Chemical composition of extracts and fractions from Miconia ibaguensis (MELASTOMATACEAE) leaves and evaluation of biological activities.

The study aimed to assess the chemical composition of Miconia ibaguensis leaves extracts and fractions obtained from the ethanolic extract (EE), along with evaluating their antifungal, antibacterial, antidiabetic, and antioxidant activities. The ethyl acetate fraction (EAF) exhibited potent antifungal activity against Candida spp (1.95 - 3.90 µg mL-1) and potent antioxidant activity in the DPPH (1.74 ± 0.07 µg mL-1), FRAP (654.01 ± 42.09 µmol ETrolox/gsample), and ORAC (3698.88 ± 37.28 µmol ETrolox/gsample) methods. The EE displayed inhibition against the α-amylase enzyme (8.42 ± 0.05 µg mL-1). Flavonoids, hydrolysable tannins, triterpenoids, and phenolic acids, identified in the EE and fractions via (-)-HPLC-ESI-MS/MS analysis, were found to contribute to the species' biological activity potentially. These findings suggest promising avenues for further research and potential applications in pharmacology and natural products, offering new possibilities in the fight against global health issues.

Exploring the antifungal, antibiofilm and antienzymatic potential of Rottlerin in an in vitro and in vivo approach.

Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7.81 to > 1000 µg/mL. Futhermore, it was able to significantly inhibit biofilm production, presenting Biofilm Inhibitory Concentration (MICB50) values that ranged from 15.62 to 250 µg/mL and inhibition of the cell viability of the biofilm by 50% (IC50) from 2.24 to 12.76 µg/mL. There was a considerable reduction in all hydrolytic enzymes evaluated, with emphasis on hemolysin where Rottlerin showed a reduction of up to 20%. In the scanning electron microscopy (SEM) analysis, Rottlerin was able to completely inhibit filamentation by C. albicans. Regarding in vivo tests, Rottlerin did not demonstrate toxicity at the therapeutic concentrations demonstrated here and was able to increase the survival of C. elegans larvae infected. The results herein presented are innovative and pioneering in terms of Rottlerin's multipotentiality against these fungal infections.

Middle-Range Theory of Occupational Stress in Health Professionals.

Introduction: Occupational stress affects health professionals; however, no literature was found on the middle-range theory for this outcome in health professionals. Methods: Methodological study for the theoretical validation of a nursing diagnosis using the theoretical framework of Walker and Avant and the Betty Neuman systems models. The research was conducted in five stages: comprehension of the system model; selection and review of studies; development of the conceptual-theoretical-empirical structure; elaboration of a diagram and proposition of a nursing diagnosis; and evaluation of the empirical adequacy of the theory and validity of the system model. These steps were conducted using a scoping review and a sample of 138 articles selected in the Scopus, Web of Science, MEDLINE/PubMed, CINAHL, PsycINFO, LILACS, Science Direct, Cochrane Library, and Google Scholar databases. A data extraction instrument was developed, and study variables (attributes, antecedents, and clinical consequences) were analyzed using descriptive statistics (absolute and relative frequencies) and presented in tables. Results: The middle-range theory comprised 16 concepts, 20 propositions, and one diagram. A total of 15 related factors, 29 defining characteristics, six at-risk populations, and one associated condition were indicated to propose the nursing diagnosis for occupational stress. Conclusion: The middle-range theory supported elaborating elements to propose a nursing diagnosis for occupational stress.

P-selectin-dependent leukocyte adhesion is governed by endolysosomal two-pore channel 2.

Upon proinflammatory challenges, endothelial cell surface presentation of the leukocyte receptor P-selectin, together with the stabilizing co-factor CD63, is needed for leukocyte capture and is mediated via demand-driven exocytosis from the Weibel-Palade bodies that fuse with the plasma membrane. We report that neutrophil recruitment to activated endothelium is significantly reduced in mice deficient for the endolysosomal cation channel TPC2 and in human primary endothelial cells with pharmacological TPC2 block. We observe less CD63 signal in whole-mount stainings of proinflammatory-activated cremaster muscles from TPC2 knockout mice. We find that TPC2 is activated and needed to ensure the transfer of CD63 from endolysosomes via Weibel-Palade bodies to the plasma membrane to retain P-selectin on the cell surface of human primary endothelial cells. Our findings establish TPC2 as a key element to leukocyte interaction with the endothelium and a potential pharmacological target in the control of inflammatory leukocyte recruitment.

