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BACKGROUND The residential aged care workforce is under pressure to care for residents with increasingly complex health conditions and multiple comorbidities, particularly dementia. (1,2) However, dementia knowledge is typically low [...], Objectives: The study investigated how senior residential aged care staff perceived the purpose, function, impact and challenges of implementing a new role in their organisation for an unregistered care worker with a Bachelor of Dementia Care: the Dementia Care Support Worker. The role was piloted over two years in an Australian organisation with three aged care facilities to examine its potential to address gaps in service provision for people with dementia. Background: The residential aged care workforce is under pressure to care for residents with increasingly complex health conditions and where most care is provided by care workers. Presently no formal leadership role exists for care workers with specialised dementia knowledge in the aged care setting. Study design and methods: A qualitative descriptive approach was taken to explore senior staff members' perceptions of the role at two time points. Twenty-three semi-structured interviews held in July-August 2017 (n = 12), soon after role commencement, and in February-March 2019 (n = 11) were thematically analysed. Results: Three themes reflected senior staff members' expectations of the role: enhancing staff and management knowledge about dementia and dementia care practices; facilitating changes to improve care for residents living with dementia; and educating and supporting residents' families. Eighteen months later, participants felt the role was helping meet the need for improved care of residents with dementia, and staff understanding of dementia. They suggested communication and support structures to improve role effectiveness. Discussion: Staff were receptive to the establishment of the Dementia Care Support Worker role and felt it resulted in improvement in dementia care. Success was contingent on strong organisational support and resourcing. Conclusion: Improving dementia knowledge of care staff is an essential first step in driving care quality improvements. The Dementia Care Support Worker role for care workers has the potential to address knowledge needs and support improved care practices. Implications for research, policy, and practice: This research models how a new role might be configured for unregistered care workers with specialist dementia knowledge. Further research is needed to explore the establishment of such a role more widely in other organisations, to investigate whether it could provide a new career development pathway for care workers and improve the skills and capacity of the aged care workforce. Substantial policy changes would also be required to support role viability, such as around increased salary. Research which examines the impact of such roles on care outcomes would complement the findings. What is already known about the topic? * While dementia is common in residential aged care, knowledge of dementia is typically low among the care staff. * Consequently, care staff are not equipped to meet the complex needs of residents with dementia and their families. * New roles for unregistered care workers with specialised dementia knowledge have been proposed, but not tested. What this paper adds * This research models how a new role might be configured for care workers with specialist dementia knowledge. * Aged care facility leaders support a role for care workers with formal specialist dementia knowledge and skills, and perceive the role helps improve the quality of resident care and develop stakeholders' dementia knowledge. * Appropriate communication and support structures are required for the effective establishment of the role. Keywords: Dementia, nursing homes, professional role, qualitative research, quality of healthcare

The term 'low vision' refers to vision loss that is uncorrectable with current medical and surgical interventions or using traditional spectacle and contact lenses. (1,2) While the Centers for Medicare [...]

Conventional polyol synthesis of silver nanowires has exclusively relied on polyvinylpyrrolidone (PVP), a nonbiodegradable polymer with no viable alternatives. The underlying reaction mechanism remains unclear. Herein, we discovered a new sustainable solution by employing biobased cellulose derivatives, including hydroxyethyl cellulose (HEC), as effective substitutes for PVP. Under mild reaction conditions (125 °C, ambient pressure), HEC facilitates the growth of ultralong silver nanowires (>100 μm) from penta-twinned silver seeds through a four-stage kinetic process. Theoretical calculations further reveal that HEC is physiosorbed onto the silver surfaces, while the presence of bromide ions (Br–) facilitates the evolution of seeds into nanowires. By varying halide ion concentrations and substitution in different cellulose derivatives, we successfully synthesized silver nanostructures with additional intriguing morphologies, including quasi-spherical nanoparticles, bipyramids, and nanocubes. Furthermore, transparent conductive films fabricated from ultralong silver nanowires synthesized with HEC demonstrated superior performance compared to those made with PVP-synthesized nanowires.

Nursing professional development practitioners are faced with meeting the onboarding needs of internationally educated nurses (IENs) recruited to work in the United States. The purpose of this secondary data analysis study was to assess differences between demographic characteristics, orientation, and onboarding variables and IEN’s length of orientation and retention to a healthcare system. A significant difference in the length of orientation by unit assigned, degree type, and retention were discovered.

