New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Robotic-assisted seminal vesiculectomy for treatment of refractory hematospermia.

Hematospermia is a common, but anxiety-provoking genitourinary condition. In instances without spontaneous resolution, pharmacologic intervention with a 5-alpha reductase inhibitor has been shown to be successful. In cases of refractory hematospermia, robotic-assisted laparoscopic seminal vesiculectomy may provide a definitive treatment option. A robotic-assisted bilateral seminal vesiculectomy was performed on a 42-year-old male with refractory painless hematospermia after failing conservative management. Three months post-operatively, the patient reported resolution of hematospermia after six ejaculations with no impact on erectile function. The robotic-assisted approach is safe and feasible with good functional outcomes and reduced morbidity.

The Relationship Between Attention, Sensory Processing, and Social Responsiveness Among Adults on the Autism Spectrum.

This study evaluated attention, sensory processing, and social responsiveness and the relationship between these constructs among autistic and neurotypical adults. Participants included 24 autistic adults (17-30 years) and 24 neurotypical peers who completed the Test of Everyday Attention, Adolescent/Adult Sensory Profile (AASP), and the Social Responsiveness Scale-2. Autistic individuals showed greater attention, sensory processing, and social responsiveness challenges compared to neurotypical peers. Using mediation models, we showed that the relationship between attention and social responsiveness was mediated by sensory processing, specifically the low registration and sensation-seeking AASP quadrants. The relationship between attention, sensory processing, and social responsiveness suggests that adults with greater attention issues may have greater sensory and social challenges. Specifically, having poor attention may lead to poor sensory processing skills which compound poor social responsiveness. Understanding the relationships between these domains is critical for developing effective interventions and support for autistic adults.

Persistent villous atrophy predicts development of complications and mortality in adult patients with coeliac disease: a multicentre longitudinal cohort study and development of a score to identify high-risk patients.

OBJECTIVE: Persistent villous atrophy (pVA) in coeliac disease (CD) despite a gluten-free diet (GFD) has unclear meaning. We aimed to (i) study the relationship between pVA and long-term outcomes and (ii) develop a score to identify patients at risk of pVA. DESIGN: This is a multicentre retrospective-prospective study consisting of a study cohort (cohort 1) and an external validation cohort (cohort 2) of patients with biopsy-proven CD diagnosed between 2000 and 2021. Cohort 1 was used to (i) compare long-term outcomes between patients with and without pVA (Marsh ≥3a) at follow-up biopsy and (ii) to develop a score to evaluate the risk of pVA, which was validated in cohort 2. RESULTS: Of 2211 patients, 694 (31%) underwent follow-up duodenal biopsy and were included in the study cohort (491F, 44±16 years). 157/694 (23%) had pVA. Risk of complications (HR 9.53, 95% CI 4.77 to 19.04, p<0.001) and mortality (HR 2.93, 95% CI 1.43 to 6.02, p<0.01) were increased in patients with pVA. A 5-point score was developed and externally validated (receiver operating characteristic area under the curve 0.78, 95% CI 0.68 to 0.89) to stratify patients by risk of pVA: low (0-1 points, 5% pVA), intermediate (2 points, 16% pVA) and high (3-5 points, 73% pVA). Predictors for pVA used in the score were age at diagnosis ≥45 years (OR 2.01, 95% CI 1.21 to 3.34, p<0.01), classical pattern of CD (OR 2.14, 95% CI 1.28 to 3.58, p<0.01), lack of clinical response to GFD (OR 2.40, 95% CI 1.43 to 4.01, p<0.001) and poor GFD adherence (OR 48.9, 95% CI 26.1 to 91.8, p<0.001). CONCLUSIONS: Risk of complications and mortality were increased in patients with pVA. We developed a score to identify patients at risk of pVA and in need of histological reassessment and closer follow-up.

Feasibility of telehealth counselling pilot for people experiencing homelessness and/or complex needs: During COVID-19 and beyond.

