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The development of diabetic foot ulcers is a common and severe complication of diabetes that can significantly affect quality of life. The physiological healing cascade does not progress tissue repair in diabetic foot ulcerations in a timely manner. Serum markers from foot ulcers have been used to characterize the healing process of the diabetic foot using various collection techniques. This study aimed to compare the use of cervical brushes and the Levine technique to collect wound fluid from foot ulcers of people with diabetes in order to determine the presence of cytokines. The collected material was used for gene expression analysis of macrophage/monocyte-associated cytokines IL1-β, IL-6, TNF-α, regulatory cytokine IL-10 and growth factor TGFβ, via quantitative polymerase chain reaction (qPCR). Both collection methods produced sufficient amounts of RNA, but significantly more RNA was collected using a cervical brush (brush 224.82 ng/μL vs. Levine 80.90 ng/μL p = 0.0001). Significantly higher levels of expression of the following cytokine genes were detected in samples collected using a cervical brush: IL1-β (p = 0.0001), IL-6 (p = 0.0106), IL-10 (p = 0.0277) and TGFβ (p = 0.0002). Understanding why some wounds are difficult to heal is important for developing more effective treatments, and biomarkers may be useful for predicting the healing trajectory. These results demonstrate that it is possible to collect material from the wound bed for RT-qPCR analysis, and the cervical brush proved to be a simple and rapid method for monitoring cytokine gene expression.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to investigate the role of PC in vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactive protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

Abstract Background Severe coronavirus disease-19 (COVID-19) presents with progressive dyspnea, which results from acute lung inflammatory edema leading to hypoxia. As with other infectious diseases that affect the respiratory tract, asthma has been cited as a potential risk factor for severe COVID-19. However, conflicting results have been published over the last few months and the putative association between these two diseases is still unproven. Methods Here, we systematically reviewed all reports on COVID-19 published since its emergence in December 2019 to June 30, 2020, looking into the description of asthma as a premorbid condition, which could indicate its potential involvement in disease progression. Results We found 372 articles describing the underlying diseases of 161,271 patients diagnosed with COVID-19. Asthma was reported as a premorbid condition in only 2623 patients accounting for 1.6% of all patients. Conclusions As the global prevalence of asthma is 4.4%, we conclude that either asthma is not a premorbid condition that contributes to the development of COVID-19 or clinicians and researchers are not accurately describing the premorbidities in COVID-19 patients.

Plasma fibrinogen (F1) and fibronectin (pFN) polymerize to form a fibrin clot that is both a hemostatic and provisional matrix for wound healing. About 90% of plasma F1 has a homodimeric pair of γ chains (γγF1), and 10% has a heterodimeric pair of γ and more acidic γ′ chains (γγ′F1). We have synthesized a novel fibrin matrix exclusively from a 1:1 (molar ratio) complex of γγ′F1 and pFN in the presence of highly active thrombin and recombinant Factor XIII (rFXIIIa). In this matrix, the fibrin nanofibers were decorated with pFN nanoclusters (termed γγ′F1:pFN fibrin). In contrast, fibrin made from 1:1 mixture of γγF1 and pFN formed a sporadic distribution of “pFN droplets” (termed γγF1+pFN fibrin). The γγ′F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells (HUVECs) relative to the γγF1+FN fibrin. Three dimensional (3D) culturing showed that the γγ′F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts. HUVECs in the 3D γγ′F1:pFN fibrin exhibited a starkly enhanced vascular morphogenesis while an apoptotic growth profile was observed in the γγF1+pFN fibrin. Relative to γγF1+pFN fibrin, mouse dermal wounds that were sealed by γγ′F1:pFN fibrin exhibited accelerated and enhanced healing. This study suggests that a 3D pFN presentation on a fibrin matrix promotes wound healing.

The pig skin architecture and physiology are similar to those of humans. Thus, the pig model is very valuable for studying skin biology and testing therapeutics. The single-cell RNA sequencing (scRNA-seq) technology allows quantitatively analyzing cell types, compositions, states, signaling, and receptor-ligand interactome at single-cell resolution and at high throughput. scRNA-seq has been used to study mouse and human skins. However, studying pig skin with scRNA-seq is still rare. A critical step for successful scRNA-seq is to obtain high-quality single cells from the pig skin tissue. Here we report a robust method for isolating and cryopreserving pig skin single cells for scRNA-seq. We showed that pig skin could be efficiently dissociated into single cells with high cell viability using the Miltenyi Human Whole Skin Dissociation kit and the Miltenyi gentleMACS Dissociator. Furthermore, the obtained single cells could be cryopreserved using 90% FBS + 10% DMSO without causing additional cell death, cell aggregation, or changes in gene expression profiles. Using the developed protocol, we were able to identify all the major skin cell types. The protocol and results from this study are valuable for the skin research scientific community.

