Role of Microfiltration Membrane Morphology on Nanoparticle Purification to Enhance Downstream Purification of Viral Vectors.

In the rapidly advancing realms of gene therapy and biotechnology, the efficient purification of viral vectors is pivotal for ensuring the safety and efficacy of gene therapies. This study focuses on optimizing membrane selection for viral vector purification by evaluating key properties, including porosity, thickness, pore structure, and hydrophilicity. Notably, we employed adeno-associated virus (AAV)-sized nanoparticles (20 nm), 200 nm particles, and bovine serum albumin (BSA) to model viral vector harvesting. Experimental data from constant pressure normal flow filtration (NFF) at 1 and 2 bar using four commercial flat sheet membranes revealed distinct fouling behaviors. Symmetric membranes predominantly showed internal and external pore blockage, while asymmetric membranes formed a cake layer on the surface. Hydrophilicity exhibited a positive correlation with recovery, demonstrating an enhanced recovery with increased hydrophilicity. Membranes with higher porosity and interpore connectivity showcased superior throughput, reduced operating time, and increased recovery. Asymmetric polyether sulfone (PES) membranes emerged as the optimal choice, achieving ∼100% recovery of AAV-sized particles, an ∼44% reduction in model cell debris (200 nm particles), an ∼35% decrease in BSA, and the fastest operating time of all membranes tested. This systematic investigation into fouling behaviors and membrane properties not only informs optimal conditions for viral vector recovery but also lays the groundwork for advancing membrane-based strategies in bioprocessing.

'The god of criminals is their belly': diet, prisoner health, and prison medical officers in mid-nineteenth-century English and Irish prisons.

Existing scholarship on prison diets has emphasised the role of food and its restriction as a key aspect of the deterrent system of prison discipline introduced in the 1860s. Here we suggest that a strong emphasis was placed on dietary regulation after the establishment of the reformist, but also 'testing', separate system of confinement in the mid-nineteenth century. While the impact of diet on the physical health of prisoners was a major concern, we argue that the psychological impact of food was also stressed, and some prison administrators and doctors argued that diet had an important protective function in preserving inmates' mental wellbeing. Drawing on a wide range of prison archives and official reports, this article explores the crucial role of prison medical officers in England and Ireland in implementing prison dietaries. It highlights the importance and high level of individual adaptations to dietary scales laid down centrally, as a means of utilising diet as a tool of discipline or as an intervention to improve prisoners' health. It examines the forays of some prison doctors into dietary experiments, as they investigated the impact of different dietaries or made more quotidian adjustments to food intake, based on local conditions and food supplies. The article concludes that, despite central policies geared to establishing uniformity and interest in new scientific discourses on nutrition, a wide range of practices were pursued in individual prisons, mostly shaped by practical rather than scientific factors, with many prison medical officers asserting their autonomy in making dietary adjustments.

Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge.

BACKGROUND: Malaria is preventable yet causes >600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication. METHODS: We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A-liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults. The primary end points were safety and reactogenicity. The secondary end points were antibody responses and Plasmodium falciparum parasitemia after homologous controlled human malaria infection. RESULTS: Participants were enrolled into 4 groups receiving rCSP/GLA-LSQ: 10 µg × 3 (n = 20), 30 µg × 3 (n = 10), 60 µg × 3 (n = 10), or 60 µg × 2 (n = 9); 10 participants received 30 µg rCSP alone × 3, and there were 6 infectivity controls. Participants experienced no serious adverse events. Rates of solicited and unsolicited adverse events were similar among groups. All 26 participants who underwent controlled human malaria infection 28 days after final vaccinations developed malaria. Increasing vaccine doses induced higher immunoglobulin G titers but did not achieve previously established RTS,S benchmarks. CONCLUSIONS: rCSP/GLA-LSQ had favorable safety results. However, tested regimens did not induce protective immunity. Further investigation could assess whether adjuvant or schedule adjustments improve efficacy. CLINICAL TRIALS REGISTRATION: NCT03589794.

