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IntroductionThe use of non-invasive vascular and perfusion diagnostics are an important part of assessing lower extremity ulceration and amputation risk in patients with diabetes mellitus. Methods for detecting impaired microvascular vasodilatory function in patients with diabetes may have the potential to identify sites at risk of ulceration prior to clinically identifiable signs. Spatial frequency domain imaging (SFDI) uses patterned near-infrared and visible light spectroscopy to determine tissue oxygen saturation and hemoglobin distribution within the superficial and deep dermis, showing distinct microcirculatory and oxygenation changes that occur prior to neuropathic and neuroischemic ulceration.Research designs and methods35 patients with diabetes mellitus and a history of diabetic foot ulceration were recruited for monthly imaging with SFDI. Two patients who ulcerated during the year-long longitudinal study were selected for presentation of their clinical course alongside the dermal microcirculation biomarkers from SFDI.ResultsPatient 1 developed a neuropathic ulcer portended by a focal increase in tissue oxygen saturation and decrease in superficial papillary hemoglobin concentration 3 months prior. Patient 2 developed bilateral neuroischemic ulcers showing decreased tissue oxygen saturation and increased superficial papillary and deep dermal reticular hemoglobin concentrations.ConclusionsWounds of different etiology show unique dermal microcirculatory changes prior to gross ulceration. Before predictive models can be developed from SFDI, biomarker data must be correlated with the clinical course of patients who ulcerate while being followed longitudinally.Trial registration numberNCT03341559.

Closure of chronic lower extremity wounds is important for minimizing the risk of infection and amputation in a very high-risk population. Developments in tissue cultures and matrix therapies have shown promise in enhancing healing. The use of autologous homologous skin constructs in wound treatment may enable the regeneration of functional dermal structures. We present the case of a chronic medial heel ulcer that dehisced following intraoperative debridement, which was subsequently treated using a combination of an autologous homologous skin construct and total contact casting. This case emphasizes the importance of proper offloading for healing and preventing recurrence of lower extremity wounds.

Abstract The use of free flaps in lower extremity reconstructive surgery has seen growing adoption for treating tissue loss in patients with diabetes mellitus and peripheral artery disease as a means for limb preservation. The superficial circumflex iliac perforator artery (SCIP) flap is one of the most commonly utilized flaps in foot reconstruction and has demonstrated benefits over amputation. Patients with impaired vascular and neurologic function are predisposed to complications following lower extremity reconstructive surgery, particularly ischemia in the angiosomes of the arteries used for flap anastomosis. We present the case of a patient who underwent successful SCIP flap reconstruction of the calcaneus but developed gangrene in the forefoot region supplied by a hypoplastic posterior tibial artery in subsequent months. The changes in tissue oxygenation and hemoglobin distribution of the foot are shown using spatial frequency domain imaging throughout the flap healing process and eventual tissue necrosis.

This prospective study examined the changes in bacterial isolates from sputum samples obtained monthly from 81 outpatients with chronic obstructive pulmonary disease. There were 374 acute exacerbations of lung disease, which were significantly associated with the acquisition of a new strain of Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (relative risk for any new strain, 2.15). An exacerbation was diagnosed at 33 percent of the clinic visits that coincided with the appearance of a new bacterial strain in the sputum. This prospective study shows a relation between clinical deterioration and the presence of a new bacterial strain. Morbidity and mortality among patients with chronic obstructive pulmonary disease are related in large part to acute exacerbations, which occur one to three times per year. 1 – 6 Our understanding of the cause and pathogenesis of these exacerbations is incomplete, and the role of bacterial pathogens is controversial. 7 – 10 In studies performed decades ago, investigators followed patients with chronic obstructive pulmonary disease longitudinally, with periodic collection of sputum samples for culture, to determine whether there was an association between the isolation of bacterial pathogens in sputum and the occurrence of exacerbations. 5 , 6 , 11 In these studies, the rate of isolation of . . .

