Immobilized photosensitizers for antimicrobial applications

Photodynamic antimicrobial chemotherapy (PACT) is a very promising alternative to conventional antibiotics for the efficient inactivation of pathogenic microorganisms; this is due to the fact that it is virtually impossible for resistant strains to develop due to the mode of action employed. PACT employs a photosensitizer, which preferentially associates with the microorganism, and is then activated with non-thermal visible light of appropriate wavelength(s) to generate high localized concentrations of reactive oxygen species (ROS), inactivating the microorganism. The concept of using photosensitizers immobilized on a surface for this purpose is intended to address a range of economic, ecological and public health issues. Photosensitising molecules that have been immobilized on solid support for PACT applications are described herein. Different supports have been analyzed as well as the target microorganism and the effectiveness of particular combinations of support and photosensitiser

Self-sterilising surfaces to combat healthcare associated infections

The immobilisation of photosensitisers on polymeric supports for use in photodynamic antimicrobial chemotherapy has become increasingly popular. The immobilisation of photosensitisers on polymeric supports has been attempted previously by covalent attachment between the photosensitiser and the support, and by entrapping the photosensitiser in a polymeric matrix. Even though porphyrins have been attached to polymeric supports there have been relatively few biological experiments carried out following immobilisation. There have also been few attempts at measuring the reusability of a surface incorporating a photosensitiser for bacterial inactivation. The work presented herein will focus on two main goals; the first is the formation of a self-sterilising surface which will activate under irradiation with visible light, allowing normal lighting conditions to be used, the second goal that will be targeted is the formation of a porphyrin immobilised on a polymeric surface which exhibits minimal leaching, and shows good anti-bacterial activity.Synthesis of a range of conjugatable porphyrins and viologens bearing complementary peripheral functionalities has been carried out, followed by conjugation to solid supports using both microwave heating and normal heating.Entrapment of polyviologens and porphyrins in two different polymeric matrices, silica and polyacrylamide, has been attempted. The entrapment was carried out using different solvent systems, and although it was found to be successful, both porphyrin and polyviologen were found to leach from the polymeric support upon washing. An alternative strategy was attempted via the formation of a water-soluble porphyrin containing a vinyl functionality for use in free radical polymerisation reactions.The synthesis of a library of water-soluble porphyrins bearing vinyl groups was carried out. The library allowed for comparison of a non-metallated porphyrin, acting as a positive control, a copper porphyrin which acted as a negative control and a palladium porphyrin, which was found to produce the highest degree of inactivation of the Gram-negative bacteria E.coli

We’re Not Going To Do Better Next Time

The poems in We’re Not Going To Do Better Next Time are anchored around the biblical parable of Samson and Delilah (spelled “Dalila” here). Approaching the story from a secular contemporary perspective, the poems focus on the two characters themselves, rather than the religious elements of the traditional narrative. We’re Not Going To Do Better explores the dynamics of a flawed relationship and how two people relate (or fail to relate) to one another. Instabilities in the narrative’s consistency reflect Dalila and Samson’s dueling perspectives and the fallibility of memory, as well as how the choices made in a relationship can lead to many possible outcomes. The work falls into four sections: Prequels (to root the work in its source text), Encounters (relaying the relationship’s beginnings and progression), Fallout (how the relationship disintegrates), and Cleanup (the characters’ lives beyond each other). While the individual poems should be able to stand on their own, this collection is intended to be read as a narrative

Housing Policy for Eviction Prevention During COVID-19

The COVID-19 pandemic has increased housing instability and put millions of renters at risk of displacement since stay-at-home orders began in the US in March 2020. Federal, state, and local actors rushed to expand and adapt existing housing policies, and create new ones, to prevent the additional public health disaster of millions of Americans being evicted. This paper examines two housing policy measures – eviction moratoria and emergency rental assistance (ERA) – taken to prevent evictions during COVID-19, exploring these policies at the federal, state, and local level. The paper uses the state of North Carolina, specifically Orange County, as a case study, examining Orange County’s Emergency Housing Assistance (EHA) fund. Finally, this paper examines how the COVID-19 pandemic has highlighted the weaknesses of US affordable housing policy, and explores potential policy proposals for the future of housing in the US.Master of City and Regional Plannin

