Pathological serum proteins with special reference to liver, heart and rheumatoid diseases

PART I Investigation of autoantibodies in the sera of patients suffering from hepatoceliular lesions.PART II The characterization of an antiglobulin present in the sera of certain patients following myocardial infarction; its comparison with and differentiation from the rheumatoid factor

Older Adults at Risk for Atrial Fibrillation Lack Knowledge and Confidence to Seek Treatment for Signs and Symptoms.

Early detection of atrial fibrillation (AF) is crucial for averting AF-related stroke and heart failure, but treatment is delayed when AF is not recognized. The critical need for early detection and treatment requires education to promote AF awareness. Knowledge deficits, attitudes, and beliefs about AF that should be addressed to improve awareness and reduce treatment-seeking delay in older adults at risk for developing AF have not been well documented. The purpose of this study was to describe knowledge, treatment-seeking attitudes, and beliefs about AF in adults ⩾ 65 years old and identify demographic characteristics associated with knowledge, attitudes, and beliefs. Patients with no history of AF recruited from an academic medical center were interviewed using the Knowledge, Attitudes, and Beliefs about Atrial Fibrillation Survey. Data were analyzed using descriptive statistics and independent t tests. Participants (N = 180) were 63% male with a mean age of ±3.± 6.0 years, and 52% held ⩾ 4-year college degree. About one third could not identify common symptoms of AF including palpitations (31%), chest pain (36%), dyspnea (30%), and fatigue (35%). A majority (84%) lacked confidence to recognize AF, and 58% were not sure when they should seek care for AF symptoms. Nearly a third (32%) believed palpitations are always present with AF, and 74% believed that low energy would not be their only symptom of AF. Higher scores for AF Symptom Knowledge (p = .02) were observed in females, and General Knowledge about AF was greater for younger participants (p < .001). Participants lacked knowledge and confidence to aid decision-making for treatment-seeking for symptoms of AF and held inaccurate beliefs about AF that could hinder early treatment-seeking. Programs to promote AF awareness should explain the spectrum of symptoms that may be manifested by AF and include action plans for responding to symptoms

DNA charge transport as a first step in coordinating the detection of lesions by repair proteins

Damaged bases in DNA are known to lead to errors in replication and transcription, compromising the integrity of the genome. We have proposed a model where repair proteins containing redox-active [4Fe-4S] clusters utilize DNA charge transport (CT) as a first step in finding lesions. In this model, the population of sites to search is reduced by a localization of protein in the vicinity of lesions. Here, we examine this model using single-molecule atomic force microscopy (AFM). XPD, a 5′-3′ helicase involved in nucleotide excision repair, contains a [4Fe-4S] cluster and exhibits a DNA-bound redox potential that is physiologically relevant. In AFM studies, we observe the redistribution of XPD onto kilobase DNA strands containing a single base mismatch, which is not a specific substrate for XPD but, like a lesion, inhibits CT. We further provide evidence for DNA-mediated signaling between XPD and Endonuclease III (EndoIII), a base excision repair glycosylase that also contains a [4Fe-4S] cluster. When XPD and EndoIII are mixed together, they coordinate in relocalizing onto the mismatched strand. However, when a CT-deficient mutant of either repair protein is combined with the CT-proficient repair partner, no relocalization occurs. These data not only indicate a general link between the ability of a repair protein to carry out DNA CT and its ability to redistribute onto DNA strands near lesions but also provide evidence for coordinated DNA CT between different repair proteins in their search for damage in the genome

Feasibility Testing of the Alert for AFib Intervention.

Improving early detection and treatment of atrial fibrillation (AF) is critical because untreated AF is a major contributor to stroke and heart failure. We sought to generate knowledge about the feasibility of conducting a randomized controlled trial to test the effect of the Alert for AFib intervention on knowledge, attitudes, and beliefs about treatment-seeking for signs and symptoms of AF. Adults ≥65 years old (96% White) at risk for developing AF were randomized to receive the Alert for AFib intervention ( n = 40) or an attention control session ( n = 40). Feasibility goals for recruitment, participant retention, adherence, perceived satisfaction and burden, and intervention fidelity were met. From baseline to study completion, knowledge ( p = .005) and attitudes ( p < .001) about treatment-seeking improved more in the intervention group compared with the control group. Results support testing the effectiveness of the Alert for AFib intervention in a large trial

