With the lifetime risk of DFU being 34% and the rate of chronic wounds increasing, there is a need for advanced therapies offering rapid, reliable, and safe healing.
A retrospective review was ...performed of 10 cases in which a novel PRBM was used for treatment of chronic DFUs. Patients who presented with DFUs refractory to topical wound care and offloading for longer than 4 weeks received weekly application of PRBM for up to 12 weeks along with a standard treatment regimen at a single outpatient center. At weekly visits, the wound was measured, inspected for signs of complications, cleaned, and debrided as necessary, followed by PRBM application until complete epithelialization or for 12 applications. The primary outcome was complete wound closure at 12 weeks. Secondary outcomes included time to closure, DFU percent area reduction, and material cost to closure.
Mean wound healing time was 6.1 weeks, with 90% of wounds closed at 12 weeks. Six wounds were healed at 6 weeks, 2 at 7 weeks, and 1 at 12 weeks. One wound did not close over the study period. Mean wound area reduction was 85% at 6 weeks and 94% at 12 weeks. Patients tolerated PRBM application with no reported pain or discomfort. No adverse events were reported. Mean PRBM cost to closure for healed wounds was $2624.
Treatment of chronic DFUs with PRBM is safe and efficient to achieve complete healing.
Reproductive strategies are defined by a combination of behavioural, morphological, and life‐history traits. Reproductive investment and offspring propagule size are two key traits defining ...reproductive strategies. While a substantial amount of work has been devoted to understanding the independent fitness effects of each of these traits, it remains unclear how coevolution between them ultimately affects the evolution of reproductive strategies, and how this might influence the relationship between dispersal and environmental factors. In this study we explore how the evolution of reproductive strategies defined by these two coevolving traits is influenced by resource availability and spatial structuring of the environment using a simulation model. We find three possible equilibrium strategies across all scenarios: a competitor strategy with high reproductive investment (producing large propagules which disperse short distances), and two coloniser strategies differing in reproductive investment (both producing small propagules which disperse long distances). The possible equilibrium strategies for each scenario depended on starting conditions, spatial structure and resource availability. Evolutionary transitions between these equilibrium strategies were more likely in heterogeneous than homogeneous landscapes and at higher resource levels. Transition from coloniser strategy to competitor strategy was usually a two‐step process, with changes in propagule size following initial evolution in investment. This highlights how the interaction between the two trait axes affects the evolution of reproductive strategies, particularly where fitness valleys preclude the simultaneous evolution of traits. Our results highlight the need to incorporate trait coevolution into evolutionary models to help develop a more integrative understanding of the structure of natural populations and how the interaction between traits constrains or hinders evolutionary processes.
Abstract
Effective coordination of group actions underlies the success of group-living organisms. Recent studies of animal personality have shown that groups composed of individuals with different ...behavioral propensities can outperform uniform groups in a range of different tasks, but we have only a rudimentary understanding of how differences in individual behavior influence the behavior of the group as a whole. In this study, we use natural variation in behavioral propensity among morphologically distinct worker castes of the small carpenter ant Camponotus yamaokai to shed new light on this. Iterative testing indicated that ants displayed consistent behavioral differences among individuals and between castes, with major workers exhibiting a lower exploratory tendency than minors. By constructing groups of different caste composition and quantifying their performance in the task of colony emigration, we show that group performance is an asymmetric humped function of caste ratio, with optimal performance achieved by groups with natural caste ratios. Using a simulation model based on our empirical data, we demonstrate that interindividual differences in social attraction and exploratory tendency are sufficient to explain the observed patterns. Our results provide new insights into how group performance in collective tasks can vary with group composition.
Abstract
Resistance mechanisms to immune checkpoint blockade therapy (ICBT) limit its response duration and magnitude. Paradoxically, Interferon γ (IFNγ), a key cytokine for cellular immunity, can ...promote ICBT resistance. Using syngeneic mouse tumour models, we confirm that chronic IFNγ exposure confers resistance to immunotherapy targeting PD-1 (α-PD-1) in immunocompetent female mice. We observe upregulation of poly-ADP ribosyl polymerase 14 (PARP14) in chronic IFNγ-treated cancer cell models, in patient melanoma with elevated
IFNG
expression, and in melanoma cell cultures from ICBT-progressing lesions characterised by elevated IFNγ signalling. Effector T cell infiltration is enhanced in tumours derived from cells pre-treated with IFNγ in immunocompetent female mice when PARP14 is pharmacologically inhibited or knocked down, while the presence of regulatory T cells is decreased, leading to restoration of α-PD-1 sensitivity. Finally, we determine that tumours which spontaneously relapse in immunocompetent female mice following α-PD-1 therapy upregulate IFNγ signalling and can also be re-sensitised upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance.