Identification of Virulence Determinants for Streptococcus sanguinis Infective Endocarditis

Streptococcus sanguinis is the second most common causative agent of bacterial infective endocarditis (IE). Risk of S. sanguinis IE is dependent on pre-disposing damage to the heart valve endothelium, which results in deposition of clotting factors for formation of a sterile thrombus (referred to as vegetation). Despite medical advances, high mortality and morbidity rates persist. Molecular characterization of S. sanguinis virulence determinants may enable development of prevention methods. In a previous screen for S. sanguinis virulence determinants by signature-tagged mutagenesis (STM) an attenuated mutant was identified with a transposon insertion in the nrdD gene, encoding an anaerobic ribonucleotide reductase. Evaluation of this mutant, as well as an nrdD in-frame deletion mutant, JFP27, by a soft-agar growth assay confirmed the anaerobic growth sensitivity of these strains. These studies suggest that an oxygen gradient occurs at the site of infection which selects for expression of anaerobic-specific genes at the nexus of the vegetation. The random STM screen failed to identify any favorable streptococcal surface-exposed prophylactic candidates. It was also apparent that additional genetic tools were required to facilitate the in vivo analyses of mutant strains. As it was desirable to insert antibiotic resistance markers into the chromosome, we identified a chromosomal site for ectopic expression of foreign genes. In vitro and in vivo analyses verified that insertion into this site did not affect important cellular phenotypes. The genetic tools developed facilitated further in vivo screening of S. sanguinis cell wall-associated (Cwa) protein mutants. A directed application of STM was employed for a comprehensive analysis of this surface protein class in the rabbit model of IE. Putative sortases, upon which Cwa proteins are dependent for cell surface localization, were also evaluated. No single S. sanguinis Cwa protein was determined essential for IE by STM screening; however competitiveness for colonization of the infection site was reduced for the mutant lacking expression of sortase A. The studies described here present a progressive picture of S. sanguinis IE, beginning with surface protein-dependent colonization of the vegetation in early IE, that later shifts to a bacterial persistence in situ dependent on condition-specific housekeeping genes, including nrdD

Outcomes Associated with Using the Identification of Seniors at Risk (ISAR) Score to Determine Geriatric Evaluations of Trauma Patients with Hip Fractures