STANDARDIZED PREDICTIVE TESTING: PRACTICES, POLICIES, AND OUTCOMES

The aims of this study were to describe current policy practice related to the use of the HESI™ Exit Exam in schools of nursing and to determine which policies result in higher HESI Exit Scores. Deans and directors of nursing schools that administered Elsevier HESI Exit Exam to students during the 2010 academic year were queried. Data were collected regarding students’ HESI Exit Exam results, national nursing licensure examination outcomes, and the schools’ standardized testing policies. A stratified random sample of schools and a total of 5438 student records were obtained, 3084 from Associate Degree (AD) and 2354 from Baccalaureate Degree (BD) programs. NCLEX®-RN outcomes were known for all but 316 (5.8%) students. Four standardized exam policy components were related to higher HESI Exit Exam scores. The study confirmed the robust predictive accuracy of the HESI Exit Exam. A national United States sample of BD and AD nursing programs has demonstrated that standardized end of program assessment results are related to faculty implementation strategies and certain policy components. Evidence-based policy strategies should be evaluated longitudinally to support policy decisions

Metal complexes for DNA-mediated charge transport

In all organisms, oxidation threatens the integrity of the genome. DNA-mediated charge transport (CT) may play an important role in the generation and repair of this oxidative damage. In studies involving long-range CT from intercalating Ru and Rh complexes to 5′-GG-3′ sites, we have examined the efficiency of CT as a function of distance, temperature, and the electronic coupling of metal oxidants bound to the base stack. Most striking is the shallow distance dependence and the sensitivity of DNA CT to how the metal complexes are stacked in the helix. Experiments with cyclopropylamine-modified bases have revealed that charge occupation occurs at all sites along the bridge. Using Ir complexes, we have seen that the process of DNA-mediated reduction is very similar to that of DNA-mediated oxidation. Studies involving metalloproteins have, furthermore, shown that their redox activity is DNA-dependent and can be DNA-mediated. Long range DNA-mediated CT can facilitate the oxidation of DNA-bound base excision repair proteins to initiate a redox-active search for DNA lesions. DNA CT can also activate the transcription factor SoxR, triggering a cellular response to oxidative stress. Indeed, these studies show that within the cell, redox-active proteins may utilize the same chemistry as that of synthetic metal complexes in vitro, and these proteins may harness DNA-mediated CT to reduce damage to the genome and regulate cellular processes

DNA Charge Transport for Sensing and Signaling

The DNA duplex is an exquisite macromolecular array that stores genetic information to encode proteins and regulate pathways. Its unique structure also imparts chemical function that allows it also to mediate charge transport (CT). We have utilized diverse platforms to probe DNA CT, using spectroscopic, electrochemical, and even genetic methods. These studies have established powerful features of DNA CT chemistry. DNA CT can occur over long molecular distances as long as the bases are well stacked. The perturbations in base stacking that arise with single base mismatches, DNA lesions, and the binding of some proteins that kink the DNA all inhibit DNA CT. Significantly, single molecule studies of DNA CT show that ground state CT can occur over 34 nm if the duplex is well stacked; one single base mismatch inhibits CT. The DNA duplex is an effective sensor for the integrity of the base pair stack. Moreover, the efficiency of DNA CT is what one would expect for a stack of graphite sheets: equivalent to the stack of DNA base pairs and independent of the sugar-phosphate backbone. Since DNA CT offers a means to carry out redox chemistry from a distance, we have considered how this chemistry might be used for long range biological signaling. We have taken advantage of our chemical probes and platforms to characterize DNA CT in the context of the cell. CT can occur over long distances, perhaps funneling damage to particular sites and insulating others from oxidative stress. Significantly, transcription factors that activate the genome to respond to oxidative stress can also be activated from a distance through DNA CT. Numerous proteins maintain the integrity of the genome and an increasing number of them contain [4Fe-4S] clusters that do not appear to carry out either structural or enzymatic roles. Using electrochemical methods, we find that DNA binding shifts the redox potentials of the clusters, activating them towards oxidation at physiological potentials. We have proposed a model that describes how repair proteins may utilize DNA CT to efficiently search the genome for lesions. Importantly, many of these proteins occur in low copy numbers within the cell, and thus a processive mechanism does not provide a sufficient explanation of how they find and repair lesions before the cell divides. Using atomic force microscopy and genetic assays, we show that repair proteins proficient at DNA CT can relocalize in the vicinity of DNA lesions and can cooperate in finding lesions within the cell. Conversely, proteins defective in DNA CT cannot relocalize in the vicinity of lesions and do not assist other proteins involved in repair within the cell. Moreover such genetic defects are associated with disease in human protein analogues. As we continue to unravel this chemistry and discover more proteins with redox cofactors involved in genome maintenance, we are learning more regarding opportunities for long range signaling and sensing, and more examples of DNA CT chemistry that may provide critical functions within the cell

