CO2 doping of organic interlayers for perovskite solar cells.

In perovskite solar cells, doped organic semiconductors are often used as charge-extraction interlayers situated between the photoactive layer and the electrodes. The π-conjugated small molecule 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9-spirobifluorene (spiro-OMeTAD) is the most frequently used semiconductor in the hole-conducting layer1-6, and its electrical properties considerably affect the charge collection efficiencies of the solar cell7. To enhance the electrical conductivity of spiro-OMeTAD, lithium bis(trifluoromethane)sulfonimide (LiTFSI) is typically used in a doping process, which is conventionally initiated by exposing spiro-OMeTAD:LiTFSI blend films to air and light for several hours. This process, in which oxygen acts as the p-type dopant8-11, is time-intensive and largely depends on ambient conditions, and thus hinders the commercialization of perovskite solar cells. Here we report a fast and reproducible doping method that involves bubbling a spiro-OMeTAD:LiTFSI solution with CO2 under ultraviolet light. CO2 obtains electrons from photoexcited spiro-OMeTAD, rapidly promoting its p-type doping and resulting in the precipitation of carbonates. The CO2-treated interlayer exhibits approximately 100 times higher conductivity than a pristine film while realizing stable, high-efficiency perovskite solar cells without any post-treatments. We also show that this method can be used to dope π-conjugated polymers.

α-synuclein-assisted oligomerization of ß-amyloid (1-42).

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders, characterized by aggregation of amyloid polypeptides, ß-amyloid (Aß) and α-synuclein (αS), respectively. Aß and αS follow similar aggregation pathways, starting from monomers, to soluble toxic oligomeric assemblies, and to insoluble fibrils. Various studies have suggested overlaps in the pathologies of AD and PD, and have shown Aß-αS interactions. Unfortunately, whether these protein-protein interactions lead to self- and co-assembly of Aß and αS into oligomers - a potentially toxic synergistic mechanism - is poorly understood. Among the various Aß isoforms, interactions of Aß containing 42 amino acids (Aß (1-42), referred to as Aß42) with αS are of most direct relevance due to the high aggregation propensity and the strong toxic effect of this Aß isoform. In this study, we carefully determined molecular consequences of interactions between Aß42 and αS in their respective monomeric, oligomeric, and fibrillar forms using a comprehensive set of experimental tools. We show that the three αS conformers, namely, monomers, oligomers and fibrils interfered with fibrillization of Aß42. Specifically, αS monomers and oligomers promoted oligomerization and stabilization of soluble Aß42, possibly via direct binding or co-assembly, while αS fibrils hindered soluble Aß42 species from converting into insoluble aggregates by the formation of large oligomers. We also provide evidence that the interactions with αS were mediated by various parts of Aß42, depending on Aß42 and αS conformers. Furthermore, we compared similarities and dissimilarities between Aß42-αS and Aß40-αS interactions. Overall, the present study provides a comprehensive depiction of the molecular interplay between Aß42 and αS, providing insight into its synergistic toxic mechanism.

Engineering of a protein probe with multiple inputs and multiple outputs for evaluation of alpha synuclein aggregation states.

The aggregation of α-synuclein (αS) into oligomers and fibrils is implicated in the pathology of Parkinson's Disease (PD). While a molecular probe for rapid and comprehensive evaluation of αS aggregation states is critical for a better understanding of PD pathology, identification of therapeutic candidates, and the development of early diagnostic strategies, no such probe has yet to be developed. A structurally flexible αS variant, PG65, was previously developed as a target binding-driven, conformation-switching molecular probe for rapid αS oligomer detection. Though informative, detection using PG65 provides no comprehensive assessment of the αS aggregation states. In the present study, we report engineering of a molecular probe, PG65-MIMO (a PG65 variant with Multiple-Inputs and Multiple-Outputs), that rapidly (within 2 hr) produces comprehensive information on αS aggregation states. PG65-MIMO generates distinct fluorescence responses to the three major αS conformers (monomers, oligomers, and fibrils). PG65-MIMO also displays unique fluorescent signals for αS oligomers, depending on the tris(2-carboxyethyl)phosphine (TCEP) concentration. Our results suggest that the TCEP dependent signaling of PG65-MIMO may be associated with its conformational states. Overall, our study illustrates engineering of an αS variant to create a molecular probe for handling multiple inputs and multiple outputs, addressing the technological gap in αS detection.