Because of the interface between coagulation and the immune response, it is expected that COVID-19-associated coagulopathy occurs via activated protein C signaling. The objective was to explore putative changes in the expression of the protein C signaling network in the liver, peripheral blood mononuclear cells, and nasal epithelium of patients with COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the COVID-19 Cell Atlas database. A functional protein–protein interaction network was constructed for the protein C gene. Patients with COVID-19 showed downregulation of protein C and components of the downstream protein C signaling cascade. The percentage of hepatocytes expressing protein C was lower. Part of the liver cell clusters expressing protein C presented increased expression of ACE2. In PBMC, there was increased ACE2, inflammatory, and pro-coagulation transcripts. In the nasal epithelium, PROC, ACE2, and PROS1 were expressed by the ciliated cell cluster, revealing co-expression of ACE-2 with transcripts encoding proteins belonging to the coagulation and immune system interface. Finally, there was upregulation of coagulation factor 3 transcript in the liver and PBMC. Protein C could play a mechanistic role in the hypercoagulability syndrome affecting patients with severe COVID-19.

Currently, experimental animals are widely used in biological and medical research. However, the scientific community has raised several bioethical concerns, such as the number of animals required to achieve reproducible and statistically relevant results. These concerns involve aspects related to pain, discomfort, and unwanted animal loss. Retrospectively, we compare two different approaches for anesthesia dosage: a mobile app for dose calculation and a standard dose calculation. A total of 939 C57BL/6J and Swiss mice were analyzed. We collected data on intraoperative and anesthesia-related mortality as described in electronic or physical handwritten records. Our results showed that the mobile app approach significantly reduces anesthetic-related deaths upon using doses of ketamine and xylazine. The results suggest that anesthesia-related mortality can be minimized even more using information technology approaches, helping to solve an old but transversal challenge for researchers working with experimental mice. The mobile app is a free and open code which could be implemented worldwide as an essential requirement for all anesthetic procedures in mice using xylazine and ketamine combination. As an open code app, the Labinsane initiative could also represent the starting point to unify and validate other anesthetic procedures in different species and strains.

Emerging data demonstrate that microglia activation plays a pivotal role in the development of hypothalamic inflammation in obesity. Early after the introduction of a high-fat diet, hypothalamic microglia undergo morphological, and functional changes in response to excessive dietary saturated fats. Initially the resident microglia are affected; however, as diet-induced obesity persists, bone marrow-derived myeloid cells gradually replace resident microglia. Genetic and pharmacological approaches aimed at dampening the inflammatory activity in the hypothalamus of experimental models of obesity have proven beneficial to correct the obese phenotype and improve metabolic abnormalities commonly associated with obesity. These approaches provide an experimental proof-of-concept that hypothalamic inflammation is central to the pathophysiology of obesity; understanding the details of the roles played by microglia in this process may help the development of preventive and therapeutic advances in the field. In this review, we discuss the potential mechanisms underlying hypothalamic microglial activation in high-fat induced obesity.

Objetivo: Analisar os tipos de barreiras de acessibilidade das pessoas com deficiências aos serviços de saúde, através das publicações online nos anos 2003-2013. Métodos: Trata-se de revisão integrativa apresentada por meio de seis etapas. Ao se aplicar os critérios de inclusão: texto completo disponível, base de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis and Retrieval System Online e Base de Dados de Enfermagem, assunto principal pessoas com deficiência, idioma português, publicações dos anos de 2003-2013 e tipo de documento em artigo, emergiram 26 artigos. Desses, 13 foram analisados, 02 não abordavam sobre tipos de barreiras de acessibilidade aos serviços de saúde e 11 estavam repetidos. Resultados: Categorias emergentes foram as barreiras arquitetônicas, atitudinais, organizacionais. Conclusão: As barreiras de acessibilidade podem influenciar negativamente na busca das PcD aos serviços de saúde. Descritores: Pessoas com deficiência, Acesso aos serviços de saúde, Estruturas de acesso.