ISSUES ADDRESSED: People experiencing homelessness and/or complex needs often require targeted health services to address unique vulnerabilities. COVID-19 restrictions acted as a barrier for this group accessing health and alcohol and other drug (AOD) treatment services. The Haymarket Foundation, an accommodation and health facility in Australia, transitioned from in-person AOD-counselling services to online consultations. Clients accessing these services were tracked, from March 2019 to November 2020, to assess the impact of the switch to telehealth on client retention. METHODS: Qualitative analysis of Haymarket clients' service experience surveys and quantitative descriptives of "no-show" (nonattended sessions) rates and survival analysis of client treatment separations were completed to assess the impact of transitioning to telehealth on client retention. RESULTS: Although the initial transition to telehealth in March 2020 minimally impacted client no-show rates, reinstated government restrictions in June/July 2020 coincided with increasing no-shows and a substantial increase in treatment exits without notice, especially amongst males. Qualitative analysis showed clients had mixed feelings towards telehealth: some attributed their dissatisfaction to the inability to build rapport with their counsellor online, or with COVID-19 in general. Others appreciated the availability and genuine care of their counsellors through either setting. CONCLUSIONS: Telehealth may be a feasible replacement for face-to-face AOD counselling for people experiencing homelessness, however further investigation needs to be conducted to understand factors associated with improved client retention. SO WHAT?: This pilot demonstrates telehealth may be a feasible ongoing feature of health promotion for vulnerable high-needs populations, including people experiencing homelessness who use substances.

The impact of the built environment on loneliness: A systematic review and narrative synthesis.

Loneliness is a pressing public health issue. Although quintessentially individual, it is shaped by wider environmental, cultural, socio-economic, and political circumstances. Using a systematic review methodology, this paper draws on interdisciplinary research to conceptualise the relationship between the built environment and loneliness. We present a narrative synthesis of 57 relevant studies to characterise the body of evidence and highlight specific built-environment elements. Our findings demonstrate the need for further conceptual and empirical explorations of the multifaceted ways in which built environments can prevent loneliness, supporting calls for investment into this public-health approach.

Measurement Properties of Smartphone Approaches to Assess Physical Activity in Healthy Young People: Systematic Review.

BACKGROUND: Physical inactivity is a preventable risk factor for several chronic diseases and one of the driving forces behind the growing global burden of disease. Recent evidence has shown that interventions using mobile smartphone apps can promote a significant increase in physical activity (PA) levels. However, the accuracy and reliability of using apps is unknown. OBJECTIVE: The aim of our review was to determine the accuracy and reliability of using mobile apps to measure PA levels in young people. We conducted a systematic review guided by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). METHODS: Studies published from 2007 to 2020 were sourced from 8 databases-Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsychINFO (EBSCOhost), CINAHL (EBSCOhost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost), and IEEE Xplore Digital Library database. Studies were conducted in young people aged 10-24 years and without chronic illnesses, who evaluated a mobile app's ability to measure PA. Primary outcomes included validity, reliability, and responsiveness of the measurement approach. Duplicate screening was conducted for eligibility, data extraction, and assessing the risk of bias. Results were reported as a systematic review. The main physical activity measures evaluated for each study were the following: total PA time (min/day or min/week), total moderate to vigorous PA per week, daily step count, intensity measure (heart rate), and frequency measure (days per week). RESULTS: Of the 149 identified studies, 5 met the inclusion criteria (322 participants, 176 female; mean age 14, SD 3 years). A total of 3 studies measured criterion validity and compared PA measured via apps against PA measured via an Actigraph accelerometer. The 2 studies that reported on construct validity identified a significant difference between self-reported PA and the objective measure. Only 1 of the 5 apps examined was available to the public, and although this app was highly accepted by young people, the app recorded PA to be significantly different to participants' self-reported PA. CONCLUSIONS: Overall, few studies assess the reliability, validity, and responsiveness of mobile apps to measure PA in healthy young people, with studies typically only reporting on one measurement property. Of the 3 studies that measured validity, all concluded that mobile phones were acceptable and valid tools. More research is needed into the validity and reliability of smartphone apps to measure PA levels in this population as well as in populations with other characteristics, including other age groups and those with chronic diseases. TRIAL REGISTRATION: PROSPERO CRD42019122242; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=122242.