Inhibition of alpha-synuclein aggregation by AM17, a synthetic resveratrol derivative.

Parkinson's disease (PD) is linked to the aberrant self-assembly of the amyloid protein, α-synuclein (αS), where αS monomers aggregate to form oligomers and fibrils. Out of the three conformers, αS oligomers are the major toxic agents in PD, while αS fibrils may work as a reservoir for toxic oligomeric conformers. Thus, compounds that inhibit aggregation of αS monomers and disaggregate αS oligomers and fibrils may serve as therapeutic agents against PD. In this regard, resveratrol and its synthetic derivatives (e.g., AM17, which contains a copper ion-selective ionophoric motif) have previously been examined for their inhibitory effects on aggregation of amyloid proteins, such as the ß-amyloid peptide implicated in Alzheimer's disease. In the current study, we employed an array of experimental tools, such as Thioflavin T fluorescence, transmission electron microscopy, immuno-dot blot assays, SDS- and native-PAGE, and circular dichroism, to determine the impact of AM17 and resveratrol on αS aggregation. To the best of our knowledge, we show for the first time that AM17 not only inhibits aggregation of αS monomers but also disaggregates αS oligomers and fibrils, independent of the copper ions. Similar αS aggregation inhibitory effects were observed with resveratrol only in the presence of the copper ion. The present study supports the high promise of applicability of AM17 as an effective amyloid aggregation inhibitor for various conformers and protein sequences.

MTADV 5-MER peptide suppresses chronic inflammations as well as autoimmune pathologies and unveils a new potential target-Serum Amyloid A.

Despite the existence of potent anti-inflammatory biological drugs e.g., anti-TNF and anti IL-6 receptor antibodies, for treating chronic inflammatory and autoimmune diseases, these are costly and not specific. Cheaper oral available drugs remain an unmet need. Expression of the acute phase protein Serum Amyloid A (SAA) is dependent on release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α during inflammation. Conversely, SAA induces pro-inflammatory cytokine secretion, including Th17, leading to a pathogenic vicious cycle and chronic inflammation. 5- MER peptide (5-MP) MTADV (methionine-threonine-alanine-aspartic acid-valine), also called Amilo-5MER, was originally derived from a sequence of a pro-inflammatory CD44 variant isolated from synovial fluid of a Rheumatoid Arthritis (RA) patient. This human peptide displays an efficient anti-inflammatory effects to ameliorate pathology and clinical symptoms in mouse models of RA, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). Bioinformatics and qRT-PCR revealed that 5-MP, administrated to encephalomyelytic mice, up-regulates genes contributing to chronic inflammation resistance. Mass spectrometry of proteins that were pulled down from an RA synovial cell extract with biotinylated 5-MP, showed that it binds SAA. 5-MP disrupted SAA assembly, which is correlated with its pro-inflammatory activity. The peptide MTADV (but not scrambled TMVAD) significantly inhibited the release of pro-inflammatory cytokines IL-6 and IL-1ß from SAA-activated human fibroblasts, THP-1 monocytes and peripheral blood mononuclear cells. 5-MP suppresses the pro-inflammatory IL-6 release from SAA-activated cells, but not from non-activated cells. 5-MP could not display therapeutic activity in rats, which are SAA deficient, but does inhibit inflammations in animal models of IBD and MS, both are SAA-dependent, as shown by others in SAA knockout mice. In conclusion, 5-MP suppresses chronic inflammation in animal models of RA, IBD and MS, which are SAA-dependent, but not in animal models, which are SAA-independent.

The incidence and risk factors for venous thromboembolism in adolescent and young adult oncology patients.