Objetivou-se analisar a contribuição do cuidado clínico de enfermagem para o conforto psicoespiritual de mulheres com Infarto Agudo do Miocárdio (IAM), mediado pela pesquisa-cuidado com base na Teoria do Conforto. Os sujeitos foram nove mulheres admitidas com IAM no período de abril a junho de 2011 em um hospital de Cardiologia em Sobral - Ceará, Brasil. O primeiro encontro ocorreu na admissão e durou em média seis horas; depois ocorreram mais três encontros. Para coleta e análise das informações, foram empregados entrevista individual semiestruturada, diário de campo, observação participante e análise temática categorial de conteúdo. Os cuidados implementados no contexto psicoespiritual foram: fortalecer a espiritualidade, esclarecer sobre o adoecimento, ajudar no enfrentamento da nova condição de saúde e nas situações de confusão mental e desorientação. A percepção do conforto psicoespiritual ocorreu por meio da implementação de cuidados clínicos neste contexto, utilizando-se pesquisa-cuidado com base na Teoria do Conforto.El objetivo del estudio fue analizar la contribución de la atención clínica de enfermería para el confort psicoespiritual de mujeres con Infarto Agudo del Miocardio (IAM), mediada por la investigación-atención basada en la Teoría del Confort. Participaron nueve mujeres que ingresaron con IAM entre abril y junio de 2011 en el hospital de Cardiología de Sobral, Ceará, Brasil. El primer encuentro ocurrió en la admisión y duró alrededor de seis horas, después ocurrieron más tres encuentros. Para recolección y análisis de las informaciones, se utilizaron entrevista semi-estructurada, diarios de campo, observación participante y análisis temático categorial de contenido. Las atenciones psicoespirituales fueron: fortalecer la espiritualidad, aclarar las dudas sobre la enfermedad, ayudar a enfrentarse el nuevo estado de salud y las situaciones de confusión mental y desorientación. La percepción de confort psicoespiritual fue presente a través de la implementación de la atención clínica en este contexto, usándose de investigación-atención basada en la Teoría del Confort.The objective was to analyze the contribution of nursing clinical care for psycho-spiritual comfort of women with acute myocardial infarction (AMI), mediated by research-care based on the Comfort Theory. The subjects were nine women admitted with AMI from April to June 2011 in a Cardiology hospital in Sobral, Ceará, Brazil. The first meeting took place at the admission and lasted around six hours, after that there were three more meetings. For data collection and analysis we used individual semi-structured interviews, field diary, participant observation and thematic category content analysis. The cares implemented in the psycho-spiritual context were: strengthen the spirituality; clarify the illness; help in coping with new the health condition and situations of mental confusion and disorientation. The perception of psycho-spiritual comfort was present through the implementation of clinical cares in this context, using research-care based on the Comfort Theory.

In recent decades, the effectiveness of early intervention programs for children with autism has been widely investigated. The importance of early and intensive care for this population is grounded in principles of neuroplasticity and developmental theories. The scientific literature documents the need for including children younger than five in early intervention programs, for a minimum of 25 hours per week. In this case, early childhood education settings and preschools become highly-promising educational scenarios for implementing intervention. In addition to working with children (birth-5) in full or part-time schedules, these educational programs focus on the integral development of the child, including physical, psychological, intellectual, and social aspects. The purpose of the current article is to describe the principles of early intervention, with an emphasis on best practices directed toward people with autism. Additionally, the relevance of this type of intervention in the context of early childhood education settings in Brazil is further discussed.

Abstract Background Interleukin-6 (IL6) produced in the context of exercise acts in the hypothalamus reducing obesity-associated inflammation and restoring the control of food intake and energy expenditure. In the hippocampus, some of the beneficial actions of IL6 are attributed to its neurogenesis-inducing properties. However, in the hypothalamus, the putative neurogenic actions of IL6 have never been explored, and its potential to balance energy intake can be an approach to prevent or attenuate obesity. Methods Wild-type (WT) and IL6 knockout (KO) mice were employed to study the capacity of IL6 to induce neurogenesis. We used cell labeling with Bromodeoxyuridine (BrdU), immunofluorescence, and real-time PCR to determine the expression of markers of neurogenesis and neurotransmitters. We prepared hypothalamic neuroprogenitor cells from KO that were treated with IL6 in order to provide an ex vivo model to further characterizing the neurogenic actions of IL6 through differentiation assays. In addition, we analyzed single-cell RNA sequencing data and determined the expression of IL6 and IL6 receptor in specific cell types of the murine hypothalamus. Results IL6 expression in the hypothalamus is low and restricted to microglia and tanycytes, whereas IL6 receptor is expressed in microglia, ependymocytes, endothelial cells, and astrocytes. Exogenous IL6 reduces diet-induced obesity. In outbred mice, obesity-resistance is accompanied by increased expression of IL6 in the hypothalamus. IL6 induces neurogenesis-related gene expression in the hypothalamus and in neuroprogenitor cells, both from WT as well as from KO mice. Conclusion IL6 induces neurogenesis-related gene expression in the hypothalamus of WT mice. In KO mice, the neurogenic actions of IL6 are preserved; however, the appearance of new fully differentiated proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons is either delayed or disturbed.

Abstract Background SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. Methods This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. Discussion Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. Trial registration Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entrance, and studies have suggested that upon viral binding, ACE2 catalytic activity could be inhibited; therefore, impacting the regulation of the renin-angiotensin-aldosterone system (RAAS). To date, only few studies have evaluated the impact of SARS-CoV-2 infection on the blood levels of the components of the RAAS. The objective of this study was to determine the blood levels of ACE, ACE2, angiotensin-II, angiotensin (1–7), and angiotensin (1–9) at hospital admission and discharge in a group of patients presenting with severe or critical evolution of coronavirus disease 2019 (COVID-19). We showed that ACE, ACE2, angiotensin (1–7), and angiotensin (1–9) were similar in patients with critical and severe COVID-19. However, at admission, angiotensin-II levels were significantly higher in patients presenting as critical, compared to patients presenting with severe COVID-19. We conclude that blood levels of angiotensin-II are increased in hospitalized patients with COVID-19 presenting the critical outcome of the disease. We propose that early measurement of Ang-II could be a useful biomarker for identifying patients at higher risk for extremely severe progression of the disease.