Background: Lumbar foraminal stenosis is a common cause of chronic lower back pain and radiculopathy often treated by epidural steroid injections. In the absence of imaging findings with a positive physical exam demonstrating symptoms, percutaneous neuroplasty (PNP) may be an alternative to transforaminal epidural steroid injections that have otherwise failed. Case Presentation: We present two cases (55-year-old man and 65-year-old woman) with chronic low back pain and radiculopathy with otherwise normal imaging demonstrating no lumbar foraminal stenosis refractory to transforaminal epidural steroid injections. PNP was performed using reference spinal needles with both patients achieving sustained > 50–75% pain relief. Conclusion: PNP offers interventional chronic pain physicians and patients with refractory chronic low back pain with lumbar radiculopathy due to fibrosis an alternative, safe treatment that offers sustained results. Furthermore, this is the first of its kind to offer a step-by-step procedural step of PNP using a reference spinal needle.

AbstractBackground:Transient acquisition of methicillin-resistant Staphylococcus aureus(MRSA) on healthcare personnel (HCP) gloves and gowns following patient care has been examined. However, the potential for transmission to the subsequent patient has not been studied. We explored the frequency of MRSA transmission from patient to HCP, and then in separate encounters from contaminated HCP gloves and gowns to a subsequent simulated patient as well as the factors associated with these 2 transmission pathways.Methods:We conducted a prospective cohort study with 2 parts. In objective 1, we studied MRSA transmission from random MRSA-positive patients to HCP gloves and gowns after specific routine patient care activities. In objective 2, we simulated subsequent transmission from random HCP gloves and gowns without hand hygiene to the next patient using a manikin proxy.Results:For the first objective, among 98 MRSA-positive patients with 333 randomly selected individual patient–HCP interactions, HCP gloves or gowns were contaminated in 54 interactions (16.2%). In a multivariable analysis, performing endotracheal tube care had the greatest odds of glove or gown contamination (OR, 4.06; 95% CI, 1.3–12.6 relative to physical examination). For the second objective, after 147 simulated HCP–patient interactions, the subsequent transmission of MRSA to the manikin proxy occurred 15 times (10.2%).Conclusion:After caring for a patient with MRSA, contamination of HCP gloves and gown and transmission to subsequent patients following HCP-patient interactions occurs frequently if contact precautions are not used. Proper infection control practices, including the use of gloves and gown, can prevent this potential subsequent transmission.

Outcome data from 6 National Institutes of Health–funded Postbaccalaureate Research Education Programs (PREPs) in the Mid-Atlantic region were combined to give a multi-institutional perspective on their scholars’ characteristics and progress through biomedical research training. The institutions hosting these programs were Johns Hopkins University School of Medicine, the Medical University of South Carolina, the University of Maryland School of Medicine, the University of North Carolina at Chapel Hill, Virginia Commonwealth University, and Virginia Polytechnic Institute and State University. The authors summarize the institutional pathways, demographics, undergraduate institutions, and graduate institutions for a total of 384 PREP scholars who completed the programs by June 2021. A total of 228 (59.4%) of these PREP scholars identified as Black or African American, 116 (30.2%) as Hispanic or Latinx, and 269 (70.0%) as female. The authors found that 376 of 384 scholars (97.9%) who started PREP finished their program, 319 of 376 (84.8%) who finished PREP matriculated into PhD or MD/PhD programs, and 284 of 319 (89.0%) who matriculated have obtained their PhD or are successfully making progress toward their PhD.

IMPORTANCE: Rapid tests for respiratory viruses, including multiplex panels, are increasingly available in emergency departments (EDs). Their association with patient outcomes remains unclear. OBJECTIVE: To determine if ED rapid respiratory virus testing in patients with suspected acute respiratory infection (ARI) was associated with decreased antibiotic use, ancillary tests, ED length of stay, and ED return visits and hospitalization and increased influenza antiviral treatment. DATA SOURCES: Ovid MEDLINE, Embase (Ovid), Scopus, and Web of Science from 1985 to November 14, 2022. STUDY SELECTION: Randomized clinical trials of patients of any age with ARI in an ED. The primary intervention was rapid viral testing. DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Two independent reviewers (T.S. and K.W.) extracted data and assessed risk of bias using the Cochrane Risk of Bias, version 2.0. Estimates were pooled using random-effects models. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. MAIN OUTCOMES AND MEASURES: Antibiotic use and secondary outcomes were pooled separately as risk ratios (RRs) and risk difference estimates with 95% CIs. RESULTS: Of 7157 studies identified, 11 (0.2%; n = 6068 patients) were included in pooled analyses. Routine rapid viral testing was not associated with antibiotic use (RR, 0.99; 95% CI, 0.93-1.05; high certainty) but was associated with higher use of influenza antivirals (RR, 1.33; 95% CI, 1.02-1.75; moderate certainty) and lower use of chest radiography (RR, 0.88; 95% CI, 0.79-0.98; moderate certainty) and blood tests (RR, 0.81; 95% CI, 0.69-0.97; moderate certainty). There was no association with urine testing (RR, 0.95; 95% CI, 0.77-1.17; low certainty), ED length of stay (0 hours; 95% CI, −0.17 to 0.16; moderate certainty), return visits (RR, 0.93; 95%, CI 0.79-1.08; moderate certainty) or hospitalization (RR, 1.01; 95% CI, 0.95-1.08; high certainty). Adults represented 963 participants (16%). There was no association of viral testing with antibiotic use in any prespecified subgroup by age, test method, publication date, number of viral targets, risk of bias, or industry funding. CONCLUSIONS AND RELEVANCE: The results of this systematic review and meta-analysis suggest that there are limited benefits of routine viral testing in EDs for patients with ARI. Further studies in adults, especially those with high-risk conditions, are warranted.

