Brazilian guidelines on diagnosis and management of traumatic vascular injuries.

Trauma is a leading cause of death, permanent disability, and health care cost worldwide. The young and economically active are the most affected population. Exsanguination due to noncompressible torso hemorrhage is one of the most frequent causes of early death, posing a significant challenge to trauma and vascular surgeons. The possibility of limb loss due to vascular injuries must also be considered. In recent decades, the approach to vascular injuries has been significantly modified. Angiotomography has become the standard method for diagnosis, endovascular techniques are currently incorporated in treatment, and damage control, such as temporary shunts, is now the preferred approach for the patients sustaining physiological derangement. Despite the importance of this topic, few papers in the Brazilian literature have offered guidelines on vascular trauma. The Brazilian Society of Angiology and Vascular Surgery has developed Projetos Diretrizes (Guideline Projects), which includes this publication on vascular trauma. Since treating trauma patients is a multidisciplinary effort, the Brazilian Trauma Society (SBAIT) was invited to participate in this project. Members of both societies reviewed the literature on vascular trauma management and together wrote these guidelines on vascular injuries of neck, thorax, abdomen, and extremities.

The value of the International Association for the Study of Pain to career development: perspectives of trainee and early career members.

ABSTRACT: Supporting its young members has been a key priority of the International Association for the Study of Pain (IASP) for the past 5 decades. The IASP, along with its federations, chapters, and special interest groups, has provided benefits to its trainee and early career members for their career development. This article summarizes various key IASP initiatives and benefits offered to IASP members and how these benefits have positively impacted their careers, including examples from the authors of this article. Suggestions are made for future directions that the IASP could implement to enhance the value provided to its trainee and early career members, which will in turn contribute to IASP achieving its mission to stimulate and support the study of pain and to translate that knowledge into improved pain relief worldwide.

Work-family boundary management profiles and well-being at work: A study with militaries on a humanitarian aid mission.

This study aims to contribute to an analysis of the well-being of military personnel who are deployed on humanitarian aid missions, taking their work-family (personal life) boundary management into consideration by analyzing the relationship between their preferences and enacted boundaries and military personnel' well-being. Specifically, this study analyzed the boundary fit approach, positing that it is the adjustment between individuals' preferences and enacted boundaries that influences their well-being. Using a sample of 327 military personnel, boundary management profiles were performed, considering the fit between their segmentation preferences and enactment. Furthermore, the relationship between these profiles and the military personnel' well-being was established. The results indicated that misfit profiles were found where the soldiers enacted less segmentation than desired or, on the contrary, more integration than desired, and a profile with a fit between the work-family segmentation they desired and enacted. The military personnel in the fit profile had significantly higher levels of well-being (i.e.,less exhaustion and more work engagement) than those in the misfit profile, who enacted less segmentation than desired. The findings have implications for the design of boundary management literature and future military missions.

Neuron-associated macrophage proliferation in the sensory ganglia is associated with peripheral nerve injury-induced neuropathic pain involving CX3CR1 signaling.

Resident macrophages are distributed across all tissues and are highly heterogeneous due to adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophages in the sensory ganglia, which have been implicated in different conditions, including neuropathic pain development. However, it is still under debate whether macrophage accumulation in the sensory ganglia after peripheral nerve injury is due to the local proliferation of resident macrophages or a result of blood monocyte infiltration. Here, we confirmed that the number of macrophages increased in the sensory ganglia after the spared nerve injury (SNI) model in mice. Using different approaches, we found that the increase in the number of macrophages in the sensory ganglia after SNI is a consequence of the proliferation of resident CX3CR1+ macrophages, which participate in the development of neuropathic pain, but not due to infiltration of peripheral blood monocytes. These proliferating macrophages are the source of pro-inflammatory cytokines such as TNF and IL-1b. In addition, we found that CX3CR1 signaling is involved in the sNAMs proliferation and neuropathic pain development after peripheral nerve injury. In summary, these results indicated that peripheral nerve injury leads to sNAMs proliferation in the sensory ganglia in a CX3CR1-dependent manner accounting for neuropathic pain development. In conclusion, sNAMs proliferation could be modulated to change pathophysiological conditions such as chronic neuropathic pain.

Effect of promethazine on biofilms of gram-positive cocci associated with infectious endocarditis.