The Impact of a Perioperative Elective on Practice Workforce Development: Content Analysis.

PURPOSE: Developing strategies to educate, employ, and retain newly graduated nurses in perioperative (periop) settings is paramount to addressing a succession crisis with unprecedented vacancy rates. The purpose of this study was to explore the impact of a prelicensure periop elective on the decision of participants to seek and accept a periop position upon graduation and to describe their transition to practice experience. DESIGN: This study used qualitative descriptive methodology. METHODS: Virtual semistructured interviews were conducted in 2021 with 20 recent graduates of an accelerated prelicensure nursing program who completed a periop elective course. Questions focused on if they did or did not seek and accept a periop position upon graduation and, for those who accepted, explored their transition to practice experience. Data were coded using conventional and directed content analyses. FINDINGS: Three themes emerged via conventional content analysis: the impact of a prelicensure periop elective, the periop environment, and recommendations for faculty and hiring managers. Concerning directed content analyses, participants used the coping factors of situation, self, support, and strategies to navigate career transitions. CONCLUSIONS: A periop elective course delivered through academic-practice partnerships appears to be a successful strategy to address the succession crisis. Graduates were prepared to make informed decisions about entering the periop specialty.

An Examination of the Career Choices of Nursing Graduates After Completing a Perioperative Elective.

In light of the perioperative nursing shortage, academic leaders at a mid-Atlantic school of nursing and leaders of three health care systems implemented an academic-practice partnership with the goal of increasing interest in this specialty. Nursing researchers used a descriptive study design to collect data from nursing alumni who participated in the perioperative elective between 2017 and 2021. They found that 25 (38%) of 65 graduates who participated in the elective entered perioperative nursing and 38 (68%) of 56 graduates who answered a question on considering future employment as a perioperative nurse indicated they would do so regardless of their current employment status. Graduates who participated in the elective and experienced a perioperative capstone placement had low anticipated turnover scores and intended to remain in a perioperative position. Academic and health care leaders should consider academic-practice partnerships as a strategy to recruit and retain perioperative nurses.

"It Has Made Me Think": Engaging the Public with the History of Health in the Modern Irish Prison.

Since the establishment of the modern prison system in the early nineteenth century, prisons and prisoners have been construed as sites of moral, social, and biological contagion. Historic and contemporary studies show that most prisoners experience severe health inequalities, higher rates of addiction and mental health issues, and lower life expectancy than the rest of the population. They also come from deprived social strata. Yet, these aspects of Irish penal history have been largely neglected in academia and popular histories. Our article discusses two public history projects-an art installation, The Trial, and a museum exhibition, Living Inside-that engaged different publics with the long history of health and welfare in Irish prisons. Developed by the research team on the Wellcome Trust Investigator Award "Prisoners, Medical Care and Entitlement to Health in England and Ireland, 1850-2000," based at University College Dublin, the projects adopted different methodologies to engage their audiences and explore the experience and management of health and welfare in nineteenth- and twentieth-century Irish prisons. We further examine the different methodological approaches of each project, their varied aims and audiences, and the impacts reported by audiences and participants. The article also considers some of the challenges of doing this kind of public history, both in terms of working with marginalized communities and presenting research about difficult subjects to various audiences.

Predictors of cognitive functioning in presentations to a community-based specialist addiction neuropsychology service.