Background: Falls are a leading cause of injury in older adults in the U.S., commonly contributing to hip fractures specifically (Centers for Disease Control, 2016; Moreland, Kakara, & Henry, 2020). Many older adults who sustain a hip fracture will not return to their baseline function and may even require nursing home placement for additional care (Rubenstein & Josephson, 2006). Henry Ford Macomb Hospital (HFMH) is a community teaching hospital with Level II Adult Trauma designation. In 2013, the Trauma Quality Improvement Program (TQIP) stressed the need for specialized geriatric care (American College of Surgeons, 2013, p.5). Falls with hip fracture accounted for 15% of Trauma admissions in 2014-2016 and 21% in 2017-2019 at HFMH. In 2016, the Identification of Seniors at Risk (ISAR) screening tool was utilized for Trauma patients 60 years and older to help capture their need for a Geriatric evaluation. It is completed by a Trauma Resident upon evaluation of the patient in the Emergency Department. A Geriatric evaluation is recommended if the patient answered “yes” to two or more questions on the screening tool. If a patient is discharged prior to being seen for the evaluation, follow up information is encouraged to be provided for the Geriatric outpatient clinic. Aim: To evaluate outcomes of older adults who sustained a hip fracture after falling as related to the implementation LIMITATIONS of the ISAR tool to determine Geriatric evaluations and assess outcomes related to individual ISAR scores (0- 6). Methodology: Retrospective program evaluation conducted via chart review. July 1, 2014-June 30, 2016, and January 1, 2017, to December 31, 2019. Data Analysis: Variables were described using standard summary measures such as means and standard deviation for continuous variables and counts/percentage for nominal data. Continuous variables that did not follow a normal distribution were described via medians and interquartile ranges. The two groups were compared with Student’s t- Tests and Chi-squared tests dependent on variables. To evaluate variables related to each ISAR score, Kruskal- Wallis analysis was used. The p-value was adjusted as needed to conclude significance using Hochberg’s adjustment. Results: A total of 1,142 charts were reviewed. Thirty-six were excluded for admission to non-trauma service, and an additional forty-six charts were excluded for patients with multiple admissions. Of the qualifying patients, 380 were included in our pre-Geriatric evaluation implementation and 680 in post. In the post period, 48/680= 7% patients did not have an ISAR completed. Many of the patients admitted to the Trauma Service with hip fractures sustained an intertrochanteric fracture, followed by proximal femur fracture and then femur shaft fracture. Majority of Trauma patients sustaining a hip fracture were white, non-Hispanic, English-speaking, Caucasian females. Outcomes Compared By ISAR Score: There is a significant difference in age between each ISAR score (p=0.001), with generally higher ISAR scores as age increases. The ISS does not correlate with increasing ISAR score (p=0.102). Length of stay increases with ISAR scores (p=0.012). The longest duration of ICU stays occurred in patient with an ISAR score of three. In-hospital mortality did not increase with increasing ISAR score (p=0.664). In-hospital mortality was highest in ISAR scores of five. Readmissions were highest in those with an ISAR score of five, and an ISAR score of one had the lowest rate of readmission. Hospice was consulted more frequently as the ISAR score increases (p=0.034), with the highest prevalence of consults noted in patients with ISARs of six. Majority of patients were discharged to SNF regardless of ISAR score (p=0.092). Outcomes Compared Before and After Geriatric Evaluation: Of the 680 patients in the post-group, 434 patients received a Geriatric Evaluation. Age and ISS was significantly higher in the Geriatric evaluation population. No significant difference was found between total LOS, though did decrease by four hours (p=0.075). In the pre-group, more patients were admitted to the ICU (5.78%) than the post-group (4.14%); however, the pre-group had a shorter ICU length of stay (5.73 vs 5.89, P = 0.847). Thirty-day readmissions trended higher in the post-group with a Geriatric evaluation (p=0.106). In-hospital mortality was lower in the post-group with a Geriatric evaluation (p=0.243). Hospice consults and discharges to Hospice were higher in the post-group with a Geriatric evaluation (p=0.083). Majority of patients were discharged to a Skilled Nursing Facility (SNF) for both the pre- and post-group, followed by home with services, or home with self-care. Discharge to inpatient rehabilitation unit (IPR) decreased in the post-group with a Geriatric evaluation. Discussion: To the existing body of literature, this current study adds outcomes broken down by each individual ISAR score for patients with hip fractures and the associated outcomes using the ISAR score to guide the need for Geriatric evaluations. The ISS does not correlate with increasing ISAR score (p=0.102). It could be suggested that the individual questions that make up the ISAR score do not address the severity and/or mechanism of injury. The longest ICU LOS occurred in patients with an ISAR score of three; however, the ISAR screening tool was not originally developed to predict ICU stays. There is limited literature to support this finding and more research could be done in this area. With 30-day readmissions being the highest in those with an ISAR scores of four and five, quality and care coordination efforts could be directed towards Geriatric Trauma patients with these scores. Patients with a Geriatric evaluation, who were older and scored a higher ISS, had a shorter LOS by approximately four hours, this is vital because it can be associated with decreased costs and increased patient satisfaction. Admissions to Inpatient Rehab (IPR) decreased in the post-group, further investigation could assist with determining causal factors, though IPR admissions are typically low due to requiring a physical and medical need for admission. In-hospital mortality decreased in the post group, even with increased age and ISS. There are inconsistencies among current studies regarding the mortality of Trauma patients after undergoing a Geriatric evaluation, therefore AIM more research is needed to fully understand the impact. Limitations: More rigorous research design would be beneficial to fully understand the studied outcomes. The six-month period during which the Geriatric evaluation service was in the early stages of development and planning the use of the ISAR score was not included in the study time frame. The ISAR score can be challenging to obtain due to altered mental status or lack of family/surrogate presence to obtain accurate information at the time of screening. This study also did not verify the accuracy of the scores obtained by the Trauma Resident. This could impact the outcomes associated with each ISAR score in addition to the outcomes related to patients that received Geriatric evaluations. Compliance of the Trauma Service in following the recommendations as well as patients and family’s adherence to the plan of care may impact outcomes. In addition, this study did not address what specifically is included in a Geriatric evaluation. It also may have been helpful to know which individual ISAR questions are most often answered “yes” to validate if the specific concerns were addressed during the evaluation.https://scholarlycommons.henryford.com/nursresconf2021/1007/thumbnail.jp

