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IntroductionThe number of American Indian and Alaska Native (AI/AN) elders is expected to double by 2060. Thus it is imperative to retain AI/AN participants in longitudinal research studies to identify novel risk factors and potential targets for intervention for Alzheimer's disease and related dementias in these communities.MethodsThe National Alzheimer's Coordinating Center houses uniformly collected longitudinal data from the network of National Institute on Aging (NIA)-funded Alzheimer's Disease Research Centers (ADRCs). We used logistic regression to quantify participant retention at 43 ADRCs, comparing self-identified AI/AN participants to non-Hispanic White (NHW) participants, adjusting for potential confounding factors including baseline diagnosis, age, sex, education, and smoking.ResultsThe odds of AI/AN participant retention at the first follow-up visit were significantly lower than those for NHW participants (adjusted odds ratio [aOR]: 0.599; 95%: 0.46-0.78; p

Abstract Cardiovascular diseases, resulting from the deposition of clots in blood vessels, are the leading cause of death worldwide. Fibrinolytic enzymatic activity can catalyze blood clot degradation. Findings show that 36 fungal isolates recovered from Caatinga soils have the potential to produce fibrinolytic protease under submerged conditions. About 58 % of the isolates displayed fibrinolytic activity above 100 U/mL, with Mucor subtilissimus UCP 1262 being the most active. The protease was biochemically and biophysically characterized, showing that the enzyme had a high affinity for SAApNA substrate and was significantly inhibited by fluoride methyl phenyl sulfonyl-C7H7FO2S, suggesting that it is a chymotrypsin-like serine protease. The highest enzyme activity was detected at pH 5.0 and 28 °C. This fibrinolytic protease’s far-UV circular dichroism (CD) showed that its secondary structure was primarily α-helical. The purified fibrinolytic enzyme may represent a novel therapeutic agent for treating thrombosis. At temperatures above 65 °C, the enzyme lost all its secondary structure. Its melting temperature was 58.1 °C, the denaturation enthalpy 85.1 kcal/mol, and the denaturation entropy 0.26 kcal/K∙mol.

Given telemetry datasets (e.g., GPS location, speed, direction, distance.), the Older Driver Classification (ODC) problem identifies two groups of drivers: normal and abnormal. The ODC problem is essential in many societal applications, including road safety, insurance risk assessment, and targeted interventions for elderly drivers with dementia or Mild Cognitive Impairment (MCI). The problem is challenging because of the volume and heterogeneity of temporally-detailed vehicle datasets. This paper proposes a novel spatial deep-learning approach that leverages Grid-Index based data augmentation to enhance the detection of abnormal driving behaviors. Through extensive experiments and a real-world case study, the proposed approach consistently identifies abnormal drivers with high accuracy. The findings demonstrate the potential of grid-based methods to improve telematics-based driving behavior analysis significantly. This approach offers valuable implications for enhancing road safety measures, optimizing insurance risk assessments, and developing targeted interventions for at-risk drivers.

Background: Models of muscle cell culture allow simple manipulation to optimize gene transfer experiments, offering a significant opportunity to model muscle effects by allowing precise control of the cell culture environment in a cost-effective manner. Often, gene transfer is performed in myoblasts, which are then differentiated into myotubes, a skeletal muscle model. In this study, we aimed to compare the efficiency of direct transfection of differentiated myotubes by chemical and physical plasmid methods. Methods: Differentiated myotubes were transfected with reporter plasmids. Transfection efficiency and cell death were quantified. Proinflammatory proteins are produced by cells and tissues after DNA transfection; therefore, the secretion of proinflammatory chemokines was quantified. Results: In this study, we demonstrate that C2C12 myotubes can be effectively transfected using multiple methods. While a chemical method did not cause cell death, myotubes were not efficiently transfected. Electroporation delivery produced a higher transfection efficiency coupled with higher cell death. A subset of proinflammatory chemokine proteins was secreted, which replicated secretion by skeletal muscle. Discussion: These results suggest that differentiated myotubes can be directly transfected invitro, which may represent a useful experimental model. However, more studies are needed to assess the value of this model in predicting invivo responses.

