Diabetic foot ulceration (DFU) is a devastating complication of diabetes whose pathogenesis remains incompletely understood. Here, we profile 174,962 single cells from the foot, forearm, and ...peripheral blood mononuclear cells using single-cell RNA sequencing. Our analysis shows enrichment of a unique population of fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1, and TNFAIP6 and increased M1 macrophage polarization in the DFU patients with healing wounds. Further, analysis of spatially separated samples from the same patient and spatial transcriptomics reveal preferential localization of these healing associated fibroblasts toward the wound bed as compared to the wound edge or unwounded skin. Spatial transcriptomics also validates our findings of higher abundance of M1 macrophages in healers and M2 macrophages in non-healers. Our analysis provides deep insights into the wound healing microenvironment, identifying cell types that could be critical in promoting DFU healing, and may inform novel therapeutic approaches for DFU treatment.
Diabetic foot ulceration is a major diabetic complication with unmet needs. We investigated the efficacy of epidermal stem cells and epidermal stem cells–derived exosomes (ESCs-Exo) in improving ...impaired diabetic wound healing and their mechanisms of action. In vitro experiments showed that ESCs-Exo enhanced the proliferation and migration of diabetic fibroblasts and macrophages and promoted alternative or M2 macrophage polarization. In wounds of db/db mice, treatment with both epidermal stem cells and ESCs-Exo, when compared with fibroblast exosomes and PBS control, accelerated wound healing by decreasing inflammation, augmenting wound cell proliferation, stimulating angiogenesis, and inducing M2 macrophage polarization. Multiplex protein quantification of wound lysates revealed TGFβ signaling influenced by ESCs-Exo. High-throughput sequencing of small RNAs contained in the ESCs-Exo showed higher proportions of microRNAs than those contained in fibroblast exosomes. In silico functional analysis showed that the ESCs-Exo microRNAs‒target genes were primarily involved in homeostatic processes and cell differentiation and highlighted regulatory control of phosphatidylinositol-3 kinase/protein kinase B and TGFβ signaling pathways. This was also validated in vitro. Collectively, our results indicate that epidermal stem cells and ESCs-Exo are equally effective in promoting impaired diabetic wound healing and that ESCs-Exo treatment may be a promising and technically advantageous alternative to stem cell therapies.
Diabetic foot ulceration is a devastating diabetic complication with unmet needs. We explored the efficacy of calcium-crosslinked alginate dressings in topically delivering primary macrophages and ...their secretome to diabetic wounds. The alginate bandages had a microporous structure that enabled even cell loading with prolonged cell survival and egress following wound placement. In vitro experiments showed that we could successfully differentiate and polarize primary murine bone marrow derived monocytes into M0, M1, M2a and M2c defined states with distinct gene expression, surface protein and secretome profiles. The primary macrophages were delivered in the bandages, migrated within the wounds and were still present for as long as 16 days post-injury. In wounds of db/db mice, treatment with all macrophage subtypes and their secretome, when compared to control, accelerated wound healing. Bulk RNA sequencing analysis and multiplex protein quantification of wound lysates revealed that M2c macrophages conditioned media had the most impact in wound healing affecting processes like neurogenesis, while M1 conditioned media promoted keratinization and epidermal differentiation. Collectively, our results indicate that alginate dressings can serve as a delivery platform for topical treatment of diabetic wounds and that conditioned media from distinctly polarized macrophages is equally or more effective than their parental cells in advancing wound healing and could therefore be a promising and technically advantageous alternative to cell therapy.
A surgical site infection (SSI) rate of 4%–8% has been reported in patients who undergo open reduction and internal fixation (ORIF) for acetabular fractures. Studies have identified risk factors for ...SSI, but none have performed a nationwide analysis of SSI in surgically managed acetabular fracture patients.
The National Inpatient Sample (NIS) database was queried for patients who underwent ORIF for acetabular fractures from 2016 to 2019. Analysis was performed on all patients who underwent ORIF for acetabular fractures, as well as those who only underwent ORIF for isolated acetabular fractures. Clinical characteristics, hospital course, discharge disposition, and hospitalization costs were compared between groups. Multivariate regression analysis was conducted to assess predictors of SSI.
41,725 patients undergoing acetabular fracture repair were identified, of which 490 (1.2%) developed SSI during hospitalization. Age (45.90 vs 49.90, p < 0.001) and Injury Severity Scale (5.99 vs 8.30, p < 0.001) were increased in patients who developed SSI. History of hypertension (HTN) (OR = 2.343, 95% CI 1.96–2.80, p < 0.001), longer hospital length of stay (30.27 days vs 10.00 days, p < 0.001) and total charges ($469,005 vs $193,032, p < 0.001) were associated with SSI. Lower rates of routine discharge were seen in SSI patients (OR = 0.333, 95% CI 0.260–0.426, p < 0.001). Higher rates of inpatient death were associated with SSI (OR = 2.210, 95% CI 1.172–4.17, p = 0.019). Multiple procedures in addition to acetabular fracture repair, iliac artery embolization, substance abuse, later time to internal fixation and HTN were predictive of SSI (p < 0.001).
Severity of injury, time to fixation, and factors associated with compromised cardiovascular integrity were predictors of SSI. Identifying patients at risk for SSI should lead to clinical maneuvers that may optimize outcome.
