Spontaneous histopathology in New Zealand White rabbits: ten years of control data.

The historical control database of a multinational laboratory services provider was queried for all histopathologic findings in New Zealand White rabbits which were used as control animals during a ten-year period (2011-2020). The query included all evaluated tissues, with or without microscopic findings, in studies conducted for safety testing for regulatory approval by the U.S. Food and Drug Agency (FDA) or the U.S. Environmental Protection Agency. A second query included studies conducted in the United Kingdom for control rabbits used in studies compliant with the Healthcare Products Regulatory Agency (MHRA) and/or the European Medicines Agency (EMA), which provide regulatory oversight in the United Kingdom and European Union, respectively. Infiltrates of inflammatory (mixed or mononuclear) cells were commonly noted in various organs including heart, digestive tract, muscle, thyroid, kidney, urinary bladder, eyelid, ocular structures, harderian gland, lacrimal gland, and lung. Mineralization was noted in aorta, kidney, urinary bladder, and ovary. Also noted were degeneration/necrosis in the myocardium, and intramuscular injection sites of the skin, degeneration/regeneration of muscle and diaphragm, ectopic tissue in the pancreas and thyroid, basophilic foci in salivary gland, increased/decreased vacuolation in adrenal gland, increased/decreased lymphocytic cellularity of lymph nodes, intrasinusoidal erythrocytes in lymph nodes, thymic atrophy, increased adipocytes in bone marrow, inflammatory cell foci in the liver and gall bladder, lacrimal gland atrophy, renal tubule basophilia, degeneration/regeneration, and dilatation; oviduct cyst; in the testis, degeneration/atrophy, cellular debris, dilatation, decreased sperm and segmental hypoplasia of seminiferous tubules; and squamous metaplasia of the testis and seminal vesicle.

Hoof wall masses removal in 30 standing sedated horses: Surgical technique, postoperative complications and long-term outcome.

OBJECTIVE: To describe the surgical technique for removal of hoof wall masses in horses under standing sedation (SS) and local anesthesia (LA), and to report complications and long-term outcome following surgery. STUDY DESIGN: Observational retrospective study. ANIMALS: Client-owned horses (n = 30). METHODS: Horses undergoing keratoma removal under SS and LA in a single equine hospital between August 2016 and July 2023 were included in the study. Signalment, affected foot, history of lameness and/or foot abscesses, degree of lameness on admission, imaging findings (radiography and magnetic resonance imaging [MRI] when available), location of the mass, surgical technique, remedial farriery, postoperative care, complications and outcome were recorded. Long-term follow-up information was obtained by telephone questionnaire. RESULTS: A total of 30 horses met the inclusion criteria. Duration of lameness ranged from 1 to 289 days (mean 90 days). The degree of lameness varied from absent to grade 4/5 (AAEP) (mean grade 3/5). All horses underwent preoperative radiographic examination and 14/30 underwent MRI. All horses underwent partial hoof wall resection. The surgery was performed safely in all cases. Postoperative complications included marked lameness in the early postoperative period in 3/30 horses and exuberant granulation tissue formation in 2/30 horses. Long-term (>6 months) follow-up information was available for 28 horses, and 26/28 horses returned to previous levels of exercise. Recurrence was suspected in 1/30 horses. CONCLUSIONS: The complication rate was lower than previously reported for keratoma removal under general anesthesia (GA). CLINICAL SIGNIFICANCE: Removal of hoof wall masses under SS and LA can be considered as an alternative to removal under GA.

Site-Specific Antimicrobial Activity of a Dual-Responsive Ciprofloxacin Prodrug.

Bacterial infections create distinctive microenvironments with a unique mix of metabolites and enzymes compared with healthy tissues that can be used to trigger the activation of antibiotic prodrugs. Here, a single and dual prodrug masking the C3 carboxylate and C7 piperazine of the fluoroquinolone, ciprofloxacin, responsive to nitroreductase (NTR) and/or hydrogen sulfide (H2S), was developed. Masking both functional groups reduced the activity of the prodrug against Staphylococcus aureus and Escherichia coli, increasing its minimum inhibitory concentration (MIC) by ∼512-fold (S. aureus) and ∼8000-fold (E. coli strains), while masking a single group only increased the MIC by ∼128-fold. Bacteria subjected to prolonged prodrug exposure did not show any increase in resistance. Triggering assays demonstrated the conversion of prodrugs to ciprofloxacin, and in a murine infection model, responsive prodrugs showed antibacterial activity comparable to that of ciprofloxacin, suggesting in vivo activation of prodrugs. Thus, the potential for site-specific antibiotic treatment with reduced threat of resistance is demonstrated.