INTRODUCTION: Cognitive impairment is common in individuals presenting to alcohol and other drug (AOD) settings and the presence of biopsychosocial complexity and health inequities can complicate the experience of symptoms and access to treatment services. A challenge for neuropsychologists in these settings is to evaluate the likely individual contribution of these factors to cognition when providing an opinion regarding diagnoses such as acquired brain injury (ABI). This study therefore aimed to identify predictors of cognitive functioning in AOD clients attending for neuropsychological assessment. METHODS: Clinical data from 200 clients with AOD histories who attended for assessment between 2014 and 2018 were analysed and a series of multiple regressions were conducted to explore predictors of cognitive impairment including demographic, diagnostic, substance use, medication, and mental health variables. RESULTS: Regression modelling identified age, gender, years of education, age of first use, days of abstinence, sedative load, emotional distress and diagnoses of ABI and developmental disorders as contributing to aspects of neuropsychological functioning. Significant models were obtained for verbal intellectual functioning (Adj R2 = 0.19), nonverbal intellectual functioning (Adj R2 = 0.10), information processing speed (Adj R2 = 0.20), working memory (Adj R2 = 0.05), verbal recall (Adj R2 = 0.08), visual recall (Adj R2 = 0.22), divided attention (Adj R2 = 0.14), and cognitive inhibition (Adj R2 = 0.07). CONCLUSIONS: These findings highlight the importance of careful provision of diagnoses in clients with AOD histories who have high levels of unmet clinical needs. They demonstrate the interaction of premorbid and potentially modifiable comorbid factors such as emotional distress and prescription medication on cognition. Ensuring that modifiable risk factors for cognitive impairment are managed may reduce experiences of cognitive impairment and improve diagnostic clarity.

A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria.

A highly effective malaria vaccine remains elusive despite decades of research. Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), a metabolically active, nonreplicating, whole parasite vaccine demonstrated safety and vaccine efficacy (VE) against endemic P. falciparum for 6 months in Malian adults receiving a five-dose regimen. Safety, immunogenicity, and VE of a three-dose regimen were assessed in adults in Balonghin, Burkina Faso in a two-component study: an open-label dose escalation trial with 32 participants followed by a double-blind, randomized, placebo-controlled trial (RCT) with 80 participants randomized to receive three doses of 2.7 × 106 PfSPZ (N = 39) or normal saline (N = 41) just before malaria season. To clear parasitemia, artesunate monotherapy was administered before first and last vaccinations. Thick blood smear microscopy was performed on samples collected during illness and every 4 weeks for 72 weeks after last vaccinations, including two 6-month malaria transmission seasons. Safety outcomes were assessed in all 80 participants who received at least one dose and VE for 79 participants who received three vaccinations. Myalgia was the only symptom that differed between groups. VE (1 - risk ratio; primary VE endpoint) was 38% at 6 months (P = 0.017) and 15% at 18 months (0.078). VE (1 - hazard ratio) was 48% and 46% at 6 and 18 months (P = 0.061 and 0.018). Two weeks after the last dose, antibodies to P. falciparum circumsporozoite protein and PfSPZ were higher in protected versus unprotected vaccinees. A three-dose regimen of PfSPZ Vaccine demonstrated safety and efficacy against malaria infection in malaria-experienced adults.

Learning Impact of Armed Forces Medical Background on Military Nursing Students in an Accelerated Bachelor of Science in Nursing Program.

ABSTRACT: The study examined differences between military students enrolled in an accelerated bachelor of science in nursing (BSN) program with and without medical experience and/or a previous bachelor's degree on graduation grade point average (GPA) and NCLEX®-RN first-time pass rates. Significant differences were found between groups with/without military medical experience on NCLEX-RN, but not graduation GPA. Significant differences were found between groups with/without prior degree on GPA, but not on NCLEX-RN. Having both medical experience and a prior degree did not make a difference on GPA or NCLEX-RN. Findings offer guidance on admission criteria to accelerated programs for this unique group of students.

Maybe It's Not the Meth: Considering Biopsychosocial Contributors to Cognitive Impairment in Methamphetamine Polydrug Use.