AbstractObjective:The gold standard for hand hygiene (HH) while wearing gloves requires removing gloves, performing HH, and donning new gloves between WHO moments. The novel strategy of applying alcohol-based hand rub (ABHR) directly to gloved hands might be effective and efficient.Design:A mixed-method, multicenter, 3-arm, randomized trial.Setting:Adult and pediatric medical-surgical, intermediate, and intensive care units at 4 hospitals.Participants:Healthcare personnel (HCP).Interventions:HCP were randomized to 3 groups: ABHR applied directly to gloved hands, the current standard, or usual care.Methods:Gloved hands were sampled via direct imprint. Gold-standard and usual-care arms were compared with the ABHR intervention.Results:Bacteria were identified on gloved hands after 432 (67.4%) of 641 observations in the gold-standard arm versus 548 (82.8%) of 662 observations in the intervention arm (P< .01). HH required a mean of 14 seconds in the intervention and a mean of 28.7 seconds in the gold-standard arm (P< .01). Bacteria were identified on gloved hands after 133 (98.5%) of 135 observations in the usual-care arm versus 173 (76.6%) of 226 observations in the intervention arm (P< .01). Of 331 gloves tested 6 (1.8%) were found to have microperforations; all were identified in the intervention arm [6 (2.9%) of 205].Conclusions:Compared with usual care, contamination of gloved hands was significantly reduced by applying ABHR directly to gloved hands but statistically higher than the gold standard. Given time savings and microbiological benefit over usual care and lack of feasibility of adhering to the gold standard, the Centers for Disease Control and Prevention and the World Health Organization should consider advising HCP to decontaminate gloved hands with ABHR when HH moments arise during single-patient encounters.Trial Registration:NCT03445676.

ABSTRACTIntroductionNeuropathic pain (NP) conditions involve lesions to the somatosensory nervous system leading to chronic and debilitating pain. Many patients suffering from NP utilize pharmacological treatments with various drugs that seek to reduce pathologic neuronal states. However, many of these drugs show poor efficacy as well as cause significant adverse effects. Because of this, there is a major need for the development of safer and more efficacious drugs to treat NP.Areas coveredIn this review, we analyzed current treatments being developed for a variety of NP conditions. Specifically, we sought drugs in phase II/III clinical trials with indications for NP conditions. Various databases were searched including Google Scholar, PubMed, and clinicaltrials.gov.Expert opinionAll the mentioned targets for treatments of NP seem to be promising alternatives for existing treatments that often possess poor side effect profiles for patients. However, gene therapy potentially offers the unique ability to inject a plasmid containing growth factors leading to nerve growth and repair. Because of this, gene therapy appears to be the most intriguing new treatment for NP.