Proteome-scale movements and compartment connectivity during the eukaryotic cell cycle.

Cell cycle progression relies on coordinated changes in the composition and subcellular localization of the proteome. By applying two distinct convolutional neural networks on images of millions of live yeast cells, we resolved proteome-level dynamics in both concentration and localization during the cell cycle, with resolution of ∼20 subcellular localization classes. We show that a quarter of the proteome displays cell cycle periodicity, with proteins tending to be controlled either at the level of localization or concentration, but not both. Distinct levels of protein regulation are preferentially utilized for different aspects of the cell cycle, with changes in protein concentration being mostly involved in cell cycle control and changes in protein localization in the biophysical implementation of the cell cycle program. We present a resource for exploring global proteome dynamics during the cell cycle, which will aid in understanding a fundamental biological process at a systems level.

Mapping of DDX11 genetic interactions defines sister chromatid cohesion as the major dependency.

DDX11/Chl1R is a conserved DNA helicase with roles in genome maintenance, DNA replication, and chromatid cohesion. Loss of DDX11 in humans leads to the rare cohesinopathy Warsaw breakage syndrome. DDX11 has also been implicated in human cancer where it has been proposed to have an oncogenic role and possibly to constitute a therapeutic target. Given the multiple roles of DDX11 in genome stability and its potential as an anticancer target, we set out to define a complete genetic interaction profile of DDX11 loss in human cell lines. Screening the human genome with clustered regularly interspaced short palindromic repeats (CRISPR) guide RNA drop out screens in DDX11-wildtype (WT) or DDX11-deficient cells revealed a strong enrichment of genes with functions related to sister chromatid cohesion. We confirm synthetic lethal relationships between DDX11 and the tumor suppressor cohesin subunit STAG2, which is frequently mutated in several cancer types and the kinase HASPIN. This screen highlights the importance of cohesion in cells lacking DDX11 and suggests DDX11 may be a therapeutic target for tumors with mutations in STAG2.

Emergency research without prior consent in the United States, Canada, European Union and United Kingdom: How regulatory differences affect study design and implementation in cardiac arrest trials.

Aim: A major barrier to performing cardiac arrest trials is the requirement for prospective informed consent, which is often infeasible during individual medical emergencies. In an effort to improve outcomes, some governments have adopted legislation permitting research without prior consent (RWPC) in these circumstances. We aimed to outline key differences between legislation in four Western locations and explore the effects of these differences on trial design and implementation in cardiac arrest research. Data sources: We performed a narrative review of RWPC legislation in the United States (US), Canada, the European Union (EU) and the United Kingdom (UK). Results: The primary criteria required to perform RWPC was similar across locations: the study must involve an individual medical emergency during which neither the prospective subject nor their authorized representative can provide informed consent. The US regulations were unique in their requirements for performing Community Consultation and Public Disclosure in the communities in which the research takes place. Another major difference was the requirement for consent for ongoing participation in Canada, the EU and the UK, while only notification of enrollment and the opportunity to discontinue participation are required in the US. Additionally, only Canada and the EU explicitly state that the subject or their representative may request withdrawal of their data. Conclusion: Regulations governing RWPC in the US, Canada, the EU and the UK have similar goals and protections for vulnerable populations during medical emergencies. Differences in the qualifying criteria and implementation procedures exist across locations and may affect study design.

The Impact of Rationing Nursing Care on Patient Safety: A Systematic Review.

BACKGROUND Rationing of nursing care (RONC) has been associated with poor patient outcomes and is a growing concern in healthcare. The aim of this systematic study was to investigate the connection between patient safety and the RONC. MATERIAL AND METHODS A thorough search of electronic databases was done to find research that examined the relationship between restricting nurse services and patient safety. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers (M.L. and A.P.) independently screened the titles and abstracts, and full-text articles were assessed for eligibility. Data were extracted, and a quality assessment was performed using appropriate techniques. RESULTS A total of 15 studies met the inclusion criteria. The studies included in the review demonstrated a correlation between rationing of nursing care and patient safety. The results of these studies revealed that there is an inverse relationship between rationing of nursing care and patient safety. The review found that when nursing care is rationed, there is a higher incidence of falls, medication errors, pressure ulcers, infections, and readmissions. In addition, the review identified that the work characteristics of nurses, such as workload, staffing levels, and experience, were associated with RONC. CONCLUSIONS RONC has a negative impact on patient safety outcomes. It is essential for healthcare organizations to implement effective strategies to prevent the RONC. Improving staffing levels, workload management, and communication amo0ng healthcare providers are some of the strategies that can support this.