Background: Photobiomodulation consists of inducing healing by irradiating light. This scoping review investigates the effect of blue light on the healing process. Methods: The MEDLINE, Web of Science, Scopus, and CINAHL databases were searched. Two reviewers independently examined the search results and extracted data from the included studies. A descriptive analysis was performed. Results: Twenty-two articles were included. Studies were categorized as in vitro/mixed, preclinical, and clinical. The power density used was 10–680 mW/cm2 in most of the in vitro/preclinical studies, the irradiation time ranged from 5 s to 10 min, and different wavelengths and energy densities were used. In clinical studies, the wavelength ranged from 405 to 470 nm, and the energy density varied from 1.5 to 30 J/cm2. Conclusions: A low energy density (2) was able to stimulate the different cell types and proteins involved in healing, while a high energy density, 20.6–50 J/cm2, significantly reduced cell proliferation, migration, and metabolism. There is a great variety of device parameters among studies, and this makes it difficult to conclude what the best technical specifications are. Thus, further studies should be performed in order to define the appropriate parameters of light to be used.

Abstract Background Peroxisome proliferator-activated receptor γ coactivator- 1alpha (PGC-1α) plays an important role in whole body metabolism and, particularly in glucose homeostasis. Its expression is highly regulated and, small variations in tissue levels can have a major impact in a number of physiological and pathological conditions. Recent studies have shown that the ubiquitin/proteasome system plays a role in the control of PGC-1α degradation. Methods Here we evaluated the interaction of PGC-1α with the protein A20, which plays a dual-role in the control of the ubiquitin/proteasome system acting as a deubiquitinase and as an E3 ligase. We employed immunoprecipitation, quantitative real-time PCR and immunofluorescence staining to evaluate PGC-1α, A20, PPARγ and ubiquitin in the adipose tissue of humans and mice. Results In distinct sites of the adipose tissue, A20 binds to PGC-1α. At least in the subcutaneous fat of humans and mice the levels of PGC-1α decrease during obesity, while its physical association with A20 increases. The inhibition of A20 leads to a reduction of PGC-1α and PPARγ expression, suggesting that A20 acts as a protective factor against PGC-1α disposal. Conclusion We provide evidence that mechanisms regulating PGC-1α ubiquitination are potentially involved in the control of the function of this transcriptional co-activator.

Abstract Background The consumption of large amounts of dietary fats activates an inflammatory response in the hypothalamus, damaging key neurons involved in the regulation of caloric intake and energy expenditure. It is currently unknown why the mediobasal hypothalamus is the main target of diet-induced brain inflammation. We hypothesized that dietary fats can damage the median eminence blood/spinal fluid interface. Methods Swiss mice were fed on a high-fat diet, and molecular and structural studies were performed employing real-time PCR, immunoblot, immunofluorescence, transmission electron microscopy, and metabolic measurements. Results The consumption of a high fat diet was sufficient to increase the expression of inflammatory cytokines and brain-derived neurotrophic factor in the median eminence, preceding changes in other circumventricular regions. In addition, it led to an early loss of the structural organization of the median eminence β1-tanycytes. This was accompanied by an increase in the hypothalamic expression of brain-derived neurotrophic factor. The immunoneutralization of brain-derived neurotrophic factor worsened diet-induced functional damage of the median eminence blood/spinal fluid interface, increased diet-induced hypothalamic inflammation, and increased body mass gain. Conclusions The median eminence/spinal fluid interface is affected at the functional and structural levels early after introduction of a high-fat diet. Brain-derived neurotrophic factor provides an early protection against damage, which is lost upon a persisting consumption of large amounts of dietary fats.

Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the kinin–kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin–kallikrein system in two markers that indicate improved disease recovery.

Treatment of chronic wounds is challenging, and the development of different formulations based on insulin has shown efficacy due to their ability to regulate oxidative stress and inflammatory reactions. The formulation of insulin with polysaccharides in biohybrid hydrogel systems has the advantage of synergistically combining the bioactivity of the protein with the biocompatibility and hydrogel properties of polysaccharides. In this study, a hydrogel formulation containing insulin, chitosan, and hydroxypropyl methyl cellulose (Chi/HPMC/Ins) was prepared and characterized by FTIR, thermogravimetric, and gel point analyses. The in vitro cell viability and cell migration potential of the Chi/HPMC/Ins hydrogel were evaluated in human keratinocyte cells (HaCat) by MTT and wound scratch assay. The hydrogel was applied to excisional full-thickness wounds in diabetic mice for twenty days for in vivo studies. Cell viability studies indicated no cytotoxicity of the Chi/HPMC/Ins hydrogel. Moreover, the Chi/HPMC/Ins hydrogel promoted faster gap closure in the scratch assay. In vivo, the wounds treated with the Chi/HPMC/Ins hydrogel resulted in faster wound closure, formation of a more organized granulation tissue, and hair follicle regeneration. These results suggest that Chi/HPMC/Ins hydrogels might promote wound healing in vitro and in vivo and could be a new potential dressing for wound healing.