The Risk of Malignant Degeneration of Müllerian Derivatives in PMDS: A Review of the Literature.

Persistent Müllerian Duct Syndrome (PMDS) is a rare autosomal recessive disorder of sex development characterized by the presence of fallopian tubes, uterus and upper one-third of the vagina in individuals with XY genotype and normal male phenotype. The main complications of PMDS are infertility and the rare risk of malignant degeneration of both testicular and Müllerian derivatives. We report the case of a 49-year-old man who, during repair of an incisional hernia, was incidentally found to have a uterine-like structure posterior to the bladder. In the past at the age of 18 months, he had undergone bilateral orchidopexies for bilateral cryptorchidism. The intraoperative decision was to preserve the uterine-like structure and make a more accurate diagnosis postoperatively. Evaluation revealed an XY chromosome and imaging consistent with PMDS. The patient was informed about the risk of neoplastic transformation of the residual Müller ducts and was offered surgical treatment, which he declined. Subsequent follow-up imaging studies, including testicular and pelvic ultrasound, were negative for findings suggestive of malignant testicular and Mullerian derivative degeneration. A review of the international literature showed that, when a decision is taken to remove the Mullerian derivatives, laparoscopy and especially robotic surgery allow for the successful removal of Müllerian derivatives. Whenever the removal of these structures is not possible or the patient refuses to undergo surgery, it is necessary to inform the patient of the need for adequate follow-up. Patients should undergo regular pelvic imaging examination and MRI might be a better method for that purpose.

Inovação organizacional nas práticas de enfermagem: redução de infecções relacionadas à assistência à saúde / Organizational innovation in nursing practices: reduction of infections related to health care / Innovación organizacional en las prácticas de enfermería: reducción de infecciones relacionadas con la atención a la salud

Objetivo: Analisar o impacto da mudança assistencial na prevenção de IRAS em uma Unidade de Terapia Intensiva Adulto de um Hospital Universitário do Paraná. Métodos: estudo epidemiológico, quantitativo, realizado em uma UTI do Paraná. Coleta de dados ocorreu em 2020. Para a intervenção, foi realizado e validado um Fast Checklist. Resultados: A média de entradas no triênio foi de 40,83, média de dias de uso de dispositivos de 256 e a média de permanência de 6,3 dias. No biênio, foi respectivamente, 42,33 (p=0,504), 284,12 (p=0,005), 6,90 (p=0,130). A incidência de infecções, no triênio obteve-se uma média de 8, com taxa 20,42 e densidade de incidência de 32,54. Após, média de 4,91 (p=0,000), taxa de 13,15 (p=0,003) e densidade de incidência de 18,41 (p=0,000). Conclusão: as mudanças propostas e validadas tiveram grande impacto na assistência na UTI estudada, reduzindo as infecções, custos, óbitos e salvando vidas.

Objective: To analyze the impact of care changes on the prevention of HAI in an Adult Intensive Care Unit of a University Hospital in Paraná. Methods: epidemiological, quantitative study, carried out in an ICU in Paraná. Data collection took place in 2020. For the intervention, a Fast Checklist was performed and validated. Results: The average number of entries in the triennium was 40.83, the average number of days of device use was 256 and the average stay was 6.3 days. In the biennium, it was, respectively, 42.33 (p=0.504), 284.12 (p=0.005), 6.90 (p=0.130). The incidence of infections in the three-year period was an average of 8, with a rate of 20.42 and an incidence density of 32.54. Afterwards, mean of 4.91 (p=0.000), rate of 13.15 (p=0.003) and incidence density of 18.41 (p=0.000). Conclusion: the proposed and validated changes had a great impact on care in the studied ICU, reducing infections, costs, deaths and saving lives.

Objetivo: Analizar el impacto de los cambios asistenciales en la prevención de las IRAS en una Unidad de Cuidados Intensivos de Adultos de un Hospital Universitario de Paraná. Métodos: estudio epidemiológico, cuantitativo, realizado en una UTI de Paraná. La recolección de datos ocurrió en 2020. Para la intervención, se realizó y validó una Lista de Verificación Rápida. Resultados: El promedio de ingresos en el trienio fue de 40,83, el promedio de días de uso del dispositivo fue de 256 y la estadía promedio de 6,3 días. En el bienio fue, respectivamente, 42,33 (p=0,504), 284,12 (p=0,005), 6,90 (p=0,130). La incidencia de contagios en el trienio fue de media 8, con una tasa de 20,42 y una densidad de incidencia de 32,54. Posteriormente, media de 4,91 (p=0,000), tasa de 13,15 (p=0,003) y densidad de incidencia de 18,41 (p=0,000). Conclusión: los cambios propuestos y validados tuvieron gran impacto en la atención en la UTI estudiada, reduciendo infecciones, costos, muertes y salvando vidas.

Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on Monocytes.

Mechanisms keeping leukocytes distant of local inflammatory processes in a resting state despite systemic release of inflammatory triggers are a pivotal requirement for avoidance of overwhelming inflammation but are ill defined. Dimers of the alarmin S100A8/S100A9 activate Toll-like receptor-4 (TLR4) but extracellular calcium concentrations induce S100A8/S100A9-tetramers preventing TLR4-binding and limiting their inflammatory activity. So far, only antimicrobial functions of released S100A8/S100A9-tetramers (calprotectin) are described. It is demonstrated that extracellular S100A8/S100A9 tetramers significantly dampen monocyte dynamics as adhesion, migration, and traction force generation in vitro and immigration of monocytes in a cutaneous granuloma model and inflammatory activity in a model of irritant contact dermatitis in vivo. Interestingly, these effects are not mediated by the well-known binding of S100A8/S100A9-dimers to TLR-4 but specifically mediated by S100A8/S100A9-tetramer interaction with CD69. Thus, the quaternary structure of these S100-proteins determines distinct and even antagonistic effects mediated by different receptors. As S100A8/S100A9 are released primarily as dimers and subsequently associate to tetramers in the high extracellular calcium milieu, the same molecules promote inflammation locally (S100-dimer/TLR4) but simultaneously protect the wider environment from overwhelming inflammation (S100-tetramer/CD69).

Biodegradable and Dual-Responsive Polypeptide-Shelled Cyclodextrin-Containers for Intracellular Delivery of Membrane-Impermeable Cargo.

The transport of membrane impermeable compounds into cells is a prerequisite for the efficient cellular delivery of hydrophilic and amphiphilic compounds and drugs. Transport into the cell's cytosolic compartment should ideally be controllable and it should involve biologically compatible and degradable vehicles. Addressing these challenges, nanocontainers based on cyclodextrin amphiphiles that are stabilized by a biodegradable peptide shell are developed and their potential to deliver fluorescently labeled cargo into human cells is analyzed. Host-guest mediated self-assembly of a thiol-containing short peptide or a cystamine-cross-linked polypeptide shell on cyclodextrin vesicles produce short peptide-shelled (SPSVss ) or polypeptide-shelled vesicles (PPSVss ), respectively, with redox-responsive and biodegradable features. Whereas SPSVss are permeable and less stable, PPSVss effectively encapsulate cargo and show a strictly regulated release of membrane impermeable cargo triggered by either reducing conditions or peptidase treatment. Live cell experiments reveal that the novel PPSVSS are readily internalized by primary human endothelial cells (human umbilical vein endothelial cells) and cervical cancer cells and that the reductive microenvironment of the cells' endosomes trigger release of the hydrophilic cargo into the cytosol. Thus, PPSVSS represent a highly efficient, biodegradable, and tunable system for overcoming the plasma membrane as a natural barrier for membrane-impermeable cargo.

Biallelic mutations in RNF220 cause laminopathies featuring leukodystrophy, ataxia and deafness.

Leukodystrophies are a heterogeneous group of rare inherited disorders that mostly involve the white matter of the CNS. These conditions are characterized by primary glial cell and myelin sheath pathology of variable aetiology, which causes secondary axonal degeneration, generally emerging with disease progression. Whole exome sequencing performed in five large consanguineous nuclear families allowed us to identify homozygosity for two recurrent missense variants affecting highly conserved residues of RNF220 as the causative event underlying a novel form of leukodystrophy with ataxia and sensorineural deafness. We report these two homozygous missense variants (p.R363Q and p.R365Q) in the ubiquitin E3 ligase RNF220 as the underlying cause of this novel form of leukodystrophy with ataxia and sensorineural deafness that includes fibrotic cardiomyopathy and hepatopathy as associated features in seven consanguineous families. Mass spectrometry analysis identified lamin B1 as the RNF220 binding protein and co-immunoprecipitation experiments demonstrated reduced binding of both RNF220 mutants to lamin B1. We demonstrate that RNF220 silencing in Drosophila melanogaster specifically affects proper localization of lamin Dm0, the fly lamin B1 orthologue, promotes its aggregation and causes a neurodegenerative phenotype, strongly supporting the functional link between RNF220 and lamin B1. Finally, we demonstrate that RNF220 plays a crucial role in the maintenance of nuclear morphology; mutations in primary skin fibroblasts determine nuclear abnormalities such as blebs, herniations and invaginations, which are typically observed in cells of patients affected by laminopathies. Overall, our data identify RNF220 as a gene implicated in leukodystrophy with ataxia and sensorineural deafness and document a critical role of RNF220 in the regulation of nuclear lamina. Our findings provide further evidence on the direct link between nuclear lamina dysfunction and neurodegeneration.