Abstract Background Driving is a complex behavior that may be affected by early changes in the cognition of older individuals. Early changes in driving behavior may include driving more slowly, making fewer and shorter trips, and errors related to inadequate anticipation of situations. Sensor systems installed in older drivers’ vehicles may detect these changes and may generate early warnings of possible changes in cognition. Method A naturalistic longitudinal design is employed to obtain continuous information on driving behavior that will be compared with the results of extensive cognitive testing conducted every 3 months for 3 years. A driver facing camera, forward facing camera, and telematics unit are installed in the vehicle and data downloaded every 3 months when the cognitive tests are administered. Results Data processing and analysis will proceed through a series of steps including data normalization, adding information on external factors (weather, traffic conditions), and identifying critical features (variables). Traditional prediction modeling results will be compared with Recurring Neural Network (RNN) approach to produce Driver Behavior Indices (DBIs), and algorithms to classify drivers within age, gender, ethnic group membership, and other potential group characteristics. Conclusion It is well established that individuals with progressive dementias are eventually unable to drive safely, yet many remain unaware of their cognitive decrements. Current screening and evaluation services can test only a small number of individuals with cognitive concerns, missing many who need to know if they require treatment. Given the increasing number of sensors being installed in passenger vehicles and pick-up trucks and their increasing acceptability, reconfigured in-vehicle sensing systems could provide widespread, low-cost early warnings of cognitive decline to the large number of older drivers on the road in the U.S. The proposed testing and evaluation of a readily and rapidly available, unobtrusive in-vehicle sensing system could provide the first step toward future widespread, low-cost early warnings of cognitive change for this large number of older drivers in the U.S. and elsewhere.

(1) Background: Polysaccharide films are promising vehicles for the delivery of bioactive agents such as collagenases, as they provide controlled release at the wound site, facilitating tissue regeneration. This study aimed to investigate the physicochemical properties of Cassia grandis polysaccharide films with immobilized collagenase from Streptomyces parvulus (DPUA/1573). (2) Methods: Galactomannan was extracted from Cassia grandis seeds for film production with 0.8% (w/v) galactomannan and 0.2% (v/v) glycerol with or without collagenases. The films underwent physical-chemical analyses: Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), color and opacity (luminosity-L*, green to red-a*, yellow to blue-b*, opacity-Y%), moisture content, water vapor permeability (WVP), thickness, contact angle, and mechanical properties. (3) Results: The results showed similar FTIR spectra to the literature, indicating carbonyl functional groups. Immobilizing bioactive compounds increased surface roughness observed in SEM. TGA indicated a better viability for films with immobilized S. parvulus enzymes. Both collagenase-containing and control films exhibited a bright-yellowish color with slight opacity (Y%). Mechanical tests revealed decreased rigidity in PCF (−25%) and SCF (−41%) and increased deformability in films with the immobilized bioactive compounds, PCF (234%) and SCF (295%). (4) Conclusions: Polysaccharide-based films are promising biomaterials for controlled composition, biocompatibility, biodegradability, and wound healing, with a potential in pharmacological applications.

