The risk of vector transmission of Trypanosoma cruzi remains high in the State of Paraná.

BACKGROUND: Monitoring and analysing the infection rates of the vector of Trypanosoma cruzi, that causes Chagas disease, helps assess the risk of transmission. OBJECTIVES: A study was carried out on triatomine in the State of Paraná, Brazil, between 2012 and 2021 and a comparison was made with a previous study. This was done to assess the risk of disease transmission. METHODS: Ecological niche models based on climate and landscape variables were developed to predict habitat suitability for the vectors as a proxy for risk of occurrence. FINDINGS: A total of 1,750 specimens of triatomines were recorded, of which six species were identified. The overall infection rate was 22.7%. The areas with the highest risk transmission of T. cruzi are consistent with previous predictions in municipalities. New data shows that climate models are more accurate than landscape models. This is likely because climate suitability was higher in the previous period. MAIN CONCLUSION: Regardless of uneven sampling and potential biases, risk remains high due to the wide presence of infected vectors and high environmental suitability for vector species throughout the state and, therefore, improvements in public policies aimed at wide dissemination of knowledge about the disease are recommended to ensure the State remains free of Chagas disease.

Synthesis, antimicrobial properties and in silico evaluation of coumarin derivatives mediated by 1,4-dibromobutane.

In this study, monobrominated coumarins (5-6) and bis-coumarins (7-9) were synthesized from 3-carboxylic coumarin and 7-hydroxy-4-methyl coumarin using 1,4-dibromobutane as a binding agent, according to the synthesis procedures described in the literature. Amongst these coumarins, three are new compounds: monobrominated coumarin 5 and bis-coumarins 7 and 9. The structures of the synthesized coumarins were confirmed by FTIR, NMR and HRMS-ESI. In vitro antimicrobial evaluation of these coumarins against strains of twelve bacteria and four fungi revealed their bactericidal and fungicidal properties, with increased antibacterial activity for monocoumarins and improved antifungal activity for bis-coumarins. It was also found that the antibacterial activity was enhanced by the etheric bond, Br atom and alkyl chain and reduced by the ester bonds at position 3 of the pyrone ring or an additional coumarin unit, while the antifungal activity was reinforced by ester bonds and deactivated by the Br atom. For the first time, the in silico investigations of such coumarins were carried out and it was observed that they are less toxic, suitable for oral administration with good permeability through cell membrane, are able to circulate freely in the bloodstream and cross Blood-Brain-Barriers. Moreover, their molecular docking in DNA indicated stable coumarin-DNA complexes with good scores. The results of molecular dynamics simulations performed for 200 ns revealed the rigidity and stability of bis-coumarins (7-9) in the DNA binding pocket and predict that they are potent binders.Communicated by Ramaswamy H. Sarma.

The risk of vector transmission of Trypanosoma cruzi remains high in the State of Paraná

BACKGROUND Monitoring and analysing the infection rates of the vector of Trypanosoma cruzi, that causes Chagas disease, helps assess the risk of transmission. OBJECTIVES A study was carried out on triatomine in the State of Paraná, Brazil, between 2012 and 2021 and a comparison was made with a previous study. This was done to assess the risk of disease transmission. METHODS Ecological niche models based on climate and landscape variables were developed to predict habitat suitability for the vectors as a proxy for risk of occurrence. FINDINGS A total of 1,750 specimens of triatomines were recorded, of which six species were identified. The overall infection rate was 22.7%. The areas with the highest risk transmission of T. cruzi are consistent with previous predictions in municipalities. New data shows that climate models are more accurate than landscape models. This is likely because climate suitability was higher in the previous period. MAIN CONCLUSION Regardless of uneven sampling and potential biases, risk remains high due to the wide presence of infected vectors and high environmental suitability for vector species throughout the state and, therefore, improvements in public policies aimed at wide dissemination of knowledge about the disease are recommended to ensure the State remains free of Chagas disease.

Supportive care decision-making processes of persons with dementia and their caregivers.

