Early Peanut Introduction in Infants: Improving Guideline Adherence With EMR Standardization.

OBJECTIVES: Peanut allergy in children is a population health problem. Evidence suggests early peanut introduction (EPI) for infants can reduce the development of peanut allergy. Primary care settings have not widely adopted guidelines recommending EPI. Peanut allergy prevention depends on primary care providers incorporating EPI guidelines into well-child check (WCC) encounters. We aimed to improve guideline adherence in a primary care setting by implementing a bundle of clinical decision support (CDS) tools. METHODS: Using quality improvement methodology, the team developed a standardized work protocol and CDS tools within an electronic medical record (EMR) at 4, 6, and 9-month WCC encounters. The team executed changes and modifications through plan-do-study-act cycles and analyzed results with statistical process control charts. RESULTS: We collected data from 445 WCC encounters from baseline through sustainability. EMR documentation of EPI guidance at 4, 6, and 9-month WCCs shifted from 13.9% to 83.5% over 12 months. Provider adoption of smart lists and templates increased from 2% to 73%, the distribution of home peanut introduction handouts increased from 5.2% to 54.1%, and caregiver-reported peanut ingestion increased from 0% to 34.6%. Diphtheria-tetanus-acellular pertussis vaccination rates remained at 100% for 6-month visits, and patient in-room time remained at 65 minutes. CONCLUSIONS: Quality improvement methodology improved documentation of EPI guidance and increased reported peanut ingestion at routine WCC encounters without impacting other measures. Broader use of bundled CDS tools and EMR standardization could further improve guideline adherence and increase early peanut introduction to prevent peanut allergy in infants.

Increased Detection of Gonorrhea and Chlamydia After Implementation of a Universal Screening Protocol in a Pediatric Primary Care Clinic.

BACKGROUND: Literature suggests that adolescents may not accurately report sexual activity to their providers, impeding risk-based screening efforts for gonorrhea and chlamydia (GC/CT). We assessed the effect of a clinic-based universal GC/CT screening initiative on GC/CT screening frequency and detection of GC/CT infections among adolescents (boys and girls ≥13 years) and the association between positive GC/CT and documented sexual activity. METHODS: We conducted a pre-post analysis of a primary care clinic affiliated with an academic institution. The electronic medical record was queried to extract all adolescent well and acute encounters for the 12 months preimplementation and postimplementation of universal GC/CT screening in January 2015. RESULTS: Eight hundred fifty-six encounters from 752 unique adolescents were included. Screening increased postimplementation (23.3% vs 61.4%, P < 0.001) of universal screening. Although there were similar rates of documented sexual activity preimplementation and postimplementation (14.6% vs 16.0%), a larger proportion of unknown sexual activity was documented (10.5% vs 23.7%, P < 0.001). Provider-level factors were the most frequent reasons for not screening. The absolute number of GC/CT cases increased, although the proportion of cases out of all eligible adolescents remained similar as more testing was completed (chlamydia, 5 of 752 vs 12 of 752; P = 0.09; gonorrhea, 0 of 752 vs 1 of 752; P = 0.32). Nearly half of positive chlamydia infections postimplementation appeared in adolescents who reported no sexual activity. CONCLUSIONS: Universal screening in a primary care clinic increased screening and detection of cases of gonorrhea and chlamydia, including in adolescents who did not report sexual activity.

A Clinic-Based Quality Improvement Initiative to Increase Screening for Gonorrhea and Chlamydia in Adolescents.

BACKGROUND: Universal screening is a strategy for addressing the limitations of risk-based screening for gonorrhea and chlamydia (GC/CT). This quality improvement (QI) initiative aimed to improve GC/CT screening by implementing universal annual screening for all adolescents ≥ 13 years old. METHODS: At an academic pediatric resident continuity clinic, an interdisciplinary team designed and conducted multiple Plan-Do-Study-Act (PDSA) cycles over one year. The primary aim, and process measure, was to increase the percentage of encounters with screening for GC/CT in the 12 months prior to the encounter to 80%. The secondary outcome measure was rate of detection of GC or CT infection. Further, pulse checks of provider/staff knowledge and adherence were conducted. The balancing measure was denied insurance claims. RESULTS: The mean screening rate of 29.2% increased during the project implementation to 65.1% with several bundles of PDSA cycles. There were no cases of gonorrhea detected in the baseline period or implementation period. The case rate of chlamydia was similar during both periods (from 9.7 per 1,000 adolescent encounters to 10.8 per 1,000 adolescent encounters, p = 0.74). There was similarly high provider/staff knowledge about (p = 0.35) and adherence to (p = 0.06) the screening protocol at 6 and 12 months of implementation. There was no increase in percentage of denied insurance claims. CONCLUSION: This QI initiative doubled rates of GC/CT screening with no statistically significant increase in number of cases.