Introdução: A conciliação medicamentosa propicia a detecção e prevenção de erros de medicação, constituindo uma importante ferramenta para o aumento da segurança da farmacoterapia instituída ao paciente internado. Alterações realizadas na terapia medicamentosa na admissão do paciente, bem como durante toda a sua permanência na unidade hospitalar, podem levar a erros de medicação e aumento de eventos adversos relacionados a medicamentos. A intervenção farmacêutica, nesse sentido, apresentase como um instrumento para prevenção ou resolução de problemas encontrados no processo de conciliação, constituindo-se como parte integrante do processo de seguimento farmacoterapêutico. Objetivo: Quantificar e avaliar as conciliações medicamentosas e intervenções realizadas por farmacêuticos da Unidade de Farmácia Clínica de um Hospital Universitário do município de Salvador-Bahia. Métodos: Trata-se de um estudo retrospectivo, quantitativo e descritivo. Foram incluídos pacientes internados em 13 unidades assistidas por farmacêuticos clínicos, no período de setembro de 2020 a setembro de 2022, com previsão de tempo de internamento superior a 48 horas. A conciliação medicamentosa foi realizada pelo confronto entre a prescrição médica da admissão e as informações obtidas com paciente e / ou familiar até 48 horas da sua admissão a partir da relação de medicamentos utilizados pelo paciente em domicílio. Já as intervenções farmacêuticas foram realizadas junto ao profissional prescritor mediante análise crítica da prescrição. Esse estudo está sob aprovação do CEP sob número 4.465.789. Resultados e Discussão: No período avaliado, foram assistidos 14.342 pacientes. Destes, 6.103 pacientes tinham critérios para conciliação medicamentosa, sendo conciliados 5.126 pacientes (84%). Do total de conciliações realizadas, foram encontradas 8.054 discrepâncias, sendo 7495 (93,06%) discrepâncias justificadas e 559 (6,94%) não justificadas. Foram realizadas 9.810 intervenções farmacêuticas, sendo 8.770 (83,4%) aceitas, 628 parcialmente aceitas (12,4%) e 412 (4,2%) não aceitas. No âmbito dessas intervenções, 874 (8,9%) estavam relacionadas a inconsistências encontradas na redação da prescrição médica. Os erros de prescrição são eventos evitáveis, mas que possuem grande potencial de levar a erros de medicação e que ainda permanecem com um alto percentual apesar da implementação das prescrições eletrônicas e portanto, constituem um desafio para a prática clínica do farmacêutico. Conclusão: O desempenho do farmacêutico clínico na conciliação medicamentosa e a sua intervenção precoce é primordial para garantia da continuidade de tratamento do paciente de forma segura, permitindo a identificação e prevenção de potenciais erros de medicação e problemas relacionados a medicamentos.

Abstract Glutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin hyperproliferative conditions such as psoriasis and skin regeneration; however, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased the expression of genes related to apoptosis in the skin, whereas glutamic acid increased cell viability and proliferation in human keratinocyte cultures. In addition, we identified the keratinocyte glutamic acid excitotoxic concentration, providing evidence for the existence of a novel skin signalling pathway mediated by a neurotransmitter that controls keratinocyte and hair follicle proliferation. Thus, glutamic acid emerges as a component of the peripheral nervous system that acts to control cell growth in the skin. These results raise the perspective of the pharmacological and nutritional use of glutamic acid to treat skin diseases.

The pig skin architecture and physiology are similar to those of humans. Thus, the pig model is very valuable for studying skin biology and testing therapeutics. The single-cell RNA sequencing (scRNA-seq) technology allows quantitatively analyzing cell types, compositions, states, signaling, and receptor-ligand interactome at single-cell resolution and at high throughput. scRNA-seq has been used to study mouse and human skins. However, studying pig skin with scRNA-seq is still rare. A critical step for successful scRNA-seq is to obtain high-quality single cells from the pig skin tissue. Here we report a robust method for isolating and cryopreserving pig skin single cells for scRNA-seq. We showed that pig skin could be efficiently dissociated into single cells with high cell viability using the Miltenyi Human Whole Skin Dissociation kit and the Miltenyi gentleMACS Dissociator. Furthermore, the obtained single cells could be cryopreserved using 90% FBS + 10% DMSO without causing additional cell death, cell aggregation, or changes in gene expression profiles. Using the developed protocol, we were able to identify all the major skin cell types. The protocol and results from this study are valuable for the skin research scientific community.