OBJECTIVE: In considering the cognitive harms of methamphetamine (MA) use, there is currently a limited appreciation of the profile of pre-existing, comorbid, or modifiable risk factors for cognitive impairment in individuals with MA-polydrug use who present to clinical services. This is in contrast to the well-recognized evidence in alcohol use groups. The aim of this study was to investigate the biopsychosocial and neuropsychological profiles of MA-polysubstance using individuals reporting cognitive impairment in comparison to an alcohol-using group. METHODS: A retrospective file audit was undertaken of individuals who presented for assessment to a specialist addiction neuropsychology service and reported either more than 1 year of heavy MA use as part of a polydrug use history (n = 40) or having only used alcohol (n = 27). Clinical histories including demographic, medical, mental health, substance use, and neuropsychological assessment results were extracted from medical records. Between group comparisons were conducted to explore differences in the MA-polydrug vs. the alcohol group. RESULTS: Individuals in the MA-polydrug group were significantly younger, commenced substance use at an earlier age, were more likely to have an offending history, and experienced an overdose than those in the alcohol group. No differences in comorbid neurodevelopmental, psychiatric or acquired brain injury diagnoses were observed between groups. For neuropsychological functioning, significant group differences were observed in overall IQ, semantic verbal fluency, and psychomotor tracking, where individuals in the alcohol group performed significantly worse. CONCLUSIONS: Neuropsychological profiles were largely equivalent between groups across cognitive domains, with minor differences in favor of the MA-polydrug group. Relative to the general population, cognitive functioning was reduced for both groups across a range of domains. High rates of comorbid mental health concerns were common across both groups, however, individuals in the MA-polydrug group presented with a higher risk of overall harm from substance use at a significantly younger age which is a unique concern for this group. These findings highlight the importance of considering the biopsychosocial factors, such as age of first use, emotional distress, indirect substance related harms including overdose and blood born virus infection that may be relevant to experiences of cognitive difficulty in MA-polydrug users.

A Veterans' Bachelor of Science in Nursing Initiative: Ten Valuable Tips.

ABSTRACT: This article describes a funded grant project whereby 10 tips are shared for those considering starting a veterans' bachelor of science in nursing initiative: secure the support of the institution; establish a point person for the initiative; maximize student success resources; acknowledge past academic work and military experience; hire prior-service Armed Forces Nurse Corps officers as faculty; deliver training opportunities for nonmilitary faculty to learn about veterans; offer students the opportunity to learn and socialize with their noncivilian peers; capitalize on the assets veterans bring to the classroom; provide a structured learning environment; and generate data-based publications.

Facilitators and challenges to military undergraduate nursing student success.

BACKGROUND: Understanding the broader community of educators and programs involved in the education of military nursing students (MNSs) is needed to develop best practices that support their academic success. PURPOSE: The purpose of this study was to 1) identify factors nursing faculty perceived would facilitate and/or challenge the success of MNSs when transitioning to and progressing through baccalaureate nursing programs, and 2) ascertain successful strategies used in teaching and working with these students. METHODS: A descriptive survey research design was used to collect data from faculty at 26 schools of nursing that received federal funding to support the transition of veterans to a career in nursing. Quantitative and qualitative data were collected, analyzed, and integrated via descriptive statistics and content analysis. RESULTS: The survey was completed by 88 faculty from 19 of the 26 schools. The top four categories for both the facilitators and challenges, based on Jeffreys' (2015) NURS Model, were student affective characteristics, student profile characteristics, professional integration factors, and environmental factors. Programmatic factors were the most commonly cited success strategies, including having culturally competent, knowledgeable, and designated faculty and staff for MNSs. CONCLUSION: Developing evidence-based strategies to use in teaching and advising MNSs ideally will ensure their academic success.

New Faculty Orientation for Nurse Educators: Offerings and Needs.

BACKGROUND: The purpose of this study was to identify the common elements for new faculty orientation (NFO) programs and then replicate two previous studies regarding NFO offerings and needs. METHOD: Using a descriptive survey research design, a 40-item survey was developed based on Morin and colleagues' surveys and disseminated via the Qualtrics platform. The survey addressed nurse faculty orientation offerings and needs. RESULTS: Some form of orientation was offered to 61% of the respondents. Only 14% identified a person responsible for orienting new faculty to their nursing program, 15% said no one person was accountable, and 69% reported they did not know who was responsible. The top three categories to be included in an orientation program were educational environment, academic environment, and social milieu. CONCLUSION: NFO programs attended by nursing faculty may not be as comprehensive or effective as they could be. [J Nurs Educ. 2021;60(5):273-276.].