We report the use of Zr-based metal–organic frameworks (MOFs) MOF-545 and MOF-545(Cu) as supports to prepare catalysts with uniformly and highly dispersed Ni nanoparticles (NPs) for CO2hydrogenation into CH4. In the first step, we studied the MOF support under catalytic conditions using operando diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, ex situ characterizations (PXRD, XPS, TEM, and EDX-element mapping), and DFT calculations. We showed that the high-temperature conditions undoubtedly confer a potential for catalytic functionality to the solids toward CH4production, while no role of the Cu could be evidenced. The MOF was shown to be transformed into a catalytically active material, amorphized but still structured with dehydroxylated Zr-oxoclusters, in line with DFT calculations. In the second step, Ni@MOF-545 catalysts were prepared using either impregnation (IM) or double solvent (DS) methods, followed by a dry reduction (R) route under H2to immobilize Ni NPs. The highest catalytic activity was obtained with the Ni@MOF-545 DS Rcatalyst (595 mmolCH4gNi–1h–1) with 100% CH4selectivity and 60% CO2conversion after ∼3 h. The higher catalytic activity of Ni@MOF-545 DS Ris a result of much smaller (∼5 nm) and better dispersed Ni NPs than in the IM sample (20–40 nm), the latter exhibiting sintering. The advantages of the encapsulation of Ni NPs by the DS method and of the use of a MOF-545-based support are discussed, highlighting the interest of designing yet-unexplored Zr-based MOFs loaded with Ni NPs for CO2hydrogenation.

The purpose of this descriptive study was to highlight how a system-level education department operationalized the 2022 Association for Nursing Professional Development Scope and Standards of Practice into a learning needs assessment (LNA) survey. This was a collaborative approach to LNA design, implementation, and evaluation. The LNA conducted among nursing professional development practitioners determined areas for educational improvement, barriers to nursing professional development, and identified standards and competencies critical to improving knowledge acquisition.

Neuropeptide Y (NPY) signaling regulation of corticolimbic communication is known to modulate binge-like ethanol consumption in rodents. In this work we sought to assess the impact of intra-BLA NPY system modulation on binge-like ethanol intake and to assess the role of the NPY1R+ projection from the BLA to the mPFC in this behavior. We used “drinking-in-the-dark” (DID) procedures in C57BL6J mice to address these questions. First, the impact of intra-BLA administration of NPY on binge-like ethanol intake was assessed. Next, the impact of repeated cycles of DID intake on NPY1R expression in the BLA was assessed with use of immunohistochemistry (IHC). Finally, chemogenetic inhibition of BLA→mPFC NPY1R+ projections was assessed to determine if limbic communication with the mPFC was specifically involved in binge-like ethanol intake. Importantly, as both the BLA and NPY system are sexually dimorphic, both sexes were assessed in these studies. Intra-BLA NPY dose-dependently decreased binge-like ethanol intake in males only. Repeated DID reduced NPY1R expression in the BLA of both sexes. Silencing of BLA→mPFC NPY1R+ neurons significantly reduced binge-like ethanol intake in both sexes in a dose-dependent manner. We provide novel evidence that (1) intra-BLA NPY reduces binge-like ethanol intake in males; (2) binge-like ethanol intake reduces NPY1R levels in the BLA; and (3) chemogenetic inhibition of BLA→mPFC NPY1R+ neurons blunts binge-like drinking in male and female mice. These observations provide the first direct evidence that NPY signaling in the BLA, and specifically BLA communication with the mPFC, modulates binge-like ethanol consumption.

Purpose: Discussions about progressive gender reform across Melanesia highlight the need for more gender-inclusive policies and improved conditions for women and girls throughout all sectors. However, for many of these countries, attempts to address the problems are marred by insufficient resources and low prioritization of the issue and traditional, cultural and religious perspectives about gender and gendered roles. This article discusses how police responses are coordinated to address domestic and family violence (DFV) and provides a critical reflection on both internal responses and the complexities of multi-partner operations beyond urban spaces. Design/methodology/approach: This article draws on the findings from a stakeholder engagement focus group with 20 participants from four Melanesian countries – Fiji, Papua New Guinea, the Solomon Islands and Vanuatu – to provide insight into policing innovations in rural contexts. Findings: There is a need for improved multisector partnerships, increased police presence and greater reliance on indigenous strategies to improve responses to DFV in resource-constrained contexts. Originality/value: The article provides insight into an under-researched area and makes recommendations for improving responses to DFV in rural areas in small-island developing states.