Using data science as a community advocacy tool to promote equity in urban renewal programs: An analysis of Atlanta's Anti-Displacement Tax Fund

Cities across the United States are undergoing great transformation and urban growth. Data and data analysis has become an essential element of urban planning as cities use data to plan land use and development. One great challenge is to use the tools of data science to promote equity along with growth. The city of Atlanta is an example site of large-scale urban renewal that aims to engage in development without displacement. On the Westside of downtown Atlanta, the construction of the new Mercedes-Benz Stadium and the conversion of an underutilized rail-line into a multi-use trail may result in increased property values. In response to community residents' concerns and a commitment to development without displacement, the city and philanthropic partners announced an Anti-Displacement Tax Fund to subsidize future property tax increases of owner occupants for the next twenty years. To achieve greater transparency, accountability, and impact, residents expressed a desire for a tool that would help them determine eligibility and quantify this commitment. In support of this goal, we use machine learning techniques to analyze historical tax assessment and predict future tax assessments. We then apply eligibility estimates to our predictions to estimate the total cost for the first seven years of the program. These forecasts are also incorporated into an interactive tool for community residents to determine their eligibility for the fund and the expected increase in their home value over the next seven years.Comment: Presented at the Data For Good Exchange 201

Charge Photoinjection in Intercalated and Covalently Bound [Re(CO)_(3)(dppz)(py)]^(+)–DNA Constructs Monitored by Time-Resolved Visible and Infrared Spectroscopy

The complex [Re(CO)_(3)(dppz)(py′-OR)]+ (dppz = dipyrido[3,2-a:2′,3′-c]phenazine; py′-OR = 4-functionalized pyridine) offers IR sensitivity and can oxidize DNA directly from the excited state, making it a promising probe for the study of DNA-mediated charge transport (CT). The behavior of several covalent and noncovalent Re–DNA constructs was monitored by time-resolved IR (TRIR) and UV/visible spectroscopies, as well as biochemical methods, confirming the long-range oxidation of DNA by the excited complex. Optical excitation of the complex leads to population of MLCT and at least two distinct intraligand states. Experimental observations that are consistent with charge injection from these excited states include similarity between long-time TRIR spectra and the reduced state spectrum observed by spectroelectrochemistry, the appearance of a guanine radical signal in TRIR spectra, and the eventual formation of permanent guanine oxidation products. The majority of reactivity occurs on the ultrafast time scale, although processes dependent on slower conformational motions of DNA, such as the accumulation of oxidative damage at guanine, are also observed. The ability to measure events on such disparate time scales, its superior selectivity in comparison to other spectroscopic techniques, and the ability to simultaneously monitor carbonyl ligand and DNA IR absorption bands make TRIR a valuable tool for the study of CT in DNA

Mutants of the Base Excision Repair Glycosylase, Endonuclease III: DNA Charge Transport as a First Step in Lesion Detection

Endonuclease III (EndoIII) is a base excision repair glycosylase that targets damaged pyrimidines and contains a [4Fe-4S] cluster. We have proposed a model where BER proteins that contain redox-active [4Fe-4S] clusters utilize DNA charge transport (CT) as a first step in the detection of DNA lesions. Here, several mutants of EndoIII were prepared to probe their efficiency of DNA/protein charge transport. Cyclic voltammetry experiments on DNA-modified electrodes show that aromatic residues F30, Y55, Y75, and Y82 help mediate charge transport between DNA and the [4Fe-4S] cluster. On the basis of circular dichroism studies to measure protein stability, mutations at residues W178 and Y185 are found to destabilize the protein; these residues may function to protect the [4Fe-4S] cluster. Atomic force microscopy studies furthermore reveal a correlation in the ability of mutants to carry out protein/DNA CT and their ability to relocalize onto DNA strands containing a single base mismatch; EndoIII mutants that are defective in carrying out DNA/protein CT do not redistribute onto mismatch-containing strands, consistent with our model. These results demonstrate a link between the ability of the repair protein to carry out DNA CT and its ability to relocalize near lesions, thus pointing to DNA CT as a key first step in the detection of base damage in the genome