The bidirectional relationship between sleep and physical activity following traumatic brain injury.

Sleep and physical activity are both modifiable behavioural factors that are associated with better health and are potentially related. Following traumatic brain injury, damage to the brain caused by an external force, sleep disturbances are common. Exploring bidirectional relationships between sleep and physical activity might provide insight into whether increasing physical activity could decrease these sleep disturbances. The current study, therefore, examined inter- and intra-individual temporal associations between sleep and daytime physical activity in 64 people with traumatic brain injury reporting sleep problems or fatigue (47 males; mean age, 40 years). Sleep and physical activity were measured using actigraphy with corroborating sleep diaries over 14 consecutive days. Multilevel models were used to examine inter- and intra-individual associations between physical activity and sleep. Inter-individual variations showed that earlier bedtimes, earlier wake-up times and lower sleep efficiency were associated with more physical activity. Intra-individual temporal variations showed no significant association of daytime physical activity with sleep duration or continuity. However, shorter sleep time and less wake after sleep onset than usual were associated with more time spent in light-intensity activity the next day. Therefore, sleep may have more of an influence on physical activity than physical activity has on sleep in people with traumatic brain injury. In conclusion, the results do not confirm a potential beneficial effect of physical activity on sleep but suggest that improving sleep quality might be relevant to support of a physically active lifestyle in people with traumatic brain injury. Further research is necessary to confirm these results.

Anxiety predicts dyadic sleep characteristics in couples experiencing insomnia but not in couples without sleep disorders.

BACKGROUND: Anxiety and depression are commonly comorbid with sleep problems. Despite growing acknowledgement that bedpartners are important determinants of sleep quality, few studies have explored mental health as a risk factor for disrupted sleep of the bedpartner. We examined whether anxiety or depression symptoms predicted an individual's sleep or their bedpartner's sleep, in couples where one partner experienced insomnia and in couples without sleep disorders. METHODS: Fifty-two bed-sharing couples where one individual had insomnia ("Patient"), and 55 non-sleep-disordered couples completed the Beck Anxiety Inventory, Patient Health Questionnaire-9, and Insomnia Severity Index (ISI). Sleep was monitored for seven nights. Actor-Partner Interdependence Models assessed whether anxiety or depression symptoms predicted individual or dyadic sleep (wake transmission). RESULTS: Greater anxiety symptoms predicted increased vulnerability to being woken by their bedpartner, as well as increased frequency of waking their bedpartner up during the night in Patients with insomnia, but not in non-sleep-disordered couples. Neither anxiety nor depression symptoms predicted an individual's or their bedpartner's sleep efficiency in either subsample. However, ISI was positively predicted by own anxiety and depression symptoms for Patients with insomnia and in non-sleep-disordered couples. LIMITATIONS: The non-sleep-disordered subsample experienced only mild symptoms of anxiety and depression, potentially reducing predictive power. CONCLUSIONS: Anxiety may help reveal social determinants of sleep in couples experiencing insomnia. These data underscore the importance of considering sleep, the bedpartner, and affective symptoms in mental health and sleep assessments.

Vulnerability and resistance to sleep disruption by a partner: A study of bed-sharing couples.

