Mast cells are upregulated in hidradenitis suppurativa tissue, associated with epithelialized tunnels and normalized by spleen tyrosine kinase antagonism.

Mast cells have traditionally been associated with allergic inflammatory responses; however, they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing-associated pathways; however, the role of mast cells in the disease is unexplored. We demonstrate that mast cell-associated gene expression (using whole tissue RNAseq) is upregulated, and in-silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive mast cells (identified using IHC) localize adjacent to epithelialized tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF-alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell-associated gene transcripts, associated biochemical pathways and the number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is paralleled with B cell/plasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.

The microbiome of diabetic foot ulcers: a comparison of swab and tissue biopsy wound sampling techniques using 16S rRNA gene sequencing.

BACKGROUND: Health-care professionals need to collect wound samples to identify potential pathogens that contribute to wound infection. Obtaining appropriate samples from diabetic foot ulcers (DFUs) where there is a suspicion of infection is of high importance. Paired swabs and tissue biopsies were collected from DFUs and both sampling techniques were compared using 16S rRNA gene sequencing. RESULTS: Mean bacterial abundance determined using quantitative polymerase chain reaction (qPCR) was significantly lower in tissue biopsies (p = 0.03). The mean number of reads across all samples was significantly higher in wound swabs [Formula: see text] = 32,014) compared to tissue ([Formula: see text] = 15,256, p = 0.001). Tissue biopsies exhibited greater overall diversity of bacteria relative to swabs (Shannon's H diversity p = 0.009). However, based on a presence/absence analysis of all paired samples, the frequency of occurrence of bacteria from genera of known and potential pathogens was generally higher in wound swabs than tissue biopsies. Multivariate analysis identified significantly different bacterial communities in swabs compared to tissue (p = 0.001). There was minimal correlation between paired wound swabs and tissue biopsies in the number and types of microorganisms. RELATE analysis revealed low concordance between paired DFU swab and tissue biopsy samples (Rho = 0.043, p = 0.34). CONCLUSIONS: Using 16S rRNA gene sequencing this study identifies the potential for using less invasive swabs to recover high relative abundances of known and potential pathogen genera from DFUs when compared to the gold standard collection method of tissue biopsy.

Evaluation of short exposure times of antimicrobial wound solutions against microbial biofilms: from in vitro to in vivo.

Objectives: Test the performance of topical antimicrobial wound solutions against microbial biofilms using in vitro, ex vivo and in vivo model systems at clinically relevant exposure times. Methods: Topical antimicrobial wound solutions were tested under three different conditions: (in vitro) 4% w/v Melaleuca oil, polyhexamethylene biguanide, chlorhexidine, povidone iodine and hypochlorous acid were tested at short duration exposure times for 15 min against 3 day mature biofilms of Staphylococcus aureus and Pseudomonas aeruginosa; (ex vivo) hypochlorous acid was tested in a porcine skin explant model with 12 cycles of 10 min exposure, over 24 h, against 3 day mature P. aeruginosa biofilms; and (in vivo) 4% w/v Melaleuca oil was applied for 15 min exposure, daily, for 7 days, in 10 patients with chronic non-healing diabetic foot ulcers complicated by biofilm. Results: In vitro assessment demonstrated variable efficacy in reducing biofilms ranging from 0.5 log10 reductions to full eradication. Repeated instillation of hypochlorous acid in a porcine model achieved <1 log10 reduction (0.77 log10, P = 0.1). Application of 4% w/v Melaleuca oil in vivo resulted in no change to the total microbial load of diabetic foot ulcers complicated by biofilm (median log10 microbial load pre-treatment = 4.9 log10 versus 4.8 log10, P = 0.43). Conclusions: Short durations of exposure to topical antimicrobial wound solutions commonly utilized by clinicians are ineffective against microbial biofilms, particularly when used in vivo. Wound solutions should not be used as a sole therapy and clinicians should consider multifaceted strategies that include sharp debridement as the gold standard.

Effect of cadexomer iodine on the microbial load and diversity of chronic non-healing diabetic foot ulcers complicated by biofilm in vivo.