BACKGROUND: Venous thromboembolism (VTE) is a known complication among pediatric and adult cancer patients. Adolescent and young adult oncology (AYAO) patients have unique biological and physiological characteristics that make them distinct from other populations. Our objective was to study the VTE incidence, risk factors, and outcomes, which have been understudied in this population. PROCEDURE: A retrospective case-control study was conducted on AYAO participants with new or relapsed cancer and an imaging confirmed VTE from January 2011 to November 2016 at our institution. Eligible AYAO participants without a history of VTE were designated as controls and were randomly selected from our institution's tumor registry. Demographics, medical history, surgeries, central venous catheter (CVC) data, VTE diagnosis and treatment, relapses, and deaths were abstracted. RESULTS: Thirty-five VTE cases and 70 controls were included in this analysis. Eighty percent of cases had leukemia or lymphoma (vs. a solid tumor) compared to 58% of controls. The majority of VTEs (57%) were CVC associated, and more than 70% of cases had more than one CVC placed during their cancer treatment versus 34% of controls. Infection was associated with increased VTE risk (OR = 6.35, 95% CI = 2.30, 17.55, p < .0001). VTE cases had increased cancer relapse (23% vs. 10%) and mortality rates (29% vs. 16%) than controls. CONCLUSION: AYAO participants with a VTE were more likely to have leukemia or lymphoma, more than one CVC or infection. Further studies are needed to identify patients who would benefit from modifiable prevention measures, such as limiting to one CVC, preventing infections, or considering prophylactic anticoagulation for those with a liquid tumor.

Assessing the Implementation and Effectiveness of the Electronic Patient-Reported Outcome Tool for Older Adults With Complex Care Needs: Mixed Methods Study.

BACKGROUND: Goal-oriented care is being adopted to deliver person-centered primary care to older adults with multimorbidity and complex care needs. Although this model holds promise, its implementation remains a challenge. Digital health solutions may enable processes to improve adoption; however, they require evaluation to determine feasibility and impact. OBJECTIVE: This study aims to evaluate the implementation and effectiveness of the electronic Patient-Reported Outcome (ePRO) mobile app and portal system, designed to enable goal-oriented care delivery in interprofessional primary care practices. The research questions driving this study are as follows: Does ePRO improve quality of life and self-management in older adults with complex needs? What mechanisms are likely driving observed outcomes? METHODS: A multimethod, pragmatic randomized controlled trial using a stepped-wedge design and ethnographic case studies was conducted over a 15-month period in 6 comprehensive primary care practices across Ontario with a target enrollment of 176 patients. The 6 practices were randomized into either early (3-month control period; 12-month intervention) or late (6-month control period; 9-month intervention) groups. The primary outcome measure of interest was the Assessment of Quality of Life-4D (AQoL-4D). Data were collected at baseline and at 3 monthly intervals for the duration of the trial. Ethnographic data included observations and interviews with patients and providers at the midpoint and end of the intervention. Outcome data were analyzed using linear models conducted at the individual level, accounting for cluster effects at the practice level, and ethnographic data were analyzed using qualitative description and framework analysis methods. RESULTS: Recruitment challenges resulted in fewer sites and participants than expected; of the 176 target, only 142 (80.6%) patients were identified as eligible to participate because of lower-than-expected provider participation and fewer-than-expected patients willing to participate or perceived as ready to engage in goal-setting. Of the 142 patients approached, 45 (32%) participated. Patients set a variety of goals related to self-management, mental health, social health, and overall well-being. Owing to underpowering, the impact of ePRO on quality of life could not be definitively assessed; however, the intervention group, ePRO plus usual care (mean 15.28, SD 18.60) demonstrated a nonsignificant decrease in quality of life (t24=-1.20; P=.24) when compared with usual care only (mean 21.76, SD 2.17). The ethnographic data reveal a complex implementation process in which the meaningfulness (or coherence) of the technology to individuals' lives and work acted as a key driver of adoption and tool appraisal. CONCLUSIONS: This trial experienced many unexpected and significant implementation challenges related to recruitment and engagement. Future studies could be improved through better alignment of the research methods and intervention to the complex and diverse clinical settings, dynamic goal-oriented care process, and readiness of provider and patient participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT02917954; https://clinicaltrials.gov/ct2/show/NCT02917954.

Interactions between Soluble Species of ß-Amyloid and α-Synuclein Promote Oligomerization while Inhibiting Fibrillization.