This study evaluated the antimicrobial activity of promethazine against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus mutans and its effect on the antimicrobial susceptibility of biofilms grown in vitro and ex vivo on porcine heart valves. Promethazine was evaluated alone and in combination with vancomycin and oxacillin against Staphylococcus spp. and vancomycin and ceftriaxone against S. mutans in planktonic form and biofilms grown in vitro and ex vivo. Promethazine minimum inhibitory concentration range was 24.4-95.31 µg/mL and minimum biofilm eradication concentration range was 781.25-3.125 µg/mL. Promethazine interacted synergistically with vancomycin, oxacillin and ceftriaxone against biofilms in vitro. Promethazine alone reduced (p < 0.05) the CFU-counts of biofilms grown on heart valves for Staphylococcus spp., but not for S. mutans, and increased (p < 0.05) the activity of vancomycin, oxacillin and ceftriaxone against biofilms of Gram-positive cocci grown ex vivo. These findings bring perspectives for repurposing promethazine as adjuvant in the treatment of infective endocarditis.

A historical, economic, and technical-scientific approach to the current crisis in the development of antibacterial drugs: Promising role of antibacterial peptides in this scenario.

The emergence of antibiotic resistance (AMR) is a global public health problem. According to estimates, drug-resistant bacteria infect 2 million patients and perish 23,000 annually. To overcome this problem, antimicrobial peptides became a potential solution based on a new mechanism of action against bacteria. This article addresses the phenomenon of antibacterial resistance in most of its nuances, responding to historical, technical-scientific, and economic aspects. Likewise, it explores new therapeutic approaches to combat multi-resistant pathogens, specifically concerning antibacterial peptides, as a potential therapeutic tool to mitigate the current crisis of antibacterial drugs. It is expected that, with technological advances, especially with the advent and adoption of artificial intelligence, there will be an increase in diversified synthetic peptide production, which can face the challenges that we have in terms of antibacterial drugs.

No Chance to Survive: Mo-CBP3-PepII Synthetic Peptide Acts on Cryptococcus neoformans by Multiple Mechanisms of Action.

Multidrug-resistant Cryptococcus neoformans is an encapsulated yeast causing a high mortality rate in immunocompromised patients. Recently, the synthetic peptide Mo-CBP3-PepII emerged as a potent anticryptococcal molecule with an MIC50 at low concentration. Here, the mechanisms of action of Mo-CBP3-PepII were deeply analyzed to provide new information about how it led C. neoformans cells to death. Light and fluorescence microscopies, analysis of enzymatic activities, and proteomic analysis were employed to understand the effect of Mo-CBP3-PepII on C. neoformans cells. Light and fluorescence microscopies revealed Mo-CBP3-PepII induced the accumulation of anion superoxide and hydrogen peroxide in C. neoformans cells, in addition to a reduction in the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT) in the cells treated with Mo-CBP3-PepII. In the presence of ascorbic acid (AsA), no reactive oxygen species (ROS) were detected, and Mo-CBP3-PepII lost the inhibitory activity against C. neoformans. However, Mo-CBP3-PepII inhibited the activity of lactate dehydrogenase (LDH) ergosterol biosynthesis and induced the decoupling of cytochrome c (Cyt c) from the mitochondrial membrane. Proteomic analysis revealed a reduction in the abundance of proteins related to energetic metabolism, DNA and RNA metabolism, pathogenicity, protein metabolism, cytoskeleton, and cell wall organization and division. Our findings indicated that Mo-CBP3-PepII might have multiple mechanisms of action against C. neoformans cells, mitigating the development of resistance and thus being a potent molecule to be employed in the production of new drugs against C. neoformans infections.

Ex vivo wound model on porcine skin for the evaluation of the antibiofilm activity of polyhexamethylene biguanide and ciprofloxacin.

