Peelethomasen8450
[Figure see text].[Figure see text].[Figure see text].High-grade gliomas with arginine or valine substitutions of the histone H3.3 glycine-34 residue (H3.3G34R/V) carry a dismal prognosis, and current treatments, including radiotherapy and chemotherapy, are not curative. Because H3.3G34R/V mutations reprogram epigenetic modifications, we undertook a comprehensive epigenetic approach using ChIP sequencing and ChromHMM computational analysis to define therapeutic dependencies in H3.3G34R/V gliomas. Our analyses revealed a convergence of epigenetic alterations, including (i) activating epigenetic modifications on histone H3 lysine (K) residues such as H3K36 trimethylation (H3K36me3), H3K27 acetylation (H3K27ac), and H3K4 trimethylation (H3K4me3); (ii) DNA promoter hypomethylation; and (iii) redistribution of repressive histone H3K27 trimethylation (H3K27me3) to intergenic regions at the leukemia inhibitory factor (LIF) locus to drive increased LIF abundance and secretion by H3.3G34R/V cells. LIF activated signal transducer and activator of transcription 3 (STAT3) signaling in an autocrine/paracrine manner to promote survival of H3.3G34R/V glioma cells. Moreover, immunohistochemistry and single-cell RNA sequencing from H3.3G34R/V patient tumors revealed high STAT3 protein and RNA expression, respectively, in tumor cells with both inter- and intratumor heterogeneity. We targeted STAT3 using a blood-brain barrier–penetrable small-molecule inhibitor, WP1066, currently in clinical trials for adult gliomas. WP1066 treatment resulted in H3.3G34R/V tumor cell toxicity in vitro and tumor suppression in preclinical mouse models established with KNS42 cells, SJ-HGGx42-c cells, or in utero electroporation techniques. Our studies identify the LIF/STAT3 pathway as a key epigenetically driven and druggable vulnerability in H3.3G34R/V gliomas. This finding could inform development of targeted, combination therapies for these lethal brain tumors.[Figure see text].[Figure see text].
We do not currently understand how spatiotemporal variations in the composition of fine particulate air pollution [fine particulate matter with aerodynamic diameter
≤
2.5
μ
m
(
PM
2.5
)] affects population health risks. However, recent evidence suggests that joint concentrations of transition metals and sulfate may influence the oxidative potential (OP) of
PM
2.5
and associated health impacts.
The purpose of the study was to evaluate how
of transition metals/OP and sulfur content in outdoor
PM
2.5
influence associations with acute cardiovascular events.
We conducted a national case-crossover study of outdoor
2.5
influences the strength of association with acute cardiovascular events in men. Regions with elevated concentrations of
sulfur and transition metals in
PM
2.5
should be examined as priority areas for regulatory interventions. https//doi.org/10.1289/EHP9449.
The combined transition metal and sulfur content of outdoor PM2.5 influences the strength of association with acute cardiovascular events in men. Regions with elevated concentrations of both sulfur and transition metals in PM2.5 should be examined as priority areas for regulatory interventions. https//doi.org/10.1289/EHP9449.
Due to the similarities of glabrous skin, the plantar region is an excellent donor area for covering complex palmar-plantar wounds. However, taking grafts from the plantar area often results in significant morbidity at the donor site or non-integration of the graft due to the greater thickness of the plantar corneal layer.
This is a prospective case series including patients with burns or wounds who have been treated with a dermal graft using the bilaminar 'trapdoor' technique. This procedure is used to remove a thin graft from the deep plantar dermis after the partial elevation of the first layer including the entire epidermis and superficial part of the dermis.
At the donor area in the four patients in this case series, we observed healing at around 10 days, and absence of hypertrophic scar in all patients. There was complete re-epithelialisation between two and three weeks from the periphery to the centre of the deep dermal graft, and from the glandular epithelium transferred with the graft. During the follow-up, patients presented aesthetic and functional features of glabrous and amelanotic skin, with similar resistance to those of the adjacent areas of the wound in the palmar-plantar region.
This technique has some advantages, such as less surgical time, minimal morbidity in the plantar donor area, easy integration of the grafts, and maintenance of the functional and aesthetic properties of glabrous skin both in the plantar donor area and in the palmar-plantar recipient region.
The authors have no conflicts of interest to declare.
The authors have no conflicts of interest to declare.
Foot ulcers are a common complication of diabetes and are associated with an increase in lower limb amputation and death. Early referral to a specialised unit is recommended. The aim of this study was to assess the characteristics of new-patient referrals to specialised diabetes foot care units across Europe and to determine the factors involved in delayed referral.
In this prospective observational study, consecutive patients with a new foot ulcer presenting to nine diabetic foot centres in five European countries (France, Germany, Italy, Spain and the UK) were included.