OBJECTIVES: Methods for analyzing sleep as a dyadic behavior remain relatively unexplored. We aimed to (1) characterize how bedpartners influence each other's sleep, and (2) identify factors that predict sensitivity to wake transmission between bedpartners. DESIGN: Cross-sectional study. SETTING: Community members in Melbourne, Australia. PARTICIPANTS: Fifty-five couples without sleep disorders, aged 18-72 years. MEASUREMENTS: Participants completed the Morningness-Eveningness Questionnaire, reduced version. Habitual sleep/wake patterns were monitored for seven nights via actigraphy and sleep diary. Epoch-by-epoch sleep/wake concordances (shared sleep/wake minutes), number of transmissions received (number of awakenings immediately preceded by bedpartner wakefulness), percent transmissions received (percentage of total awakenings that were transmissions), transmissibility (percentage of all bedpartner awakenings transmitted), and percent minutes resistant to transmission (percentage of bedpartner's wake minutes that an individual slept), were calculated. Mixed-effects modeling assessed predictors of dyadic sleep. RESULTS: We described rates of sleep concordance (M = 66.8% ± 6.8%), wake concordance (M = 6.8% ± 3.1%), number of transmissions received (M = 6.0 ± 2.7), percent transmissions received (M = 18.9% ± 7.5%), transmissibility (M = 20.0% ± 6.2%), and percent minutes resistant (M = 52.1% ± 13.6%). Average couple-level percent transmissions received were highest and percent minutes resistant lowest in couples who had similar bedtime (within 30 minutes), compared to couples with greater differences in bedtime. CONCLUSIONS: Wake transmission is a useful metric of dyadic sleep, which varies according to relative bedtimes, and chronotypes of bedpartners. Higher wake transmissions for couples with similar bedtimes suggest dyadic preferences for shared bedtimes may be due to psychosocial benefits of shared sleep timing, rather than minimization of bedpartner-driven sleep disruption.

The impact of prolonged exposure on sleep and enhancing treatment outcomes with evidence-based sleep interventions: A pilot study.

OBJECTIVE: Insomnia and nightmares are central features of posttraumatic stress disorder (PTSD). However, often they are inadequately assessed and ineffectively resolved following gold-standard PTSD treatment. Here we: (a) evaluate effects of prolonged exposure (PE) on subjectively measured sleep and (b) present pilot results of an examination of whether adding sleep interventions (imagery rehearsal therapy [IRT] and cognitive-behavioral therapy for insomnia [CBT-I]) to PE improves treatment response, relative to PE alone, for night- and/or daytime PTSD symptoms among returning U.S. veterans and postdeployment personnel. METHOD: In a parallel-groups, randomized controlled trial, participants received 12 sessions of PE followed by IRT (5 weeks) and CBT-I (7 weeks) or PE followed by 12 weeks supportive care therapy (SCT). RESULTS: PE did not improve sleep to a clinically meaningful degree, despite significant improvements in both Clinical Administered PTSD Scale and PTSD Checklist. Enhancing treatment with IRT/CBT-I led to greater improvements in insomnia (diary-recorded sleep efficiency) symptoms with large effect size, relative to SCT (p = .068, d = 1.07). There were large improvements in nightmare frequency relative SCT that did not reach statistical significance (p = .11, d = 0.90). Moreover, there was small improvement in daytime symptoms (Clinical Administered PTSD Scale) that did not reach statistical significance (p = .54, d = .31). CONCLUSION: The addition of targeted, validated sleep treatment improves effects of PE and improves nighttime symptoms. Thus, evidence-based sleep treatment should be considered in comprehensive PTSD treatment. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Validity, potential clinical utility and comparison of a consumer activity tracker and a research-grade activity tracker in insomnia disorder II: Outside the laboratory.

Accurate assessment of sleep can be fundamental for monitoring, managing and evaluating treatment outcomes within diseases. A proliferation of consumer activity trackers gives easy access to objective sleep. We evaluated the performance of a commercial device (Fitbit Alta HR) relative to a research-grade actigraph (Actiwatch Spectrum Pro) in measuring sleep before and after a cognitive behavioural intervention in insomnia disorder. Twenty-five individuals with DSM-5 insomnia disorder (M = 50.6 ± 15.9 years) wore Fitbit and Actiwatch and completed a sleep diary during an in-laboratory polysomnogram, and for 1 week preceding and following seven weekly sessions of cognitive-behavioural intervention for insomnia. Device performance was compared for sleep outcomes (total sleep time, sleep latency, sleep efficiency and wake after sleep onset). The analyses assessed (a) agreement between devices across days and pre- to post-treatment, and (b) whether pre- to post-treatment changes in sleep assessed by devices correlated with clinical measures of change. Devices generally did not significantly differ from each other on sleep variable estimates, either night to night, in response to sleep manipulation (pre- to post-treatment) or in response to changes in environment (in the laboratory versus at home). Change in sleep measures across time from each device showed some correlation with common clinical measures of change in insomnia, but not insomnia diagnosis as a categorical variable. Overall, the Fitbit provides similar estimates of sleep outside the laboratory to a research grade actigraph. Despite the similarity between Fitbit and Actiwatch performance, the use of consumer technology is still in its infancy and caution should be taken in its interpretation.

