Integra at Home: A flexible continuum of in-home medical care for older adults with complex needs.

BACKGROUND: As individuals age, they may need new strategies to manage exacerbations of chronic disease to maintain their dignity and independence. Many end up in a revolving cycle of emergency department visits, hospitalizations, and post-acute care. Support to stay at home, which is often their preference, becomes a challenge and varies with insurance coverage, location, and financial status. There are few home-based options sufficiently agile enough to respond when acute conditions arise particularly with exacerbations of chronic disease. METHODS: In 2018, Integra designed a home-based option to treat acute exacerbations of chronic illness. A partnership with community paramedicine enabled faster response times and provided additional treatment tools. Using process improvement methodology, we developed "Integra at Home" workflows and team-based care. We counted averted emergency visits and hospitalizations, patient and staff satisfaction, and evidence of financial sustainability as a result of our program. RESULTS: Integra successfully developed a suite of home-based services, including responses to acute problems, to address beneficiaries' fluctuating medical needs. Following responses to 415 acute events, 74% (N = 307) resulted in averted emergency department visits. Based on InterQual® criteria, 34% (N = 103) of averted visits would have qualified as an averted hospitalization. All 64 respondents to patient surveys (N = 170) stated they would recommend our program. The staff indicated the model is a better way of caring for patients with higher rewards than traditional settings. The average length of stay in hospice for patients referred from the program (N = 22) was 4 weeks. CONCLUSIONS: Home-based care continuums are feasible, yet resources to manage acute exacerbations remain inadequate. To fill this gap, we created higher acuity services to respond to urgent needs and monitor symptoms between episodes. Amid successes and challenges, we are serving higher acuity older adults in Integra's home-based continuum model. We encourage further spread of longitudinal home-based acute care models.

Turbulence tracks recurrent solutions.

Despite a long and rich history of scientific investigation, fluid turbulence remains one of the most challenging problems in science and engineering. One of the key outstanding questions concerns the role of coherent structures that describe frequently observed patterns embedded in turbulence. It has been suggested, but not proved, that coherent structures correspond to unstable, recurrent solutions of the governing equation of fluid dynamics. Here, we present experimental and numerical evidence that three-dimensional turbulent flow tracks, episodically but repeatedly, the spatial and temporal structure of multiple such solutions. Our results provide compelling evidence that coherent structures, grounded in the governing equations, can be harnessed to predict how turbulent flows evolve.

Circle Method for Robust Estimation of Local Conduction Velocity High-Density Maps From Optical Mapping Data: Characterization of Radiofrequency Ablation Sites.

Conduction velocity (CV) slowing is associated with atrial fibrillation (AF) and reentrant ventricular tachycardia (VT). Clinical electroanatomical mapping systems used to localize AF or VT sources as ablation targets remain limited by the number of measuring electrodes and signal processing methods to generate high-density local activation time (LAT) and CV maps of heterogeneous atrial or trabeculated ventricular endocardium. The morphology and amplitude of bipolar electrograms depend on the direction of propagating electrical wavefront, making identification of low-amplitude signal sources commonly associated with fibrotic area difficulty. In comparison, unipolar electrograms are not sensitive to wavefront direction, but measurements are susceptible to distal activity. This study proposes a method for local CV calculation from optical mapping measurements, termed the circle method (CM). The local CV is obtained as a weighted sum of CV values calculated along different chords spanning a circle of predefined radius centered at a CV measurement location. As a distinct maximum in LAT differences is along the chord normal to the propagating wavefront, the method is adaptive to the propagating wavefront direction changes, suitable for electrical conductivity characterization of heterogeneous myocardium. In numerical simulations, CM was validated characterizing modeled ablated areas as zones of distinct CV slowing. Experimentally, CM was used to characterize lesions created by radiofrequency ablation (RFA) on isolated hearts of rats, guinea pig, and explanted human hearts. To infer the depth of RFA-created lesions, excitation light bands of different penetration depths were used, and a beat-to-beat CV difference analysis was performed to identify CV alternans. Despite being limited to laboratory research, studies based on CM with optical mapping may lead to new translational insights into better-guided ablation therapies.

Characteristics of home-based care provided by accountable care organizations.