Dairy product consumption, eating habits, sedentary behaviour and physical activity association with bone mineral density among adolescent boys: a cross-sectional observational study.

BACKGROUND: During childhood and adolescence, skeletal microarchitecture and bone mineral density (BMD) undergo significant changes. Peak bone mass is built and its level significantly affects the condition of bones in later years of life. Understanding the modifiable factors that improve bone parameters at an early age is necessary to early prevent osteoporosis. To identify these modifiable factors we analysed the relationship between dairy product consumption, eating habits, sedentary behaviour, and level of physical activity with BMD in 115 young boys (14-17 years). METHODS: Bone parameters were measured by dual energy x-ray absorptiometry using paediatric specific software to compile the data. Dairy product consumption and eating habits were assessed by means of a dietary interview. Sedentary behaviour and physical activity was assessed in a face-to-face interview conducted using the International Physical Activity Questionnaire. Data collection on total physical activity level was performed by collecting information on the number of days and the duration of vigorous and moderate intensity (MVPA) and average daily time spent in sitting (SIT time). RESULTS: The strongest relationships with BMD in distal part of forearm were found for moderate plus vigorous activity, sit time, and intake of dairy products, intake of calcium, protein, vitamin D, phosphorus from diet. Relationships between BMD, bone mineral content (BMC) in the distal and proximal part of the forearm and PA, sit time and eating parameters were evaluated using the multiple forward stepwise regression. The presented model explained 48-67% (adjusted R2 = 0.48-0.67; p < 0.001) of the variance in bone parameters. The predictor of interactions of three variables: protein intake (g/person/day), vitamin D intake (µg/day) and phosphorus intake (mg/day) was significant for BMD dis (adjusted R2 = 0.59; p < 0.001). The predictor of interactions of two variables: SIT time (h/day) and dairy products (n/day) was significant for BMD prox (adjusted R2 = 0.48; p < 0.001). Furthermore, the predictor of interactions dairy products (n/day), protein intake (g/person/day) and phosphorus intake (mg/day) was significant for BMC prox and dis (adjusted R2 = 0.63-0.67; p < 0.001). CONCLUSIONS: High physical activity and optimal eating habits especially adequate intake of important dietary components for bone health such as calcium, protein, vitamin D and phosphorus affect the mineralization of forearm bones.

Rationing of nursing care in Internal Medicine Departments-a cross-sectional study.

BACKGROUND: Implicit rationing of nursing care refers to a situation in which necessary nursing care is not performed to meet all of the patients' needs. PURPOSE: To examine the factors influencing the rationing of nursing care, nurses' assessment of the quality of patient care, and their job satisfaction in Internal Medicine Departments. METHODS: A cross-sectional descriptive study was undertaken. The study included 1164 nurses working in the Internal Medicine Departments in 8 hospitals (Lower Silesia, Poland). The Perceived Implicit Rationing of Nursing Care instrument was used. RESULTS: Respondents rarely ration nursing care, with a mean score of 1.12 (SD = 0.68). The mean score for quality of patient care was 6.99 (SD = 1.92). In contrast, the mean job satisfaction score was 6.07 points (SD = 2.22). The most important predictors of high rates of rationing of nursing care were work experience of 16-20 years (regression parameter: 0.387) and a Bachelor's degree in nursing (regression parameter: 0.139). Nurses' assessment of the quality of patient care ratings were increased by having a Master's degree in nursing (regression parameter: 0.41), and significantly decreased by work experience of 16-20 years (regression parameter: -1.332). Independent predictors of job satisfaction ratings in both univariate and multivariate analysis were Master's degree and long-shift working patterns. CONCLUSION: The factors that influence an increased level of nursing care rationing on medical wards are nurse seniority, exceeding 16 years and female gender. Obtaining a Master's degree in nursing indicates improved nurses' assessment of the quality of patient care.

Cell projection plots: A novel visualization of bone marrow aspirate cytology.