Little is known about the decision-making processes around seeking more supportive care for dementia. Persons with dementia are often left out of decision-making regarding seeking more supportive care as their dementia progresses. This paper provides a description of findings from the Decision-making in Alzheimer's Research project (DMAR) investigating the process of decision-making about transitions to more supportive care. We conducted 61 qualitative interviews with two stakeholder groups: 24 persons with dementia, and 37 informal caregivers to explore supportive care decisions and associated decision-making factors from the perspectives of persons with dementia and their caregivers. We identified four main decisions that persons with dementia and their informal caregivers played a role in: (1) sharing household responsibilities; (2) limiting routine daily activities; (3) bringing in formal support; and (4) moving to a care facility. Based on our findings we developed a schematized roadmap of decision-making that we used to guide the discussion of our findings. Four crosscutting themes emerged from our analysis: unknowns and uncertainties, maintaining life as you know it, there's no place like home and resource constraints. These results will be incorporated into the development of instruments whose goal is to identify preferences of persons with dementia and their caregivers, in order to include persons with dementia in care decisions even as their dementia progresses.

In vitro and in silico studies of antibacterial activities of secofriedelane derivatives from Senna alata (L) Roxb.

In this study, six compounds were obtained from a methanolic extract of air-dried leaves of Senna alata and one of them, a triterpenoid (secofriedelane) named as 7-(2-carboxyethyl)-3, 4b, 6a, 8, 10a, 12a-hexamethyl-8-vinyloctadecahydrochrysene-3-carboxylic acid (5) was isolated for the first time from this plant. Then, its chemical structure was detailed and characterised by FT-IR, 1H and 13C- NMR and ESI-MS. Besides, two chemical-modified derivatives of secofriedelane (5a, 5b) were synthesised by methylation and allylation reactions, respectively, and their in vitro antibacterial activities were also evaluated. The results revealed that all the triterpenes showed, against gram-positive and -negative bacterial strains, good and moderate antibacterial activities with bactericidal effects that were enhanced by the methyl groups and altered with the allyl ones. Moreover, the molecular docking results of 5, 5a and 5b in the DNA gyrase (2XCT) active site showed that triterpene 5 has a good score very close to reference (ciprofloxacin).

Antigen Specific T Cells in People with Obesity at Five Months Following ChAdOx1 COVID-19 Vaccination

Background/ObjectivesPeople with obesity (PWO) face an increased risk of severe outcomes from COVID-19, including hospitalisation, ICU admission and death. Obesity has been seen to impair immune memory following vaccination against influenza, hepatitis B, tetanus, and rabies. Little is known regarding immune memory in PWO following COVID-19 adenovirus vector vaccination. Subjects/MethodsWe investigated SARS-CoV-2 specific T cell responses in 50 subjects, five months following a two-dose primary course of ChAdOx1 nCoV-19 (AZD1222) vaccination. We further divided our cohort into PWO (n=30) and matched controls (n=20). T cell (CD4+, CD8+) cytokine responses (IFN{gamma}, TNF) to SARS-CoV-2 spike peptide pools were determined using multicolour flow cytometry. ResultsCirculating T cells specific for SARS-CoV-2 were readily detected across our cohort, with robust responses to spike peptide stimulation across both T cell lines. PWO and controls had comparable levels of both CD4+ and CD8+ SARS-CoV-2 spike specific T cells. Polyfunctional T cells - associated with enhanced protection against viral infection - were detected at similar frequencies in both PWO and controls. ConclusionsThese data indicate that PWO who have completed a primary course of ChAdOx1 COVID-19 vaccination have robust, durable, and functional antigen specific T cell immunity that is comparable to that seen in people without obesity.

Challenges and opportunities in conducting research with older adults with dementia during COVID-19 and beyond.

The coronavirus disease 19 (COVID-19) pandemic has created significant and new challenges for the conduct of clinical research involving older adults with Alzheimer's disease and related dementias (ADRD). It has also stimulated positive adaptations in methods for engaging older adults with ADRD in research, particularly through the increased availability of virtual platforms. In this paper, we describe how we adapted standard in-person participant recruitment and qualitative data collection methods for virtual use in a study of decision-making experiences in older adults with ADRD. We describe key considerations for the use of technology and virtual platforms and discuss our experience with using recommended strategies to recruit a diverse sample of older adults. We highlight the need for research funding that supports the community-based organizations on which improving equity in ADRD research participation often depends.

