Age-related changes in blood-brain barrier integrity in C57BL/6J mice

The blood-brain barrier (BBB) is formed by the endothelial cells of the brain microvasculature, which control the molecular traffic between the blood and brain to maintain the neural microenvironment

Ultrastructural analysis of changes in neurons of the mouse internal anal sphincter during ageing

Gastrointestinal disorders, including chronic constipation, faecal impaction and incontinence, are a major cause of morbidity in the elderly

Age-related changes to lumbosacral spinal cord motoneurons that modulate bladder and bowel functions in male C57BL/6 mice

Incontinence and sexual dysfunction are often increased in the aged human population. In rats and mice the pattern of micturition and faecal clearance also changes with ageing and is suggestive of bladder and bowel dysfunction

Improving Patient Outcomes with Post-Op Education for Nurses Caring for Patients Undergoing Total Joint Replacement

Background: Surgical site infections (SSI) are the third most reported nosocomial infection causing an increased length of stay, increased healthcare cost, and a substantial increase in morbidity. A SSI is an infection developing within 30 days of surgery without using an implant and within one year of surgery utilizing any form of implant. Typically SSI occurs at the time of incision. However, poor postoperative wound care can lead to an SSI. Purpose: This project aims to educate nursing staff on care of the total joint replacement (TJR) patient to reduce readmission rates for postoperative SSI. Design Methods: This quality improvement project delivered education to participants during a 30-minute session. Education included the different wound dressings and associated care, SSI risks and prevention, and patient discharge education. A quasi-experimental design was utilized with pre- and post-education testing to evaluate effectiveness. Conclusion: Comparison of the pre- and post-educational session testing revealed a substantial increase in staff knowledge of TJR patient care and associated wound dressings and care guidelines, as well as a decrease in SSI readmission rates. Implications for Nursing: Success of the educational sessions led to this education being added to new hire orientation and yearly staff competency education. Keywords: surgical site infection, wound care, education, evidence-based practice, NPWT, silver, sterile gauze, TJ

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Characterization of Postoperative Recovery After Cardiac Surgery- Insights into Predicting Individualized Recovery Pattern

Understanding the patterns of postoperative recovery after cardiac surgery is important from several perspectives: to facilitate patient-centered treatment decision making, to inform health care policy targeted to improve postoperative recovery, and to guide patient care after cardiac surgery. Our works aimed to address the following: 1) to summarize existing approaches to measuring and reporting postoperative recovery after cardiac surgery, 2) to develop a framework to efficiently measure patient-reported outcome measures to understand longitudinal recovery process, and 3) to explore ways to summarize the longitudinal recovery data in an actionable way, and 4) to evaluate whether addition of patient information generated through different phases of care would improve the ability to predict patient’s outcome. We first conducted a systematic review of the studies reporting on postoperative recovery after cardiac surgery using patient-reported outcome measures. Our systematic review demonstrated that the current approaches to measuring and reporting recovery as a treatment outcome varied widely across studies. This made synthesis of collective knowledge challenging and highlighted key gaps in knowledge, which we sought to address in our prospective cohort study. We conducted a prospective single-center cohort study of patients after cardiac surgery to measure their recovery trajectory across multiple domains of recovery. Using a digital platform, we measured patient recovery in various domains over 30 days after surgery to visualize a granular evolution of patient recovery after cardiac surgery. We used a latent class analysis to facilitate identification of dominant trajectory patterns that had been obscured in a conventional way of reporting such time-series data using group-level means. For the pain domain, we identified 4 trajectory classes, one of which was a group of patients with persistently high pain trajectory that only became distinguishable from less concerning group after 10 days. Therefore, we obtained a potentially actionable insights to tailoring individualized follow-up timing after surgery to improve the pain control. The prospective study embodied several important features to successfully conducting such studies of patient-reported outcomes. This included the use of digital platform to facilitate efficient data collection extending after hospital discharge, iteratively improving the protocol to optimize patient engagement including evaluation of potential barriers to survey completion, and using latent class analysis to identify dominant patterns of recovery trajectories. We outlined these insights in the protocol manuscript to inform subsequent studies aiming to leverage such a digital platform to measure longitudinal patient-centered outcome. Finally, we evaluated the potential value of incorporating health care data generated in the different phases of patient care in improving the prediction of postoperative outcomes after cardiac surgery. The current standard of risk prediction in cardiac surgery is the Society of Thoracic Surgeons’ (STS) risk model, which only uses patient information available preoperatively. We demonstrated through prediction models fitted on the national STS risk model for coronary artery bypass graft surgery that the addition of intraoperative variables to the conventional preoperative variable set improved the performance of prediction models substantially. Using machine learning approach to such a high-dimensional dataset proved to be marginally important. This work demonstrated the potential value and importance of being able to leverage health care data to continuously update the prediction to inform patient outcomes and guide clinical care. Our work collectively advanced knowledge in several key aspects of postoperative recovery. First, we highlighted the knowledge gap in the existing literature through characterizing the variability in the ways such studies had been conducted. Second, we designed and described a framework to measure postoperative recovery and an analytical approach to informatively characterize longitudinal patient recovery. Third, we employed these designs in a prospective cohort study to measure and analyze recovery trajectories and described clinical insights obtained from the study. Finally, we demonstrated the potential value of a dynamic risk model to iteratively improve its predictive performance by incorporating new data generated as the patient progresses through the phase of care. Such a platform has the potential to individualize patient’s post-acute care in a data-driven manner