Deep models for cell detection have demonstrated utility in bone marrow cytology, showing impressive results in terms of accuracy and computational efficiency. However, these models have yet to be implemented in the clinical diagnostic workflow. Additionally, the metrics used to evaluate cell detection models are not necessarily aligned with clinical goals and targets. In order to address these issues, we introduce novel, automatically generated visual summaries of bone marrow aspirate specimens called cell projection plots (CPPs). Encompassing relevant biological patterns such as neutrophil maturation, CPPs provide a compact summary of bone marrow aspirate cytology. To gauge clinical relevance, CPPs were inspected by 3 hematopathologists, who decided whether corresponding diagnostic synopses matched with generated CPPs. Pathologists were able to match CPPs to the correct synopsis with a matching degree of 85%. Our finding suggests CPPs can represent clinically relevant information from bone marrow aspirate specimens and may be used to efficiently summarize bone marrow cytology to pathologists. CPPs could be a step toward human-centered implementation of artificial intelligence (AI) in hematopathology, and a basis for a diagnostic-support tool for digital pathology workflows.

Rationing in healthcare-a scoping review.

Healthcare rationing has been the subject of numerous debates and concerns in the field of health economics in recent years. It is a concept which refers to the allocation of scarce healthcare resources and involves the use of different approaches to the delivery of health services and patient care. Regardless of the approach used, healthcare rationing fundamentally involves withholding potentially beneficial programs and/or treatments from certain people. As the demands placed on health services continue to rise and with that significant increases to the cost, healthcare rationing has become increasingly popular and is deemed necessary for the delivery of affordable, patient-care services. However, public discourse on this issue has largely been centered on ethical considerations with less focus on economic rationality. Establishing the economic rationality of healthcare rationing is essential in healthcare decision-making and consideration of its adoption by healthcare authorities and organizations. This scoping review of seven articles demonstrates that the economic rationality of healthcare rationing is the scarcity of healthcare resources amidst increased demand and costs. Therefore, supply, demand, and benefits are at the core of healthcare rationing practices and influence decisions on its suitability. Given the increased costs of care and resource scarcity, healthcare rationing is a suitable practice towards ensuring healthcare resources are allocated to people in a rational, equitable, and cost-effective manner. The rising costs and demands for care place significant pressure on healthcare authorities to identify suitable strategies for the allocation of healthcare resources. Healthcare rationing as a priority-setting strategy would support healthcare authorities identify mechanisms to allocate scarce resources in a cost-effective manner. When used in the context of a priority-setting approach, healthcare rationing helps healthcare organizations and practitioners to ensure that patient populations achieve maximum benefits at reasonable costs. It represents a fair allocation of healthcare resources to all populations, especially in low-income settings.

Exploratory Study of Determinants of the Spread of COVID-19 before Shelter-in-Place Orders.

This study explores the impact of relevant characteristics of counties and their relationship with increases in COVID-19 cases before shelter-in-place (SIP) orders in the U.S. The recent emergence of COVID-19 occurs when there is little understanding of the related factors affecting the growth and spread of the disease. These relationships are examined through an analysis of 672 counties before SIP orders were issued. Areas that experienced the most significant transmission of disease are identified, and their characteristics are analyzed. A meaningful relationship was found between the increase of COVID-19 cases and several factors. Average commute time and the proportion of commuters using transit had a positive relationship. Along with other socio-economic factors, such as median house value and proportion of the Black population, several transportation-related factors had a significant association with the transmission of the disease. The decrease rate of total vehicle miles traveled (VMT) before and after SIP orders also had a solid and positive relationship with the expansion of the disease. The findings suggest that planners and transportation service providers must integrate evolving public health considerations into transportation services which affect the increase in the transmission of infectious diseases.

The Core Curriculum for Cardiovascular Nurses and Allied Professionals.

This 2023 update of the Core Curriculum in Cardiovascular Nursing (2015) embraces the formation of the Association of Cardiovascular Nursing and Allied Professionals and reflects the diverse professional backgrounds of our members, including nurses, allied health professionals, and healthcare scientists (in this document referred to collectively as Nurses and Allied Professionals).

Community consultation in the pediatric intensive care unit for an exception from informed consent Trial: A survey of patient caregivers.