Aggregations of ß-amyloid (Aß) and α-synuclein (αS) into oligomeric and fibrillar assemblies are the pathological hallmarks of Alzheimer's and Parkinson's diseases, respectively. Although Aß and αS affect different regions of the brain and are separated at the cellular level, there is evidence of their eventual interaction in the pathology of both disorders. Characterization of interactions of Aß and αS at various stages of their aggregation pathways could reveal mechanisms and therapeutic targets for the prevention and cure of these neurodegenerative diseases. In this study, we comprehensively examined the interactions and their molecular manifestations using an array of characterization tools. We show for the first time that αS monomers and oligomers, but not αS fibrils, inhibit Aß fibrillization while promoting oligomerization of Aß monomers and stabilizing preformed Aß oligomers via coassembly, as judged by Thioflavin T fluorescence, transmission electron microscopy, and SDS- and native-PAGE with fluorescently labeled peptides/proteins. In contrast, soluble Aß species, such as monomers and oligomers, aggregate into fibrils, when incubated alone under the otherwise same condition. Our study provides evidence that the interactions with αS soluble species, responsible for the effects, are mediated primarily by the C-terminus of Aß, when judged by competitive immunoassays using antibodies recognizing various fragments of Aß. We also show that the C-terminus of Aß is a primary site for its interaction with αS fibrils. Collectively, these data demonstrate aggregation state-specific interactions between αS and Aß and offer insight into a molecular basis of synergistic biological effects between the two polypeptides.

Amyloid Aggregation of Bacillus circulans Xylanase under Native Conditions and its Modulation by ß-Amyloid-Derived Peptide Fragments.

The aggregation of intrinsically disordered proteins into fibrils is implicated in many neurodegenerative diseases. Amyloid aggregation is a generic property of proteins as evidenced by globular proteins that often form amyloid aggregates under partially denaturing conditions. Recently, multiple lines of evidence have suggested that the amyloid aggregation of globular proteins can also occur under native conditions. Unfortunately, amyloid aggregation under native conditions has been demonstrated in only a handful of cases. Engineering a globular protein's amyloid aggregation might benefit from its fusion to an amyloid-derived fragment with reduced aggregation propensity. Unfortunately, the impacts of such fragments on the amyloid aggregation under native conditions have yet to be examined. In this study, we show that a globular protein, Bacillus circulans xylanase (BCX), can aggregate to form amyloid fibrils under native conditions. When BCX was mixed with or fused to the non-self-aggregating fragments, KLVFWAK and ELVFWAE-which were derived from ß-amyloid (Aß)-they modulated the BCX amyloid aggregation to differing extents. This study also provides insight into a correlation between the kinetic stability and amyloid aggregation of BCX, and supports a view that Aß-derived fragments can be useful for the modulating amyloid aggregation of some, though not all, proteins.

Molecular Determinants for Protein Stabilization by Insertional Fusion to a Thermophilic Host Protein.

A universal method that improves protein stability and evolution has thus far eluded discovery. Recently, however, studies have shown that insertional fusion to a protein chaperone stabilized various target proteins with minimal negative effects. The improved stability was derived from insertion into a hyperthermophilic protein, Pyrococcus furiosus maltodextrin-binding protein (PfMBP), rather than from changes to the target protein sequence. In this report, by evaluating the thermodynamic and kinetic stability of various inserted ß-lactamase (BLA) homologues, we were able to examine the molecular determinants of stability realized by insertional fusion to PfMBP. Results indicated that enhanced stability and suppressed aggregation of BLA stemmed from enthalpic and entropic mechanisms. This report also suggests that insertional fusion to a stable protein scaffold has the potential to be a useful method for improving protein stability, as well as functional protein evolution.

A Missed Case of Vasospastic Angina, Clinched by a Personal Handheld ECG Device.

We describe a case of vasospastic angina diagnosed via a personal electrocardiography monitoring device in a middle-aged woman who initially presented with chest pain and angiographic findings demonstrating coronary emboli. (Level of Difficulty: Beginner.).

Grounding alcohol simulation models in empirical and theoretical alcohol research: a model for a Northern Plains population in the United States.

The growing number of systems science simulation models for alcohol use (AU) are often disconnected from AU models within empirical and theoretical alcohol research. As AU prevention/intervention efforts are typically grounded in alcohol research, this disconnect may reduce policy testing results, impact, and implementation. We developed a simulation model guided by AU research (accounting for the multiple AU stages defined by AU behavior and risk for harm and diverse transitions between stages). Simulated projections were compared to historical data to evaluate model accuracy and potential policy leverage points for prevention and intervention at risky drinking (RD) and alcohol use disorder (AUD) stages. Results indicated prevention provided the greatest RD and AUD reduction; however, focusing exclusively on AUD prevention may not be effective for long-term change, given the continued increase in RD. This study makes a case for the strength and importance of aligning subject-based research with systems science simulation models.

Perceived Discrimination During Prenatal Care at a Community Health Center.