Objectives: The performance of cadexomer iodine was determined against microbial populations from chronic non-healing diabetic foot ulcers (DFUs) complicated by biofilm in vivo , using molecular, microscopy and zymography methods. Methods: Chronic non-healing DFUs due to suspected biofilm involvement were eligible for enrolment. DNA sequencing and real-time quantitative PCR was used to determine the microbial load and diversity of tissue punch biopsies obtained pre- and post-treatment. Scanning electron microscopy and/or fluorescence in situ hybridization confirmed the presence or absence of biofilm. Zymography was used to determine levels of wound proteases. Results: Seventeen participants were recruited over a 6 month period. Scanning electron microscopy and or fluorescence in situ hybridization confirmed the presence of biofilm in all samples. Eleven participants exhibited log 10 reductions in microbial load after treatment (range 1-2 log 10 ) in comparison with six patients who experienced <1 log 10 reduction ( P = 0.04). Samples were tested for levels of wound proteases pre- and post-treatment. Reductions in the microbial load correlated to reductions in wound proteases pre- and post-treatment ( P = 0.03). Conclusions: To the best of our knowledge, this study represents the first in vivo evidence, employing a range of molecular and microscopy techniques, of the ability of cadexomer iodine to reduce the microbial load of chronic non-healing DFUs complicated by biofilm. Further analyses correlating log reductions to optimal duration of therapy and improvements in clinical parameters of wound healing in a larger cohort are required.

Can molecular DNA-based techniques unravel the truth about diabetic foot infections?

Diabetes foot infections are a common condition and a major causal pathway to lower extremity amputation. Identification of causative pathogens is vital in directing antimicrobial therapy. Historically, clinicians have relied upon culture-dependent techniques that are now acknowledged as both being selective for microorganisms that thrive under the physiological and nutritional constraints of the microbiology laboratory and that grossly underestimate the microbial diversity of a sample. The amplification and sequence analysis of the 16S rRNA gene has revealed a diversity of microorganisms in diabetes foot infections, extending the view of the diabetic foot microbiome. The interpretation of these findings and their relevance to clinical care remains largely unexplored. The advent of molecular methods that are culture-independent and employ massively parallel DNA sequencing technology represents a potential 'game changer'. Metagenomics and its shotgun approach to surveying all DNA within a sample (whole genome sequencing) affords the possibility to characterize not only the microbial diversity within a diabetes foot infection (i.e. 'which microorganisms are present') but the biological functions of the community such as virulence and pathogenicity (i.e. 'what are the microorganisms capable of doing'), moving the focus from single species as pathogens to groups of species. This review will examine the new molecular techniques for exploration of the microbiome of infected and uninfected diabetic foot ulcers, exploring the potential of these new technologies and postulating how they could translate to improved clinical care. Copyright © 2016 John Wiley & Sons, Ltd.

Surfactants and their role in wound cleansing and biofilm management.

Surfactants are widely used as detergents, emulsifiers, wetting agents, foaming agents and dispersants in the cosmetics, hygiene, food and oil industries. Their use in a clinical setting is also common, particularly within the field of wound care. Many wound cleansers contain surfactants and subsequently there is available data that shows the growing potential of these wound cleansers in the enhancement of wound closure. The presence of microorganisms in wounds has been recognised as a significant factor that delay healing. In complex or chronic wounds that are complicated by biofilms, persistent inflammation or the production of non-viable tissue and slough, the use of surfactants has been shown to aid in the removal of these barriers to wound healing. The use of concentrated surfactant(poloxamer) based wound dressings represent an important component of wound management. Consequently, this article will discuss the effect of clinically used surfactants, with specific focus on a concentrated poloxamer for use against wound biofilm.

The prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data.

The presence of biofilms in chronic non-healing wounds, has been identified through in vitro model and in vivo animal data. However, human chronic wound studies are under-represented and generally report low sample sizes. For this reason we sought to ascertain the prevalence of biofilms in human chronic wounds by undertaking a systematic review and meta-analysis. Our initial search identified 554 studies from the literature databases (Cochrane Library, Embase, Medline). After removal of duplicates, and those not meeting the requirements of inclusion, nine studies involving 185 chronic wounds met the inclusion criteria. Prevalence of biofilms in chronic wounds was 78.2 % (confidence interval [CI 61.6-89, p<0.002]). The results of our meta-analysis support our clinical assumptions that biofilms are ubiquitous in human chronic non-healing wounds.

AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies.

BACKGROUND: AZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD). METHODS: In study 1 and 2, castration-resistant prostate cancer (CRPC) patients (pts) were initially recruited into a once daily (QD) oral schedule (A). In study 1, pharmacokinetic assessments led to twice daily (BID) dosing (schedule B) to increase exposure. Study 2 explored a once daily schedule. RESULTS: In study 1, 49 pts were treated with escalating doses of AZD3514 (A 35 pts, B 14 pts). Starting doses were 100 mg (A) and 1000 mg (B). The AZD3514 formulation was switched from capsules to tablets at 1000 mg QD. 2000 mg BID was considered non-tolerable due to grade (G) 2 toxicities (nausea [N], vomiting [V]). No adverse events (AEs) met the dose-limiting toxicity (DLT) definition. Thirteen pts received AZD3514 in study 2, with starting doses of 250 mg QD. The most frequent drug-related AEs were N: G1/2 in 55/70 pts (79 %); G3 in 1 pt (1.4 %); & V: G1/2 in 34/70 pts (49 %) & G3 in 1 pt (1.4 %). PSA declines (≥50 %) were documented in 9/70 patients (13 %). Objective soft tissue responses per RECIST1.1 were observed in 4/24 (17 %) pts in study 1. CONCLUSION: AZD3514 has moderate anti-tumour activity in pts with advanced CRPC but with significant levels of nausea and vomiting. However, anti-tumour activity as judged by significant PSA declines, objective responses and durable disease stabilisations, provides the rationale for future development of SARD compounds.

Providers' beliefs about the effectiveness of the HPV vaccine in preventing cancer and their recommended age groups for vaccination: Findings from a provider survey, 2012.

BACKGROUND: The human papillomavirus (HPV) vaccine was recommended in 2007 by the Advisory Committee on Immunization Practices (ACIP) to preadolescent and adolescent girls. Vaccination initiation was recommended at age 11-12 years with the option to start at age 9. Catchup vaccination was recommended to females aged 13-26 previously not vaccinated. However, vaccination coverage remains low. Studies show that the HPV vaccine can prevent cervical, vulvar, vaginal, anal and some oropharyngeal cancers and that provider recommendation of vaccines can improve low vaccination rates. METHODS: Using data from 2012 DocStyles, an annual, web-based survey of U.S. healthcare professionals including physicians and nurse practitioners (n=1753), we examined providers' knowledge about the effectiveness of the HPV vaccine in preventing cancer and their vaccine recommendation to all age-eligible females (9-26 years). Descriptive statistics and Chi-square tests were used to assess differences across specialties. RESULTS: Knowledge about HPV vaccine effectiveness in preventing cervical cancer was highly prevalent (96.9%), but less so for anal, vaginal, vulvar and oropharyngeal cancers. Only 14.5% of providers recommended the vaccine to all age-eligible females and 20.2% recommended it to females aged 11-26 years. Knowledge assessment of cancers associated with HPV and vaccination recommendations varied significantly among providers (p<0.01). Providers more frequently recommended the vaccine to girls older than 11-12 years. CONCLUSIONS: Improving providers' knowledge about HPV-associated cancers and the age for vaccination initiation, communicating messages focusing on the vaccine safety and benefits in cancer prevention and on the importance of its delivery prior to sexual onset, may improve HPV vaccine coverage.

The effect of diabetes mellitus on costs and length of stay in patients with peripheral arterial disease undergoing vascular surgery.

