Improving inpatient hyperglycaemia in non-critically ill adults in resident wards through audit and feedback.

Inpatient hyperglycaemia is associated with an increase in morbidity and mortality, number of rehospitalisations and length of hospitalisation. Although the advantages of proper glycaemic control in hospitalised patients with diabetes are well established, a variety of barriers limit accomplishment of blood glucose targets. Our primary aim was to decrease the number of glucose values above 180 mg/dL in non-critical care hospitalised patients using an audit and feedback intervention with pharmacy and internal medicine residents. A resident-led multidisciplinary team implemented the quality improvement (QI) project including conception, literature review, educating residents, iterative development of audit and feedback tools and data analysis. The multidisciplinary team met every 5 weeks and undertook three 'plan-do-study-act' cycles over an 8-month intervention period (August 2022 to March 2023) to educate residents on inpatient hyperglycaemia management, develop and implement an audit and feedback process and assess areas for improvement. We performed 1045 audits analysing 16 095 accu-checks on 395 non-duplicated patients. Most audits showed compliance with guidelines. The monthly run-on chart shows per cent of glucose values above 180 mg/dL in our non-ICU hospitalised patients and an overall pre-to-post comparison of 25.1%-23.0% (p value<0.05). The intervention was well accepted by residents evidenced by survey results. We did not meet our primary aim to reduce hyperglycaemia by 30% and this combined with the audits showing mostly compliance with guidelines suggests that prescribing behaviour was not a key driver of inpatient hyperglycaemia in our population. This internal medicine resident and pharmacy interprofessional collaboration with audit and feedback for inpatient hyperglycaemia was feasible, well accepted and had a statistically significant yet small improvement in inpatient hyperglycaemia. The project may be helpful to others wishing to explore inpatient hyperglycaemia, interprofessional QI with pharmacists, resident-led QI and audit and feedback.

Neuroprotective effect of the RNS60 in a mouse model of transient focal cerebral ischemia.

BACKGROUND: Stroke is a major cause of death, disability, and public health problems. Its intervention is limited to early treatment with thrombolytics and/or endovascular clot removal with mechanical thrombectomy without any available subacute or chronic neuroprotective treatments. RNS60 has reduced neuroinflammation and increased neuronal survival in several animal models of neurodegeneration and trauma. The aim here was to evaluate whether RNS60 protects the brain and cognitive function in a mouse stroke model. METHODS: Male C57BL/6J mice were subjected to sham or ischemic stroke surgery using 60-minute transient middle cerebral artery occlusion (tMCAo). In each group, mice received blinded daily administrations of RNS60 or control fluids (PNS60 or normal saline [NS]), beginning 2 hours after surgery over 13 days. Multiple neurobehavioral tests were conducted (Neurological Severity Score [mNSS], Novel Object Recognition [NOR], Active Place Avoidance [APA], and the Conflict Variant of APA [APAc]). On day 14, cortical microvascular perfusion (MVP) was measured, then brains were removed and infarct volume, immunofluorescence of amyloid beta (Aß), neuronal density, microglial activation, and white matter damage/myelination were measured. SPSS was used for analysis (e.g., ANOVA for parametric data; Kruskal Wallis for non-parametric data; with post-hoc analysis). RESULTS: Thirteen days of treatment with RNS60 reduced brain infarction, amyloid pathology, neuronal death, microglial activation, white matter damage, and increased MVP. RNS60 reduced brain pathology and resulted in behavioral improvements in stroke compared to sham surgery mice (increased memory-learning in NOR and APA, improved cognitive flexibility in APAc). CONCLUSION: RNS60-treated mice exhibit significant protection of brain tissue and improved neurobehavioral functioning after tMCAo-stroke. Additional work is required to determine mechanisms, time-window of dosing, and multiple dosing volumes durations to support clinical stroke research.

Cultural Competence Guides for COVID-19 Messaging in Hispanic Communities.

PURPOSE: The Rio Grande Valley in South Texas comprises 5% percent of Texas's population yet 17%of Texas's COVID-19 deaths. We aimed to address underlying mistrust and systemic racism in our Hispanic community that contributes to health inequities by developing a cultural competence guide for public health messaging. METHODS: We employed a mixed method design (e.g., focus groups, surveys, interviews) to develop and implement a cultural competence guide in an iterative community-informed process. We created a general cultural competence guide, one for the Hispanic community and one for the hard-of-hearing community. RESULTS: Our cultural competence guides provide an interpretation as to whether the message is culturally competent or requires revisions. The guides have the following five categories: content and clarity, emotions and values, audience and inclusivity, call to action, and gestalt. CONCLUSIONS: The Hispanic community needs more culturally competent public health messaging to address a key root cause of health inequities surrounding COVID-19. Our novel, concise guides can help organizations and individuals seeking to create culturally sensitive and, therefore, more effective public health messaging for Hispanic or deaf and hard-of-hearing communities.