Electrophysiological premotor processing in Huntington's disease: an issue of functional connectivity

Huntington’s disease is a neurodegenerative disease which presents with cognitive, motor and emotional-behavioural changes. Neural degeneration begins up to 20 years prior to symptom onset, arising initially in the striatum. Motor symptoms are a hallmark; disturbances occur due to disruption of crucial motor pathways through atrophy. However, these are not seen until much later in the disease. Such findings raise questions about the role internal processes play in maintenance of function, but little is known about functional motor connectivity during early stages. Electroencephalography is a sensitive measure of the integrity of neural process occurring prior to, and at, motor execution. This thesis explores the relationship between electrophysiological premotor/motor activation and structural integrity of critical neuroanatomy providing intra-hemispheric and inter-hemispheric connectivity – the striatum and corpus callosum. In the principal study, presymptomatic persons showed abnormal premotor activation (Contingent Negative Variation); greater relative activation across the premotor period, accompanied by normal motor potentials (Readiness Potential) and execution (response time). Aberrant premotor activation likely reflects disruption of critical inter-hemispheric circuitry such as fronto-striatal networks and the corpus callosum. Results implicated compensation in a context of early atrophy and/or an inability to regulate responses. Extending this hypothesis, Study Two examines the relationship between premotor electrophysiological activity and morphology of the striatum using magnetic resonance imaging. Structural integrity of the caudate and putamen was theorised to determine the fronto-striatal neuroanatomical circuits subserving electrophysiological responses. Quantification of volume/shape yielded structure and function associations in our combined sample: timing (latency) and consistency (relative activation/slope) of the premotor response was determined by degeneration, with greater atrophy predicting later and less consistent activation. This suggests compromise to motor pathways is progressive, and may first emerge as delayed, inefficient, and inconsistent electrophysiology. In Study Three, investigation was extended to the corpus callosum, which provides inter-hemispheric connectivity between primary and supplementary motor regions distinct from fronto-striatal pathways. It was proposed that atrophy to the corpus callosum (thinning) would disrupt both homotopic (e.g. parietal to frontal lobe) and heterotopic (e.g. left and right frontal lobe) circuits supporting premotor/motor connectivity. Raw correlations suggested compromise to mid- posterior (motor) and mid-anterior (frontal cortex/premotor/supplementary motor) affects premotor performance (extent and consistency of response). While results did not survive stringent FDR error corrections, they followed known anatomical relationships, suggesting functional motor connectivity and premotor processing are also determined by structural integrity of the corpus callosum. These findings are important in showing early, disease-related morphological changes to the striatum and corpus callosum do disrupt critical fronto-striatal and inter-hemispheric networks. Morphological changes accompanied by abnormal electrophysiological premotor activation support hypotheses of dysfunctional connectivity arising from atrophy to anatomical landmarks. Progression of circuit derangement may be mediated by secondary activation (e.g. supplementary motor areas, executive circuits) and typically indirect subcortical structures, which preserve function as connectivity with the primary motor area declines. Future studies using technology such as transcranial magnetic stimulation and diffusion tensor imaging may allow identification and stimulation of vulnerable and robust circuits respectively, potential intervention targets to preserve function and quality of life for longer