O artigo analisa algumas consequências da implantação do Programa Minha Casa Minha Vida para moradores de dois residenciais de Interesse Social na cidade de Montes Claros/MG. As reflexões enfatizam as estratégias e/ou adaptações utilizadas na vida cotidiana das famílias para contornar as limitações impostas pelo novo contexto habitacional. Dados documentais e pesquisas de campo descortinaram situações de vulnerabilidade social, segregação espacial urbana e a ausência de infraestrutura. O acesso à casa própria trouxe também novas perspectivas de apropriação do espaço e adaptação à realidade. O artigo conclui pela necessidade de revisão de diretrizes da política no sentido de garantir o direito social humano ‘a moradia e a dignidade às famílias.

Objetivo: Analisar os tipos de barreiras de acessibilidade das pessoas com deficiências aos serviços de saúde, através das publicações online nos anos 2003-2013. Métodos: Trata-se de revisão integrativa apresentada por meio de seis etapas. Ao se aplicar os critérios de inclusão: texto completo disponível, base de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis and Retrieval System Online e Base de Dados de Enfermagem, assunto principal pessoas com deficiência, idioma português, publicações dos anos de 2003-2013 e tipo de documento em artigo, emergiram 26 artigos. Desses, 13 foram analisados, 02 não abordavam sobre tipos de barreiras de acessibilidade aos serviços de saúde e 11 estavam repetidos. Resultados: Categorias emergentes foram as barreiras arquitetônicas, atitudinais, organizacionais. Conclusão: As barreiras de acessibilidade podem influenciar negativamente na busca das PcD aos serviços de saúde. Descritores: Pessoas com deficiência, Acesso aos serviços de saúde, Estruturas de acesso.

Objetivo: Analisar os tipos de barreiras de acessibilidade das pessoas com deficiências aos serviços de saúde, através das publicações online nos anos 2003-2013. Métodos: Trata-se de revisão integrativa apresentada por meio de seis etapas. Ao se aplicar os critérios de inclusão: texto completo disponível, base de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis and Retrieval System Online e Base de Dados de Enfermagem, assunto principal pessoas com deficiência, idioma português, publicações dos anos de 2003-2013 e tipo de documento em artigo, emergiram 26 artigos. Desses, 13 foram analisados, 02 não abordavam sobre tipos de barreiras de acessibilidade aos serviços de saúde e 11 estavam repetidos. Resultados: Categorias emergentes foram as barreiras arquitetônicas, atitudinais, organizacionais. Conclusão: As barreiras de acessibilidade podem influenciar negativamente na busca das PcD aos serviços de saúde. Descritores: Pessoas com deficiência, Acesso aos serviços de saúde, Estruturas de acesso.

Objetivo: Analisar os tipos de barreiras de acessibilidade das pessoas com deficiências aos serviços de saúde, através das publicações online nos anos 2003-2013. Métodos: Trata-se de revisão integrativa apresentada por meio de seis etapas. Ao se aplicar os critérios de inclusão: texto completo disponível, base de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis and Retrieval System Online e Base de Dados de Enfermagem, assunto principal pessoas com deficiência, idioma português, publicações dos anos de 2003-2013 e tipo de documento em artigo, emergiram 26 artigos. Desses, 13 foram analisados, 02 não abordavam sobre tipos de barreiras de acessibilidade aos serviços de saúde e 11 estavam repetidos. Resultados: Categorias emergentes foram as barreiras arquitetônicas, atitudinais, organizacionais. Conclusão: As barreiras de acessibilidade podem influenciar negativamente na busca das PcD aos serviços de saúde. Descritores: Pessoas com deficiência, Acesso aos serviços de saúde, Estruturas de acesso.

Na prática hospitalar, a Educação Permanente é indispensável à formação dos trabalhadores, os quais necessitam ter conhecimentos renovados em sua prática profissional. Nesta perspectiva, buscou-se analisar por meio dessa pesquisa a percepção dos enfermeiros de um hospital de ensino acerca da educação permanente no ambiente hospitalar. Trata-se de uma pesquisa descritiva com abordagem qualitativa, realizada com nove enfermeiros coordenadores de setores, utilizando-se três grupos focais, constituído por três enfermeiros em cada grupo. A investigação ocorreu no Hospital do Coração do município de Sobral, Ceará. Utilizaram-se entrevistas que foram gravadas nas reuniões dos grupos. A análise de conteúdo de Bardin estruturou os achados encontrados. Esses resultados foram separados por unidades temáticas. Foram respeitados os princípios éticos de acordo com a resolução 466/12. A primeira unidade temática investigou o conhecimento dos sujeitos acerca da Educação Permanente, Continuada e em Serviço. Os primeiros achados identificaram divergências de opiniões dos participantes quando conceituaram a diferenciação entre as modalidades de educação em saúde. A segunda unidade resgatou a opinião dos sujeitos sobre as estratégias para implantar uma comissão de educação permanente no hospital. As falas dos participantes revelaram que a comissão deveria motivar os profissionais a continuarem se qualificando no serviço. Ainda indagaram que essas comissões deveria ter caráter multidisciplinar. A última unidade analisada referiu-se a forma de atuar das comissões de educação permanente. Os investigados assinalaram que elas deveriam proporcionar a melhoria do ensino aos profissionais aplicando as metodologias ativas.