Sleep and wake are shared and transmitted between individuals with insomnia and their bed-sharing partners.

Patients with insomnia frequently report disturbing, or being disturbed by, their bedpartner. We aimed to (1) characterize how individuals with insomnia and their bedpartners influence each other's sleep and (2) identify characteristics predicting vulnerability to wake transmission. Fifty-two couples (aged 19-82 years), where one individual was diagnosed with insomnia, participated. Sleep/wake patterns were monitored via actigraphy and sleep diaries for seven nights. Minute-by-minute sleep and wake concordance (simultaneous sleep/wake epochs), number of wake transmissions received (awakenings immediately preceded by wakefulness in the bedpartner), percent wake transmissions received (percentage of total awakenings that were transmitted), and percent of bedpartner's wake minutes resistant to transmission (ability to sleep through bedpartner wakefulness) were calculated. Mixed-effects modeling assessed within-couple bedtime and chronotype differences as predictors of dyadic sleep. We described rates of sleep concordance (MPatient = 63.8%, MPartner = 65.6%), wake concordance (MPatient = 6.6%, MPartner = 6.6%), total transmissions received (MPatient = 5.5, MPartner = 6.9 per night), percent transmissions received (MPatient = 18.5%, MPartner = 23.4% of total awakenings), and percent minutes resistant (MPatient = 56.4%, MPartner = 58.6% of bedpartner's wake time). Partners received wake transmissions at 1.25 times the rate of patients. Percent transmissions received was increased in couples with concordant bedtimes and individuals with later chronotype than their bedpartner. Patterns of chronotype and bedtime order predicting percent minutes resistant to transmission differed across the length of the rest interval. Transmission provides a novel characterization of how bedpartners influence sleep and provide insight into mechanisms of insomnia generation and maintenance. Understanding modifiable risk factors may provide ways to personalize insomnia treatments. Clinical Trial Researching Effective Sleep Treatments (Project REST), ANZCTR Registration: ACTRN12616000586415.

An Ambulatory Antimicrobial Stewardship Initiative to Improve Diagnosis and Treatment of Urinary Tract Infections in Children.

BACKGROUND: Antibiotic stewardship efforts should standardize treatment of common infections when possible. Urinary tract infections (UTIs) are common in children and require appropriate diagnostic methods and treatment. A pediatric emergency department (ED) identified an opportunity to improve care by standardizing uncomplicated UTI diagnostic testing and treatment according to local bacterial resistance patterns from January 2017 to December 2018. METHODS: Using the Model for Improvement, researchers undertook a quality improvement (QI) initiative to standardize the diagnosis and treatment of uncomplicated UTI in children ages 3 months to 12 years in a pediatric ED. Multiple Plan-Do-Study-Act (PDSA) cycles were used, engaging both nurses and physicians, to implement an evidence-based clinical algorithm. Primary aims were to achieve 100% of targeted patients with suspected UTI having appropriately ordered and collected specimens and to increase the frequency of targeted patients receiving algorithm-recommended antibiotics at discharge to 80%. Balancing measures included ED length of stay and revisits to the ED related to UTI. RESULTS: During this initiative, 458 children were assessed for UTI, of whom 75 received a UTI diagnosis. Guideline-concordant urine collection procedure improved from 54.7% to 96.2%. After project initiation, 100% of all antibiotic prescriptions for UTI were guideline-concordant. These changes have been sustained for 19 months since the initiative began. There was no change in UTI-related ED revisits or ED length of stay. CONCLUSIONS: This QI initiative achieved standardization of specimen collection and treatment for pediatric UTI in the ED setting, and no adverse outcomes were observed at the institution.

Longitudinal trends in all healthcare-associated infections through comprehensive hospital-wide surveillance and infection control measures over the past 12 years: substantial burden of healthcare-associated infections outside of intensive care units and "other" types of infection.