To estimate the number of deaths and the cost of deaths attributable to wood heater smoke in the Australian Capital Territory. Rapid health impact assessment, based on fine particulate matter (PM2.5) data from three outdoor air pollution monitors and published exposure–response functions for natural cause mortality attributed to PM2.5exposure. Australian Capital Territory (population, 2021: 454 000), 2016–2018, 2021, and 2022 (2019 and 2020 excluded because of the impact of extreme bushfires on air quality). Proportion of PM2.5exposure attributable to wood heaters; numbers of deaths and associated cost of deaths (based on the value of statistical life: $5.3 million) attributable to wood heater smoke. Wood heater emissions contributed an estimated 1.16–1.73 μg/m3to the annual mean PM2.5concentration during the three colder years (2017, 2018, 2021), or 17–25% of annual mean exposure, and 0.72 μg/m3(15%) or 0.89 μg/m3(13%) during the two milder years (2016, 2022). Using the most conservative exposure–response function, the estimated annual number of deaths attributable to wood heater smoke was 17–26 during the colder three years and 11–15 deaths during the milder two years. Using the least conservative exposure–response function, an estimated 43–63 deaths per year (colder years) and 26–36 deaths per year (milder years) were attributable to wood heater smoke. The estimated annual equivalent cost of deaths was $57–136 million (most conservative exposure–response function) and $140–333 million (least conservative exposure–response function). The estimated annual number of deaths in the ACT attributable to wood heater PM2.5pollution is similar to that attributed to the extreme smoke of the 2019–20 Black Summer bushfires. The number of wood heaters should be reduced by banning new installations and phasing out existing units in urban and suburban areas.

Cluster headache (CH) is an excruciating and debilitating primary headache disorder. The prevalence is up to 1.3%, and the typical onset is around age 30. Often misdiagnosed as migraine, particularly in children, the diagnosis rate of CH has been increasing among women. CH is characterized by intense unilateral pain and autonomic symptoms, significantly impacting patients’ quality of life, mental health, and productivity.

Background/objectives: Adherence to a “Western” style dietary pattern has been related to behavior problems in children in high-income countries; however, dietary patterns may differ in countries undergoing the nutrition transition. Associations of dietary patterns with behavior problems in a Latin American context have not been evaluated. Subjects/Methods: Mothers of 385 children 5 to 12 y old completed a food frequency questionnaire (FFQ) on the children’s usual intake at enrollment into a cohort study. Four dietary patterns were identified through principal component analysis of the FFQ: animal protein, snacking, cheaper protein, and traditional/starch. After a median 6 y follow-up, adolescents reported behavior problems via the Youth Self Report, a standardized questionnaire. We compared the continuous distributions of externalizing and internalizing behavior problems and their subscales across quartiles of adherence to the four dietary patterns using multivariable linear regression. Results: Boys in the highest quartile of adherence to the animal protein pattern in middle childhood had an adjusted 5.5 units lower (95% CI −9.5, −1.5) mean total externalizing problems score compared with boys in the lowest quartile (Ptrend =0.008). Adherence to the animal protein pattern was also inversely related to the aggressive behavior externalizing subscale in a dose–response manner among boys (Ptrend = 0.009). There were no associations between adherence to other dietary patterns and externalizing problems in boys or girls. There were no associations with internalizing problems. Conclusion: Adherence to an animal protein dietary pattern in middle childhood was associated with less externalizing behavior problems in adolescent boys.

Corrosive groundwater can cause lead, copper, and other metals to leach from pipes and plumbing fixtures in water distribution systems. Metals, if ingested, could lead to serious health implications to the nearly 2.9 million people in Louisiana who obtain their drinking water from groundwater sources. Four indices—the Langelier Saturation Index (LSI), Ryznar Stability Index (RSI), Puckorius Scaling Index (PSI), and the Potential to Promote Galvanic Corrosion (PPGC)—in addition to an analysis which normalized the results from the existing indices, the Combined Index (CI), were used to assess the corrosivity of groundwater in Louisiana and identify areas within eight major aquifers and aquifer systems with moder- ate to high corrosivity potential. The purpose of this study is to provide State and local governments, public water system managers, and the nearly 500,000 private well owners in Louisiana with information needed to manage drinking-water supplies and mitigate potential health risks related to leaching of metals from water pipes and fixtures. The average scores of untreated groundwater samples from approximately 375 wells by index are as follows: LSI, −1.28; RSI, 9.78; PSI, 9.34; and CI, 4.14. The PPGC does not produce a numerical score, but the total percentage of class counts can be used to assign a classification; overall, samples in Louisiana were classified as significant concern. The percentages of groundwater samples from wells classified as potentially corrosive, by index, are as follows: LSI, 53 percent; RSI, 94 percent; PSI, 81 percent; PPGC, 98 percent; and CI, 81 percent. The percentages of samples classified as indeterminate, by index, are as follows: LSI, 46 percent; RSI, 5 percent; PSI, 12 percent; PPGC, 0 percent; and CI, 18 percent. [ABSTRACT FROM AUTHOR]

Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children’s blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion as well as cell–cell communications point towards increased immune cell migration and inflammation in SD progressors. Concurrently, antigen-presenting cells from SD progressors demonstrate intact uptake yet impaired interferon response and antigen processing and presentation signatures, which are partly modulated by DENV. Increased activation, regulation and exhaustion of effector responses and expansion of HLA-DR-expressing adaptive-like NK cells also characterize SD progressors. These findings reveal DENV target cells in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.