OBJECTIVES: To describe the use of home-based services in accountable care organizations (ACOs). STUDY DESIGN: Cross-sectional analysis of 2019 ACO survey. METHODS: We analyzed surveys completed by 151 ACOs describing the characteristics of home-based care programs serving high-need, high-cost patients. We linked survey results to publicly available information about ACO characteristics, governance, and risk model participation. RESULTS: Twenty-five percent of respondent ACOs had formal home-based care programs, 25% offered occasional home visits, and 17% were actively developing new programs. Home-based primary care was the most common program type. Half of programs were established within the past 3 years. The programs utilized multidisciplinary care teams, but two-thirds had fewer than 500 visits annually. Funding sources included direct billing for services, health system subsidies, and ACO shared savings. A majority of respondents expressed interest in expanding services but were concerned about their ability to demonstrate a return on investment (ROI), which was reported as a major or moderate challenge by three-quarters of respondents. CONCLUSIONS: ACOs deliver a diverse array of home-visit services including primary care, acute medical care, palliative care, care transitions, and interventions to address social determinants of health. Many services provided are not billable, and therefore ACO leaders are hesitant to fund expansions without strong evidence of ROI. Expanding Medicare ACO home-visit waivers to all risk-bearing ACOs and covering integrated telehealth services would improve the financial viability of these programs.

Tinea and Tattoo: A Man Who Developed Tattoo-Associated Tinea Corporis and a Review of Dermatophyte and Systemic Fungal Infections Occurring Within a Tattoo.

Fungal infections may occur within tattoos. These include not only dermatophyte infections (tattoo-associated tinea) but also systemic mycoses (tattoo-associated systemic fungal infections). The PubMed search engine, accessing the MEDLINE database, was used to search for all papers with the terms: (1) tinea and tattoo, and (2) systemic fungal infection and tattoo. Tattoo-associated tinea corporis has been observed in 12 individuals with 13 tattoos; this includes the 18-year-old man who developed a dermatophyte infection, restricted to the black ink, less than one-month after tattoo inoculation on his left arm described in this report. Tattoo-associated tinea typically occurred on an extremity in the black ink. The diagnosis was established either by skin biopsy, fungal culture, and/or potassium hydroxide preparation. The cultured dermatophytes included Trichophyton rubrum, Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, and Trichophyton tonsurans. Several sources for the tinea were documented: autoinfection (two patients), anthrophilic (tinea capitis from the patient's son), and zoophilic (either the patient's cat or dog). Three patients presented with tinea incognito resulting from prior corticosteroid treatment. Tinea appeared either early (within one month or less after inoculation during tattoo healing) in six patients or later (more than two months post-inoculation in a healed tattoo) in six patients. Injury to the skin from the tattoo needle, or use of non-sterile instruments, or contaminated ink, and/or contact with a human or animal dermatophyte source are possible causes of early tinea infection. Tattoo ink-related phenomenon (presence of nanoparticles, polycyclic aromatic hydrocarbons, and cytokine-enhancement) and/or the creation of an immunocompromised cutaneous district are potential causes of late tinea infection. Treatment with topical and/or oral antifungal agents provided complete resolution of the dermatophyte for all the patients with tattoo-associated tinea. Tattoo-associated systemic fungal infection has been reported in six patients: five men and one patient whose age, sex, immune status, and some tattoo features (duration, color, and treatment) were not reported. The onset of infection after tattoo inoculation was either within less than one month (two men), three months (two men), or 69 months (one man). The tattoo was dark (either black or blue) and often presented as papules (three men) or nodules (two men) that were either individual or multiple and intact or ulcerated. The lesion was asymptomatic (one man), non-tender (one man), or painful (one man). The systemic fungal organisms included Acremonium species, Aspergillus fumigatus, Purpureocillium lilacinum, Saksenaea vasiformis, and Sporothrix schenckii. Contaminated tattoo ink was a confirmed cause of the systemic fungal infection in one patient; other postulated sources included non-professional tattoo inoculation, infected tattooing tool and/or ink in an immunosuppression host, and contaminated ritual tattooing instruments and dye. Complete resolution of the tattoo-associated systemic fungal infection occurred following systemic antifungal drug therapy. In conclusion, several researchers favor that tattoo inoculation can be implicated as a causative factor in the development of tattoo-associated tinea; however, in some of the men, tattoo-associated systemic fungal infection may have merely been coincidental.