Background Existing guidance for developing public health interventions does not provide information for researchers about how to work with intervention providers to co-produce and prototype the content and delivery of new interventions prior to evaluation. The ASSIST + Frank study aimed to adapt an existing effective peer-led smoking prevention intervention (ASSIST), integrating new content from the UK drug education resource Talk to Frank ( www.talktofrank.com ) to co-produce two new school-based peer-led drug prevention interventions. A three-stage framework was tested to adapt and develop intervention content and delivery methods in collaboration with key stakeholders to facilitate implementation. Methods The three stages of the framework were: 1) Evidence review and stakeholder consultation; 2) Co-production; 3) Prototyping. During stage 1, six focus groups, 12 consultations, five interviews, and nine observations of intervention delivery were conducted with key stakeholders (e.g. Public Health Wales [PHW] ASSIST delivery team, teachers, school students, health professionals). During stage 2, an intervention development group consisting of members of the research team and the PHW ASSIST delivery team was established to adapt existing, and co-produce new, intervention activities. In stage 3, intervention training and content were iteratively prototyped using process data on fidelity and acceptability to key stakeholders. Stages 2 and 3 took the form of an action-research process involving a series of face-to-face meetings, email exchanges, observations, and training sessions. Results Utilising the three-stage framework, we co-produced and tested intervention content and delivery methods for the two interventions over a period of 18 months involving external partners. New and adapted intervention activities, as well as refinements in content, the format of delivery, timing and sequencing of activities, and training manuals resulted from this process. The involvement of intervention delivery staff, participants and teachers shaped the content and format of the interventions, as well as supporting rapid prototyping in context at the final stage. Conclusions This three-stage framework extends current guidance on intervention development by providing step-by-step instructions for co-producing and prototyping an intervention’s content and delivery processes prior to piloting and formal evaluation. This framework enhances existing guidance and could be transferred to co-produce and prototype other public health interventions. Trial registration ISRCTN14415936 , registered retrospectively on 05 November 2014.

Increased bacterial concentration (load) in the lower airways and new bacterial strain acquisition have been posited as mechanisms for chronic obstructive pulmonary disease (COPD) exacerbations. Bacterial concentrations are higher during exacerbation than during stable disease; however, these studies are cross sectional and devoid of strain typing. To determine if the increased bacterial concentrations function as a separate mechanism for exacerbation induction independent of new strain acquisition. In a prospective, longitudinal cohort of patients with COPD, the relationship between exacerbation occurrence, sputum bacterial concentrations, and new strain acquisition was examined. Clinical information, quantitative sputum cultures, and molecular typing of potential bacterial pathogen isolates. Over 81 months, 104 subjects completed 3,009 clinic visits, 560 (19.6%) during exacerbations and 2,449 (80.4%) during stable disease. Among preexisting strains, sputum concentrations of Nontypeable Haemophilus influenzae and Haemophilus haemolyticus were not different in exacerbation versus stable disease. Moraxella catarrhalis (stable, 10(8.38 +/- 0.13) [mean +/- SEM] vs. exacerbation, 10(7.78 +/- 0.26); p = 0.02) and Streptococcus pneumoniae (stable, 10(8.42 +/- 0.21) vs. exacerbation, 10(7.76 +/- 0.52); p = 0.07) concentrations were lower during exacerbations compared with stable periods. Concentrations of new strains of H. influenzae (stable, 10(7.28 +/- 0.15) vs. exacerbation, 10(7.76 +/- 0.17); p = 0.04) and M. catarrhalis (stable, 10(7.85 +/- 0.15) vs. exacerbation, 10(8.37 +/- 0.14); p = 0.02), were increased during exacerbations; however, the differences were small. Change in bacterial load is unlikely to be an important mechanism for exacerbations. Better understanding of the host-pathogen interaction, rather than enumerating bacteria in respiratory samples, is required to provide new insights into bacterial infection in COPD.