OBJECTIVE: Targeted surveillance has focused on device-associated infections and surgical site infections (SSIs) and is often limited to healthcare-associated infections (HAIs) in high-risk areas. Longitudinal trends in all HAIs, including other types of HAIs, and HAIs outside of intensive care units (ICUs) remain unclear. We examined the incidences of all HAIs using comprehensive hospital-wide surveillance over a 12-year period (2001-2012). METHODS: This retrospective observational study was conducted at the University of North Carolina (UNC) Hospitals, a tertiary care academic facility. All HAIs, including 5 major infections with 14 specific infection sites as defined using CDC criteria, were ascertained through comprehensive hospital-wide surveillance. Generalized linear models were used to examine the incidence rate difference by infection type over time. RESULTS: A total of 16,579 HAIs included 6,397 cases in ICUs and 10,182 cases outside ICUs. The incidence of overall HAIs decreased significantly hospital-wide (-3.4 infections per 1,000 patient days), in ICUs (-8.4 infections per 1,000 patient days), and in non-ICU settings (-1.9 infections per 1,000 patient days). The incidences of bloodstream infection, urinary tract infection, and pneumonia in hospital-wide settings decreased significantly, but the incidences of SSI and lower respiratory tract infection remained unchanged. The incidence of Clostridium difficile infection (CDI) increased remarkably. The outcomes were estimated to include 700 overall HAIs prevented, 40 lives saved, and cost savings in excess of $10 million. CONCLUSIONS: We demonstrated success in reducing overall HAIs over a 12-year period. Our data underscore the necessity for surveillance and infection prevention interventions outside of the ICUs, for non-device-associated HAIs, and for CDI.

Feeding, growth, nutrition, and optimal interstage surveillance for infants with hypoplastic left heart syndrome.

Improvement in operative survival of patients with hypoplastic left heart syndrome has led to increasing emphasis on prevention of interstage mortality. Many centres have improved interstage results through programmes of home monitoring following discharge after the Norwood (Stage 1) operation. Experience with heightened interstage surveillance has identified failure to thrive during infancy as a modifiable risk factor for this population, one that has been linked to concerning outcomes at subsequent palliative surgeries. Ensuring normal growth as an infant has thus become a priority of management of patients with functionally univentricular hearts. Herein, we review the existing evidence for best practices in interstage surveillance and optimal nutrition in infants with functionally univentricular hearts. In addition, we highlight data presented at HeartWeek 2011, from Cardiology 2011, the 15th Annual Update on Pediatric and Congenital Cardiovascular Disease, and the 11th Annual International Symposium on Congenital Heart Disease.

Role of histidine-86 in the catalytic mechanism of ferredoxin:thioredoxin reductase.

Ferredoxin:thioredoxin reductase catalyzes the reduction of thioredoxins in plant chloroplasts using the [Fe2S2] ferredoxin as a one-electron donor and as such plays a central role in light regulation of oxygenic photosynthesis. The active-site comprises a [Fe4S4] cluster next to a redox-active disulfide that is cleaved in sequential one-electron steps and the combination of spectroscopic and crystallographic studies have revealed a catalytic mechanism involving novel site specific cluster chemistry in the oxidized, one-electron- and two-electron-reduced redox states. Histidine-86 has emerged as a potential proton donor/acceptor in the catalytic mechanism based on redox-related changes in the positioning of the imidazole ring during redox cycling and greatly decreased activity for the H86Y variant. Here we report on spectroscopic and redox characterization of the [Fe4S4] center in Synechocystis sp. PCC 6803 H86Y ferredoxin:thoredoxin reductase in the accessible redox states of both the as purified and N-ethylmaleimide-modified forms, using the combination of UV-visible absorption and variable-temperature magnetic circular dichroism, EPR, resonance Raman and Mössbauer spectroscopies. The results demonstrate that His86 is required for formation of the partially valence-localized [Fe4S4]2+ cluster that is the hallmark of two-electron-reduced intermediate. Taken together with the available structural data, the spectroscopic results indicate a functional role for His86 in protonation/deprotonation of the cluster-interacting thiol and anchoring the cluster interacting thiol in close proximity to the cluster in the two-electron-reduced intermediate.

Spectroscopic characterization of site-specific [Fe(4)S(4)] cluster chemistry in ferredoxin:thioredoxin reductase: implications for the catalytic mechanism.