Methodology for Cross-Talk Elimination in Simultaneous Voltage and Calcium Optical Mapping Measurements With Semasbestic Wavelengths.

Most cardiac arrhythmias at the whole heart level result from alteration of cell membrane ionic channels and intracellular calcium concentration ([Ca2+] i ) cycling with emerging spatiotemporal behavior through tissue-level coupling. For example, dynamically induced spatial dispersion of action potential duration, QT prolongation, and alternans are clinical markers for arrhythmia susceptibility in regular and heart-failure patients that originate due to changes of the transmembrane voltage (V m) and [Ca2+] i . We present an optical-mapping methodology that permits simultaneous measurements of the V m - [Ca2+] i signals using a single-camera without cross-talk, allowing quantitative characterization of favorable/adverse cell and tissue dynamical effects occurring from remodeling and/or drugs in heart failure. We demonstrate theoretically and experimentally in six different species the existence of a family of excitation wavelengths, we termed semasbestic, that give no change in signal for one dye, and thus can be used to record signals from another dye, guaranteeing zero cross-talk.

Hospital at Home services: An inventory of fee-for-service payments to inform Medicare reimbursement.

BACKGROUND: Hospital at Home (HaH) is a growing model of care with proven patient benefits. However, for the types of services required to provide an episode of HaH, full Medicare reimbursement is traditionally paid only if care is provided in inpatient facilities. DESIGN: This project identifies HaH services that could be reimbursable under Medicare to inform episodic care within fee-for-service (FFS) Medicare. SETTING: All data are derived from acute services provided from the Mount Sinai HaH program between 2014 and 2017 as part of a Center for Medicare and Medicaid Innovation (CMMI) demonstration program. PARTICIPANTS: The sample was limited to patients with one of the following five admitting diagnoses: urinary tract infection (n = 70), pneumonia (n = 60), cellulitis (n = 45), heart failure (n = 37), and chronic lung disease (n = 24) for a total of 236 acute episodes. MEASUREMENTS: HaH services were inventoried from three sources: electronic medical records, Medicare billing and itemized vendor billing. For each admitting diagnosis, four reimbursement scenarios were evaluated: (1) FFS Medicare without a home health episode, (2) FFS Medicare with a home health episode, (3) two-sided risk ACO with a home health episode, and (4) two-sided risk ACO without a home health episode. RESULTS: Across diagnoses, there were 1.5-1.9 MD visits and 1.5-2.7 nursing visits per episode. The Medicare FFS model without home health care had the lowest reimbursement potential ($964-$1604) per episode. The Medicare fee-for-service within ACO models with home health care had the greatest potential for reimbursement $4519-$4718. There was limited variation in costs by diagnosis. CONCLUSION AND RELEVANCE: Though existing payment models might be used to pay for many HaH acute services, significant gaps in reimbursement remain. Extending the benefits of HaH to the Medicare beneficiaries that are likely to derive the greatest benefit will require new payment models for FFS Medicare.

Reducing Emergency Department Transfers from Skilled Nursing Facilities Through an Emergency Physician Telemedicine Service.

INTRODUCTION: Transfers of skilled nursing facility (SNF) residents to emergency departments (ED) are linked to morbidity, mortality and significant cost, especially when transfers result in hospital admissions. This study investigated an alternative approach for emergency care delivery comprised of SNF-based telemedicine services provided by emergency physicians (EP). We compared this on-site emergency care option to traditional ED-based care, evaluating hospital admission rates following care by an EP. METHODS: We conducted a retrospective, observational study of SNF residents who underwent emergency evaluation between January 1, 2017-January 1, 2018. The intervention group was comprised of residents at six urban SNFs in the Northeastern United States, who received an on-demand telemedicine service provided by an EP. The comparison group consisted of residents of SNFs that did not offer on-demand services and were transferred via ambulance to the ED. Using electronic health record data from both the telemedicine and ambulance transfers, our primary outcome was the odds ratio (OR) of a hospital admission. We also conducted a subanalysis examining the same OR for the three most common chronic disease-related presentations found among the telemedicine study population. RESULTS: A total of 4,606 patients were evaluated in both the SNF-based intervention and ED-based comparison groups (n=2,311 for SNF based group and 2,295 controls). Patients who received the SNF-based acute care were less likely to be admitted to the hospital compared to patients who were transferred to the ED in our primary and subgroup analyses. Overall, only 27% of the intervention group was transported to the ED for additional care and presumed admission, whereas 71% of the comparison group was admitted (OR for admission = 0.15 [9% confidence interval, 0.13-0.17]). CONCLUSION: The use of an EP-staffed telemedicine service provided to SNF residents was associated with a significantly lower rate of hospital admissions compared to the usual ED-based care for a similarly aged population of SNF residents. Providing SNF-based care by EPs could decrease costs associated with hospital-based care and risks associated with hospitalization, including cognitive and functional decline, nosocomial infections, and falls.