El objetivo fue describir la contribución de la atención clínica de enfermería para el confort ambiental de mujeres con infarto agudo de miocardio, mediada por la investigación-cuidado basada de la Teoría del Confort. La recolección se llevó a cabo entre abril y junio del 2011 con nueve mujeres con infarto en el Hospital del Corazón en Sobral, Ceará, Brasil. Hubo cuatro reuniones a partir de la admisión. Se les informó de los objetivos y el método y el cuidado ocurrió basado en el método y la teoría. Para la recolección de las informaciones, se utilizaron la entrevista semiestructurada, diarios de campo, observación participante y análisis temático categorial de contenido. Los cuidados clínicos buscaron promover la adaptación a la unidad de cuidados coronarios, proporcionar un entorno adecuado para promover la comodidad y el ambiente relajado. La atención clínica para promover el confort ambiental contribuye al bienestar de las mujeres con infarto.

Las alteraciones en los niveles de tensión se encuentran comúnmente en los pacientes sometidos a cirugía cardíaca. Este estudio tuvo como objetivo analizar los niveles presóricos de los pacientes en el perioperatorio de cirugía cardiaca. Investigación descriptiva y documental, la muestra fue de 176 historiales médicos de pacientes sometidos a cirugía cardíaca en el año 2007 en el Hospital del Corazón de Sobral-CE. El perfil predominante punteó pacientes de sexo masculino, casados, que viven en municipios lejanos de los servicios de salud y población de más de cuarenta años de edad. La cirugía de revascularización de miocardio fue realizada en más de la mitad de los pacientes. Hubo oscilaciones en los valores de presión arterial, pero la normotensión predominó en todas las fases de la cirugía cardiaca, alteraciones más importantes ocurrieron en el postoperatorio. Debido a las alteraciones en la presión arterial en los pacientes sometidos a cirugía cardiaca, el equipo de enfermería debe estar cada vez más capacitado y apto para la monitorización de este parámetro.

Estudio descriptivo cuya meta es verificar si los hospitales de la ciudad de Sobral,Ceará, tienen instalaciones sanitarias adecuadas, espacios en auditorios, ascensores, salidas de emergencia y aparcamientos que obedezcan las necesidades de personas portadoras de deficiencia física. Con base en la NBR 9050 de la ABNT con instrumento tipo chequeo de lista. Dados recogidos en mayo de 2004. La muestra abarcó los cuatro hospitales existentes. Dos hospitales poseen instalaciones sanitarias, con artefacto sanitario y lavabo adaptados. Ninguno de ellos tiene vestuarios y baños accesibles. No existen ni ascensores, ni salidas de emergencia, ni aparcamiento demarcado y tampoco hay señalización de acceso. Queda así evidente la necesidad de que se cumplan las normas legales que permitirán el acceso de las personas portadoras de deficiencia física.

Pesquisa sobre as barreiras físicas encontradas pelos portadores de deficiência em áreas internas de quatro hospitais de Sobral-Ceará. Estudo quantitativo no qual a coleta de dados foi realizada por cheque-lista baseada na NBR 9050 da Associação Brasileira de Normas Técnicas (ABNT), em maio de 2004. A análise constatou o seguinte: presença de rampas de acesso (100%); escadaria sem corrimão (50%); portas possuem largura ideal (100%); as de vai-e-vem não têm visor (100%); áreas internas de circulação possuem obstáculos (100%); piso das rampas não antiderrapantes (100%); rampas e escadas com corrimão (50%), mas fora do padrão legal. Um hospital é térreo, os outros possuem treze escadas internas; balcões (80%) e assentos públicos (33%) atendem à legislação; bebedouros e telefones não são acessíveis (97%). Concluiu-se que há barreiras físicas e que a legislação está sendo desrespeitada.Pesquisa sobre las barreras físicas encontradas por los portadores de deficiencia en áreas internas de cuatro hospitales de Sobral - Ceará. Estudio cuantitativo en el cual la colecta de datos fue realizada por cheque-lista basada en la NBR 9050 de la Asociación Brasileña de Normas Técnicas (ABNT), en mayo de 2004. La análisis constató lo siguiente: presencia de rampas de acceso (100%); escaleras sin pasamano (50%); puertas poseen largura ideal (100%); las de ida y vuelta no tiene visor (100%); áreas internas de circulación poseen obstáculos (100%); suelo que no derrapan (100%) ;rampas y escaleras con pasamano (50%), pero fuera del padrón legal. Un hospital es plano, los otros poseen trece escaleras inter-nas; balcones (80%) y asientos públicos (33%) atienden a la legislación; lugares para beber agua y teléfono no son accesibles (97%). Se concluye que hay barreras físicas y que la legislación está siendo desacata.The objective of this research was to identify architectural barriers for the physically handicapped in the internal areas of four hospitals in the city of Sobral, in the State of Ceará. This is a quantitative study for which data collection was carried out in May of 2004 using a checklist based on the NBR 9050, of the Brazilian Technical Standards Organization (ABNT). The analysis identified the presence of access ramps (100%); staircases without banisters (50%); doors with ideal width (100%); swinging doors with no windows (100%); internal circulation areas with obstacles (100%); ramps with no antiskid floors (100%); ramps and staircases with banisters (50%), but out of legal standards. One hospital was built entirely on the ground floor, but the others have thirteen internal staircases; 80% of the counters and 33% of the seats for the public comply with legal standards; 97% of the drinking fountains and telephones are not accessible. The conclusion is that there are physical barriers in these institutions and that the legislation is not being complied with.