AbstractA survey was conducted among Canadian tertiary neonatal intensive care units. Of the 27 sites who responded, 9 did not have any form of antimicrobial stewardship, and 11 used vancomycin for empirical coverage in late-onset-sepsis evaluations. We detected significant variations in the diagnostic criteria for urinary tract infection and ventilator-associated pneumonia.

Neuroendocrine tolerance to alcohol, i.e., a blunted cortisol response to alcohol, has been linked to Ventromedial Prefrontal Cortex (VmPFC) alcohol cue reactivity and relapse risk in severe Alcohol Use Disorders (AUDs), but its role in the development of AUDs is not clear. Recent work suggests that blunted cortisol responses to alcohol cues in individuals who engage in binge drinking (BD) may play a role in motivation to consume larger amounts of alcohol, but the link between this dysregulated endocrine response and BD’s neural responses to alcohol cues remains unclear. To examine this, two groups of participants were recruited based on their recent drinking history. Thirty-three BD and 31 non-binging, social drinkers (SD) were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for alcohol and a post-experiment, one-month prospective measurement of their “real world” drinking behavior. During each scan session, blood plasma was collected repeatedly to examine the separate effects of alcohol cues and alcohol consumption on cortisol levels. Relative to water cues and SD, BD demonstrated blunted cortisol cue reactivity that was negatively associated with VmPFC cue reactivity. In BD, both blunted cortisol and greater VmPFC cue reactivity were related to immediate and future alcohol consumption in the month following the scans. Thus, neuroendocrine tolerance in BD may be associated with increased incentive salience of cues and contribute mechanistically to increased alcohol consumption seen in the development of AUDs.

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to exciting developments in the computational drug design field, facilitating biological activity prediction and de novo drug design for molecular targets of interest. Here, we describe current and future synergies between these developments to effectively identify drug candidates from the plethora of molecules produced by nature. We also discuss how to address key challenges in realizing the potential of these synergies, such as the need for high-quality datasets to train deep learning algorithms and appropriate strategies for algorithm validation.

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Healthcare assistants are a vital part of the nursing team, but turnover rates are high. Implementation of a multidisciplinary approach could increase job satisfaction and reduce turnover rates.

A study was conducted using the Generalized Intelligent Framework for Tutoring (GIFT) intelligent tutoring system (ITS) software and an Army Schoolhouse course. Existing materials were provided and used to create 9 computer-based GIFT lessons that included adaptive tutoring versions of the materials. These lessons included a Pre-Test, 7 content lessons (on the areas of Detect, Engage, and Assess), and a Post-Test. Six participants completed the Pre-Test, Post-Test, and all lessons. Overall Post-Test scores were significantly higher than Pre-Test scores, and remediation also had a positive impact on Post-Test scores. This study demonstrates that completing self-paced ITS lessons prior to initial class instruction can lead to positive learning impacts prior to the start of a class.

This study provides an approach to determine more robust estimates of access to trauma care at the state level. It highlights the need for a national trauma system, where all components of state-managed trauma systems are assembled in a national dataset to identify gaps in care.

We describe the convergent total syntheses of lycibarbarines A and B which are potent neuroprotective agents recently isolated from the fruits of Lycium barbarum. The synthesis highlights the construction of a unique spiro oxazine heterocyclic motif imbedded in these natural products. The synthesis is accomplished from the commercially available 8-hydroxyquinaline and 2-deoxy-d-ribose as key starting materials. The synthesis features a Reimer–Tiemann reaction, selective amine alkylation with a keto tosylate derivative, and spiroketalization to form an oxazine core.

The late Sidney Poitier was a Hollywood icon who took on film roles that broke racial barriers. But not many people know the part he played in changing another side [...]

As companies prepare for the second year of filings under the Securities and Exchange Commission's (SEC) new conflict minerals rule, many companies are looking for guidance from the first annual [...], The initial filings under the SEC&apos;s new conflict minerals rules for calendar year 2013 were made in June 2014. As companies address their compliance programs and disclosures for the 2014 calendar year, practitioners offer some observations for companies to consider.