OBJECTIVE: To determine the impact of diabetes mellitus (DM) and other comorbidities on length of stay (LOS) and costs in patients with peripheral arterial disease (PAD) admitted to a vascular surgical unit. METHODS: A retrospective study was conducted between January 2011 and July 2012 at a tertiary referral hospital in Sydney. Demographic, laboratory, and operative data were obtained from the Australasian Vascular Audit database and hospital diagnostic-related group (DRG) reports. Patients with confirmed PAD with or without DM requiring hospital admission for a diagnosis of claudication, rest pain, ulcer/gangrene, and infection that required lower limb surgical intervention were included. Associations between LOS, surgical procedure, and DRG were explored. RESULTS: Five hundred and sixty-eight admissions (492 patients) were identified: 292 admissions with PAD and 276 admissions with PAD in conjunction with DM (PADDM). Mean LOS for patients with PAD was 10 ± 13.7 days compared with 15 ± 18.2 days for PADDM (p < .01; 95% confidence interval 2.7-8.0). LOS and costs were greatest in patients with PADDM undergoing major amputation (37 ± 13.7 days; US$42,236; p < .01). Analysis of variance indicated that the best predictors of LOS were the presence of DM, bypass surgery, amputation, chronic kidney disease (CKD) stage V, infection, and emergency admission. Over 18 months, the estimated total inpatient costs associated with lower limb intervention for PAD with and without DM amounted to US$7,598,597. People with DM incurred greater inpatient costs, averaging US$1,912 more per episode of admission and a total of US$528,029 over 18 months. CONCLUSION: The impact of diabetes as a comorbid condition in patients with PAD is significant, both clinically and economically. Factors that predict increased LOS in patients with PAD are DM, bypass surgery, amputation, CKD stage V, infection, and emergency admission.

Deep wound cultures correlate well with bone biopsy culture in diabetic foot osteomyelitis.

BACKGROUND: Osteomyelitis is a major complication in patients with diabetic foot ulceration. Accurate pathogenic identification of organisms can aid the clinician to a specific antibiotic therapy thereby preventing the need for amputation. METHODS: All diabetic patients with bone biopsy-confirmed osteomyelitis were included into the study: biopsies were performed either during surgical removal of infected bone or percutaneously under guided fluoroscopy through non-infected tissue. The depth and extent of the ulcer was assessed using a sterile blunt metal probe. Deep wound cultures were taken from the wound base after sharp debridement. RESULTS: Of 66 cases of suspected osteomyelitis in 102 joints, 34 patients had both bone biopsies and deep wound cultures over the study period. Thirty two of 34 (94%), had a history of preceding foot ulceration, and in 25 of the cases a positive probe to bone test was recorded. In a high proportion of patients, at least one similar organism was isolated from both the deep wound culture and bone biopsy procedures (25 of 34 cases, 73.5%, p<0.001). When organisms were isolated from both wound cultures and bone biopsies, the identical strain was identified in both procedures in a significant proportion of cases (16 of 25 cases, 64%, p<0.001, total sample analysis in 16 of 34 cases, 47%). CONCLUSIONS: Deep wound cultures correlate well with osseous cultures and provide a sensitive method in assessing and targeting likely pathogens that cause osseous infections. This will help aid the clinician in guiding antibiotic therapy in centers where bone biopsies may not be readily available.

First Report of Verticillium Wilt Caused by Verticillium nonalfalfae on Tree-of-Heaven (Ailanthus altissima) in Ohio.