Light regulation of enzyme activities in oxygenic photosynthesis is mediated by ferredoxin:thioredoxin reductase (FTR), a novel class of disulfide reductase with an active site comprising a [Fe(4)S(4)](2+) cluster and an adjacent disulfide, that catalyzes reduction of the thioredoxin disulfide in two sequential one-electron steps using a [Fe(2)S(2)](2+/+) ferredoxin as the electron donor. In this work, we report on spectroscopic (EPR, VTMCD, resonance Raman, and Mössbauer) and redox characterization of the active site of FTR in various forms of the enzyme, including wild-type FTR, point-mutation variants at each of the active-site cysteine residues, and stable analogues of the one-electron-reduced FTR-Trx heterodisulfide intermediate. The results reveal novel site-specific Fe(4)S(4)-cluster chemistry in oxidized, one-electron-reduced, and two-electron-reduced forms of FTR. In the resting enzyme, a weak interaction between the Fe(4)S(4) cluster and the active-site disulfide promotes charge buildup at a unique Fe site and primes the active site to accept an electron from ferredoxin to break the disulfide bond. In one-electron-reduced analogues, cleavage of the active-site disulfide is accompanied by coordination of one of the cysteine residues that form the active-site disulfide to yield a [Fe(4)S(4)](3+) cluster with two cysteinate ligands at a unique Fe site. The most intriguing result is that two-electron-reduced FTR in which the disulfide is reduced to a dithiol contains an unprecedented electron-rich [Fe(4)S(4)](2+) cluster comprising both valence-delocalized and valence-localized Fe(2+)Fe(3+) pairs. These results provide molecular level insights into the catalytic mechanism of FTR, and two viable mechanisms are proposed.

Ferredoxin:thioredoxin Reductase: Disulfide Reduction Catalyzed via Novel Site-specific [4Fe-4S] Cluster Chemistry.

Thioredoxin-mediated light regulation in plant chloroplasts involves a unique class of disulfide reductases that catalyze disulfide reduction in two one-electron steps using a [2Fe-2S] ferredoxin as the electron donor and an active site comprising a [4Fe-4S] cluster and a redox-active disulfide. This review summarizes structural and spectroscopic studies of ferredoxin:thioredoxin reductase (FTR) and a chemically modified form, termed NEM-FTR, which provides a stable analog of the one-electron reduced catalytic intermediate. Detailed spectroscopic characterization of FTR and NEM-FTR using absorption, EPR, electron-nuclear double resonance, variable-temperature magnetic circular dichroism, resonance Raman and Mössbauer spectroscopies indicate that the one-electron reduced catalytic intermediate involves two-electron disulfide reduction coupled with one-electron cluster oxidation of a [4Fe-4S](2+) cluster to yield a unique type of S= 1/2 [4Fe-4S](3+) cluster with two cysteine residues ligated at a specific Fe site. The results provide the basis for a novel mechanism for disulfide cleavage in two one-electron steps involving site-specific [4Fe-4S] cluster chemistry. A similar mechanism is proposed for direct [4Fe-4S]-mediated cleavage of the CoM-S-S-CoB heterodisulfide in methanogenic archaea by heterodisulfide reductases.

Spectroscopic evidence for site specific chemistry at a unique iron site of the [4Fe-4S] cluster in ferredoxin:thioredoxin reductase.

Ferredoxin:thioredoxin reductase (FTR) catalyzes the reduction of the disulfide in thioredoxin in two one-electron steps using an active site comprising a [4Fe-4S] in close proximity to a redox active disulfide. Mössbauer spectroscopy has been used to investigate the ligation and electronic properties of the [4Fe-4S] cluster in as-prepared FTR which has the active-site disulfide intact and in the N-ethylmaleimide (NEM)-modified form which provides a stable analogue of the one-electron-reduced heterodisulfide intermediate and has one of the cysteines of the active-site disulfide alkylated with NEM. The results reveal novel site-specific cluster chemistry involving weak interaction of the active-site disulfide with a unique Fe site of the [4Fe-4S]2+ cluster in the resting enzyme and cleavage of the active-site disulfide with concomitant coordination of one of the cysteines to yield a [4Fe-4S]3+ cluster with a five-coordinate Fe site ligated by two cysteine residues in the NEM-modified enzyme. The results provide molecular-level insight into the catalytic mechanism of FTR and other Fe-S-cluster-containing disulfide reductases, and suggest a possible mechanism for the reductive cleavage of S-adenosylmethionine by the radical SAM family of Fe-S enzymes.