Non-Classic (Surrepticius) Scabies Presenting as Erythematous Painful Palmar Pustules in an Octagenarian.

Sarcoptes scabiei classically presents with pruritic burrows. In addition to finger and toe web lesions, the penis and scrotum of men, the breast and areola of women, and the buttocks and axillae of both gender are common locations for mite-associated lesions. Scabies surrepticius refers to mite-related lesions that are not classical in morphology and/or distribution; there are several subtypes of non-classic or atypical scabies. Scabies surrepticius not only occurs in immunosuppressed individuals, but also in infants and children, and in elderly patients. An elderly woman developed mite-related bilateral erythematous painful palmar pustules that were clinically suspicious for a primary neutrophilic dermatosis; she also had a concurrent bacterial infection. The diagnosis of surrepticius scabies was established after evaluation of the deeper levels of her tissue biopsy specimen demonstrated a mite in the epidermis. All of her symptoms and lesions resolved after treatment with oral and topical antiscabetic therapy, and systemic antibiotics. Since the clinical presentation of the mite-related lesions can mimic those of other dermatologic or systemic conditions, a high degree of suspicion for the diagnosis of mite infestation must be entertained. Therefore, the clinician should consider the possibility of scabies surrepticius in any patient who develops new cutaneous lesions that are not typical for a defined dermatosis or do not resolve or improve after treatment.

Tinea Corporis-associated Erythroderma: Case Report and Review of Erythrodermic Patients with Chronic Dermatophyte Infection.

Erythroderma presents as generalized skin redness. The features of a 39-year-old man who presented with erythroderma are described. His skin biopsy revealed hyphae in the stratum corneum, which established the diagnosis of tinea corporis. His erythroderma resolved following treatment with an oral antifungal agent. Several conditions can be associated with erythroderma. Common etiologies for erythroderma include medications, neoplasms, and papulosquamous disorders. Superficial dermatophyte-associated erythroderma is rare. However, although erythroderma caused by generalized superficial mycosis is infrequently encountered, tinea corporis should be included in the new-onset or chronic erythroderma. The detection of fungal hyphae in the stratum corneum of a biopsy of the erythrodermic skin can not only establish dermatophyte infection as the underlying cause of the individual's erythroderma but also an alternative cause of erythroderma.

A Method for Segmenting Medicare Expenditures to Inform Cost Effective Care Delivery for Older Adults.

INTRODUCTION: Faced with growing populations of older, medically complex patients, health systems are now incentivized to deliver cost-effective, high-value care. We evaluated a new method that builds upon existing Medicare spending concentration studies to further segment these expenditures, revealing use patterns to inform care redesign. METHODS: We obtained monthly Medicare expenditure data and derived baseline comparison data using typical methods for identifying a yearly high-cost subpopulation. We then applied the new methodology, ordering monthly patient expenditures from highest to lowest to more extensively segment the baseline data. Our evaluation examined the following within the new more extensive segmentation: monthly expenditure distribution, corresponding patient counts, and occupancy of specific patient subgroups within the extended segmentation of baseline data. RESULTS: Compared to the baseline data, we found further spending concentration, with 16.7 percent of high-cost patients being responsible for about two-thirds of baseline expenditures. The remaining 83.3 percent of the high-cost subpopulation exhibited lower spending, collectively accounting for about one third of baseline expenditures. Additionally, we found that unique patient subgroups occupied different segments over time, with specific subgroups comprising 8.3 percent of the study subpopulation patients migrating into and out of each highest spending segment, accounting for almost half of monthly baseline expenditures. CONCLUSIONS: With monthly health care expenditures concentrated among small numbers of migrating patients, our evaluation suggested potential cost-effectiveness in tiered care delivery models, where small subgroups receive direct, active care interactions, while the remainder experience surveillance-level care, designed to both address ongoing medical needs and to detect emergent migration.