ABSTRACTSocial work faculty have had to manage the complexities of delivering quality education amid the coronavirus pandemic. While some faculty had support from their institution, factors of service, scholarship, student advising, and technology capacity became meaningful lessons for faculty development. The authors relied on strength as a mechanism to navigate through this unprecedented time. Strong Black Woman (SBW) schema and resilience theory are the anchors of this continuum on opposite sides. The shared perspectives of three Black women faculty as (a) an instructor with an administrative appointment, (b) a teaching fellow, and (c) an adjunct instructor at varying institutions will demonstrate how the SBW schema and resilience theory have guided their ability to adapt to changes during the global pandemic.

There are numerous indications for hybrid breast reconstruction, with the most common being patients who have inadequate donor site volume to achieve the desired breast volume. This article reviews all aspects of hybrid breast reconstruction, including preoperative and assessment, operative technique and considerations, and postoperative management.

Dopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons.

In response to tissue injury, within seconds the ultra-large glycoprotein von Willebrand factor (VWF) is released from endothelial storage organelles (Weibel−Palade bodies) into the lumen of the blood vasculature, where it leads to the recruitment of platelets. The marked size of VWF multimers represents an unprecedented burden on the secretory machinery of endothelial cells (ECs). ECs have evolved mechanisms to overcome this, most notably an actomyosin ring that forms, contracts, and squeezes out its unwieldy cargo. Inhibiting the formation or function of these structures represents a novel therapeutic target for thrombotic pathologies, although characterizing proteins associated with such a dynamic process has been challenging. We have combined APEX2 proximity labeling with an innovative dual loss-of-function screen to identify proteins associated with actomyosin ring function. We show that p21 activated kinase 2 (PAK2) recruits septin hetero-oligomers, a molecular interaction that forms a ring around exocytic sites. This cascade of events controls actomyosin ring function, aiding efficient exocytic release. Genetic or pharmacological inhibition of PAK2 or septins led to inefficient release of VWF and a failure to form platelet-catching strings. This new molecular mechanism offers additional therapeutic targets for the control of thrombotic disease and is highly relevant to other secretory systems that employ exocytic actomyosin machinery.

AbstractPublic engagement and awareness programs are important components of many conservation programs today as such engagements are often critical for successful conservation. In this study, we examined if delivery of educational material increased awareness of the Pallas’s cat and its environment in a southern Mongolia herder community. We found that knowledge was greater and attitudes toward the Pallas’s cat and wildlife in general were more positive one year after the delivery of the educational material. This study thus suggests that educational material can be effective at increasing awareness of small and elusive species such as the Pallas’s cat.

Cerebrospinal fluid (CSF) shunts are commonly used for the long-term management of hydrocephalus in children. Shunt infection remains a common complication, occurring in about 5%–15% of CSF shunts. This narrative review summarises key evidence from recent literature on the epidemiology, pathogenesis, clinical presentation, diagnosis, management, outcomes and prevention of CSF shunt infections in children. The majority of shunt infections occur due to contamination at the time of surgery, with coagulase-negative staphylococci and Staphylococcus aureusbeing the most common infecting organisms. Clinical presentations of shunt infection can be varied and difficult to recognise. CSF cultures are the primary test used for diagnosis. Other CSF and blood parameters may aid in diagnosis but lack sensitivity and specificity. Core aspects of management of shunt infections include systemic antimicrobial therapy and surgical removal of the shunt. However, many specific treatment recommendations are limited by a lack of robust evidence from large studies or controlled trials. Shunt infections may result in long hospital stays, worsening hydrocephalus, neurological sequelae and other complications, as well as death. Therefore, reducing the incidence of infection and optimising management are high priorities. Antibiotic prophylaxis at the time of shunt placement, improved surgical protocols and antibiotic-impregnated shunts are key strategies to prevent shunt infections. Nevertheless, further work is needed to identify additional strategies to prevent complications and improve outcomes.

ObjectiveA portable, low-field MRI system is now Food and Drug Administration cleared and has been shown to be safe and useful in adult intensive care unit settings. No neonatal studies have been performed. The objective is to assess our preliminary experience and assess feasibility of using the portable MRI system at the bedside in a neonatal intensive care unit (NICU) at a quaternary children’s hospital.Study designThis was a single-site prospective cohort study in neonates ≥2 kg conducted between October and December 2020. All parents provided informed consent. Neonates underwent portable MRI examination in the NICU with support equipment powered on and attached to the neonate during the examination. A paediatric radiologist interpreted each portable MRI examination. The study outcome variable was percentage of portable MRI examinations completed without artefacts that would hinder diagnosis. Findings were compared between portable MRI examinations and standard of care examinations.ResultsEighteen portable, low-field MRI examinations were performed on 14 neonates with an average age of 29.7 days (range 1–122 days). 94% (17 of 18) of portable MRI examinations were acquired without significant artefact. Significant intracranial pathology was visible on portable MRI, but subtle abnormalities were missed. The examination reads were concordant in 59% (10 of 17) of cases and significant pathology was missed in 12% (2 of 17) of cases.ConclusionThis single-centre series demonstrated portable MRI examinations can be performed safely with standard patient support equipment present in the NICU. These findings demonstrate that portable MRI could be used in the future to guide care in the NICU setting.Trial registration numberNCT04629469.