Low dose recombinant full-length circumsporozoite protein-based Plasmodium falciparum vaccine is well-tolerated and highly immunogenic in phase 1 first-in-human clinical testing.

Plasmodium falciparum circumsporozoite protein (CSP) is a major sporozoite surface protein and a key target of pre-erythrocytic malaria subunit vaccines. A full-length recombinant CSP (rCSP) based strategy could be advantageous, as this antigen includes a region critical to sporozoite cell attachment and hepatocyte invasion. The adjuvant Glucopyranosyl Lipid A-liposome Quillaja saponaria 21 (GLA-LSQ) functions as a TLR4 agonist, promotes antigen-specific TH1 responses and stimulates cytotoxic T cell production. To date, one study has reported the clinical acceptability of GLA-LSQ. We present interim results of a phase 1 first-in-human dose-escalation clinical trial of full-length rCSP vaccine given with or without GLA-LSQ adjuvant. Participants experienced only mild to moderate related solicited adverse events. The lowest adjuvanted vaccine dose achieved >90-fold rise in geometric mean anti-CSP IgG antibody titer. These favorable safety and immunogenicity results confirm the immunostimulatory capacity of this relatively new adjuvant and support next steps in clinical product development. Trial registration: ClinicalTrials.gov Identifier NCT03589794 (registered 18 July 2018).

Neurocognitive functioning among people accessing an addiction neuropsychology clinic with and without a history of offending behaviour.

Effectiveness of interventions for violent behaviour may be undermined by the presence of neurocognitive impairment, which is known to be common among alcohol and other drug (AOD) users and violent offenders. The current study aimed to examine whether the cognitive functioning of individuals with AOD histories presenting to a specialist addiction neuropsychology service differed according to their offending history (i.e. non-offending, non-violent offending and violent offending), using a retrospective case file audit design. Data were extracted from 190 clients. Tests assessed a breadth of cognitive domains. Violent offenders demonstrated the lowest premorbid IQ out of the three groups, and a significantly higher proportion of violent offenders presented with impaired divided attention and impaired cognitive inhibition compared to non-violent offenders. Rates of impairment across groups were well beyond those expected within the general population. Delivery of both AOD and violence interventions should be adapted to accommodate individuals' cognitive difficulties.

Faculty Perceptions in Facilitating Success for Accelerated BSN Student Veterans.

ABSTRACT: Student veterans enrolled in nursing programs often experience challenges transitioning to higher education environments. This study investigated faculty perspectives regarding the strengths and challenges of student veterans in an accelerated bachelor's of science in nursing program; faculty (N = 21) participated in focus groups. Four themes emerged: No Man Left Behind, Acclimating to the Higher Education Environment, Not Wanting to Be Different, and Professionalism/Maturity. Faculty perceived student veterans possess strengths and approaches to learning different from students without a military background. Integrating these strengths into the curriculum, with strategies such as team-based learning and group assignments, will leverage their skills and facilitate academic success.

Experience of Caring for a Child With Type 1 Diabetes Mellitus in a Food-Insecure Household: A Qualitative Evaluation.