Verticillium wilt of the highly invasive tree-of-heaven [Ailanthus altissima (Mill.) Swingle], caused by Verticillium nonalfalfae Interbitzin et al. (1), formerly classified as V. albo-atrum Reinke and Berthold, has been reported in the United States from two states: Pennsylvania (2) and Virginia (3). Infected A. altissima in both states exhibited similar symptoms of wilt, premature defoliation, terminal dieback, yellow vascular discoloration, and mortality. In June 2012, the second author observed dead and dying A. altissima trees in southern Ohio (Pike County) that exhibited symptoms similar to those on diseased A. altissima trees in Pennsylvania and Virginia. Samples were collected from stems of three symptomatic A. altissima trees and sent to Penn State for morphological and molecular identification. Immediately upon arrival, samples were surface-disinfected and plated onto plum extract agar (PEA), a semi-selective medium for Verticillium spp., amended with neomycin and streptomycin (2). The samples yielded six isolates, two from each of the three symptomatic trees, all of which were putatively identified as V. nonalfalfae based on the presence of verticillate conidiophores and formation of melanized hyphae. DNA was extracted from three isolates and molecular analyses performed using known primers (1) coding for elongation factor 1-alpha (EF), glyceraldehyde-3-phosphate dehydrogenase (GPD), and tryptophan synthase (TS). A BLAST search generated sequences that revealed 100% similarity to V. nonalfalfae for all three protein coding genes among the three Ohio isolates and reference sequences from Ailanthus, including isolates VnAaPA140 (GenBank Accession Nos. KC307764, KC307766, and KC307768) and VnAaVA2 (KC307758, KC307759, and KC307760), as well as isolate PD592 from potato (JN188227, JN188163, and JN188035), thereby confirming taxonomic placement of the Ohio Ailanthus isolates among those recovered from Ailanthus in Pennsylvania and Virginia. Aligned sequences from one representative isolate, VnAaOH1, were deposited into GenBank as accessions KC307761 (EF), KC307762 (GPD), and KC307763 (TS). In August 2012, the pathogenicity of all six isolates was confirmed by root-dipping 10 healthy 3-week-old A. altissima seedlings (seeds collected in University Park, PA) into conidial suspensions of 1 × 107 cfu/ml, wherein all inoculated seedlings wilted and died within 4 and 9 weeks, respectively. V. nonalfalfae was reisolated from all inoculated seedlings; control seedlings inoculated with distilled water remained asymptomatic. Ohio is the third state from which V. nonalfalfae has been reported to be pathogenic on A. altissima. If V. nonalfalfae proves to be widespread, it may represent a natural biocontrol for the invasive A. altissima. Also, since USDA APHIS evaluates and regulates new potential biocontrol agents on a state-by-state basis, it is important to document each state in which V. nonalfalfae is killing A. altissima, so that in-state inoculum can be used for biocontrol efforts, simplifying the regulatory process. References: (1) P. Inderbitzin et al. 2011 PLoS ONE, 6, e28341, 2011. (2) M. J. Schall and D. D. Davis. Plant Dis. 93:747, 2009. (3) A. L. Snyder et al. Plant Dis. 96:837, 2013.

Pedal osteomyelitis in patients with diabetes: a retrospective audit from Saudi Arabia.

OBJECTIVE: To examine the characteristics of patients presenting to the emergency room and the specialist diabetes foot clinic with pedal osteomyelitis (PO). METHOD: A retrospective study was conducted at a regional hospital. The charts of patients with suspected PO who presented during the period 1 January to 31 December 2011 were analysed. Demographics, biochemistry and microbiological data were obtained. Bone biopsies were performed by the attending clinician either during surgical removal of infected bone, or percutaneously under guided fluoroscopy through non-infected tissue. RESULTS: Sixty-six cases of osteomyelitis affecting 102 joints were noted. The study population consisted of 44 men, mean age 62.9 +/- 1.3 years, and 22 women, mean age of 57.6 +/- 10.6 years. Gram-positive bacteria were the predominating pathogens (p < 0.05). Staphylococcus aureus was cultured in 36% of all bone biopsy cases. A predictive trend in HbA1c was observed,where every increase of 1% from the recommended level of 7% was associated with a 10% increase in the likelihood of receiving surgical intervention. CONCLUSION: S. aureus infection is a major cause of osteomyelitis in interphalangeal joints of the feet of diabetic patients.There is an apparent association with patients who present with diabetic foot osteomyelitis and sub-optimal glycaemic control, requiring surgical intervention.

Rabi and Larmor nuclear quadrupole double resonance of spin-1 nuclei.

We demonstrate the creation of two novel double-resonance conditions between spin-1 and spin-1/2 nuclei in a crystalline solid. Using a magnetic field oscillating at the spin-1/2 Larmor frequency, the nuclear quadrupole resonance (NQR) frequency is matched to the Rabi or Rabi plus Larmor frequency, as opposed to the Larmor frequency as is conventionally done. We derive expressions for the cross-polarization rate for all three conditions in terms of the relevant secular dipolar Hamiltonian, and demonstrate with these expressions how to measure the strength of the heterogenous dipolar coupling using only low magnetic fields. In addition, the combination of different resonance conditions permits the measurement of the spin-1/2 angular momentum vector using spin-1 NQR, opening up an alternate modality for the monitoring of low-field nuclear magnetic resonance. We use ammonium nitrate to explore these resonance conditions, and furthermore use the oscillating field to increase the signal-to-noise ratio per time by a factor of 3.5 for NQR detection of this substance.