Some 25% of the 332 patients included had presented with a foot ulcer >3 months before referral to the participating foot clinic. Compared with patients referred earlier, patients with a long time to referral (>3 months) were older (p=0.006) and had a less severe wound according to Infectious Diseases Society of America (IDSA) classification (p=0.003) and University of Texas classification (grade D=infection + peripheral artery disease, p=0.004).
The proportion of patients with a diabetic foot ulcer (DFU) referred to a specialised unit >3 months after the beginning of the ulcer remained high throughout Europe. Patients with severe DFU were, however, referred more quickly by front line health professionals. Primary care professionals need to be made aware of the importance of early referral to a specialised unit in order to improve the management of foot disease in patients with diabetes.
The authors have no conflicts of interest to declare.
The authors have no conflicts of interest to declare.
This study evaluated the impact of four weeks of treatment with Prontosan Wound Irrigation Solution and Prontosan Wound Gel (B. Braun Medical Inc., US) on adults with hard-to-heal leg wounds. Overall change (weeks 1-5) in the Global Quality of Life scale (GQOL), changes in body, psyche and everyday life (EDL) quality of life (QoL) subscores, and changes in wound appearance and size after treatment were assessed.
In this prospective, open-label, single-arm, five-centre study, non-hospitalised patients with no more than two wounds below the knee were recruited into the study; wounds were ≥5cm
and ≤50cm
and present for ≥4 weeks. The investigator or a designee applied the wound solution and gel to the wounds at clinic visits, and patients/caregivers applied the wound solution and gel at home. selleckchem Wound-QoL questionnaires were completed at the initial screening and at each week of treatment. Wound size and photographs were obtained at pre- and post-treatment during clinic visits.
A total of 43 patients were enrolled in the study. Mean GQOL scores decreased by 1.11 (46.1%). Body, psyche and EDL decreased by 1.17 (60.0%), 1.26 (41.8%) and 1.00 (42.2%), respectively. Wounds also showed improvement in odour, appearance and size. Adverse events were mild in intensity and transient in nature.
This study demonstrated marked improvement in the QoL of patients with hard-to-heal leg wounds below the knee during four weeks of treatment with the wound solution and gel. Wounds also showed improvement in odour, appearance and size, and the treatment solution and gel were well tolerated.
B. Braun Medical Inc. funded the research and preparation of this article. AK, DV, CRC and WC are employees of B. link2 Braun Medical Inc. AO and RS declare no conflict of interest.
B. Braun Medical Inc. funded the research and preparation of this article. AK, DV, CRC and WC are employees of B. Braun Medical Inc. AO and RS declare no conflict of interest.
The authors have no conflicts of interest to declare.
The authors have no conflicts of interest to declare.
The aim of this systematic review was to determine the impact of topical oxygen therapy (TOT) on diabetic foot ulcer (DFU) healing.
Using systematic review methodology, we considered randomised controlled trials (RCTs), controlled trials, pilot studies and observational studies. The search was conducted in January 2019, using PubMed, CINAHL, Ovid, Cochrane, Web of Science and EMBASE databases. Data analysis was undertaken using RevMan and a narrative synthesis. link3 The article titles were assessed by two authors independently, and the abstracts (when available) of the studies identified by the search strategy were screened for their eligibility, according to the inclusion and exclusion criteria. The full-text version of potentially relevant studies was obtained and two authors independently screened this against the inclusion criteria. Data were extracted using a predesigned extraction tool and all included studies were quality appraised using the Evidence-Based Librarianship checklist.
The search returned in the studies were generally small, thus, more RCTs are warranted to further validate these findings.
The authors have no conflicts of interest to declare.
The authors have no conflicts of interest to declare.
Immediately following a two-year prospective case series in which the wounds of 60 patients with hard-to-heal ulcers were treated with a hypochlorous acid oxidising solution (AOS) in addition to standard of care (SoC) for 70 days (T0-T70), a subset of 31 patients (51.7%) whose wounds had not fully healed by T70 opted to continue with treatment for a further 22 weeks (days T70-T224, a total treatment time of 32 weeks (224 days). The objective was to provide long-term evidence on the clinical performance and safety of AOS when used in association with the usual SoC in patients with stalled, hard-to-heal ulcers of various aetiologies.
As per the main study, wounds were formally assessed by the study lead at 28 days (±14 days, depending on patient attendance). Parameters assessed at fortnightly visits included area, depth and duration of ulcer; pain; wound bed preparation (WBP) score; and infection status. Wounds were managed in accordance with the SoC protocol.
By T224, 35.5% (n=11) of wounds healed completely and 83.