Germline-encoded pattern recognition receptors [PRRs] in mammalian cells function in the detection of molecular patterns associated with pathogen invasion or cellular damage. A PRR subset is activated by the atypical presence and location of double-stranded RNA [dsRNA] or its synthetic analogue polyinosinic-polycytidylic acid [poly(I:C)], triggering pro-inflammatory signalling and death in many cell types. Poly(I:C) has been tested as a sole or combination cancer therapy in preclinical studies and clinical trials. The purpose of this study was to evaluate the effects of poly(I:C) transfection via electroporation on cell lines from a cancer of epithelial origin, 4T1 mammary carcinoma, and a cancer of mesenchymal origin, WEHI 164 fibrosarcoma. The effects of the poly(I:C) delivery on cell metabolism implicate the induction of cell death. A pro-inflammatory response was demonstrated by mRNA upregulation and the secretion of Type I interferon and several cytokines and chemokines. The mRNAs of dsRNA sensor DExD/H-box helicase 58/retinoic acid-inducible gene I protein [Ddx58/RIG-I] and sensor/co-sensor DEAH-box helicase 9 [Dhx9] were not regulated, but the mRNAs of RNA sensors toll-like receptor 3 [TLR3], interferon-induced with helicase C domain 1/melanoma differentiation-associated protein 5 [Ifih1/MDA5] and Z-DNA binding protein 1 [Zbp1] and co-sensors DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 [Ddx60] and interferon-inducible protein 204 [Ifi204] were upregulated in both cell lines. The mRNAs encoding signalling pathways components were present or upregulated in both cell types. These data demonstrate that RNA sensing effects can be amplified by electroporation delivery, potentially expanding the practicality of this immunotherapeutic approach.

Gene therapy approaches may target skeletal muscle due to its high protein-expressing nature and vascularization. Intramuscular plasmid DNA (pDNA) delivery via pulsed electric fields (PEFs) can be termed electroporation or electrotransfer. Nonviral delivery of plasmids to cells and tissues activates DNA-sensing pathways. The central signaling complex in cytosolic DNA sensing is the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING). The effects of pDNA electrotransfer on the signaling of STING, a key adapter protein, remain incompletely characterized. STING undergoes several post-translational modifications which modulate its function, including palmitoylation. This study demonstrated that in mouse skeletal muscle, STING was constitutively palmitoylated at two sites, while an additional site was modified following electroporation independent of the presence of pDNA. This third palmitoylation site correlated with STING polymerization but not with STING activation. Expression of several palmitoyl acyltransferases, including zinc finger and DHHC motif containing 1 (zDHHC1), coincided with STING activation. Expression of several depalmitoylases, including palmitoyl protein thioesterase 2 (PPT2), was diminished in all PEF application groups. Therefore, STING may not be regulated by active modification by palmitate after electroporation but inversely by the downregulation of palmitate removal. These findings unveil intricate molecular changes induced by PEF application.

Bruce Springsteen has repeatedly reinvented himself through a long process of vocational discernment that often draws on a distinctly Catholic imagination. In this process, he has repeatedly explored complex relationships between religious faith, American identity, older traditions of popular music, and race. At pivotal moments in his career, his vocational discernment has led him to the work of musicians raised in Pentecostal and Holiness churches. From this perspective, this essay explores the relationship between Springsteen's "Land of Hope and Dreams" and Sister Rosetta Tharpe's "This Train," the gospel-inspired song that she first recorded in 1938. Both of these songs arise from Christian imaginations nurtured in local communities of faith—in Tharpe's case, a congregation of the Church of God in Christ in Cotton Plant, Arkansas, and in Springsteen's case, an immigrant Catholic parish in Freehold, New Jersey. Tharpe draws directly from Holiness traditions, combining her belief in a distinctly embodied version of sanctification with the religious practice of tongues speaking, most powerfully in her guitar improvisations. Like Springsteen, Tharpe brings to contemporary music the performance dynamics of Holiness and Pentecostal preachers, possessed by the Holy Spirit, accompanied by a choir, before an enraptured congregation. In these respects, the resemblances between these two songs are not a matter of "direct influence." Rather, these resemblances provide a critical test case in a kind of artistic influence that is multi-directional, unpredictable, and often subversive. They arise from shared sources, particularly a long tradition of train songs that find their way into country and gospel music. Even more important, they arise from similarities in the faith traditions—and the religious imaginations—of the two musicians. From this perspective, Tharpe and Springsteen both belong to a larger tradition of "gospel redemption" in American popular music, which becomes particularly evident when "Land of Hope and Dreams" ends with a cover of Curtis Mayfield's "People Get Ready," invoking the ideals of the early civil rights movement and, at the same time, our repeated failures to achieve these ideals. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study aims to evaluate a leadership fellowship program through perspectives of Ethiopian women medical faculty participants. METHODS: An intensive two-week leadership development fellowship was designed for women faculty from Ethiopian medical schools and conducted from 2011-2015 at the University of Wisconsin-School of Medicine and Public Health in Madison, Wisconsin. Nine Ethiopian women working in early- or mid-level academic positions were selected. Semi-structured interviews were conducted with the fellows. Transcripts were reviewed through qualitative analysis to assess the perceived impact of the training on their careers. Three male academic leaders were interviewed to solicit feedback on the program. RESULTS: Eight of 9 fellows were interviewed. Themes describing the benefits of the fellowship included: increased awareness of gender inequities; enhanced motivation for career advancement; increased personal confidence; and improved leadership skills. Fellows provided suggestions for future training and scaling up efforts to promote gender equity. Male leaders described the benefits of men promoting gender equity within academic health centers. CONCLUSIONS: This paper provides evidence that targeted brief training programs can enhance womens motivation and skills to become effective leaders in academic medicine in Ethiopia. Promoting gender equity in academic medicine is an important strategy to address health workforce shortages and to provide professional role models for female students in the health professions.