OBJECTIVES: An earlier study from Nova Scotia showed that food insecurity (FI) is more prevalent (21.9%) in families of children with diabetes, yet little is known about its impact on these families. We aimed to describe the day-to-day experiences of families living with FI while caring for a child with type 1 diabetes (T1D). METHODS: This investigation was a qualitative study with thematic analyses using semistructured interviews to explore perceptions of caregivers living with pediatric T1D and FI (N=13 households). RESULTS: Three major themes emerged: 1) FI had a disproportionate impact on families after T1D diagnosis compared with before diagnosis. The cost of healthy food threatened food security before T1D; however, there is increased hardship once high-quality food and hypoglycemia supplies are required. 2) Sacrifices to combat FI have disproportionate impacts among family members. At times, caregivers sacrificed the needs (food, medicine) of other family members (including children) to prioritize the needs of the child with T1D. 3) Caregivers perceived T1D needs as posing unique barriers to traditional FI supports, such as school breakfast programs. CONCLUSIONS: This study provides insight into the realities of life with pediatric T1D and FI. Living with T1D and FI poses challenges, and caregivers often cope by making difficult choices when providing for their family. Caregivers struggled to meet dietary recommendations while finding that T1D needs are often not met by traditional FI supports. This suggests that T1D clinicians should assess FI and help families in problem solving to mitigate its impact.

Perfluorooctanesulfonic Acid-Induced Toxicity on Zebrafish Embryos in the Presence or Absence of the Chorion.

Perfluorooctanesulfonic acid (PFOS) is a perfluorinated compound used in many industrial and consumer products. It has been linked to a broad range of adverse effects in several species, including zebrafish (Danio rerio). The zebrafish embryo is a widely used vertebrate model to elucidate potential adverse effects of chemicals because it is amenable to medium and high throughput. However, there is limited research on the full extent of the impact the chorion has on those effects. Results from the present study indicate that the presence of the chorion affected the timing and incidence of mortality as well as morphometric endpoints such as spinal curvature and swim bladder inflation in zebrafish embryos exposed to PFOS. Furthermore, removal of the chorion prior to exposure resulted in a lower threshold of sensitivity to PFOS for effects on transcriptional expression within the peroxisome proliferator-activated receptor (PPAR) nuclear signaling pathway. Perturbation of PPAR pathway gene expression can result in disruption of metabolic signaling and regulation, which can adversely affect development, energy availability, and survival. It can be concluded that removal of the chorion has significant effects on the timing and incidence of impacts associated with PFOS exposure, and more research is warranted to fully elucidate the protective role of the chorion and the critical timing of these events. Environ Toxicol Chem 2021;40:780-791. Published 2020. This article is a US Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Characterisation of presentations to a community-based specialist addiction neuropsychology service: Cognitive profiles, diagnoses and comorbidities.

INTRODUCTION AND AIMS: Cognitive impairment is a common feature of individuals with substance-use disorders. However, research tends to exclude highly complex clinical cases, limiting the generalisability of findings for 'real-world' populations. The objective of this study was to examine the complexities associated with addiction, substance use and cognitive impairment through the characterisation of client presentations to a newly established specialised addiction neuropsychology service. DESIGN AND METHODS: Retrospective case file audit. Neuropsychological assessment reports for consenting clients over a 4-year period were de-identified and reviewed. Cognitive domains assessed included attention, processing speed, working memory, intellectual functioning, memory and executive functioning. RESULTS: Of the 200 case files examined, the majority were male clients, with 11 years or lower of education and a history of daily substance use, with 30% continuing to use daily. Seventy-one percent had a formal mental health diagnosis and 41% had reported a history of trauma. The most prevalent cognitive impairments were observed in complex attention (50%) and memory (40%). New diagnoses were conveyed in 25% of cases, comprising acquired brain injury (16%) and neurodevelopmental disabilities (9%). DISCUSSION AND CONCLUSIONS: It is common for clients with substance use histories referred to an addiction neuropsychology service to present with complex histories including psychosocial difficulties, comorbid mental health and medical issues and cognitive impairment. As such, careful diagnostic formulations are required when multiple factors may contribute to cognitive deficits. This study highlights the importance of a state-wide specialist addiction neuropsychology service in supporting diagnostic clarification and informing relevant treatment approaches.

Military nursing: A primer for new recruits.

This article offers an overview of military nursing and provides three examples that illustrate how nurses can advance their careers within each service.