This study assessed the relationship between magnesium status and C-reactive protein concentration in obese and nonobese women. This cross-sectional study included 131 women, aged between 20 and ...50 years, who were divided into two groups: obese (
n
= 65) and control (
n
= 66) groups. Magnesium intake was monitored using 3-day food records and NutWin software version 1.5. The plasma, erythrocyte, and urinary magnesium concentrations were determined by flame atomic absorption spectrophotometry. C-reactive protein concentration in serum was measured by immunoturbidimetric assay. The mean values of the magnesium content in the diet were lower than those recommended, though there was no significant difference between groups (
p
> 0.05). The mean concentrations of plasma and erythrocyte magnesium were within the normal range, with no significant difference between groups (
p
> 0.05). Urinary excretion of this mineral was less than the reference values in both groups, with no significant difference (
p
> 0.05). The mean concentration of serum C-reactive protein was within the normal range in both groups, with no significant difference (
p
> 0.05). There was a positive correlation between urinary magnesium and serum C-reactive protein (
p
= 0.015). Obese patients ingest low dietary magnesium content, which seems to induce hypomagnesuria as a compensatory mechanism to keep plasma concentrations of the mineral at adequate levels. The study shows a positive correlation between urinary magnesium concentrations and serum C-reactive protein, suggesting the influence of hypomagnesuria on this inflammatory protein in obese women.
Diante de um mercado econômico cada vez mais globalizado e concorrencial, a formação de economias solidárias e a prática de cooperação são oportunidades plausíveis para pequenas empresas se ...desenvolverem e manterem a competitividade e sobrevivência, tornando-se um caminho não somente para o desenvolvimento econômico, mas também humano e social. Sendo assim, esta pesquisa teve como objetivo estudar quais os ganhos competitivos podem ser proporcionados a pequenos produtores de farinha de mandioca da vila de Manoel dos Santos, zona rural do município de Tracuateua, PA, caso eles constituíssem uma cooperativa de trabalho. Foi estudado o perfil de cooperação entre os produtores e o ambiente econômico, caso a cooperação se concretize, caracterizando este trabalho como exploratório e qualitativo. Para a coleta dados, utilizou-se o pesquisador observador e o pesquisador participante para a realização de entrevistas, guiadas por um questionário semiestruturado e adotando a análise de discurso para formulação dos resultados. Concluiu-se que a constituição da cooperativa de trabalho torna-se viável por ter a capacidade de proporcionar os quatro ganhos competitivos estudados (acesso a soluções; aprendizagem e inovação; redução de riscos; e custos e relações sociais). Além de os resultados apresentarem positiva projeção dos ganhos econômicos futuros com a cooperativa instalada, a maioria dos produtores se caracterizaram como engajados e comprometidos com o projeto. Este estudo torna-se relevante ao demonstrar que o conhecimento acadêmico pode transformar um grupo de pequenos agricultores individuais, fornecendo possíveis alternativas de geração de renda e desenvolvimento social.
Adesão ao tratamento da urticária crônica Ferreira, Eleonora Arnaud Pereira; Mendonça, Mariana Barreira; Lobão, Antonio Carlos
Estudos de Psicologia (Campinas),
12/2007, Volume:
24, Issue:
4
Journal Article
Peer reviewed
Open access
Este trabalho apresenta o estudo de caso de uma mulher encaminhada ao serviço de psicologia de um hospital universitário com diagnóstico de urticária crônica. A queixa principal foi de que, apesar da ...adesão ao tratamento, os sintomas permaneciam. O objetivo foi auxiliar a cliente na instalação de novos repertórios e na generalização de padrões adequados já instalados, buscando melhor controle da urticária. Realizaram-se dez sessões de atendimento ambulatorial utilizando-se o modelo construcional, da abordagem analítico-comportamental, por meio de análises funcionais de episódios relatados pela cliente. Resultados indica-ram multicausalidade no desencadeamento e manutenção dos sintomas. O treino em análise de contingências favoreceu melhor controle dos fatores ambientais. A cliente aderiu adequadamente ao uso do medicamento após estabelecer relações funcionais entre sintomas e estressores ambientais, promovendo redução dos sintomas e melhor controle da doença. Concluiu-se que o atendimento auxiliou na melhora da qualidade de vida da cliente, destacando-se a relevância da adesão ao tratamento.
This thesis focuses on the issue of energy efficiency, including the contribution of cable losses in the investment analysis on efficient electrical equipment, whether domestic, industrial or public ...lighting. A new decision support computational application is proposed based on the inclusion of the joint effect of all equipment’s and respective load diagrams that share sections of various installation types. Particularly, the influence of the conductors’ losses is taken into account, which is often overlooked in the economic analysis of efficient and sustainable electrical equipment in industrial installations and public lighting, taking also into account the influence on the reduction of greenhouse gases emissions. The computational application presented, encompassing the simultaneous influence of all consumption places in the economic analysis for choosing the best equipment, poses an original contribution over the state-of-the-art. The new computational application developed allows analyzing the installation and suggesting the most adequate electrical equipment, efficient and sustainable, in light of all the existing components in the installation, helping to support the decision of entrepreneurs in the energy sector or of the general consumer, which is an important aspect in the competitive energy environment. The results obtained in realistic case studies, having computational simulations validated with experimental results in the laboratory, allow concluding about the performance of the new computational application proposed in this thesis.
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