studies, qualitative studies, and articles of poor methodological quality., Results: The final sample consisted of 69 studies. The psychosocial interventions shown to be effective were cognitive behavioral therapy, family interventions, self-help interventions using the Internet, couples behavioral therapy, community strengthening and family training, telephone monitoring and support, and integrated therapy for substance abuse disorder with anxiety and depression comorbidity. Pharmacological interventions of demonstrated effectiveness were acamprosate, lysergic acid diethylamide (LSD), and benzodiazepines in problematic alcohol use, as well as maintenance therapy with high-dose opioids., Conclusions: The demonstrated effectiveness of psychosocial and pharmacological interventions is slight but significant. However, strongly multidisciplinary interventions that use a cognitive behavioral approach and the involvement of people close to the consumer, as well as some of the specific pharmacological interventions, have been shown to yield the best results in terms of indicators of abstinence and prevention of relapses.

People with autism spectrum disorder (ASD) are characterized by deficits in social interaction, language, and behavioral flexibility. Rare mutations and copy number variations have been identified in individuals with ASD, but in most patients, the causal variants remain unknown. A genome-wide association study (GWAS), designed to identify genes and pathways that contribute to ASD, indicated a genome-wide significant association of ASD with the single-nucleotide polymorphism (SNP) rs4307059 (P = 10⁻¹⁰), which is located in a gene-poor region of chromosome 5p14.1. We describe here a 3.9-kb noncoding RNA that is transcribed from the region of the chromosome 5p14.1 ASD GWAS association SNP. The noncoding RNA was encoded by the opposite (antisense) strand of moesin pseudogene 1 (MSNP1), and we therefore designated it as MSNP1AS (moesin pseudogene 1, antisense). Chromosome 5p14.1 MSNP1AS was 94% identical and antisense to the X chromosome transcript of MSN, which encodes a protein (moesin) that regulates neuronal architecture. Individuals who carry the ASD-associated rs4307059 T allele showed increased expression of MSNP1AS. The MSNP1AS noncoding RNA bound to MSN, was highly overexpressed (12.7-fold) in postmortem cerebral cortex of individuals with ASD, and could regulate levels of moesin protein in human cell lines. These data reveal a biologically functional element that may contribute to ASD risk.

Abstract This paper outlines the process employed by a Nurse Unit Manager and her senior nursing team to introduce action learning sets (ALSs) to the nursing staff of an inpatient medical unit. During the process, a workplace culture creative visioning exercise was also facilitated. A key finding of the exercise was that the process enabled others to act while challenging the process and encouraging the heart. Effective leadership enabled staff involved to foster growth.

Protein farnesyltransferase (FTase) catalyzes an essential posttranslational lipid modification of more than 60 proteins involved in intracellular signal transduction networks. FTase inhibitors have emerged as a significant target for development of anticancer therapeutics and, more recently, for the treatment of parasitic diseases caused by protozoan pathogens, including malaria (Plasmodium falciparum). We present the X-ray crystallographic structures of complexes of mammalian FTase with five inhibitors based on an ethylenediamine scaffold, two of which exhibit over 1000-fold selective inhibition of P. falciparum FTase. These structures reveal the dominant determinants in both the inhibitor and enzyme that control binding and selectivity. Comparison to a homology model constructed for the P. falciparum FTase suggests opportunities for further improving selectivity of a new generation of antimalarial inhibitors.

New chemotherapeutics are urgently needed to combat malaria. We previously reported on a novel series of antimalarial, ethylenediamine-based inhibitors of protein farnesyltransferase (PFT). In the current study, we designed and synthesized a series of second generation inhibitors, wherein the core ethylenediamine scaffold was varied in order to examine both the homology model of Plasmodium falciparum PFT (PfPFT) and our predicted inhibitor binding mode. We identified several PfPFT inhibitors (PfPFTIs) that are selective for PfPFT versus the mammalian isoform of the enzyme (up to 136-fold selectivity), that inhibit the malarial enzyme with IC50 values down to 1 nM, and that block the growth of P. falciparum in infected whole cells (erythrocytes) with ED50 values down to 55 nM. The structure-activity data for these second generation, ethylenediamine-inspired PFT inhibitors were rationalized by consideration of the X-ray crystal structure of mammalian PFT and the homology model of the malarial enzyme.