This study aimed to standardize the use of an ex vivo wound model for the evaluation of compounds with antibiofilm activity. The in vitro susceptibility of Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 27853 to ciprofloxacin and polyhexamethylene biguanide (PHMB) was evaluated in planktonic and biofilm growth. The effects of ciprofloxacin and PHMB on biofilms grown on porcine skin explants were evaluated by colony-forming unit (CFU) counting and confocal microscopy. Minimum inhibitory concentrations (MICs) against S. aureus and P. aeruginosa were, respectively, 0.5 and 0.25 µg mL-1 for ciprofloxacin, and 0.78 and 6.25 µg mL-1 for PHMB. Minimum biofilm eradication concentrations (MBECs) against S. aureus and P. aeruginosa were, respectively, 2 and 8 µg mL-1 for ciprofloxacin, and 12.5 and >25 µg mL-1 for PHMB. Ciprofloxacin reduced (P < 0.05) log CFU counts of the biofilms grown ex vivo by 3 and 0.96 for S. aureus and P. aeruginosa, respectively, at MBEC, and by 0.58 and 8.12 against S. aureus and P. aeruginosa, respectively, at 2xMBEC. PHMB (100 µg/mL) reduced (P < 0.05) log CFU counts by 0.52 for S. aureus and 0.68 log for P. aeruginosa, leading to an overall decrease (P < 0.05) in biofilm biomass. The proposed methodology to evaluate the susceptibility of biofilms grown ex vivo led to reproducible and reliable results.

Giving a Hand: Synthetic Peptides Boost the Antifungal Activity of Itraconazole against Cryptococcus neoformans.

Cryptococcus neoformans is a multidrug-resistant pathogen responsible for infections in immunocompromised patients. Here, itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic antimicrobial peptides (SAMPs), Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The Mo-CBP3-PepII was designed based on the sequence of MoCBP3, purified from Moringa oleifera seeds. RcAlb-PepII and RcAlb-PepIII were designed using Rc-2S-Alb, purified from Ricinus communis seed cakes. The putative sequence of a chitinase from Arabidopsis thaliana was used to design PepGAT and PepKAA. All SAMPs have a positive liquid charge and a hydrophobic potential ranging from 41-65%. The mechanisms of action responsible for the combined effect were evaluated for the best combinations using fluorescence microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and the overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR against C. neoformans. Therefore, synthetic peptides are potential molecules to assist antifungal agents in treating Cryptococcal infections.

Diretrizes brasileiras de diagnóstico e tratamento de lesões vasculares traumáticas / Brazilian guidelines on diagnosis and management of traumatic vascular injuries

Resumo Trauma é uma causa importante de morbimortalidade, que acomete principalmente jovens. A hemorragia incoercível é o principal mecanismo de óbito precoce nessas vítimas, e as lesões vasculares não compressíveis representam grandes desafios para os cirurgiões. O traumatismo vascular impacta diretamente a viabilidade de membros traumatizados, aumentando o risco de amputação. Nas últimas décadas, muitas condutas de diagnóstico e tratamento de lesões vasculares traumáticas foram modificadas. A angiotomografia suplantou a angiografia como padrão ouro para diagnóstico, as técnicas endovasculares foram incorporadas ao arsenal terapêutico e o conceito de "controle de danos" foi estabelecido. No entanto, há lacunas na literatura nacional sobre a normatização de condutas em trauma vascular, principalmente considerando as limitações do Brasil. Por isso, a Sociedade Brasileira de Angiologia e de Cirurgia Vascular e a Sociedade Brasileira de Atendimento Integrado ao Traumatizado revisaram a literatura disponível sobre trauma vascular e organizaram diretrizes sobre o diagnóstico e tratamento dessas lesões.

Abstract Trauma is a leading cause of death, permanent disability, and health care cost worldwide. The young and economically active are the most affected population. Exsanguination due to noncompressible torso hemorrhage is one of the most frequent causes of early death, posing a significant challenge to trauma and vascular surgeons. The possibility of limb loss due to vascular injuries must also be considered. In recent decades, the approach to vascular injuries has been significantly modified. Angiotomography has become the standard method for diagnosis, endovascular techniques are currently incorporated in treatment, and damage control, such as temporary shunts, is now the preferred approach for the patients sustaining physiological derangement. Despite the importance of this topic, few papers in the Brazilian literature have offered guidelines on vascular trauma. The Brazilian Society of Angiology and Vascular Surgery has developed Projetos Diretrizes (Guideline Projects), which includes this publication on vascular trauma. Since treating trauma patients is a multidisciplinary effort, the Brazilian Trauma Society (SBAIT) was invited to participate in this project. Members of both societies reviewed the literature on vascular trauma management and together wrote these guidelines on vascular injuries of neck, thorax, abdomen, and extremities.