A process evaluation of Promotional Guides used by health visitors to support men's transition to fatherhood: a qualitative study.

BACKGROUND: Health visitors play an important role in supporting new parents in their transition to parenthood. A programme known as the Promotional Guide system is used by many health visitors in England with mothers and fathers to support this transition, but there is little known about health visitors' views of the Promotional Guides, how they are used in practice or barriers to effective implementation with fathers. AIMS: The aim of this study was to explore the following: (1) health visitors' use of Promotional Guides with fathers, (2) health visitors' assessment of father's mental health and wellbeing and (3) facilitators and barriers to using Promotional Guides in practice. METHODS: A prospective observational cohort study and a process evaluation informed by the Medical Research Council guidance were conducted. A purposive sample of 11 health visitors was interviewed, and an additional seven were observed using the Promotional Guides in practice. Data were analysed using framework analysis. RESULTS: Five main themes were identified from interview and observational data as follows: (1) Enquiry into fathers' mental health, (2) Promotional Guides in practice, (3) health visitors' perceptions of the Promotional Guides system, (4) barriers to using Promotional Guides with fathers and (5) facilitators and recommendations for using Promotional Guides with fathers. This study identified a number of barriers and facilitators to the use of Promotional Guides with fathers. Recommendations were made for improving services for first-time fathers, implementing the Promotional Guide system with fathers and highlighting areas for future research. CONCLUSION: This study considered the acceptability, feasibility and fidelity of using the Promotional Guide programme with fathers from the health visitor's perspective. The findings provided an insight into health visitors' experiences of working with fathers, inquiring about men's mental health needs and their use of the Promotional Guides with men during the perinatal period.

Flexible and rigid casting tape as a novel approach to offloading diabetic foot ulcers.

Offloading diabetic ulceration is a key component to the success in healing ulcers on the plantar aspect of the foot. New advances in offloading techniques allow for differing approaches in sometimes complex diabetic foot pathologies with associated ulceration. This case study looks at the use of flexible and rigid casting technique as part of the treatment in offloading plantar foot ulceration.

Staphylococcal toxins in sudden unexpected death in infancy: experience from a single specialist centre.

Around two thirds of sudden unexpected deaths in infancy (SUDI) remain unexplained following post-mortem examination. It has been postulated that a subset of unexplained SUDI may be caused by toxigenic Staphylococcus aureus. The aim of this study was to compare the prevalence of toxigenic S aureus strains in unexplained and explained SUDI (those in whom a cause of death is determined at autopsy). A retrospective review was performed of 546 SUDI autopsies as part of a larger review of >1,500 pediatric autopsies over a 10-year period, 1996-2005 inclusive. SUDI was defined as the sudden and unexpected death of an infant aged 7-365 days, and categorized into unexplained, explained with histological evidence of infection (bacterial infection group) or explained due to non-infective causes. Toxin gene profiling was carried out by PCR in cases in whom S aureus was isolated as part of clinical investigation. Of the 507 SUDI included in this analysis, bacteriological investigations were performed in 470, and S aureus was isolated on post-mortem culture from at least one site in 173 (37%). There were significantly more cases with S aureus isolated in unexplained SUDI (40%) compared to non-infective SUDI (21%; difference 19.0%, 95% CI 5.4% to 29.3%, P = 0.006). 46% of all cases with S aureus isolated underwent routine testing for a panel of staphylococcal toxin genes (including SEA to SEE, SEG to SEJ, TSST-1, and exfoliative toxins A and B). There were more cases with at least one toxigenic strain of S aureus in the unexplained SUDI (81%) and bacterial infection groups (77%) than in the non-infection group (63%), but these differences were not statistically significant (Fisher exact test, P = 0.44). Toxin gene-carrying S aureus is commonly detected at autopsy in SUDI, accounting for 78% of S aureus isolates submitted for toxin gene profiling in this series. There is a significantly higher prevalence of S aureus in unexplained SUDI compared to non-infective SUDI, but no significant difference in the proportion with toxigenic S aureus strains isolated between the groups. These data are consistent with the hypothesis that a subset of otherwise unexplained SUDI may be related to the presence of S aureus colonization/infection, but do not indicate routine testing for toxin-associated genotypes.