Isosbestic Point in Optical Mapping; Theoretical and Experimental Determination With Di-4-ANBDQPQ Transmembrane Voltage Sensitive Dye.

Optical mapping methods utilize fluorescence dyes to measure dynamic response of cardiac tissue such as changes in transmembrane potential (Vm). For the commonly used Vm sensitive dyes, a dye absorption and emission spectra shift as Vm changes. Signals relevant to Vm are calculated as a relative fluorescence change with respect to the fluorescence baseline. The amplitude of the change depends on the long-pass (LP) filter cut-on wavelength, placed on the sensor side, and the excitation wavelength. An excitation wavelength near the absorption peak, termed the isosbestic point, results in minimal absorption coefficient change as absorption spectra shifts. Consequentially the fluorescence intensity virtually does not change, when fluorescence across the entire emission spectra is measured, irrelevant of Vm changes. In this study we experimentally determined the isosbestic point for a near infrared dye Di-4-ANBDQPQ. We then present a theoretical study examining the dye linear or non-linear response as the fractional fluorescence change of Vm change, due to emission spectra shift and amplitude change, over a range of excitation wavelengths and LP filters. Linear "optical" response is important to quantify certain aspects of cardiac dynamics such as the action potential (AP) shape and duration, especially when studying drug effects and dynamical substrates for arrhythmia development.

Structure of the human volume regulated anion channel.

SWELL1 (LRRC8A) is the only essential subunit of the Volume Regulated Anion Channel (VRAC), which regulates cellular volume homeostasis and is activated by hypotonic solutions. SWELL1, together with four other LRRC8 family members, potentially forms a vastly heterogeneous cohort of VRAC channels with different properties; however, SWELL1 alone is also functional. Here, we report a high-resolution cryo-electron microscopy structure of full-length human homo-hexameric SWELL1. The structure reveals a trimer of dimers assembly with symmetry mismatch between the pore-forming domain and the cytosolic leucine-rich repeat (LRR) domains. Importantly, mutational analysis demonstrates that a charged residue at the narrowest constriction of the homomeric channel is an important pore determinant of heteromeric VRAC. Additionally, a mutation in the flexible N-terminal portion of SWELL1 affects pore properties, suggesting a putative link between intracellular structures and channel regulation. This structure provides a scaffold for further dissecting the heterogeneity and mechanism of activation of VRAC.

National Survey of Emergency Physicians Concerning Home-Based Care Options as Alternatives to Emergency Department-Based Hospital Admissions.

BACKGROUND: Emergency departments (EDs) in the United States play a prominent role in hospital admissions, especially for the growing population of older adults. Home-based care, rather than hospital admission from the ED, provides an important alternative, especially for older adults who have a greater risk of adverse events, such as hospital-acquired infections, falls, and delirium. OBJECTIVE: The objective of the survey was to understand emergency physicians' (EPs) perspectives on home-based care alternatives to hospitalization from the ED. Specific goals included determining how often EPs ordered home-based care, what they perceive as the barriers and motivators for more extensive ordering of home-based care, and the specific conditions and response times most appropriate for such care. METHODS: A group of 1200 EPs nationwide were e-mailed a six-question survey. RESULTS: Participant response was 57%. Of these, 55% reported ordering home-based care from the ED within the past year as an alternative to hospital admission or observation, with most doing so less than once per month. The most common barrier was an "unsafe or unstable home environment" (73%). Home-based care as a "better setting to care for low-acuity chronic or acute disease exacerbation" was the top motivator (79%). Medical conditions EPs most commonly considered for home-based care were cellulitis, urinary tract infection, diabetes, and community-acquired pneumonia. CONCLUSIONS: Results suggest that EPs recognize there is a benefit to providing home-based care as an alternative to hospitalization, provided they felt the home was safe and a process was in place for dispositioning the patient to this setting. Better understanding of when and why EPs use home-based care pathways from the ED may provide suggestions for ways to promote wider adoption.