Avaliação da satisfação profissional dos enfermeiros num Centro Hospitalar da Região Lisboa / Assessment of nurses' professional satisfaction in a Hospital in the Lisbon Region

A satisfação profissional (SP) tem sido alvo de um crescente interesse por parte dos investigadores, motivados pelas consequências que pode ter na saúde e na qualidade de vida dos trabalhadores e na qualidade de cuidados prestados aos doentes. É assim, uma condição importante para o bom funcionamento das organizações, servindo como indicador para os gestores iniciarem estratégias que promovam a satisfação profissional. Realizou-se um estudo observacional e transversal, seguindo um modelo de análise descritivo - correlacional, num hospital da região de Lisboa, com vista a satisfação profissional dos enfermeiros. A partir deste, pretendeu-se, também, a relação entre a satisfação profissional, os fatores sociodemográficos e os profissionais nos diferentes serviços hospitalares estudados. Para a recolha de dados foi utilizado o Instrumento de Avaliação de Satisfação Profissional (IASP), desenvolvido e adaptado pelo CEISUC de preenchimento via intranet. Utilizou-se o programa informático Statistical Package for the Social Sciences (SPSS) para o tratamento de dados, recorrendo a medidas estatísticas descritivas e de comparação. A amostra ficou constituída por 136 profissionais de saúde, que traduz uma taxa de adesão de 43%. A maioria da amostra é do gênero feminino com 82,6%. O nível médio de satisfação profissional dos enfermeiros nos serviços estudados, foi de 57,1%. Quanto à relação da satisfação com os fatores sociodemográficos e profissionais, apenas nos fatores género e na acumulação de funções evidenciaram-se significâncias estatística, em que os homens se sentem mais satisfeitos que as mulheres e os que acumulam funções em outros locais expressam-se menos satisfeitos. Existem diferenças na satisfação entre as várias áreas de cuidados tendo-se apurado valores médios mais baixos no serviço de medicina e os mais elevados nas unidades de cuidados intensivos. Apesar dos valores baixos obtidos, maioritariamente, os enfermeiros optariam pela mesma profissão, o que significa que se identificam com a profissão e reconhecem na Enfermagem enquanto disciplina científica e profissional, o cuidar do outro, o principal motivo para trabalharem. Os resultados evidenciam necessidade de implementação de medidas que visem a melhoria da satisfação profissional dos enfermeiros.

ob satisfaction (SP) has been the subject of growing interest on the part of researchers, motivated by the consequences it can have on the health and quality of life of workers and on the quality of care provided to users. It is thus an important condition for the proper functioning of organizations, serving as an indicator for managers to initiate strategies that promote job satisfaction. An observational and cross-sectional study was carried out, following a descriptive - correlational analysis model, in a hospital in the Lisbon region, with a view to the professional satisfaction of nurses. From this, it was also intended to establish a relationship between professional satisfaction, sociodemographic factors and professional factors and in the different hospital services studied. For data collection, the Professional Satisfaction Assessment Instrument (IASP) was used, developed and adapted by CEISUC by via intranet. The Statistical Package for the Social Sciences (SPSS) computer program was used for data processing, using descriptive and comparative statistical measures. The sample consisted of 136 health professionals, which translates into a rate. Most of the sample is female with 82.6%. The average level of professional satisfaction of nurses in the services studied was 57.1%. As for the relationship of satisfaction with sociodemographic and professional factors, only the gender factors and the accumulation of functions showed statistical significance, in which men feel more satisfied than women and those who accumulate functions in other places express themselves less satisfied. There are differences in satisfaction between the various areas of care, with the lowest mean values being found in the medical service and the highest in the intensive care units. Despite the low values obtained, most of the nurses would opt for the same profession, which means that they identify with the profession and recognize Nursing as a scientific and professional discipline, caring for others, the main reason for working. The results show the need to implement measures aimed at improving the professional satisfaction of nurses.

Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice.

Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO1-expressing dendritic cells (DCs) accumulated in the dorsal root leptomeninges and led to an increase in kynurenine levels in the spinal cord. In the spinal cord, kynurenine was metabolized by kynurenine-3-monooxygenase-expressing astrocytes into the pronociceptive metabolite 3-hydroxykynurenine. Ultimately, 3-hydroxyanthranilate 3,4-dioxygenase-derived quinolinic acid formed in the final step of the canonical KYNPATH was also involved in neuropathic pain development through the activation of the glutamatergic N-methyl-D-aspartate receptor. In conclusion, these data revealed a role for DCs driving neuropathic pain development through elevation of the KYNPATH. This paradigm offers potential new targets for drug development against this type of chronic pain.