Breakpoint modelling of temporal associations between non-pharmaceutical interventions and the incidence of symptomatic COVID-19 in the Republic of Ireland

BackgroundTo constrain propagation and mitigate the burden of COVID-19, most countries initiated and continue to implement several non-pharmaceutical interventions (NPIs), including national and regional lockdowns. In the Republic of Ireland, the first national lockdown was decreed on 23rd of March 2020, followed by a succession of restriction increases and decreases (phases) over the the following year. To date, the effects of these interventions remain unclear, and particularly within differing population subsets. The current study sought to assess the impact of individual NPI phases on COVID-19 transmission patterns within delineated population subgroups in the Republic of Ireland. Methods and FindingsConfirmed, anonymised COVID-19 cases occurring between the 29th of February 2020 and 30th November 2020 (n= 72,654) were obtained. Segmented modelling via breakpoint regression with multiple turning points was employed to identify structural breaks across sub-populations, including primary/secondary infections, age deciles, urban/commuter/rural areas, patients with underlying health conditions, and socio-demographic profiles. These were subsequently compared with initiation dates of eight overarching NPI phases. Five distinct breakpoints were identified. The first breakpoint, associated with a decrease in the daily COVID-19 incidence, was reported within 14 days of the first set of restrictions in mid-March 2020 for most population sub-groups. Results suggest that moderately strict NCIs were more effective than the strictest Phase 5 (National Lockdown). Divergences were observed across population sub-groups; lagged response times were observed among populations >80 years, residents of rural/ commuter regions, and cases associated with a below-median deprivation score. ConclusionsStudy findings suggest that many NPIs have been successful in decreasing COVID-19 incidence rates, however the strictest Phase 5 NPI was not. Moreover, NPIs were not equally successful across all sub-populations, with differing response times noted. Mitigation strategies and interventions may need to be increasingly bespoke, based on sub-population profiles and required responses.

Personal health information management among healthy older adults: Varying needs and approaches.

OBJECTIVE: With age, older adults experience a greater number of chronic diseases and medical visits, and an increased need to manage their health information. Technological advances in consumer health information technologies (HITs) help patients gather, track, and organize their health information within and outside of clinical settings. However, HITs have not focused on the needs of older adults and their caregivers. The goal of the SOARING (Studying Older Adults and Researching their Information Needs and Goals) Project was to understand older adult personal health information management (PHIM) needs and practices to inform the design of HITs that support older adults. MATERIALS AND METHODS: Drawing on the Work System Model, we took an ecological approach to investigate PHIM needs and practices of older adults in different residential settings. We conducted in-depth interviews and surveys with adults 60 years of age and older. RESULTS: We performed on-site in-person interview sessions with 88 generally healthy older adults in various settings including independent housing, retirement communities, assisted living, and homelessness. Our analysis revealed 5 key PHIM activities that older adults engage in: seeking, tracking, organizing, sharing health information, and emergency planning. We identified 3 major themes influencing older adults' practice of PHIM: (1) older adults are most concerned with maintaining health and preventing illness, (2) older adults frequently involve others in PHIM activities, and (3) older adults' approach to PHIM is situational and context-dependent. DISCUSSION: Older adults' approaches to PHIM are dynamic and sensitive to changes in health, social networks, personal habits, motivations, and goals. CONCLUSIONS: PHIM tools that meet the needs of older adults should accommodate the dynamic nature of aging and variations in individual, organizational, and social contexts.

Older adults' personal health information management: The role and perspective of various healthcare providers.

The management of personal health information (PHI) by older adults (OAs) takes place within a socio-technical context and requires the support of various stakeholders, including healthcare providers. This study investigates provider roles in supporting OA personal health information management (PHIM), barriers they face, and related design implications for health information technology (HIT). We interviewed 27 providers serving OAs in Seattle, WA. Providers support OA PHIM through medication management, interpreting HI, and providing resources. Barriers to OA PHIM described by providers include (1) challenges with communication between OAs, providers, and caregivers, (2) limited time and resources, and (3) limitations of tools such as secure messaging. Considering these barriers, provider roles, and the socio-technical context for HIT implementation, we recommend the design of HIT that facilitates communication across multiple provider types, integrates caregivers and patient-generated data, supports understanding of OA home environments, and offers credible health resources designed for OAs.