Measurement Properties of Smartphone Approaches to Assess Diet, Alcohol Use, and Tobacco Use: Systematic Review.

BACKGROUND: Poor diet, alcohol use, and tobacco smoking have been identified as strong determinants of chronic diseases, such as cardiovascular disease, diabetes, and cancer. Smartphones have the potential to provide a real-time, pervasive, unobtrusive, and cost-effective way to measure these health behaviors and deliver instant feedback to users. Despite this, the validity of using smartphones to measure these behaviors is largely unknown. OBJECTIVE: The aim of our review is to identify existing smartphone-based approaches to measure these health behaviors and critically appraise the quality of their measurement properties. METHODS: We conducted a systematic search of the Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsycINFO (EBSCOhost), CINAHL (EBSCOHost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost), and IEEE Xplore Digital Library databases in March 2020. Articles that were written in English; reported measuring diet, alcohol use, or tobacco use via a smartphone; and reported on at least one measurement property (eg, validity, reliability, and responsiveness) were eligible. The methodological quality of the included studies was assessed using the Consensus-Based Standards for the Selection of Health Measurement Instruments Risk of Bias checklist. Outcomes were summarized in a narrative synthesis. This systematic review was registered with PROSPERO, identifier CRD42019122242. RESULTS: Of 12,261 records, 72 studies describing the measurement properties of smartphone-based approaches to measure diet (48/72, 67%), alcohol use (16/72, 22%), and tobacco use (8/72, 11%) were identified and included in this review. Across the health behaviors, 18 different measurement techniques were used in smartphones. The measurement properties most commonly examined were construct validity, measurement error, and criterion validity. The results varied by behavior and measurement approach, and the methodological quality of the studies varied widely. Most studies investigating the measurement of diet and alcohol received very good or adequate methodological quality ratings, that is, 73% (35/48) and 69% (11/16), respectively, whereas only 13% (1/8) investigating the measurement of tobacco use received a very good or adequate rating. CONCLUSIONS: This review is the first to provide evidence regarding the different types of smartphone-based approaches currently used to measure key behavioral risk factors for chronic diseases (diet, alcohol use, and tobacco use) and the quality of their measurement properties. A total of 19 measurement techniques were identified, most of which assessed dietary behaviors (48/72, 67%). Some evidence exists to support the reliability and validity of using smartphones to assess these behaviors; however, the results varied by behavior and measurement approach. The methodological quality of the included studies also varied. Overall, more high-quality studies validating smartphone-based approaches against criterion measures are needed. Further research investigating the use of smartphones to assess alcohol and tobacco use and objective measurement approaches is also needed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-https://doi.org/10.1186/s13643-020-01375-w.

Unusual Thyroid Mass in an Adolescent Patient.

Hurthle cell tumors are rare follicular-derived thyroid neoplasms. Hurthle cell tumors may be benign or malignant. Workup includes imaging, fine needle aspiration, and treatment usually consists of observation versus thyroidectomy. We describe a case of Hurthle cell adenoma in an adolescent; to the best of our knowledge, this represents only the third case described in the English literature of adolescent Hurthle cell adenoma.

Biochemical transition during triphasic postpartum thyroiditis: confusion with central hypothyroidism.

SUMMARY: Hypothyroidism occurring in the postpartum period can be due to pituitary or hypothalamic disease as in Sheehan's syndrome and postpartum autoimmune hypophysitis or due to a primary thyroid disease as in postpartum thyroiditis. It is important that the correct diagnosis is ascertained because hypothalamic or pituitary disorders are often associated with other pituitary hormone deficiencies, especially life-threatening adrenal insufficiency or adrenal crisis. A combination of various symptoms and biochemical markers, especially serum thyroid-stimulating hormone levels dictate the initial diagnostic pathway. We present a case of a woman who presented with a 2-month history of tiredness and neck discomfort following delivery. A thyroid function test demonstrated results, which we initially interpreted as central hypothyroidism. Follow-up results indicated that this was in fact the transition period between the thyrotoxic phase and hypothyroid phases of postpartum thyroiditis. This case highlights the potential for diagnostic confusion between central hypothyroidism and postpartum thyroiditis. LEARNING POINTS: Postpartum thyroiditis affects one in twenty mothers within 12 months of delivery. The majority of patients have transient thyrotoxicosis only, some have transient hypothyroidism only, and the rest has a triphasic pattern (thyrotoxic, hypothyroid then a euthyroid phase). During the transition from the thyrotoxic phase to hypothyroid phase, when serum TSH is still suppressed, the biochemical results can resemble that of central hypothyroidism. If central hypothyroidism is suspected, then urgent diagnostic investigations should be carried out along with the assessment of adrenal function. There is a potential for diagnostic confusion between postpartum central hypothyroidism and postpartum thyroiditis; however, the obstetric history, clinical symptoms, and signs (headaches, breastfeeding, goitre, etc.) and serum adrenocorticotropic levels should help with the differential diagnosis.