INTRODUCTION: Discrimination in healthcare is associated with fetal growth restriction, preterm birth, and postpartum depression. A community-based participatory research study was designed to measure perceived discrimination and healthcare quality during prenatal care and delivery by a community health center, where the majority of patients served belong to historically marginalized ethnic and racial groups. METHODS: A 34-question phone survey was administered to women 18 years and older who received prenatal care at the study site during 2020-2021. The primary outcome was perceived discrimination during obstetric care, measured by the 7-question Discrimination in the Medical Setting (DMS) survey. Secondary outcomes included the association of race with perceived discrimination, quality of care, trust of healthcare providers, and perceived control over medical choices. RESULTS: Ninety-seven women completed the survey, 95 of whom were women of color. The sample was dichotomized into Black (n = 49) and non-Black (n = 46). Perceived discrimination for all participants was 21% (20/95), with 31% (15/49) of Black women reporting any discrimination during prenatal care and delivery. Compared to other women of color, Black women reported higher rates of perceived discrimination (31% vs 11%, aOR 3.9 [1.2-12.1], p < 0.05), lower control over health choices (84% vs 98%, aOR 0.1 [0.0-0.8], p < 0.05), and were more likely to perceive lack of respect (12% vs 2%, p = 0.045). CONCLUSION: Although perceived discrimination at this community health center was low compared to prior studies, Black women experienced higher rates of discrimination than other women of color.

Same-Day Home Recovery for Benign Foregut Surgery.

Importance: Same-day home recovery (SHR) is now the standard of care for many major surgical procedures and has the potential to become standard practice for benign foregut procedures (eg, hiatal hernia repair, fundoplication, and Heller myotomy). Objective: To determine whether SHR for patients undergoing benign foregut surgery is feasible, safe, and effective. Design, Setting, and Participants: This prospective cohort study took place across 19 medical centers within an integrated health care system in northern California from January 2019 through September 2021. Participants included consecutive patients undergoing elective benign foregut surgery. Exposures: Standardized SHR program. Main Outcomes and Measures: The primary end point was the rate of SHR. The secondary end points were 7-day and 30-day rates of postoperative emergency department visits, hospital readmissions, and reoperations. Results: Of 1248 patients who underwent benign foregut surgery from January 2017 through September 2021, 558 were patients before implementation of the SHR program and 690 were patients postimplementation. The mean age of patients was 60 years, and 759 (59%) were female. The preimplementation SHR rate was 64 of 558 patients (11.5%) in 2018 and increased to 82 of 113 patients (72.6%) by 2021 (94/350 [26.9%] in 2019 and 112/227 [49.3%] in 2020; P < .001). There were no statistical differences in the 7-day and 30-day rates of postoperative emergency visits, hospital readmissions, and reoperations or 30-day mortality in the SHR vs non-SHR groups in the postimplementation era. Conclusions and Relevance: In this study, implementation of a regional SHR program among patients undergoing elective benign foregut surgery was feasible, safe, and effective. The changes in perioperative care require comprehensive patient education and full multidisciplinary support. An SHR program for benign foregut procedures has the potential to improve patient care and cost-effectiveness in care delivery.

Association between continuity of care and subsequent diagnosis of multimorbidity in Ontario, Canada from 2001-2015: A retrospective cohort study.

BACKGROUND: Continuity of care is a well-recognized principle of the primary care discipline owing to its medical, interpersonal, and cost-saving benefits. Relationship continuity or the ongoing therapeutic relationship between a patient and their physician is a particularly desirable goal, but its role in preventing the accumulation of chronic conditions diagnoses in individuals is unknown. The objective of this study was to investigate the effect of continuity of care with physicians on the rate of incident multimorbidity diagnoses in patients with existing conditions. METHODS: This was a population-based, retrospective cohort study from 2001 to 2015 that focused on patients aged 18 to 105 years with at least one chronic condition (n = 166,665). Our primary exposure was relationship continuity of care with general practitioners and specialists measured using the Bice-Boxerman Continuity of Care Index (COCI). COCI was specified as a time-dependent exposure prior to the observation period. Our outcomes of interest were the time to diagnosis of a second, third, and fourth chronic condition estimated using cause-specific hazard regressions accounting for death as a competing risk. FINDINGS: We observed that patients with a single chronic condition and high continuity of care (>0.50) were diagnosed with a second chronic condition or multimorbidity at an 8% lower rate compared to individuals with low continuity (cause-specific hazard ratio (HR) 0.92 (95% Confidence Interval 0.90-0.93; p<0.0001) after adjusting for age, sex, income, place of residence, primary care enrolment, and the annual number of physician visits. Continuity remained protective as the degree of multimorbidity increased. Among patients with two conditions, the risk of diagnosis of a third chronic condition was also 8% lower for individuals with high continuity (HR 0.92; CI 0.90-0.94; p<0.0001). Patients with three conditions and high continuity had a 9% lower risk of diagnosis with a fourth condition (HR 0.91; CI 0.89-0.93; p<0.0001). CONCLUSIONS: Continuity of care is a potentially modifiable health system factor that reduces the rate at which diagnoses of chronic conditions are made over time in patients with multimorbidity. Additional research is needed to explain the underlying mechanisms through which continuity is related to a protective effect and the clinical sequalae.