Diabetic foot ulcers (DFUs) are characterised by the presence of many microbes, some of which may not be identified by traditional culture techniques. Total contact casting (TCC) remains the ...gold-standard for offloading, yet little is known about the microbiome of wounds that progress from hard-to-heal to closed within a TCC.
A patient with a DFU underwent weekly treatment with TCC to closure. Samples for next-generation sequencing (NGS) and bioinformatics analysis of tissue samples were collected during each visit. Detection, identification, characterisation of the microbial community and abundance of microbes in each sample were compared.
Abundance of microbes, identified by species and strain, changed with each treatment visit. By the final week of treatment, species diversity of the wound microbiome had decreased significantly, highlighted by an observed decrease in the number of total microorganisms present. Resistance genes for tetracyclines were detected in the first sample, but not in subsequent samples.
The results of this study suggest dynamic microbiological changes associated with DFUs as they progress to healing within a TCC. As NGS becomes more readily available, further studies will be helpful to gain an improved understanding of the significance of the wound microbiome in patients with DFUs.
A fibro-osseous pseudotumor (FOPT) is a rare, rapidly enlarging, benign soft-tissue neoplasm that presents with localized pain, swelling, and redness. It typically presents in the hands and much less ...frequently in the feet. FOPT is characterized histologically by foci of osseous differentiation within the proliferated fibroblasts. This must be differentiated from other benign and malignant lesions. FOPT of the toes has been described in a few reports, but recurrence, following surgical excision, is extremely rare. Here we report a young, healthy female patient who presented with a rapidly growing FOPT of the left great toe. This unusual case had recurred twice following surgical excision, all within a 2-month period of time. The lesion was again completely excised, with no recurrences at follow-ups of 18 and 36 months. In conclusion, FOPT is a rare soft tissue lesion of the toes. It features fibroblastic proliferation and osseous differentiation, which needs to be differentiated from other benign and malignant tumors. The standard treatment is complete surgical excision with an excellent prognosis.
Consistent inter-individual variation in the propensity to perform different tasks (animal personality) can contribute significantly to the success of group-living organisms. The distribution of ...different personalities in a group influences collective actions and therefore how these organisms interact with their environment. However, we have little understanding of the proximate mechanisms underlying animal personality in animal groups, and research on this theme has often been biased towards organisms with advanced social systems. The goal of this study is to investigate the mechanistic basis for personality variation during collective behaviour in a species with rudimentary societies: the American cockroach. We thus use an approach which combines experimental classification of individuals into behavioural phenotypes (‘bold’ and ‘shy’ individuals) with comparative gene expression. Our analyses reveal differences in gene expression between behavioural phenotypes and suggest that social context may modulate gene expression related to bold/shy characteristics. We also discuss how cockroaches could be a valuable model for the study of genetic mechanisms underlying the early steps in the evolution of social behaviour and social complexity. This study provides a first step towards a better understanding of the molecular mechanisms associated with differences in boldness and behavioural plasticity in these organisms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The use of negative pressure wound therapy (NPWT) as a bolster for split-thickness skin grafts has been well documented in the literature. It facilitates the removal of transudate, which can result ...in the formation of seroma, and mitigates shear stress, which can detach the graft from the underlying wound bed. Its widespread use may be limited by factors such as increased cost and length of hospitalization. Recently, mechanically powered devices (Smart Negative Pressure; Spiracur, Inc., Sunnyvale, Calif.) have been reported as showing promise in healing wounds with outcomes surprisingly comparable to standard NPWT in the populations studied. We are unaware of any reports in the literature that have detailed the use of a mechanically powered NPWT device as a postoperative bolster for split-thickness skin grafts.
Ion packets introduced from gates, ion funnel traps, and other conventional ion injection mechanisms produce ion pulse widths typically around a few microseconds or less for ion mobility spectrometry ...(IMS)-based separations on the order of 100 milliseconds. When such ion injection techniques are coupled with ultralong path length traveling wave (TW)-based IMS separations (i.e., on the order of seconds) using structures for lossless ion manipulations (SLIMs), typically very low ion utilization efficiency is achieved for continuous ion sources e.g., electrospray ionization (ESI). Even with the ability to trap and accumulate much larger populations of ions than being conventionally feasible over longer time periods in SLIM devices, the subsequent long separations lead to overall low ion utilization. Here, we report the use of a highly flexible SLIM arrangement, enabling concurrent ion accumulation and separation and achieving near-complete ion utilization with ESI. We characterize the ion accumulation process in SLIM, demonstrate >98% ion utilization, and show both increased signal intensities and measurement throughput. This approach is envisioned to have broad utility to applications, for example, involving the fast detection of trace chemical species.
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