Cerebrovascular disease promotes tau pathology in Alzheimer's disease.

Small vessel cerebrovascular disease, visualized as white matter hyperintensities on T2-weighted magnetic resonance imaging, contributes to the clinical presentation of Alzheimer's disease. However, the extent to which cerebrovascular disease represents an independent pathognomonic feature of Alzheimer's disease or directly promotes Alzheimer's pathology is unclear. The purpose of this study was to examine the association between white matter hyperintensities and plasma levels of tau and to determine if white matter hyperintensities and tau levels interact to predict Alzheimer's disease diagnosis. To confirm that cerebrovascular disease promotes tau pathology, we examined tau fluid biomarker concentrations and pathology in a mouse model of ischaemic injury. Three hundred ninety-one participants from the Alzheimer's Disease Neuroimaging Initiative (74.5 ± 7.1 years of age) were included in this cross-sectional analysis. Participants had measurements of plasma total-tau, cerebrospinal fluid beta-amyloid, and white matter hyperintensities, and were diagnosed clinically as Alzheimer's disease (n = 97), mild cognitive impairment (n = 186) or cognitively normal control (n = 108). We tested the relationship between plasma tau concentration and white matter hyperintensity volume across diagnostic groups. We also examined the extent to which white matter hyperintensity volume, plasma tau, amyloid positivity status and the interaction between white matter hyperintensities and plasma tau correctly classifies diagnostic category. Increased white matter hyperintensity volume was associated with higher plasma tau concentration, particularly among those diagnosed clinically with Alzheimer's disease. Presence of brain amyloid and the interaction between plasma tau and white matter hyperintensity volume distinguished Alzheimer's disease and mild cognitive impairment participants from controls with 77.6% and 63.3% accuracy, respectively. In 63 Alzheimer's Disease Neuroimaging Initiative participants who came to autopsy (82.33 ± 7.18 age at death), we found that higher degrees of arteriosclerosis were associated with higher Braak staging, indicating a positive relationship between cerebrovascular disease and neurofibrillary pathology. In a transient middle cerebral artery occlusion mouse model, aged mice that received transient middle cerebral artery occlusion, but not sham surgery, had increased plasma and cerebrospinal fluid tau concentrations, induced myelin loss, and hyperphosphorylated tau pathology in the ipsilateral hippocampus and cerebral hemisphere. These findings demonstrate a relationship between cerebrovascular disease, operationalized as white matter hyperintensities, and tau levels, indexed in the plasma, suggesting that hypoperfusive injury promotes tau pathology. This potential causal association is supported by the demonstration that transient cerebral artery occlusion induces white matter damage, increases biofluidic markers of tau, and promotes cerebral tau hyperphosphorylation in older-adult mice.

Protein targets of thiazolidinone derivatives in Toxoplasma gondii and insights into their binding to ROP18.

BACKGROUND: Thiazolidinone derivatives show inhibitory activity (IC50) against the Toxoplasma gondii parasite, as well as high selectivity with high therapeutic index. To disclose the target proteins of the thiazolidinone core in this parasite, we explored in silico the active sites of different T. gondii proteins and estimated the binding-free energy of reported thiazolidinone molecules with inhibitory effect on invasion and replication of the parasite inside host cells. This enabled us to describe some of the most suitable structural characteristics to design a compound derived from the thiazolidinone core. RESULTS: The best binding affinity was observed in the active site of kinase proteins, we selected the active site of the T. gondii ROP18 kinase, because it is an important factor for the virulence and survival of the parasite. We present the possible effect of a derivative of thiazolidinone core in the active site of T. gondii ROP18 and described some characteristics of substituent groups that could improve the affinity and specificity of compounds derived from the thiazolidinone core against T. gondii. CONCLUSIONS: The results of our study suggest that compounds derived from the thiazolidinone core have a preference for protein kinases of T. gondii, being promising compounds for the development of new drugs with potential anti-toxoplasmosis activity. Our findings highlight the importance of use computational studies for the understanding of the action mechanism of compounds with biological activity.