Absence of Synergism between a Dual-AMP Biogel and Antibiotics Used as Therapeutic Agents for Diabetic Foot Infections.

Diabetic foot infections (DFIs) are frequently linked to diabetic-related morbidity and death because of the ineffectiveness of conventional antibiotics against multidrug-resistant bacteria. Pexiganan and nisin A are antimicrobial peptides (AMPs), and their application may complement conventional antibiotics in DFI treatment. A collagen 3D model, previously established to mimic a soft-tissue collagen matrix, was used to evaluate the antibacterial efficacy of a guar gum gel containing pexiganan and nisin alone and combined with three antimicrobials toward the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa isolated from infected foot ulcers. Antimicrobials and bacterial diffusion were confirmed by spot-on-lawn and bacterial growth by bacterial count (cfu/mL). Our main conclusion was that the dual-AMP biogel combined with gentamicin, clindamycin, or vancomycin was not able to significantly reduce bacterial growth or eradicate S. aureus and P. aeruginosa DFI isolates. We further reported an antagonism between dual-AMP and dual-AMP combined with antibiotics against S. aureus.

Identification of a conserved neutralizing epitope present on spike proteins from highly pathogenic coronaviruses

Three pathogenic human coronaviruses have emerged within the last 20 years, with SARS-CoV-2 causing a global pandemic. Although therapeutic antibodies targeting the SARS-CoV-2 spike currently focus on the poorly conserved receptor-binding domain, targeting essential neutralizing epitopes on the more conserved S2 domain may provide broader protection. We report an antibody binding an epitope conserved in the pre-fusion core of MERS-CoV, SARS-CoV and SARS-CoV-2 spike S2 domains. Antibody 3A3 binds a conformational epitope with ~2.5 nM affinity and neutralizes spike from SARS-CoV, SARS-CoV-2 and variants of concern in in vitro pseudovirus assays. Hydrogen-deuterium exchange mass spectrometry identified residues 980-1006 in the flexible hinge region at the S2 apex as the 3A3 epitope, suggesting 3A3 prevents the S2 conformational rearrangements required for conversion to the spike post-fusion state and virus-host cell fusion. This work defines a conserved vulnerable site on the SARS-CoV-2 S2 domain and guides the design of pan-protective spike immunogens.

Influence of Storage on the Antimicrobial and Cytotoxic Activities of a Nisin-biogel with Potential to be Applied to Diabetic Foot Infections Treatment.

Staphylococcus aureus is the most prevalent pathogen in diabetic foot infections (DFIs). In addition to its ability to express several virulence factors, including the formation of recalcitrant biofilms, S. aureus is also becoming increasingly resistant to most antibiotics used in clinical practice. The search for alternative treatment strategies for DFI is urgently needed. Antimicrobial peptides (AMPs), namely, nisin, are emerging as potential new therapeutics for managing DFIs. Our team has developed a nisin-guar gum biogel to be applied to DFIs. In this study, to confirm its future in vivo applicability, we evaluated the influence of four storage temperatures (-20 °C, 4 °C, 22 °C, and 37 °C) during a 24 months storage period on its antimicrobial activity towards DFI S. aureus, and its cytotoxicity, to a human keratinocyte cell line. When stored at temperatures below 22 °C, the biogel antimicrobial activity was not significantly influenced by storage duration or temperature. Moreover, nisin incorporated within the guar gum biogel exhibited no significant levels of cytotoxicity on human keratinocyte cells, confirming its potential for DFIs therapeutics. In conclusion, results confirm that the nisin-biogel is a potential candidate to be used as an alternative or complement compound for conventional DFI therapeutics.

Stress, burnout e avaliação cognitiva: estudo na classe de enfermagem / Stress, burnout and cognitive appraisal: a study with nurses / Estres, agotamiento y evaluacion cognitiva: un estudio dos profesionales de enfermeria