One Health is a collaborative, interdisciplinary effort that seeks optimal health for people, animals, plants, and the environment. Toxoplasmosis, caused by Toxoplasma gondii, is an intracellular protozoan infection distributed worldwide, with a heteroxenous life cycle that practically affects all homeotherms and in which felines act as definitive reservoirs. Herein, we review the natural history of T. gondii, its transmission and impacts in humans, domestic animals, wildlife both terrestrial and aquatic, and ecosystems. The epidemiology, prevention, and control strategies are reviewed, with the objective of facilitating awareness of this disease and promoting transdisciplinary collaborations, integrative research, and capacity building among universities, government agencies, NGOs, policy makers, practicing physicians, veterinarians, and the general public.

Adequate nutrient intake is important for supporting reproductive health. Few studies have examined the role of nutrients for fertility among women, resulting in a critical evidence gap. The aim of this study was to explore the usual intake and prevalence of nutrient inadequacies from foods only and foods plus dietary supplements among women of child bearing age with and without infertility. This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES), a national survey in the United States. Participants included women aged 18-44 years from 2013-2020 with or without infertility (difficulty trying to conceive for at least one-year). The mean usual intakes and prevalence of inadequacy (% < EAR/AI) of key nutrients- vitamins A, B1, B2, niacin, B6, B12, C, D, E, K, lycopene, lutein + zeaxanthin, folate, choline, zinc, selenium, iron, calcium, magnesium, EPA and DHA were determined from 24-hr dietary recalls. Women aged 18-44 years who reported infertility had significantly lower intakes of vitamin A, E and K and lutein and zeaxanthin from foods and foods + supplements compared to women without infertility. Lower intakes of selenium (foods only, 96.6 ug/d vs 100 ug/d), vitamin C (foods only, 66.9 mg/d vs. 74.2 mg/d) and calcium (foods + dietary supplements, 941 mg/d vs. 974 mg/d) were also observed in women reporting infertility. Fewer women with infertility met nutrient requirements. For example, 21.5% of women with infertility were below the EAR for vitamin B6 versus 14.6% of women without infertility and over 50% of those with infertility were below the EAR/AI for vitamins A, C, E, and magnesium and potassium. Differences in nutrient intakes by fertility status were particularly pronounced for women aged 35-44 years. These findings suggest lower intake of key nutrients among women with infertility, especially those aged 35-44. Future studies are needed to understand the implications of nutrient gaps for conception. Across all age groups, and fertility status, gaps in nutrients that are important for overall health were evident, underscoring the need for public health strategies to address broad dietary improvements.

A copper-nitrosyl intermediate forms during the catalytic cycle of nitrite reductase, the enzyme that mediates the committed step in bacterial denitrification. The crystal structure of a type 2 copper-nitrosyl complex of nitrite reductase reveals an unprecedented side-on binding mode in which the nitrogen and oxygen atoms are nearly equidistant from the copper cofactor. Comparison of this structure with a refined nitrite-bound crystal structure explains how coordination can change between copper-oxygen and copper-nitrogen during catalysis. The side-on copper-nitrosyl in nitrite reductase expands the possibilities for nitric oxide interactions in copper proteins such as superoxide dismutase and prions.

The determinants of the structure, functioning and resilience of pelagic ecosystems across most of the polar regions are not well known. Improved understanding is essential for assessing the value of biodiversity and predicting the effects of change (including in biodiversity) on these ecosystems and the services they maintain. Here we focus on the trophic interactions that underpin ecosystem structure, developing comparative analyses of how polar pelagic food webs vary in relation to the environment. We highlight that there is not a singular, generic Arctic or Antarctic pelagic food web, and, although there are characteristic pathways of energy flow dominated by a small number of species, alternative routes are important for maintaining energy transfer and resilience. These more complex routes cannot, however, provide the same rate of energy flow to highest trophic-level species. Food-web structure may be similar in different regions, but the individual species that dominate mid-trophic levels vary across polar regions. The characteristics (traits) of these species are also different and these differences influence a range of food-web processes. Low functional redundancy at key trophic levels makes these ecosystems particularly sensitive to change. To develop models for projecting responses of polar ecosystems to future environmental change, we propose a conceptual framework that links the life histories of pelagic species and the structure of polar food webs.