PD-1/PD-L1 Inhibition Enhances Chemotherapy-Induced Neuropathic Pain by Suppressing Neuroimmune Antinociceptive Signaling.

Cytotoxic agents synergize with immune checkpoint inhibitors and improve outcomes for patients with several cancer types. Nonetheless, a parallel increase in the incidence of dose-limiting side effects, such as peripheral neuropathy, is often observed. Here, we investigated the role of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in the modulation of paclitaxel-induced neuropathic pain. We found that human and mouse neural tissues, including the dorsal root ganglion (DRG), expressed basal levels of PD-1 and PD-L1. During the development of paclitaxel-induced neuropathy, an increase in PD-L1 expression was observed in macrophages from the DRG. This effect depended on Toll-like receptor 4 activation by paclitaxel. Furthermore, PD-L1 inhibited pain behavior triggered by paclitaxel or formalin in mice, suggesting that PD-1/PD-L1 signaling attenuates peripheral neuropathy development. Consistent with this, we observed that the combined use of anti-PD-L1 plus paclitaxel increased mechanical allodynia and chronic neuropathy development induced by single agents. This effect was associated with higher expression of inflammatory markers (Tnf, Il6, and Cx3cr1) in peripheral nervous tissue. Together, these results suggest that PD-1/PD-L1 inhibitors enhance paclitaxel-induced neuropathic pain by suppressing PD-1/PD-L1 antinociceptive signaling.

Propylthiouracil-Induced Skin Vasculitis.

The use of propylthiouracil (PTU) is associated with the development of autoantibodies, namely, antineutrophil cytoplasmic antibodies (ANCAs), which are associated with the pathogenesis of ANCA-associated systemic vasculitis, most often related to the myeloperoxidase subtype (ANCA-MPO). The authors report the case of a 61-year-old woman on PTU for one year who was referred to Internal Medicine for a three-month evolution of painless non-blanching purple patches, non-pruriginous, involving the chest and legs. The autoimmunity revealed ANCA antibody positivity, with a cutaneous biopsy compatible with leukocytoclastic vasculitis/necrotizing vasculitis with involvement of small and medium-sized vessels. Clinical improvement was noted after the drug was discontinued, with the resolution of the analytical changes.

Antimicrobial susceptibility and production of virulence factors by bacteria recovered from bitches with pyometra.

Pyometra is one of the most common diseases in adult female dogs, characterized by a suppurative bacterial infection of the uterus with accumulation of inflammatory exudate and a variety of local and systemic clinical manifestations. This study aimed to identify the bacteria within the uterine content and vaginal canal of bitches with pyometra and evaluate their antimicrobial susceptibility and production of virulence factors. Uterine and vaginal content were collected with sterile swabs from 30 bitches diagnosed with pyometra. Bacteria were identified and assessed for their antimicrobial susceptibility and production of virulence factors, including biofilms, siderophores, proteases and hemolysins, both in planktonic and biofilm forms. A total of 82 bacterial isolates (35 uterus, 47 vagina), belonging to 21 species, were identified, with Escherichia coli as the most prevalent species (32/82, 39%). As for susceptibility, 39/79 (49.4%) isolates were resistant to one or more drugs, with resistance proportion among Gram-positive bacteria (87.5%) higher (p < .05) than that observed for Gram-negative bacteria (32.7%). Four coagulase-negative Staphylococcus species were resistant to methicillin. Regarding virulence, the isolates had low production of biofilms, siderophores, proteases and hemolysins, suggesting that the occurrence of pyometra might be more associated with host-related factors than bacterial virulence.

Biological and Molecular Docking Evaluation of a Benzylisothiocyanate Semisynthetic Derivative From Moringa oleifera in a Pre-clinical Study of Temporomandibular Joint Pain.