Characteristics of Methamphetamine-associated Cardiomyopathy and the Impact of Methamphetamine Use on Cardiac Dysfunction.

Methamphetamine-associated cardiomyopathy (MACM) in an increasingly prevalent disease yet presenting clinical characteristics have not been well studied. We studied consecutive patients with MACM presenting between June 2018 and March 2020 who were interviewed for drug use and medical history. We retrospectively identified an age- and gender-matched cohort of Non-MACM (NMACM) patients and compared clinical characteristics. 140 patients (70 MACM and 70 NMACM) were studied. MACM patients were young (49.6 ± 10 years) and predominantly male (94%). Compared to NMACM, MACM patients were more likely to be Caucasian (21% vs 6%, p = 0.007) and homeless (47% vs 7%, p = 0.001). MACM was characterized by lower left ventricular ejection fraction (EF) (p <0.001) and greater LV end diastolic volume (LVEDV) (p = 0.024). Right ventricular (RV) dilation was present more often (p = s0.001) and was more often severe (p = 0.03). Among MACM cases, half of the cohort developed MACM within 5 years of starting MA (18% within 1 year). There was no apparent relationship between frequency or amount of MA used weekly with time until heart failure onset. Drug use patterns were not clearly related to the degree of LV structural change however there were more consistent, significant associations with RV and right atrial (RA) size parameters. In conclusion, patients with MACM have more severe myocardial impairment with lower EF, greater LVEDV and RV dilation. Drug use patterns do not clearly impact degree of LV structural changes by echocardiography however may be related to RV and RA size.

Exploring the relationship between the usability of a goal-oriented mobile health application and non-usage attrition in patients with multimorbidity: A blended data analysis approach.

BACKGROUND: Mobile health applications are increasingly used to support the delivery of health care services to a variety of patients. Based on data obtained from a pragmatic trial of the electronic Patient Reported Outcome (ePRO) app designed to support goal-oriented care primary care, this study aims to (1) examine how patient-reported usability changed over the one-year intervention period, and (2) explore participant attrition rate of the electronic Patient Reported Outcome app over one year study period. METHODS: We performed a secondary analysis of 44 older adults with complex chronic needs enrolled in the electronic Patient Reported Outcome-digital health intervention. App usage and attrition were measured using device-generated usage logs; usability was measured using the patient-reported post-study system usability questionnaire collected at 3, 6, 9, and 12 months. Research memos were used to interpret potential contextual contributing factors to patients' overall usage and usability score pattern. A data triangulation method of both quantitative and qualitative data was used to analyze and interpret study findings. RESULTS: While there was gradual attrition in the use of the ePRO app, patients' usability scores remained consistent throughout the study period. Qualitative memos suggested patients' encounters with technical difficulties and relationship dynamics with primary providers influenced patients' adherence to the ePRO app. CONCLUSION: This study highlights that the patient-provider relationship is a key determining factor that influences complex patients' continued engagement with a Mobile health app. The finding calls attention to the measurement of usability of a Mobile health app, its impact on attrition, and contributing factors that influence patients' attrition. Trial registration: Clinicaltrials.gov Identified NCT02917954.

Acute ST-Segment Elevation Myocardial Infarction as Initial Presentation of Atypical Hemolytic-Uremic Syndrome.

A young woman presented with an acute ST-segment elevation myocardial infarction. Her clinical course was complicated by cardiogenic shock and acute renal failure. Work-up revealed thrombocytopenia and hemolytic anemia. A diagnosis of atypical hemolytic-uremic syndrome was made on the basis of clinical and pathological findings. (Level of Difficulty: Intermediate.).