Estudo quantitativo sobre barreiras arquitetônicas no percurso do deficiente físico aos hospitais de Sobral, Ceará, com o objetivo de identificar as condições de acesso arquitetônico dos portadores de deficiência física aos quatro hospitais da mencionada cidade. Apoiado na NBR 9050 da ABNT utilizou instrumento tipo cheque-lista, cuja coleta de dados ocorreu em maio de 2004. A análise estatística constatou ausência de faixas para pedestres e apenas um apresentava rebaixamento de meio-fio em pontos estratégicos; obras públicas e particulares, desprotegidas de tapumes; calçadas com buracos e desnivelamento; metade das avenidas livres de buracos ; placas de sinalização de trânsito visíveis em três dos hospitais; percurso para a instituição sinalizado; mas não há semáforos em pontos estratégicos. Um hospital possui rebaixamento de guias; ausência de estacionamento para pessoa portadora de deficiência física. Conforme se concluiu, há barreiras arquitetônicas no percurso casa/hospital. Com isso os hospitais requerem melhores estruturas com vistas a minimizar as barreiras arquitetônicas no percurso do deficiente físico a esses serviços.

Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats.The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway.We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing.Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1α in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes.ClinicalTrials.gov NCT01295177.

BACKGROUND:Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade. METHODOLOGY/PRINCIPAL FINDINGS:Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression. CONCLUSION/SIGNIFICANCE:Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue.

In Brazil, with regard to public policies for disable persons with barriers in access to health services1, there are challenges for implementation. Depending on the experience as a participant in the design of accessibility of people with physical disabled and/or Sensory Services Health: study of physical and or communication, funded by the Ministry of Health, urged the reflection about the importance of strengthening this population forward the construction of spaces available to hospital services. Facing this, and attempt to break the biomedical model2, we believe that community participation is a sine qua non situation in the process of execution of health policies, highlighting the Empowerment3, understood as involving and strengthening growth in the activation of potential analysis of individuals as to their circumstances of life. In this perspective, motivate Disabled Persons for the construction of spaces available, with views to the autonomy ad safe use of buildings, including furniture and urban equipment, is to ensure basic human rights.

Quantitative study on architectural barriers in the passage of the deficient physicist to the hospitals of Sobral, Ceará, with the objective of mapear the access conditions architectural of the carriers of physical deficiency to the four hospitals of the mentioned city. Supported in NBR 9050 of the ABNT, it used instrument type check-list, whose collection of data occurred in May of 2004. The analysis statistics evidenced absence of bands for pedestrians and only one to show degradation of curb in strategical points; unproctected public works and particular of fences; sidewalk with holes and making uneven; half of free avenues of holes; visible plates of transit signaling in tree of hospital; passage for the signaled institution; but it does not have traffic lights in strategical points. One hospital possess degradation of guides; absence of parking for carrying person of physical deficiency. As it was concluded, has architectural barriers in the way of house / hospital. With this the hospitals require better structures with sights to minimize the barriers architectural in the passage of the deficient physicist to these services.

Resumo A atual política educacional no contexto brasileiro preconiza a garantia de um sistema educacional inclusivo em todos os níveis de ensino. Dados do Censo da Educação Superior de 2013 registram um aumento de 575.4%, entre os anos de 2003 e 2013, no número de estudantes com deficiência nas instituições de ensino superior. Esse crescimento decorre de um conjunto de medidas inseridas na legislação brasileira para garantir o acesso e as condições de atendimento adequadas às pessoas com deficiência nesse nível de ensino. O presente estudo descritivo-analítico de base documental utiliza normativas institucionais como fonte de dados, no período de 2011 a 2015, objetivando descrever a atuação do Núcleo de Acessibilidade na Universidade Federal do Rio Grande do Norte/UFRN, e discorrer algumas reflexões acerca dessa experiência. O estudo busca contribuir com as discussões sobre a inclusão no ensino superior brasileiro, bem como o aprimoramento dos serviços de apoio oferecido neste contexto.