A Multiple Health Behavior Change, Self-Monitoring Mobile App for Adolescents: Development and Usability Study of the Health4Life App.

BACKGROUND: The link between chronic diseases and the Big 6 lifestyle risk behaviors (ie, poor diet, physical inactivity, smoking, alcohol use, sedentary recreational screen time, and poor sleep) is well established. It is critical to target these lifestyle risk behaviors, as they often co-occur and emerge in adolescence. Smartphones have become an integral part of everyday life, and many adolescents already use mobile apps to monitor their lifestyle behaviors and improve their health. Smartphones may be a valuable platform for engaging adolescents with interventions to prevent key chronic disease risk behaviors. OBJECTIVE: The aim of this paper is to describe the development, usability, and acceptability of the Health4Life app, a self-monitoring smartphone app for adolescents that concurrently targets the Big 6 lifestyle behaviors. METHODS: The development of the Health4Life app was an iterative process conducted in collaboration with adolescents and experts. The development process consisted of three stages: scoping the literature; end user consultations, which included a web-based survey (N=815; mean age 13.89, SD 0.89 years) and a focus group (N=12) among adolescents; and app development and beta testing. Following this development work, 232 adolescents were asked to rate the usability and acceptability of the app. RESULTS: The process resulted in a self-monitoring smartphone app that allows adolescent users to track and set goals for the Big 6 health behaviors, using in-app rewards and notifications to enhance engagement. The overall adolescent feedback was positive in terms of user-friendly design, content, relevance, and helpfulness. Commonly identified areas for improvement were to increase interactive features and display recorded health behaviors differently to improve interpretability. CONCLUSIONS: The Health4Life app is a co-designed, self-monitoring smartphone app for adolescents that concurrently targets the Big 6 lifestyle behaviors. Adolescents rated the app as highly acceptable and usable. The app has the potential to efficiently and effectively modify important risk factors for chronic disease among young people and is currently being evaluated in a world-first trial of 6640 secondary school students in 71 schools across Australia.

Measurement properties of smartphone approaches to assess key lifestyle behaviours: protocol of a systematic review.

BACKGROUND: Six core behavioural risk factors (poor diet, physical activity, sedentary behaviour, alcohol misuse, smoking and unhealthy sleep patterns) have been identified as strong determinants of chronic disease, such as cardiovascular disease, diabetes and cancers. Smartphones have the potential to provide a real-time, pervasive, unobtrusive and cost-effective way to measure health behaviours and deliver instant feedback to users. Despite this, validity of using smartphones to measure these six key behaviours is largely unknown. The proposed systematic review aims to address this gap by identifying existing smartphone-based approaches to measure these health behaviours and critically appraising, comparing and summarizing the quality of their measurement properties. METHODS: A systematic search of the Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsychINFO (EBSCOhost), CINAHL (EBSCOHost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost) and IEEE Xplore Digital Library databases will be conducted from January 2007 to March 2020. Eligible studies will be those written in English that measure at least one of the six health behaviours of interest via a smartphone and report on at least one measurement property. The primary outcomes will be validity, reliability and/or responsiveness of these measurement approaches. A secondary outcome will be the feasibility (e.g. user burden, usability and cost) of identified approaches. No restrictions will be placed on the participant population or study design. Two reviewers will independently screen studies for eligibility, extract data and assess the risk of bias. The study methodological quality (or bias) will be appraised using an appropriate tool. Our results will be described in a narrative synthesis. If feasible, random effects meta-analysis will be conducted where appropriate. DISCUSSION: The results from this review will provide important information about the types of smartphone-based approaches currently available to measure the core behavioural risk factors for chronic disease and the quality of their measurement properties. It will allow recommendations on the most suitable and effective measures of these lifestyle behaviours using smartphones. Valid and reliable measurement of these behaviours and risk factor opens the door to targeted and real-time delivery of health behaviour interventions, providing unprecedented opportunities to offset the trajectory toward chronic disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42019122242.