Objective: Moringa oleifera possesses multiple biological effects and the 4-[(4'-O-acetyl-α-L- rhamnosyloxy) benzyl] isothiocyanate accounts for them. Based on the original isothiocyanate molecule we obtained a semisynthetic derivative, named 4-[(2',3',4'-O-triacetyl-α-L-rhamnosyloxy) N-benzyl] hydrazine carbothioamide (MC-H) which was safe and effective in a temporomandibular joint (TMJ) inflammatory hypernociception in rats. Therefore, considering that there is still a gap in the knowledge concerning the mechanisms of action through which the MC-H effects are mediated, this study aimed to investigate the involvement of the adhesion molecules (ICAM-1, CD55), the pathways heme oxygenase-1 (HO-1) and NO/cGMP/PKG/K+ ATP, and the central opioid receptors in the efficacy of the MC-H in a pre-clinical study of TMJ pain. Methods: Molecular docking studies were performed to test the binding performance of MC-H against the ten targets of interest (ICAM-1, CD55, HO-1, iNOS, soluble cGMP, cGMP-dependent protein kinase (PKG), K+ ATP channel, mu (µ), kappa (κ), and delta (δ) opioid receptors). In in vivo studies, male Wistar rats were treated with MC-H 1 µg/kg before TMJ formalin injection and nociception was evaluated. Periarticular tissues were removed to assess ICAM-1 and CD55 protein levels by Western blotting. To investigate the role of HO-1 and NO/cGMP/PKG/K+ ATP pathways, the inhibitors ZnPP-IX, aminoguanidine, ODQ, KT5823, or glibenclamide were used. To study the involvement of opioid receptors, rats were pre-treated (15 min) with an intrathecal injection of non-selective inhibitor naloxone or with CTOP, naltrindole, or norbinaltorphimine. Results: All interactions presented acceptable binding energy values (below -6.0 kcal/mol) which suggest MC-H might strongly bind to its molecular targets. MC-H reduced the protein levels of ICAM-1 and CD55 in periarticular tissues. ZnPP-IX, naloxone, CTOP, and naltrindole reversed the antinociceptive effect of MC-H. Conclusion: MC-H demonstrated antinociceptive and anti-inflammatory effects peripherally by the activation of the HO-1 pathway, as well as through inhibition of the protein levels of adhesion molecules, and centrally by µ and δ opioid receptors.

Skin-resident dendritic cells mediate postoperative pain via CCR4 on sensory neurons.

Inflammatory pain, such as hypersensitivity resulting from surgical tissue injury, occurs as a result of interactions between the immune and nervous systems with the orchestrated recruitment and activation of tissue-resident and circulating immune cells to the site of injury. Our previous studies identified a central role for Ly6Clow myeloid cells in the pathogenesis of postoperative pain. We now show that the chemokines CCL17 and CCL22, with their cognate receptor CCR4, are key mediators of this response. Both chemokines are up-regulated early after tissue injury by skin-resident dendritic and Langerhans cells to act on peripheral sensory neurons that express CCR4. CCL22, and to a lesser extent CCL17, elicit acute mechanical and thermal hypersensitivity when administered subcutaneously; this response abrogated by pharmacological blockade or genetic silencing of CCR4. Electrophysiological assessment of dissociated sensory neurons from naïve and postoperative mice showed that CCL22 was able to directly activate neurons and enhance their excitability after injury. These responses were blocked using C 021 and small interfering RNA (siRNA)-targeting CCR4. Finally, our data show that acute postoperative pain is significantly reduced in mice lacking CCR4, wild-type animals treated with CCR4 antagonist/siRNA, as well as transgenic mice depleted of dendritic cells. Together, these results suggest an essential role for the peripheral CCL17/22:CCR4 axis in the genesis of inflammatory pain via direct communication between skin-resident dendritic cells and sensory neurons, opening therapeutic avenues for its control.

Bisalbuminemia en un paciente con adenocarcinoma de colon-caso clínico / Bisalbuminemia in a patient with colon adenocarcinoma-clinical case

Bisalbuminemia is a rare congenital or acquired disorder of serum proteins, characterized by the presence in the same individual of two typesof proteins, with bicuspid patterns on the electrophoretic graphic. Wepresent the case of an independent 70 year-old woman with no relevant medical history or taking regular medication. She was admitteddue to symptomatic microcytic and hypochromic anemia (Hb 7.7g / dL).Protein electrophoretic study revealed bisalbuminemia. The colonoscopy revealed an ulcerated, vegetating, stenosing lesion in the ascendingcolon. Biopsy results were compatible with colon adenocarcinoma.Hereditary bisalbuminemia is generally not pathologically significant,unlike acquired, which may be associated with exposure to high dosesof beta-lactam antibiotics, ruptured pancreatic cyst and multiple myeloma. To this date the pathophysiology of bisalbuminemia associatedwith colon adenocarcinoma remains without explanation. (AU)