Background: The secretome of adipose-derived mesenchymal stem cells (ASCs) offers a unique approach to understanding and treating wounds, including the critical process of epidermal regeneration orchestrated by keratinocytes. However, 2D culture techniques drastically alter the secretory dynamics of ASCs, which has led to ambiguity in understanding which secreted compounds (e.g., growth factors, exosomes, reactive oxygen species) may be driving epithelialization. Methods: A novel tissue-mimetic 3D hydrogel system was utilized to enhance the retainment of a more regenerative ASC phenotype and highlight the functional secretome differences between 2D and 3D. Subsequently, the ASC-secretome was stratified by molecular weight and the presence/absence of extracellular vesicles (EVs). The ASC-secretome fractions were then evaluated to assess for the capacity to augment specific keratinocyte activities. Results: Culture of ASCs within the tissue-mimetic system enhanced protein secretion ~ 50%, exclusively coming from the > 100 kDa fraction. The ASC-secretome ability to modulate epithelialization functions, including migration, proliferation, differentiation, and morphology, resided within the “> 100 kDa” fraction, with the 3D ASC-secretome providing the greatest improvement. 3D ASC EV secretion was enhanced two-fold and exhibited dose-dependent effects on epidermal regeneration. Notably, ASC-EVs induced morphological changes in keratinocytes reminiscent of native regeneration, including formation of stratified cell sheets. However, only 3D-EVs promoted collective cell sheet migration and an epithelial-to-mesenchymal-like transition in keratinocytes, whereas 2D-EVs contained an anti-migratory stimulus. Conclusion: This study demonstrates how critical the culture environment is on influencing ASC-secretome regenerative capabilities. Additionally, the critical role of EVs in modulating epidermal regeneration is revealed and their translatability for future clinical therapies is discussed.

Military medicine has a long history of humanitarian efforts globally, including responses to natural disasters and as planned medical civil action projects. However, ending two decades of war in Afghanistan, Walter Reed National Military Medical Center (WRNMMC) was tasked to receive up to 63 injured patients with less than 96-hour notice on August 27, 2021. As part of Operation Allies Refuge and transition to Operation Allies Welcome, this article highlights the complicated cross-organizational and multidisciplinary response at WRNMMC where ultimately 277 Afghan patients and nonmedical attendants received medical care and other requirements for resettlement. Lessons learned from coordinating the complex short suspense medical, cultural, and logistic efforts are noted as considerations and practical recommendations for future missions.

Doliolids are common gelatinous grazers in marine ecosystems around the world and likely influence carbon cycling due to their large population sizes with high growth and excretion rates. Aggregations or blooms of these organisms occur frequently, but they are difficult to measure or predict because doliolids are fragile, under sampled with conventional plankton nets, and can aggregate on fine spatial scales (1–10 m). Moreover, ecological studies typically target a single region or site that does not encompass the range of possible habitats favoring doliolid proliferation. To address these limitations, we combined in situ imaging data from six coastal ecosystems, including the Oregon shelf, northern California, southern California Bight, northern Gulf of Mexico, Straits of Florida, and Mediterranean Sea, to resolve and compare doliolid habitat associations during warm months when environmental gradients are strong and doliolid blooms are frequently documented. Higher ocean temperature was the strongest predictor of elevated doliolid abundances across ecosystems, with additional variance explained by chlorophyll afluorescence and dissolved oxygen. For marginal seas with a wide range of productivity regimes, the nurse stage tended to comprise a higher proportion of the doliolids when total abundance was low. However, this pattern did not hold in ecosystems with persistent coastal upwelling. The doliolids tended to be most aggregated in oligotrophic systems (Mediterranea and southern California), suggesting that microhabitats within the water column favor proliferation on fine spatial scales. Similar comparative approaches can resolve the realized niche of fast‐reproducing marine animals, thus improving predictions for population‐level responses to changing oceanographic conditions.