Este estudo analisa o stress laboral em enfermeiros, observando igualmente a importancia dos processos de avaliação cognitiva no ajustamento aos contextos de trabalho. Foram aplicados, em um único momento, a 153 profissionais da classe de enfermagem instrumentos de avaliação do stress ocupacional, da avaliação cognitiva primaria e secundária, do burnout e da sintomatologia depressiva. Os níveis de stress, de burnout e de sintomatologia depressiva confirmaram que essa profissão exigente do ponto de vista emocional e psicológico. Os processos de avaliação cognitiva foram determinantes na explicação da experiência de stress ocupacional, burnout e sintomatologia depressiva. O stress ocupacional e a avaliação cognitiva foram variáveis importantes na predição do burnout. Os resultados deste estudo evidenciaram o papel central da avaliação cognitiva na adaptação humana aos contextos de trabalho bem como a utilidade do modelo transacional no estudo do stress laboral(AU)

This study analyzes the occupational stress in nurses, observing also the importance of cognitive appraisal in the adjustment to work contexts. In a single moment, evaluation protocols that included instruments of occupational stress, primary and secondary cognitive appraisals, burnout, and depressive symptomatology were applied to 153 nurses. Levels of occupational stress, burnout, and depressive symptomatology have confirmed that this activity is very demanding, both on emotional and psychological levels. The processes of cognitive appraisal were determining factors in the comprehension of occupational stress, burnout, and depressive symptomatology. Occupational stress and cognitive appraisals dimensions were predictors of the burnout experience. The results of this study pointed out the central role of the cognitive appraisals in the human adaptation to the work contexts and the usefulness of the transactional model in the study of occupational stress(AU)

Este estudio analiza el estres laboral en profesionales de enfermeria, observando también la importancia de la evaluacion cognitiva en la adaptacion al trabajo. Mediante una metodologМa transversal, se aplicó un protocolo de evaluacion a 153 profesionales de enfermeria con instrumentos de estres ocupacional, evaluacion cognitivas primaria y secundaria, agotamiento y sintomatologia depresiva. Los niveles de estres laboral, agotamiento y sintomatologia depresiva confirmaron que esta actividad es muy exigente a nivel psicológico y emocional. Los procesos de evaluacion cognitiva fueron cruciales para explicar la experiencia de estres laboral, de agotamiento y de sintomatologia depresiva. El estres laboral y la evaluacion cognitiva fueron variables importantes en la prediccion de agotamiento. Los resultados de este estudio demonstraron el papel central de la evaluacion cognitiva en la adaptacion humana al trabajo y la utilidad del modelo transaccional en el estudio del estres laboral(AU)

Stress, burnout e avaliação cognitiva: estudo na classe de enfermagem / Stress, burnout and cognitive appraisal: a study with nurses / Estrés, agotamiento y evaluación cognitiva: un estudio dos profesionales de enfermería

Este estudo analisa o stress laboral em enfermeiros, observando igualmente a importância dos processos de avaliação cognitiva no ajustamento aos contextos de trabalho. Foram aplicados, em um único momento, a 153 profissionais da classe de enfermagem instrumentos de avaliação do stress ocupacional, da avaliação cognitiva primária e secundária, do burnout e da sintomatologia depressiva. Os níveis de stress, de burnout e de sintomatologia depressiva confirmaram que essa profissão é exigente do ponto de vista emocional e psicológico. Os processos de avaliação cognitiva foram determinantes na explicação da experiência de stress ocupacional, burnout e sintomatologia depressiva. O stress ocupacional e a avaliação cognitiva foram variáveis importantes na predição do burnout. Os resultados deste estudo evidenciaram o papel central da avaliação cognitiva na adaptação humana aos contextos de trabalho bem como a utilidade do modelo transacional no estudo do stress laboral.

This study analyzes the occupational stress in nurses, observing also the importance of cognitive appraisal in the adjustment to work contexts. In a single moment, evaluation protocols that included instruments of occupational stress, primary and secondary cognitive appraisals, burnout, and depressive symptomatology were applied to 153 nurses. Levels of occupational stress, burnout, and depressive symptomatology have confirmed that this activity is very demanding, both on emotional and psychological levels. The processes of cognitive appraisal were determining factors in the comprehension of occupational stress, burnout, and depressive symptomatology. Occupational stress and cognitive appraisals dimensions were predictors of the burnout experience. The results of this study pointed out the central role of the cognitive appraisals in the human adaptation to the work contexts and the usefulness of the transactional model in the study of occupational stress.