Surgical management of Staphylococcus capitis prosthetic valve infective endocarditis: Retrospective review of a 10-year single center experience and review of the literature.

BACKGROUND: Staphylococcus capitis (S. capitis) is a subtype of coagulase-negative staphylococci and a commensal of the skin of the human scalp and forehead. S. capitis has been occasionally reported in infective endocarditis and rarely in prosthetic valve endocarditis (PVE). The purpose of this report is to present the clinical course and the surgical management of a series of four patients with S. capitis PVE. METHODS: The medical records of 190 adult patients with a definite diagnosis of infective endocarditis by the Duke modified criteria and who underwent surgery at our center between January 2008 and December 2018 were retrospectively reviewed. RESULTS: There were four cases of S. capitis infective endocarditis among 190 patients. All were male with an average age of 70.25 years (range, 58-80 years). The four cases were PVE: 3 aortic (1 mechanical and 2 biological bioprostheses) and 1 mitral (bioprosthesis). Their mean Euroscore II was 32.43 (range, 9.19-50.8). Three patients had underlying diseases (diabetes mellitus=2, chronic obstructive pulmonary disease=3, chronic kidney disease=1, peripheral arterial disease=2, ischemic heart disease=1, dilated cardiomyopathy=1). Preoperative clinical presentation was characterized by the occurrence of sepsis in three patients and heart failure and sepsis in one patient. Two patients presented with vegetation (mitral bioprosthesis, aortic bioprosthesis). A prosthetic dehiscence was present in all patients, and two presented with a localized annular abscess. All but one patient received triple antibiotic treatment with vancomycin plus rifampicin plus gentamycin. Surgery was performed on an urgent basis in all patients, and the in-hospital mortality rate was 50%. CONCLUSIONS: While limited by the small number of patients, our series highlights the aggressive clinical course of S. capitis PVE with a mortality rate close to that of Staphylococcus aureus PVE. Therefore, early surgical management is recommended to improve the clinical outcome of this serious disease.

Older Adult Health-Related Support Networks: Implications for the Design of Digital Communication Tools.

BACKGROUND AND OBJECTIVES: Digital communication tools facilitate the provision of health-related social support to older adults. However, little is known about what design features make such tools most useful and feasible. The purpose of this study was to describe health-related social support networks of older adults and outline recommendations for the design of tools that facilitate the giving and receiving of support. RESEARCH DESIGN AND METHODS: We collected data through validated instruments and semistructured qualitative interviews with 88 older adults. We calculated descriptive statistics for the quantitative data and analyzed qualitative data using directed content analysis. RESULTS: Health-related support networks described by our sample of generally healthy older adults varied in size from 0 to 10 members. Some networks did not include any family members, and others did not include any friends. Seventy-four percent of network members lived in the same state as the older adult participant, but only 15% of them lived with the participant. Emotional support was the main type of health-related support provided, followed by instrumental, informational, and appraisal support. DISCUSSION AND IMPLICATIONS: Health-related support networks of older adults are varied and complex. Our results suggest that digital communication tools to promote and leverage support from network members should facilitate the involvement of friends and family regardless of their physical location, allow for the transparent allocation of concrete tasks to prevent overburdening any one network member, and facilitate sharing of personal health information with family and friends while ensuring privacy and autonomy.

Recruiting older adult participants through crowdsourcing platforms: Mechanical Turk versus Prolific Academic.

BACKGROUND: Recruiting older adults (OA) into research is challenging. OBJECTIVE: To assess the feasibility of using two crowdsourcing platforms, Amazon's Mechanical Turk (MTurk) and Prolific Academic (ProA), as efficient and low-cost venues for recruiting survey participants aged 65 and older. METHODS: We developed an online survey to investigate and compare the demographics, technology use, and motivations for research participation of OA on MTurk and ProA. Qualitative responses, response time, word count, and recruitment costs were analyzed. RESULTS: We recruited 97 OA survey participants on both MTurk and ProA. Participants were similar in terms ofdemographics, technology usage, and motivations for participation (topic interest and payment). CONCLUSION: Both crowdsourcing platforms are useful for rapid and low-cost recruitment of OA. The OA recruitment process was more efficient with ProA. Crowdsourcing platforms are potential sources of OA research participants; however, the pool is limited to generally healthy, technologically active, and well-educated older adults.

