Efforts Toward Synthesis of Novel Analogs of the Bacterial Second-Messenger, c-di-GMP

The formation of bacterial biofilms is a common mechanism for antibiotic resistance. It has been shown that bis-(3'-5')-cyclic dimeric guanosine monophosphate, c-di-GMP, plays a key role in bacterial biofilm formation; therefore, the proteins that regulate the metabolism or adaptive response of c-di-GMP are favorable targets for novel antimicrobials. We herein describe a solid-support methodology developed in the Sintim Laboratory and efforts toward its application to the synthesis of novel c-di-GMP analogs. Our selected targets are a series of analogs bearing various substitutions at the 2'-position of the ribose backbone. Syntheses of 2'-deoxy and 2'-methoxy analogs were achieved as well as that of key intermediates toward the 2'-fluoro and conformationally flexible analogs

Social work scope of practice with Parkinson's disease: A qualitative study

Summary The field of social work has seen increased recognition across many sectors in recent years. Evolving racial, political, and medical paradigms and the COVID-19 pandemic have shown the importance of a person-centered approach to health and mental health. One such area of practice is neurology, specifically work with people with Parkinson's disease (PD), which is the second most common neurodegenerative disease, currently impacting more than 10 million people worldwide. While social workers have long played key roles in multidisciplinary teams in PD care settings, research and literature offering assessment and evidence in this area remain limited. This research study used a mixed-methods approach with additional in-depth qualitative interviews conducted with 11 social workers. This article presents findings from the 11 interviewees who are presently working with people with PD using thematic analysis. Findings Themes emerging were an in-depth detailed role of the social worker, the importance of strong relationships working with people with PD and their families, multidisciplinary teams, and the community. Institutional challenges were highlighted concerning supporting social work positions and encouraging social work intervention from the beginning of diagnosis to the end stages of the disease. COVID-19 proved very challenging for social workers, multidisciplinary teams, and families, and yet positive practices were identified as well. Applications The impact of this study reinforces the essential role specialized PD social workers play in multidisciplinary PD teams and recognition needed to increase their role through early intervention reflected in increasing social work positions in neurology

More than medications: a patient-centered assessment of Parkinson’s disease care needs during hospitalization

BackgroundParkinson’s disease (PD) increases the risk of hospitalization and complications while in the hospital. Patient-centered care emphasizes active participation of patients in decision-making and has been found to improve satisfaction with care. Engaging in discussion and capturing hospitalization experience of a person with PD (PwP) and their family care partner (CP) is a critical step toward the development of quality improvement initiatives tailored to the unique hospitalization needs of PD population.ObjectivesThis qualitative study aimed to identify the challenges and opportunities for PD patient-centered care in hospital setting.MethodsFocus groups were held with PwPs and CPs to capture first-hand perspectives and generate consensus themes on PD care during hospitalization. A semi-structured guide for focus group discussions included questions about inpatient experiences and interactions with the health system and the clinical team. The data were analyzed using inductive thematic analysis.ResultsA total of 12 PwPs and 13 CPs participated in seven focus groups. Participants were 52% female and 28% non-white; 84% discussed unplanned hospitalizations. This paper focuses on two specific categories that emerged from the data analysis. The first category explored the impact of PD diagnosis on the hospital experience, specifically during planned and unplanned hospitalizations. The second category delves into the unique needs of PwPs and CPs during hospitalization, which included the importance of proper PD medication management, the need for improved hospital ambulation protocols, and the creation of disability informed hospital environment specific for PD.ConclusionPD diagnosis impacts the care experience, regardless of the reason for hospitalization. While provision of PD medications was a challenge during hospitalization, participants also desired flexibility in ambulation protocols and an environment that accommodated their disability. These findings highlight the importance of integrating the perspectives of PwPs and CPs when targeting patient-centered interventions to improve hospital experiences and outcomes

More than medications: a patient-centered assessment of Parkinson’s disease care needs during hospitalization

Background Parkinson’s disease (PD) increases the risk of hospitalization and complications while in the hospital. Patient-centered care emphasizes active participation of patients in decision-making and has been found to improve satisfaction with care. Engaging in discussion and capturing hospitalization experience of a person with PD (PwP) and their family care partner (CP) is a critical step toward the development of quality improvement initiatives tailored to the unique hospitalization needs of PD population. Objectives This qualitative study aimed to identify the challenges and opportunities for PD patient-centered care in hospital setting. Methods Focus groups were held with PwPs and CPs to capture first-hand perspectives and generate consensus themes on PD care during hospitalization. A semi-structured guide for focus group discussions included questions about inpatient experiences and interactions with the health system and the clinical team. The data were analyzed using inductive thematic analysis. Results A total of 12 PwPs and 13 CPs participated in seven focus groups. Participants were 52% female and 28% non-white; 84% discussed unplanned hospitalizations. This paper focuses on two specific categories that emerged from the data analysis. The first category explored the impact of PD diagnosis on the hospital experience, specifically during planned and unplanned hospitalizations. The second category delves into the unique needs of PwPs and CPs during hospitalization, which included the importance of proper PD medication management, the need for improved hospital ambulation protocols, and the creation of disability informed hospital environment specific for PD. Conclusion PD diagnosis impacts the care experience, regardless of the reason for hospitalization. While provision of PD medications was a challenge during hospitalization, participants also desired flexibility in ambulation protocols and an environment that accommodated their disability. These findings highlight the importance of integrating the perspectives of PwPs and CPs when targeting patient-centered interventions to improve hospital experiences and outcomes

Mucins and Pathogenic Mucin-Like Molecules Are Immunomodulators During Infection and Targets for Diagnostics and Vaccines