BackgroundBuilding the capacity of local health systems to provide high-quality, self-sustaining medical education and health care is the central purpose for many global health partnerships (GHPs). Since 2001, our global partner consortium collaborated to establish Family Medicine in Ethiopia; the first Ethiopian family physicians graduated in February 2016.MethodsThe authors, representing the primary Ethiopian, Canadian, and American partners in the GHP, identified obstacles, accomplishments, opportunities, errors, and observations from the years preceding residency launch and the first 3 years of the residency.ResultsCommon themes were identified through personal reflection and presented as lessons to guide future GHPs. LESSON 1: Promote Family Medicine as a distinct specialty. LESSON 2: Avoid gaps, conflict, and redundancy in partner priorities and activities. LESSON 3: Building relationships takes time and shared experiences. LESSON 4: Communicate frequently to create opportunities for success. LESSON 5: Engage local leaders to build sustainable, long-lasting programs from the beginning of the partnership.ConclusionsGHPs can benefit individual participants, their organizations, and their communities served. Engaging with numerous partners may also result in challenges-conflicting expectations, misinterpretations, and duplication or gaps in efforts. The lessons discussed in this article may be used to inform GHP planning and interactions to maximize benefits and minimize mishaps.

Cross-cultural differences in the association between neuropsychiatric symptoms and Alzheimer's disease (AD) biomarkers are not well understood. This study aimed to (1) compare depressive symptoms and frequency of reported apathy across diagnostic groups of participants with normal cognition (CN), mild cognitive impairment (MCI), and dementia, as well as ethnic groups of Hispanic Americans (HA) and European Americans (EA); (2) evaluate the relationship between depression and apathy with Aβ deposition and brain atrophy. Statistical analyses included ANCOVAs, chi-squared, nonparametric tests, correlations, and logistic regressions. Higher scores on the Geriatric Depression Scale (GDS-15) were reported in the MCI and dementia cohorts, while older age corresponded with lower GDS-15 scores. The frequency of apathy differed across diagnoses within each ethnicity, but not when comparing ethnic groups. Reduced volume in the rostral anterior cingulate cortex (ACC) significantly correlated with and predicted apathy for the total sample after applying false discovery rate corrections (FDR), controlling for covariates. The EA group separately demonstrated a significant negative relationship between apathy and superior frontal volume, while for HA, there was a relationship between rostral ACC volume and apathy. Apathy corresponded with higher Aβ levels for the total sample and for the CN and HA groups. [ABSTRACT FROM AUTHOR]