Reversal of pathological cardiac hypertrophy via the MEF2-coregulator interface.

Cardiac hypertrophy, as a response to hemodynamic stress, is associated with cardiac dysfunction and death, but whether hypertrophy itself represents a pathological process remains unclear. Hypertrophy is driven by changes in myocardial gene expression that require the MEF2 family of DNA-binding transcription factors, as well as the nuclear lysine acetyltransferase p300. Here we used genetic and small-molecule probes to determine the effects of preventing MEF2 acetylation on cardiac adaptation to stress. Both nonacetylatable MEF2 mutants and 8MI, a molecule designed to interfere with MEF2-coregulator binding, prevented hypertrophy in cultured cardiac myocytes. 8MI prevented cardiac hypertrophy in 3 distinct stress models, and reversed established hypertrophy in vivo, associated with normalization of myocardial structure and function. The effects of 8MI were reversible, and did not prevent training effects of swimming. Mechanistically, 8MI blocked stress-induced MEF2 acetylation, nuclear export of class II histone deacetylases HDAC4 and -5, and p300 induction, without impeding HDAC4 phosphorylation. Correspondingly, 8MI transformed the transcriptional response to pressure overload, normalizing almost all 232 genes dysregulated by hemodynamic stress. We conclude that MEF2 acetylation is required for development and maintenance of pathological cardiac hypertrophy, and that blocking MEF2 acetylation can permit recovery from hypertrophy without impairing physiologic adaptation.

Perspectives on Home-based Healthcare as an Alternative to Hospital Admission After Emergency Treatment.

INTRODUCTION: The study objective was to explore emergency physicians' (EP) awareness, willingness, and prior experience regarding transitioning patients to home-based healthcare following emergency department (ED) evaluation and treatment; and to explore patient selection criteria, processes, and services that would facilitate use of home-based healthcare as an alternative to hospitalization. METHODS: We provided a five-question survey to 52 EPs, gauging previous experience referring patients to home-based healthcare, patient selection, and motivators and challenges when considering home-based options as an alternative to admission. In addition, we conducted three focus groups and four interviews. RESULTS: Of participating EPs, 92% completed the survey, 38% reported ordering home-based healthcare from the ED as an alternative to admission, 90% ranked cellulitis among the top three medical conditions for home-based healthcare, 90% ranked "reduce unnecessary hospitalizations and observation stays" among their top three perceived motivators for using home-based care, and 77% ranked "no existing process in place to refer to home-based care" among their top three perceived barriers. Focus group and interview themes included the need for alternatives to admission; the longer-term benefits of home-based healthcare; the need for streamlined transition processes; and the need for highly qualified home-care staff capable of responding the same day or within 24 hours. CONCLUSION: The study found that EPs are receptive to referring patients for home-based healthcare following ED treatment and believe people with certain diagnoses are likely to benefit, with the dominant barrier being the absence of an efficient referral process.

Survey and Chart Review to Estimate Medicare Cost Savings for Home Health as an Alternative to Hospital Admission Following Emergency Department Treatment.

BACKGROUND: Almost 70% of hospital admissions for Medicare beneficiaries originate in the emergency department (ED). Research suggests that some of these patients' needs may be better met through home-based care options after evaluation and treatment in the ED. OBJECTIVE: We sought to estimate Medicare cost savings resulting from using the Home Health benefit to provide treatment, when appropriate, as an alternative to inpatient admission from the ED. METHODS: This is a prospective study of patients admitted from the ED. A survey tool was used to query both emergency physicians (EPs) and patient medical record data to identify potential candidates and treatments for home-based care alternatives. Patient preferences were also surveyed. Cost savings were estimated by developing a model of Medicare Home Health to serve as a counterpart to the actual hospital-based care. RESULTS: EPs identified 40% of the admitted patients included in the study as candidates for home-based care. The top three major diagnostic categories included diseases and disorders of the respiratory system, digestive system, and skin. Services included intravenous hydration, intravenous antibiotics, and laboratory testing. The average estimated cost savings between the Medicare inpatient reimbursement and the Home Health counterpart was approximately $4000. Of the candidate patients surveyed, 79% indicated a preference for home-based care after treatment in the ED. CONCLUSIONS: Some Medicare beneficiaries could be referred to Home Health from the ED with a concomitant reduction in Medicare expenditures. Additional studies are needed to compare outcomes, develop the logistical pathways, and analyze infrastructure costs and incentives to enable Medicare Home Health options from the ED.