The Perceived Credibility of Complementary and Alternative Medicine: A Survey of Undergraduate and Graduate Students.

The popularity of complementary and alternative medicine (CAM) appears to be increasing, especially among college students. We surveyed 146 undergraduate and graduate students with the CAM Health Belief Questionnaire and obtained credibility and frequency ratings for a select group of CAM therapies: yoga, meditation, massage, chiropractic medicine, biofeedback, hypnosis, acupuncture, spirituality/religion, therapeutic touch, the use of herbs/vitamins, and aromatherapy/essential oils. Graduate students held more favorable views about integrating CAM into conventional medical practice. Female students reported using a wider variety of therapies than male students. Spirituality/religion and herbs/vitamins were the most popular CAM approaches. Students rated yoga, meditation, and massage as being highly credible practices. They rated hypnosis and therapeutic touch low in credibility. We discuss hypnosis as an example of a therapy that suffers from poor public perception despite having a relatively strong evidentiary base.

Use of a High-Throughput Phenotypic Screening Strategy to Identify Amplifiers, a Novel Pharmacological Class of Small Molecules That Exhibit Functional Synergy with Potentiators and Correctors.

Cystic fibrosis (CF) is a lethal genetic disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite recent groundbreaking approval of genotype-specific small-molecule drugs, a significant portion of CF patients still lack effective therapeutic options that address the underlying cause of the disease. Through a phenotypic high-throughput screen of approximately 54,000 small molecules, we identified a novel class of CFTR modulators called amplifiers. The identified compound, the characteristics of which are represented here by PTI-CH, selectively increases the expression of immature CFTR protein across different CFTR mutations, including F508del-CFTR, by targeting the inefficiencies of early CFTR biosynthesis. PTI-CH also augments the activity of other CFTR modulators and was found to possess novel characteristics that distinguish it from CFTR potentiator and corrector moieties. The PTI-CH-mediated increase in F508del-CFTR did not elicit cytosolic or endoplasmic reticulum-associated cellular stress responses. Based on these data, amplifiers represent a promising new class of CFTR modulators for the treatment of CF that can be used synergistically with other CFTR modulators.

A tale of two rain gardens: Barriers and bridges to adaptive management of urban stormwater in Cleveland, Ohio.

Green infrastructure installations such as rain gardens and bioswales are increasingly regarded as viable tools to mitigate stormwater runoff at the parcel level. The use of adaptive management to implement and monitor green infrastructure projects as experimental attempts to manage stormwater has not been adequately explored as a way to optimize green infrastructure performance or increase social and political acceptance. Efforts to improve stormwater management through green infrastructure suffer from the complexity of overlapping jurisdictional boundaries, as well as interacting social and political forces that dictate the flow, consumption, conservation and disposal of urban wastewater flows. Within this urban milieu, adaptive management-rigorous experimentation applied as policy-can inform new wastewater management techniques such as the implementation of green infrastructure projects. In this article, we present a narrative of scientists and practitioners working together to apply an adaptive management approach to green infrastructure implementation for stormwater management in Cleveland, Ohio. In Cleveland, contextual legal requirements and environmental factors created an opportunity for government researchers, stormwater managers and community organizers to engage in the development of two distinct sets of rain gardens, each borne of unique social, economic and environmental processes. In this article we analyze social and political barriers to applying adaptive management as a framework for implementing green infrastructure experiments as policy. We conclude with a series of lessons learned and a reflection on the prospects for adaptive management to facilitate green infrastructure implementation for improved stormwater management.