Home Care Nurses' Perspectives Regarding Health Information Management Among Older Adults.

Aging is associated with comorbidities and increased utilization of healthcare services, which results in a large amount of personal health information (PHI) to manage. Older adults often have difficulty managing this increased load of health information. Although many home healthcare nurses (HCNs) provide assistance to older adults after discharge from medical facilities, little is known about HCNs' experiences with older adults regarding the management and transfer of PHI in their homes. The purpose of this qualitative study was to 1) determine how HCNs obtain and provide health information, 2) describe the perspective of HCNs regarding older adult PHI, and 3) identify the potential role of technology in older adult health information transfer. We conducted and analyzed semistructured phone interviews with 17 HCNs from two home healthcare agencies. Five thematic areas emerged from interviews with HCNs: 1) common practices of obtaining health information; 2) barriers to obtaining health information; 3) ideal ways to obtain and provide health information; 4) use of patient portals; and 5) HCNs' use of technology for health information exchange. Most HCNs reported that it would be difficult for older adult patients to update their PHI without assistance, but HCNs lack the time and resources to assist older adults in PHI management activities.

Personal Health Information Management Practices of Older Adults: One Size Does Not Fit All.

Older adults are the largest consumers of health care, have the greatest number of chronic conditions, and generate the greatest amount of health data. Yet, information systems designed to aid health information management do not align with their needs and practices. We describe a process of identifying the personal health information management (PHIM) activities and objectives of older adults (60 years and older) from different residential settings.

Connected Personas: Translating the Complexity of Older Adult Personal Health Information Management for Designers of Health Information Technologies.

Human-centered design (HCD) can be used to communicate research study findings to designers of health information technologies (HIT). We used the HCD approach to develop personas, scenarios, and design guidelines for designers with the aim that it would lead to new HIT designs that support the autonomy and health of older adults. The foundation of the personas, scenarios, and design guidelines was a study that focused on understanding how older adults manage their health information and the role that stakeholders play in that process. In this paper, we describe how we carried out a HCD approach and how it led us to expand the persona process to create a network of connected personas. The connected personas allowed us to show the complexities of personal health information management for older adults and emphasize the importance of relationships with family, friends, and providers.

Highly disordered histone H1-DNA model complexes and their condensates.

Disordered proteins play an essential role in a wide variety of biological processes, and are often posttranslationally modified. One such protein is histone H1; its highly disordered C-terminal tail (CH1) condenses internucleosomal linker DNA in chromatin in a way that is still poorly understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that correlates with changes in the chromatin condensation level. Here we present a model system that recapitulates key aspects of the in vivo process, and also allows a detailed structural and biophysical analysis of the stages before and after condensation. CH1 remains disordered in the DNA-bound state, despite its nanomolar affinity. Phase-separated droplets (coacervates) form, containing higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine residues, spaced along the length of the tail, has little effect on the local properties of the condensate. However, it dramatically alters higher-order structure in the coacervate and reduces partitioning to the coacervate phase. These observations show that disordered proteins can bind tightly to DNA without a disorder-to-order transition. Importantly, they also provide mechanistic insights into how higher-order structures can be exquisitely sensitive to perturbation by posttranslational modifications, thus broadening the repertoire of mechanisms that might regulate chromatin and other macromolecular assemblies.

Monitoring for change: the role of family and friends in helping older adults manage personal health information.