Aim: To explore perspectives of families in the pediatric intensive care unit (PICU) about an emergency interventional trial on peri-arrest bolus epinephrine for acute hypotension using Exception From Informed Consent (EFIC). Methods: We performed face-to-face interviews with families whose children were hospitalized in the PICU. A research team member provided an educational presentation about the planned trial and administered a survey with open- and closed-ended items. Analyses included descriptive statistics for quantitative data and thematic analysis for qualitative data. Results: Sixty-seven participants contributed to 60 survey responses (53 individuals and 7 families for whom 2 family members participated). Most participants answered favorably toward the planned trial: 55/58 (95%) reported that the trial seemed "somewhat" or "very important"; 52/57 (91%) felt the use of EFIC was "somewhat" or "completely acceptable"; and 43/58 (74%) said they would be "somewhat" or "very likely" to allow their child to participate. Five themes emerged supporting participation in the planned trial: 1) trust in the clinical team; 2) familiarity with the study intervention (epinephrine); 3) study protocol being similar to standard care; 4) informed consent during an emergency was not feasible; and 5) importance of research. Barriers to potential participation included requests for additional time to decide about participating and misconceptions about study elements, especially eligibility. Conclusions: Families of PICU patients generally supported plans for an emergency interventional trial using EFIC. Future inpatient EFIC studies may benefit from highlighting the themes identified here in their educational materials.

Anxiety and Depressive Symptoms, Frailty and Quality of Life in Atrial Fibrillation.

Introduction: Symptoms of atrial fibrillation (AF) can significantly affect functioning in daily life and reduce patients' quality of life (QoL). The severity and type of AF symptoms affects not only patient's QoL, but can be a cause of the development of emotional and psychological disorders. In addition, frailty syndrome (FS) plays important role from the point of view of developing disability and dependence on others, as well as reducing QoL. Aim: To assess the symptoms of anxiety and depression, to evaluate the co-occurrence of frailty syndrome and the impact of these factors on the quality of life of patients with AF. Methods: The study used a Polish adaptation of the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia part III (ASTA part III), the Tilburg Frailty Indicator (TFI) and the Hospital Anxiety Depression Scale (HADS). Results: Analysis showed that anxiety symptoms and depressive symptoms correlate significantly (p < 0.05) and positively with the physical (r = 0.24; p < 0.001, r = 0.29, p = 0.002, respectively), psychological (r = 0.34, p < 0.001, r = 0.49 p < 0.001, respectively) and total quality of life (r = 0.31, p = 0.001, r = 0.414; p < 0.001, respectively) ASTA III domains. A significant (p < 0.05) positive correlation was observed between the TFI total score and the physical (r = 0.34, p < 0.001), psychological (r = 0.36, p < 0.001) and overall quality of life (r = 0.38, p < 0.001) in ASTA III domains. Conclusions: Both FS and depressive and anxiety symptoms significantly affect QoL. Understanding the relationship between anxiety and depressive symptoms, FS and QoL may allow for a more targeted approach to the treatment and care of patients with AF.

In-Hospital Cardiac Arrest in Adult Patients Admitted to a Quaternary Children's Center.

OBJECTIVE: This study aimed to describe baseline and event characteristics and outcomes for adult patients who experience in-hospital cardiac arrest (IHCA) in a quaternary children's hospital and compare IHCA outcomes in younger (18-24 years) versus older (≥25 years) adults. We hypothesized that the rate of survival to hospital discharge would be lower in the older adult group. METHODS: We performed a retrospective single-center cohort study of inpatient areas of a quaternary children's center. Adult patients (≥18 years of age) with an index pulseless IHCA requiring at least 1 minute of cardiopulmonary resuscitation or defibrillation were included. RESULTS: Thirty-three events met the inclusion criteria with a median patient age of 23.9 years (interquartile range, 20.2-33.3 years). Twenty-one (64%) patients had congenital heart disease, and 25 (76%) patients had comorbidities involving ≥2 organ systems. The most common prearrest interventions were invasive mechanical ventilation (76%) and vasoactive infusions (55%). Seventeen patients (52%) survived to hospital discharge.Survival to discharge was lower in patients 25 years or older compared with patients aged 18 to 24 years old (3 of 15 [20%] vs 14 of 18 [78%], respectively; P = 0.002). CONCLUSIONS: The majority of adult patients with IHCA in our pediatric hospital had preexisting multisystem comorbidities, the most common of which was congenital heart disease. Overall survival to discharge after IHCA was 52%, similar to that reported for the general pediatric population. Survival to discharge was significantly lower in the subgroup of patients 25 years or older when compared with those between the ages of 18 and 24 years.