Yellow hair following sequential application of bacitracin zinc and selenium sulfide: Report of acquired xanthotrichosis and review of yellow hair discoloration.

BackgroundAcquired yellow hair (xanthotrichosis) can result from the deposition of pigmented compounds on the hair shaft or from chemical modification of hair pigment and protein molecules.PurposeA white-haired 77-year-old woman who developed xanthotrichosis of her scalp hair following the sequential application of bacitracin zinc ointment and selenium sulfide 2.5% lotion is described and the causes of yellow hair discoloration are reviewed.Materials and methodsThe clinical features of a woman with acquired yellow hair discoloration are presented. Using PubMed and Google Scholar, the following terms were searched and relevant citations were assessed: bacitracin zinc, hair discoloration, selenium sulfide, xanthotrichosis, and yellow hair.ResultsYellow hair was observed on the scalp in areas treated with the following regimen: prior to bedtime, several areas of the scalp were treated with a single application of bacitracin zinc ointment. The next morning, selenium sulfide 2.5% lotion was applied and then rinsed from the scalp during showering. Yellow hair discoloration was apparent in co-treated areas immediately following rinsing; the discoloration gradually faded over 2-5 days with regular shampooing.ConclusionsAcquired yellow hair shaft discoloration has been reported secondary to multiple etiologies, including environmental and occupational exposures, iatrogenic causes (including topical and systemic drugs) and protein-calorie malnutrition. To this list, we add yellow discoloration of white scalp hair due to application of selenium sulfide following topical use of bacitracin zinc in the affected areas as an unexpected adverse effect that may occur in individuals with white hair.

Structure of a bacterial microcompartment shell protein bound to a cobalamin cofactor.

The EutL shell protein is a key component of the ethanolamine-utilization microcompartment, which serves to compartmentalize ethanolamine degradation in diverse bacteria. The apparent function of this shell protein is to facilitate the selective diffusion of large cofactor molecules between the cytoplasm and the lumen of the microcompartment. While EutL is implicated in molecular-transport phenomena, the details of its function, including the identity of its transport substrate, remain unknown. Here, the 2.1 Šresolution X-ray crystal structure of a EutL shell protein bound to cobalamin (vitamin B12) is presented and the potential relevance of the observed protein-ligand interaction is briefly discussed. This work represents the first structure of a bacterial microcompartment shell protein bound to a potentially relevant cofactor molecule.

Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage.

Asparaginyl endopeptidase (AEP) is an endo/lysosomal cysteine endopeptidase with a preference for an asparagine residue at the P1 site and plays an important role in the maturation of toll-like receptors 3/7/9. AEP is known to undergo autoproteolytic maturation at acidic pH for catalytic activation. Here, we describe crystal structures of the AEP proenzyme and the mature forms of AEP. Structural comparisons between AEP and caspases revealed similarities in the composition of key residues and in the catalytic mechanism. Mutagenesis studies identified N44, R46, H150, E189, C191, S217/S218 and D233 as residues that are essential for the cleavage of the peptide substrate. During maturation, autoproteolytic cleavage of AEP's cap domain opens up access to the active site on the core domain. Unexpectedly, an intermediate autoproteolytic maturation stage was discovered at approximately pH 4.5 in which the partially activated AEP could be reversed back to its proenzyme form. This unique feature was confirmed by the crystal structure of AEPpH4.5 (AEP was matured at pH 4.5 and crystallized at pH 8.5), in which the broken peptide bonds were religated and the structure was transformed back to its proenzyme form. Additionally, the AEP inhibitor cystatin C could be digested by the fully activated AEP, but could not be digested by activated cathepsins. Thus, we demonstrate for the first time that cystatins may regulate the activity of AEP through substrate competition for the active site.