Modeling the hydrologic and economic efficacy of stormwater utility credit programs for US single family residences.

As regulatory pressure to reduce the environmental impact of urban stormwater intensifies, US municipalities increasingly seek a dedicated source of funding for stormwater programs, such as a stormwater utility. In rare instances, single family residences are eligible for utility discounts for installing green infrastructure. This study examined the hydrologic and economic efficacy of four such programs at the parcel scale: Cleveland (OH), Portland (OR), Fort Myers (FL), and Lynchburg (VA). Simulations were performed to model the reduction in stormwater runoff by implementing bioretention on a typical residential property according to extant administrative rules. The EPA National Stormwater Calculator was used to perform pre- vs post-retrofit comparisons and to demonstrate its ease of use for possible use by other cities in utility planning. Although surface slope, soil type and infiltration rate, impervious area, and bioretention parameters were different across cities, our results suggest that modeled runoff volume was most sensitive to percent of total impervious area that drained to the bioretention cell, with soil type the next most important factor. Findings also indicate a persistent gap between the percentage of annual runoff reduced and the percentage of fee reduced.

Dynamics and impact of footrot and climate on hoof horn length in 50 ewes from one farm over a period of 10 months.

Footrot, including interdigital dermatitis, is caused by Dichelobacter nodosus cause the majority of lameness in sheep in the UK. Lame sheep often have overgrown hoof horn but recent evidence has indicated that trimming overgrown hoof horn increases recovery time, and that routine foot trimming of the flock does not reduce the prevalence or incidence of lameness. The objectives of this study were to investigate the temporal associations between hoof horn length, footrot and climate. Fifty multiparous ewes were monitored for 10 months. On eight occasions hoof horn length, foot lesions and body condition were recorded. At the first examination, ewes were assigned to one of two treatment groups. All ewes that became lame with footrot were treated at one time point per week, either by trimming hoof horn and applying a topical antibiotic spray or with parenteral antibiotic and topical antibiotic spray. Hoof horn length in ewes at pasture varied over the year and was associated with temperature and rainfall. New cases of footrot occurred all year round and were associated with prior prevalence of footrot in the flock and prior temperature and rainfall. Overgrown hoof horn did not precede lameness but occurred once the sheep were lame. One year of prompt treatment of footrot reduced the range in hoof horn length in the sheep in both treatment groups. At the end of the study the hoof lengths of ewes in both groups were not significantly different. On this farm, hoof horn length was self-regulating in both non-lame and treated lame sheep whether trimming was part of the treatment or not and there would have been no benefit from routine foot trimming of this flock.

Role of Hfq in iron-dependent and -independent gene regulation in Neisseria meningitidis.

In Neisseria meningitidis, iron-responsive gene regulation is mediated primarily by the ferric uptake regulator (Fur) protein. When complexed with iron, Fur represses gene expression by preventing transcription initiation. Fur can also indirectly activate gene expression via the repression of regulatory small RNAs (sRNA). One such Fur- and iron-regulated sRNA, NrrF, was previously identified in N. meningitidis and shown to repress expression of the sdhA and sdhC genes encoding subunits of the succinate dehydrogenase complex. In the majority of Gram-negative bacteria, sRNA-mediated regulation requires a cofactor RNA-binding protein (Hfq) for proper gene regulation and stabilization. In this study, we examined the role of Hfq in NrrF-mediated regulation of the succinate dehydrogenase genes in N. meningitidis and the effect of an hfq mutation on iron-responsive gene regulation more broadly. We first demonstrated that the stability of NrrF, as well as the regulation of sdhC and sdhA in vivo, was unaltered in the hfq mutant. Secondly, we established that iron-responsive gene regulation of the Fur-regulated sodB gene was dependent on Hfq. Finally, we demonstrated that in N. meningitidis, Hfq functions in a global manner to control expression of many ORFs and intergenic regions via iron-independent mechanisms. Collectively these studies demonstrate that in N. meningitidis, iron- and NrrF-mediated regulation of sdhC and sdhA can occur independently of Hfq, although Hfq functions more globally to control regulation of other N. meningitidis genes primarily by iron-independent mechanisms.