Objective: Although family and friends (FF) often play a significant support role in the health of older adults (OA), we know little about their role in personal health information management (PHIM). To address this gap and inform the design of PHIM tools, we describe the work, needs, and barriers of FF in the context of PHIM for OAs. Methods: We conducted semi-structured telephone interviews with 52 FF identified by OA as being important in their health and PHIM. We analyzed interview transcripts for themes about FF information work, barriers, and support needs. Results: FF play a supportive role in OA health maintenance, medical encounters, decision making, and daily activities. Monitoring, the ongoing process of seeking information related to the OA status, emerged as a key activity comprised of 3 phases: detection, interpretation, and action. Barriers to monitoring included OA choices and constraints, FF constraints, and difficulty with technological tools, resources, health information exchange between providers, social network dynamics, and physical distance. Conclusions: FF frequently monitor for change in OA well-being, seeking up-to-date information to facilitate support of OA PHIM. Health information technology tools designed for FF can support all phases of monitoring by providing: (1) timely and granular levels of access to OA health information as the OA ages; (2) tailored health education for FF that is based on OA clinical data; and (3) networking platforms that integrate delegation, volunteering, and relevant resources, along with tools to facilitate support of OA appointment calendars and medication management. Such tools could reduce the burden of PHIM for OA and their loved ones.

Iatrogenic risk factors associated with hospital readmission of elderly patients: A matched case-control study using a clinical data warehouse.

WHAT IS KNOWN: Hospital readmission within 30 days of patient discharge has become a standard to judge the quality of hospitalizations. It is estimated that 14% of the elderly, people over 75 years old or those over 65 with comorbidities, are at risk of readmission, of which 23% are avoidable. It may be possible to identify elderly patients at risk of readmission and implement steps to reduce avoidable readmissions. OBJECTIVE: The aim of this study was to identify iatrogenic risk factors for readmission. The secondary objective was to evaluate the rate of drug-related readmissions (DRRs) among all readmissions and compare it to the rate of readmissions for other reasons. METHODS: We conducted a retrospective, matched, case-control study to identify non-demographic risk factors for avoidable readmission, specifically DRRs. The study included patients hospitalized between 1 September 2014 and 31 October 2015 in an 800-bed university hospital. We included patients aged 75 and over. Cases consisted of patients readmitted to the emergency department within 30 days of initial discharge. Controls did not return to the emergency department within 30 days. Cases and controls were matched on sex and age because they are known as readmissions risk factors. After comparison of the mean or percentage between cases and controls for each variable, we conducted a conditional logistic regression. RESULTS: The risk factors identified were an emergency admission at the index hospitalization, returning home after discharge, a history of unplanned readmissions and prescription of nervous system drugs. Otherwise, 11.4% of the readmissions were DRRs, of which 30% were caused by an overdose of antihypertensive. The number of drugs at readmission was higher, and potentially inappropriate medications were more widely prescribed for DRRs than for readmissions for other reasons. WHAT IS NEW AND CONCLUSION: In this matched case-control retrospective study, after controlling for gender and age, we identified the typical profile of elderly patients at risk of readmission. These patients had an unplanned admission at the index hospitalization and prescribed nervous system drugs at discharge from the index admission; they have a history of unplanned readmission within 30 days and return home after discharge.

[Blood management in geriatric hospitalized population]. / Épargne transfusionnelle dans la population âgée hospitalisée.

INTRODUCTION: In France, nearly 50% of patients transfused in packed red blood cells are 75 or older. The benefit of restrictive transfusion policies is no longer to be demonstrated, but the practices are still far from it. The objective of our study was to show the impact of a decision support tool on transfusion practices, specifically in a hospitalized elderly population. METHOD: A clinical decision support, validated in the improvement of practices, was created, based on the latest transfusion recommendations of 2014. Our study was interventional, monocentric, within the departments of internal medicine and geriatrics of a university hospital from February to July 2016. The clinical decision support was available for any request of transfusion of packed red blood cells for 75 years old or older patient who was hospitalized in one of these two services. RESULTS: There were 134 transfusions out of 173 for which the prescriber used our tool. Comparing 2016 with the previous two years, our tool decreased the rate of packed red blood cells delivered by 11% compared to 2014 (P<0.005), but there was no significant difference compared to 2015. It has also reduced the transfusion rate of multi-unit transfusions by 35% compared with 2014 and by 29% compared with 2015 (P<0.005). CONCLUSION: Our tool, applied specifically to the elderly, is useful to improve transfusion practices and requires to be validated on a larger scale.