Genomic Methods for Bacterial Infection Identification

Hospital-acquired infections (HAIs) have high mortality rates around the world and are a challenge to medical science due to rapid mutation rates in their pathogens. A new methodology is proposed to identify bacterial species causing HAIs based on sets of universal biomarkers for next-generation microarray designs (i.e., nxh chips), rather than a priori selections of biomarkers. This method allows arbitrary organisms to be classified based on readouts of their DNA sequences, including whole genomes. The underlying models are based on the biochemistry of DNA, unlike traditional edit-distance based alignments. Furthermore, the methodology is fairly robust to genetic mutations, which are likely to reduce accuracy. Standard machine learning methods (neural networks, self-organizing maps, and random forests) produce results to identify HAIs on nxh chips that are very competitive, if not superior, to current standards in the field. The potential feasibility of translating these techniques to a clinical test is also discussed

Development of Inducible Anti-influenza Therapies

Influenza viruses continue to cause significant morbidity and mortality each year despite the development of vaccines and antiviral therapies targeting these viruses. The inherent ability of influenza viruses to accumulate mutations over time has led to the emergence of strains resistant to antiviral therapies. Furthermore, genetic reassortment creates antigenically diverse viruses, making it difficult to develop vaccines that yield broad protection. The objective of the following research studies is to develop two alternative approaches to current methods of antiviral therapeutics.;Six new siRNAs targeting influenza protein expression by RNA interference (RNAi) were characterized. Three siRNAs (M747, M776, M832) knocked down the expression of matrix protein 2 and attenuated influenza infection to a similar degree as MDCK cells treated with a previously published siRNA, M950. The three siRNAs (NS570, NS595, NS615) that target the nonstructural protein 1 and 2 genes promoted the expression of type I interferons, but were unable to attenuate the production of infectious virus. However NS595- and NS615-siRNAs promoted the production of defective interfering viruses. Another siRNA, M331, was able knock down the expression matrix 1 and matrix 2 and attenuate viral replication. Combination siRNA treatment was found to attenuate 20.9% more infectious virus than M950-siRNA treatment alone. Treatment with a single siRNA (M331, NS570, NS595, or NS615) that targets two protein coding sequences was able to knock down the expression of two proteins, thus enhancing the utilities of the siRNAs.;To further take advantage of RNAi as a mechanism to attenuate influenza infection, we developed an inducible anti-influenza therapy containing the influenza conserved promoter that expresses asRNAs only after influenza infection or in the presence of the influenza virus RNA-dependent RNA polymerase (RdRP). asRNA expression was restricted to pM950, pM776, pNS595, or pNA105 treated cells containing the RdRP. The asRNAs expressed from the inducible asRNA expression vectors (pM776 or pNS595) were 84- to 343-fold below the concentration needed to reduce influenza virus infection by RNAi, thus illustrating the need for improved expression kinetics. Limiting expression of asRNAs within influenza infected cells could potentially reduce the adverse effects and limitation of RNAi therapeutics.;In an attempt to reverse antigenic variation and attenuate influenza titer, we developed additional inducible anti-influenza therapies (pUC57 NF-NA and pUC57 F-NA), similar to the inducible asRNA expression vector, which express nonfunctional or functional neuraminidases (NF-NA or F-NA) upon influenza infection. The presence of vector expressed RdRP or influenza infection induced the expression of NF-NA and F-NA. Overexpression of NF-NA was originally hypothesized to attenuate influenza titer; however, NF-NA regained its sialidase activity after RdRP-mediated transcription. pUC57 NF-NA or F-NA transfected cells produced an RNA-intermediate regardless of the presence of the RdRP, whereas the polymerase was required for NF-NA mRNA and protein expression. Interestingly, reinfection of MDCK cells with the supernatant from pUC57 NF-NA or F-NA treated and influenza (N1 subtype) infected cells revealed that the naive MDCK cells generated N2 subtype viruses, indicating the induced N2 viral RNA could be packaged into progeny viruses forcing the N1 virus to become an N2 virus.;These studies demonstrate that RNAi can be an effective means to attenuate influenza infection. Furthermore, incorporation of the influenza conserved promoter into asRNA or neuraminidase expression vectors can be exploited to promote influenza infected cell-specific expression of anti-influenza molecules. This approach may impact the design and advancement of antiviral therapeutics by overcoming the limitations associated with RNAi and allow for current vaccines to protect against influenza infection by forcing influenza viruses to converge into a single subtype

Neuroimaging Research into Disorders of Consciousness: Moral Imperative or Ethical and Legal Failure?

This article explores the ethical and legal implications of enrolling individuals with disorders of consciousness (DOC) in neuroimaging research studies. Many scientists have strongly emphasized the need for additional neuroimaging research into DOC, characterizing the conduct of such studies as morally imperative. On the other hand, institutional review boards charged with approving research protocols, scientific journals deciding whether to publish study results, and federal agencies that disburse grant money have limited the conduct, publication, and funding of consciousness investigations based on ethical and legal concerns. Following a detailed examination of the risks and benefits of neuroimaging research involving individuals with DOC, the author urges IRBs, scientific journals, and funding agencies to no longer stall the conduct, publication, and funding of neuroimaging research into DOC if certain criteria designed to protect the health and safety of individuals with DOC are satisfied