Randomized Controlled Trial of a Cohesive Eight-Week Evolution Unit That Incorporates Molecular Genetics and Principles of the Next Generation Science Standards.

In response to calls for curricular materials that integrate molecular genetics and evolution and adhere to the K-12 Next Generation Science Standards (NGSS), the Genetic Science Learning Center (GSLC) at the University of Utah has developed and tested the "Evolution: DNA and the Unity of Life" curricular unit for high school biology. The free, 8-week unit illuminates the underlying role of molecular genetics in evolution while providing scaffolded opportunities to engage in making arguments from evidence and analyzing and interpreting data.  We used a randomized controlled trial design to compare student learning when using the new unit with a condition in which teachers used their typical (NGSS-friendly) units with no molecular genetics. Results from nationwide testing with 38 teachers (19 per condition) and their 2269 students revealed that students who used the GSLC curriculum had significantly greater pre/post gain scores in their understanding of evolution than students in the comparison condition; the effect size was moderate. Further, teacher implementation data suggest that students in the treatment condition had more opportunities to engage in argumentation from evidence and have in-class discussions than students in the comparison classes. We consider study implications for the secondary and postsecondary science education community.

Transition of care for pediatric and adult patients with venous thromboembolism: A National Quality Improvement Project from the American Thrombosis and Hemostasis Network (ATHN).

BACKGROUND: Transition of care (TOC) for management of anticoagulation from inpatient to outpatient setting for patients with acute venous thromboembolism (VTE) poses serious safety concerns. We implemented a national quality improvement educational initiative to address this issue. METHODS: Pediatric and adult patients admitted for their first VTE were prospectively enrolled at 16 centers from January 2016 to December 2018. Patient demographics, VTE diagnosis, risk factors, and treatment characteristics were collected. There were two phases: pre-intervention (PI) and quality intervention (QI). The PI phase assessed the quality and patient understanding and satisfaction of anticoagulation instructions given at hospital discharge and adherence to these instructions via a patient and/or caregiver feedback questionnaire (PFQ) and a patient knowledge questionnaire (PKQ) at 30 days. The QI phase provided patient and/or caregiver enhanced education regarding anticoagulation therapy and VTE at hospital discharge using a comprehensive discharge instruction module and a phone call follow-up at one week. Patient and/or caregiver knowledge at 7 and 30 days was assessed with the same PFQ and PKQ and compared to the PI baseline measures. RESULTS: Of the 409 study patients, 210 (51%) were adults, 218 (53%) females, and 316 (77%) White. Deep vein thrombosis (62.8%) and pulmonary embolism (47.9%) were the most common VTE in children and adults, respectively. Day 30 PFQ scores were significantly higher in the QI phase compared to the PI phase by 11% (p < 0.01). Day 30 PKQ demonstrated enhanced teaching (93.7% vs. 83.5%, p-value 0.004) and disease recognition (89.6% vs. 84.6% p = 0.03) in the QI phase than the PI phase. CONCLUSION: Comprehensive VTE discharge instructions followed by a 1-week post-discharge phone call strengthen patient and caregiver knowledge, satisfaction of education given and care provided, and disease recognition.

Remission of paroxysmal atrial fibrillation with iron reduction in haemophilia A.

SUMMARY: Two male first cousins with mild haemophilia A had baseline factor VIII levels of 12-15% and experienced bleeding requiring coagulation factor infusion therapy with trauma and surgical procedures. Both the patients with haemophilia A also had electrocardiographically documented symptomatic paroxysmal atrial fibrillation (PAF) for several years that had become resistant to pharmacological suppression. Radiofrequency ablation was considered in both the cases but deferred considering refusal of consent by the patients to undergo the procedure. Remission of arrhythmias has been reported in patients with iron-overload syndromes. Body iron stores assessed by serum ferritin levels were elevated in both men but neither had the C282Y or H63D genes for haemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was followed by remission of symptomatic PAF in both cases. Iron reduction may be an effective treatment for arrhythmias apart from the classic iron-overload syndromes and deserves further study particularly in patients with bleeding disorders who might be at risk for arrhythmias and other diseases of ageing.