Mucins and mucin-like molecules are highly O-glycosylated proteins present on the cell surface of mammals and other organisms. These glycoproteins are highly diverse in the apoprotein and glycan cores and play a central role in many biological processes and diseases. Mucins are the most abundant macromolecules in mucus and are responsible for its biochemical and biophysical properties. Mucin-like molecules cover various protozoan parasites, fungi and viruses. In humans, modifications in mucin glycosylation are associated with tumors in epithelial tissue. These modifications allow the distinction between normal and abnormal cell conditions and represent important targets for vaccine development against some cancers. Mucins and mucin-like molecules derived from pathogens are potential diagnostic markers and targets for therapeutic agents. In this review, we summarize the distribution, structure, role as immunomodulators, and the correlation of human mucins with diseases and perform a comparative analysis of mucins with mucin-like molecules present in human pathogens. Furthermore, we review the methods to produce pathogenic and human mucins using chemical synthesis and expression systems. Finally, we present applications of mucin-like molecules in diagnosis and prevention of relevant human diseases

The Biophysical Role of the Cellular Glycocalyx: Engineering Glycoproteins to Control Cell-Surface Properties

The glycocalyx is the sugary coating on the surface of essentially all mammalian cells. Despite being a major class of biomolecules, research into carbohydrates has lagged behind other classes of biomolecules such as nucleic acids and proteins. The constituent parts of the glycocalyx are not encoded in our genome, but rather dynamically regulated by protein expression rates, post-translational modification rates, and metabolic flux. Therefore, we can view the glycocalyx as a complex and dynamic biomaterial on the surface of cells; however, research into the impact of the glycocalyx as a biomaterial is lacking. Coating the cellular surface, the glycocalyx is uniquely positioned to impact many different cell-surface properties including regulation of cell-cell and cell-extracellular matrix interactions, cell-surface features, and cellular migration. Throughout this work, we approach the glycocalyx as a biomaterial coating on the surface of cells with the goal of appreciating the physical properties and implications of the material. We first use an engineering approach to develop a new set of genetically encoded mucin biopolymers to facilitate in studying the cancer glycocalyx. We then apply our expertise in synthetic biology approaches and mucin biopolymer expression to produce some of the first ever recombinant mucins for therapeutic applications. Taking advantage of the anti-adhesive properties of mucin, we apply mucin expression as an innovative technology for reduced aggregation of cells grown in suspension in bioreactors. With our unique viewpoint of the glycocalyx from a physical perspective, we apply polymer brush theory to develop a model for membrane bending driven by glyco-biopolymers. Finally, we investigate what role the anti-adhesive glycocalyx may play in regulating cellular migration both in vitro and in vivo. Together, these projects utilize engineered glycoproteins to elucidate new functions for the mammalian glycocalyx in various avenues of cellular behavior and inform future research into the physical role of the glycocalyx at the cell surface

Table_1_More than medications: a patient-centered assessment of Parkinson’s disease care needs during hospitalization.pdf

BackgroundParkinson’s disease (PD) increases the risk of hospitalization and complications while in the hospital. Patient-centered care emphasizes active participation of patients in decision-making and has been found to improve satisfaction with care. Engaging in discussion and capturing hospitalization experience of a person with PD (PwP) and their family care partner (CP) is a critical step toward the development of quality improvement initiatives tailored to the unique hospitalization needs of PD population.ObjectivesThis qualitative study aimed to identify the challenges and opportunities for PD patient-centered care in hospital setting.MethodsFocus groups were held with PwPs and CPs to capture first-hand perspectives and generate consensus themes on PD care during hospitalization. A semi-structured guide for focus group discussions included questions about inpatient experiences and interactions with the health system and the clinical team. The data were analyzed using inductive thematic analysis.ResultsA total of 12 PwPs and 13 CPs participated in seven focus groups. Participants were 52% female and 28% non-white; 84% discussed unplanned hospitalizations. This paper focuses on two specific categories that emerged from the data analysis. The first category explored the impact of PD diagnosis on the hospital experience, specifically during planned and unplanned hospitalizations. The second category delves into the unique needs of PwPs and CPs during hospitalization, which included the importance of proper PD medication management, the need for improved hospital ambulation protocols, and the creation of disability informed hospital environment specific for PD.ConclusionPD diagnosis impacts the care experience, regardless of the reason for hospitalization. While provision of PD medications was a challenge during hospitalization, participants also desired flexibility in ambulation protocols and an environment that accommodated their disability. These findings highlight the importance of integrating the perspectives of PwPs and CPs when targeting patient-centered interventions to improve hospital experiences and outcomes.</p

Manual examination in the diagnosis of cervicogenic headache: A systematic literature review

Design: Systematic literature review. Objective: To evaluate the diagnostic validity of manual examination techniques used to diagnose cervicogenic headache (CGH). Background: Cervicogenic headache is a specific type of headache that originates from the cervical spine and is typically chronic in nature. Diagnostic criteria for CGH have been established by the International Headache Society (IHS) and are cited extensively in the literature. Diagnosis of CGH through manual examination is a more recent practice. To our knowledge, no systematic review of manual diagnosis of CGH has been performed. Methods: Searches of electronic databases (CINAHL, Cochrane Library, Medline, PEDro, Scopus, and SPORTDiscus) were conducted for research studies from July 2003 to February 2014. The GRADE approach was used to determine the quality of each paper. Results: Twelve papers that fulfilled the inclusion and exclusion criteria were identified (12 observational studies). The level of evidence ranged from very low to low, and recommendations for use of specific manual techniques ranged from weak to strong. Conclusions: Despite low levels of evidence, manual examination of the cervical spine appears to aid the diagnostic process related toCGHand can be implemented by both experienced and inexperienced examiners