La bisalbuminemia es una anomalía congénita o adquirida, rara, de lasproteínas séricas, caracterizada por la presencia en un mismo individuo de dos tipos de proteínas, con patrones bicúspides en el gráficoelectroforético. Describimos el caso de una mujer de 70 años autónoma. Sin antecedentes personales conocidos y sin tratamiento ambulatorio. Ingresada para estudio de una anemia microcítica e hipocrómicasintomática (Hb 7,7g/dL). El estudio electroforético de proteínas revelóbisalbuminemia. La colonoscopia total reveló una lesión ulcerada, vegetante, estenosante en el colon ascendente, cuyo resultado de biopsia fue compatible con adenocarcinoma de colon. La bisalbuminemiahereditaria generalmente no tiene importancia patológica, a diferenciade la adquirida, que puede estar asociada con la exposición a altasdosis de antibióticos betalactámicos, rotura de quiste pancreático ymieloma múltiple. La fisiopatología de la bisalbuminemia asociada conel adenocarcinoma de colon continúa sin explicación. (AU)

Development of sheep secondary follicles and preservation of aromatase and metalloproteinases 2 and 9 after vitrification and in vitro culture.

The cryopreservation of secondary follicles (SF) is a promising alternative to preserve the reproductive potential both in humans and animals in situations in which the transplantation of ovarian tissue is not possible. The objective of the present study was cryopreserved SF isolated sheep. Beyond follicular morphology, viability and development, we investigated proteins related to steroidogenic function and basement membrane remodeling [metalloproteinases 2 (MMP-2) and 9 (MMP-9)] in fresh SF (FSF) and vitrified SF (VSF) followed by in vitro culture for 6 (D6) or 12 days (D12). The percentage of intact follicles, follicular and oocyte diameter of the VSF were lower than FSF on both days of culture (P < 0.05). The VSF viability was statistically reduced from D6 (95.5%) to D12 (77.3%) but did not differ from the FSF on both days (D6:96.2% to D12:86.5%). Antrum formation in the VSF (D6: 59.13%; D12: 79.56%) was significantly lower than the FSF (D6: 79.61%; D12: 92.23%). However, an increase in this percentage was observed from D6 to D12 in both groups. Aromatase showed stronger labeling on FSF D6 and VSF D12 compared to other treatments (P < 0.05). MMP-2 showed a similar pattern of labeling in FSF D6 and VSF D12, similarly to that observed in FSF D12 and VSF D6. MMP-9 was similar in FSF and VSF cultivated for 6 and 12 days. In conclusion, VSF are able to grow and develop during 12 days of in vitro culture and showed evidence of preservation of steroidogenic function and remodeling of the basement membrane.

Brazilian dental students and COVID-19: A survey on knowledge and perceptions.

OBJECTIVE: This study evaluated the knowledge and perceptions of Brazilian dental students about COVID-19 and the undergraduate clinical practice during the COVID-19 outbreak by a self-administered Web-based questionnaire. METHODS: A social network campaign on Instagram was raised to approach the target population. The survey covered demographic and academic profile, general knowledge, preventive measures and perception about COVID-19. Descriptive statistics were used to identify frequencies and distributions of variables, which were compared by type of institution and current year of enrolment using the Chi-square or Fisher's exact tests (α = 0.05). RESULTS: A total of 833 valid responses were received over 10 days. Students were able to identify the incubation period, main symptoms and contagious routes of the disease but struggled in recognising the name of the virus responsible for the pandemic. Hand washing before and after a dental appointment with a patient (97.7%) followed by the use of barriers to protect mucosa (97.2%) were the more frequently recognised measures to prevent COVID-19 spread in the dental office. As for the perception of COVID-19, 73.2% of the dental students perceived the disease as severe, whilst only 11.1% of them thought that COVID-19 is severe only for people presenting risk factors. Dental student's knowledge and perception were associated with the type of institution and year of enrolment. CONCLUSION: In summary, the dental students demonstrated an acceptable general knowledge about COVID-19, but dental schools will need to address gaps in knowledge, preventive measures, and perceptions to ensure a safer return to in person activities.