Este estudio analiza el estrés laboral en profesionales de enfermería, observando también la importancia de la evaluacion cognitiva en la adaptación al trabajo. Mediante una metodología transversal, se aplicó un protocolo de evaluación a 153 profesionales de enfermería con instrumentos de estrés ocupacional, evaluación cognitivas primaria y secundaria, agotamiento y sintomatología depresiva. Los niveles de estrés laboral, agotamiento y sintomatología depresiva confirmaron que esta actividad es muy exigente a nivel psicológico y emocional. Los procesos de evaluación cognitiva fuerwon cruciales para explicar la experiencia de estrés laboral, de agotamiento y de sintomatología depresiva. El estrés laboral y la evaluación cognitiva fueron variables importantes en la predicción de agotamiento. Los resultados de este estudio demonstraron el papel central de la evaluación cognitiva en la adaptación humana al trabajo y la utilidad del modelo transaccional en el estudio del estrés laboral.

Novel SNPs and INDEL polymorphisms in the 3'UTR of DGAT1 gene: in silico analyses and a possible association.

Diacylglycerol-O-acyltransferase (DGAT1) gene encodes the rate-limiting enzyme of triglyceride synthesis. A polymorphism in this gene, DGAT1 K232A, has been associated with milk production and composition in taurine breeds. However, this polymorphism is not a good tool for ascertaining the effects of this QTL in Bos indicus (Zebu), since the frequency of the DGAT1 232A allele is too low in these breeds. We sequenced the 3'-untranslated region of DGAT1 gene in a sample of bulls of the breeds Guzerá (Bos indicus) and Holstein (Bos taurus) and, using in silico analysis, we searched for genetic variation, evolutionary conservation, regulatory elements, and possible substitution effects. Six single nucleotide (SNPs) and one insertion-deletion (INDEL) polymorphisms were found in the Guzerá bulls. Additionally, we developed a preliminary association study, using this INDEL polymorphism as a genetic marker. A significant association was detected (P ≤ 0.05) between the INDEL (DGAT1 3'UTR INDEL) and the breeding values (BV) for protein, fat, and milk yields over a 305-day lactation period. The DGAT1 3' UTR INDEL genotype I/I (I, for insertion) was associated with lower BVs (-38.77 kg for milk, -1.86 kg for fat, and -1.48 kg for protein yields), when compared to the genotype I/D (D, for deletion). I/D genotype was lower D/D genotype (-34.98 kg milk, -1.73 kg fat, and -1.09 kg protein yields). This study reports the first polymorphism of DGAT1 3'UTR in the Guzerá breed, as well as its association with BV for milk protein, fat, and milk yields.

Diagnosis of gastric syphilis by direct immunofluorescence staining and real-time PCR testing.

We report on a case of gastric syphilis in a patient with chronic dyspepsia. The diagnosis was established by serology and the demonstration of spirochetes in diffusely inflammed gastric mucosa by staining with a fluorescent monoclonal antibody specific for pathogenic treponemes and by the detection of specific treponemal DNA sequences by a real-time PCR.

A novel hereditary small vessel disease of the brain.

OBJECTIVE: Only few hereditary ischemic small vessel diseases of the brain (SVDB) have been reported so far. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent of them. Herein, we report a family affected by a SVDB distinct from CADASIL. METHODS: After the occurrence of a small deep infarct associated with white matter lesions both in a 46-year-old man and in his 52-year-old sister, clinical and neuroimaging investigations were conducted in 13 of their relatives originating from Portugal. Other investigations included (1) skin biopsy immunostaining with a Notch3 monoclonal antibody, (2) sequencing of the 23 exons encoding the epidermal growth factor-like domains of the NOTCH3 gene, and (3) a NOTCH3 locus haplotype analysis. RESULTS: Diffuse white matter hyperintensities were observed on T2-weighted magnetic resonance imaging (MRI) in six individuals. In contrast with MRI results in the father and paternal uncle of the proband who were hypertensive, white matter lesions were extensive in the mother who had no vascular risk factor. MRI data in four asymptomatic family members together with the results in the two initial cases were suggestive of an underlying hereditary small vessel disease of the brain. Skin biopsy and NOTCH3 gene mutation screening were negative. Haplotype analysis excluded the NOTCH3 locus. INTERPRETATION: These data strongly suggest that this family is affected by a novel hereditary small vessel disease of the brain and that the mutated gene is distinct from NOTCH3.