TSC1 binding to lysosomal PIPs is required for TSC complex translocation and mTORC1 regulation.

The TSC complex is a critical negative regulator of the small GTPase Rheb and mTORC1 in cellular stress signaling. The TSC2 subunit contains a catalytic GTPase activating protein domain and interacts with multiple regulators, while the precise function of TSC1 is unknown. Here we provide a structural characterization of TSC1 and define three domains: a C-terminal coiled-coil that interacts with TSC2, a central helical domain that mediates TSC1 oligomerization, and an N-terminal HEAT repeat domain that interacts with membrane phosphatidylinositol phosphates (PIPs). TSC1 architecture, oligomerization, and membrane binding are conserved in fungi and humans. We show that lysosomal recruitment of the TSC complex and subsequent inactivation of mTORC1 upon starvation depend on the marker lipid PI3,5P2, demonstrating a role for lysosomal PIPs in regulating TSC complex and mTORC1 activity via TSC1. Our study thus identifies a vital role of TSC1 in TSC complex function and mTORC1 signaling.

Severe rectal prolapse and solitary rectal ulcer in a young anorectic woman with myxoid degeneration of visceral adipose tissue.

Rectal prolapse is a disorder in which the rectum protrudes from the anal canal. Solitary rectal ulcer may coexist. Both conditions have been associated with chronic constipation and excessive straining during defecation. Rectal prolapse has been rarely reported in women suffering from anorexia nervosa. Lack of rectal support because of loss of ischiorectal fat has been proposed as one of the possible mechanisms in this condition, together with chronic constipation and abuse of laxative. We report the case of an anorexic woman with a severe rectal prolapse and bleeding requiring urgent Altmeier's procedure. Surgery was complicated by dehiscence of the anastomosis and volvulus, requiring ileostomy and laciniae debridement. Pathological analysis of all the surgical samples taken from different abdominal sites highlighted changes in the visceral adipose tissue consisting in nodular aggregates of small adipocytes dispersed in a myxoid matrix surrounding blood vessels within abundant fibrosis. The morphologic features resemble those observed in primordial fetal fat and are comparable to those observed in cancer associated cachexia. The diffuse myxoid degeneration of visceral adipose tissue may play a role in the pathogenesis of rectal prolapse in patients with anorexia nervosa. Besides starvation, the mechanism sustaining myxoid degeneration of the adipose tissue is not entirely clear. Whenever possible improving nutritional and clinical conditions should be ideal before any surgical approach.

An Imidazolium-Based Lipid Analogue as a Gene Transfer Agent.

A dicationic imidazolium salt is described and investigated towards its application for gene transfer. The polar head group and the long alkyl chains in the backbone contribute to a lipid-like behavior, while an alkyl ammonium group provides the ability for crucial electrostatic interaction for the transfection process. Detailed biophysical studies regarding its impact on biological membrane models and the propensity of vesicle fusion are presented. Fluorescence spectroscopy, atomic force microscopy and confocal fluorescence microscopy show that the imidazolium salt leads to negligible changes in lipid packing, while displaying distinct vesicle fusion properties. Cell culture experiments reveal that mixed liposomes containing the novel imidazolium salt can serve as plasmid DNA delivery vehicles. In contrast, a structurally similar imidazolium salt without a second positive charge showed no ability to support DNA transfection into cultured cells. Thus, we introduce a novel and variable structural motif for cationic lipids, expanding the field of lipofection agents.

Membrane Binding Promotes Annexin A2 Oligomerization.

Annexin A2 (AnxA2) is a cytosolic Ca2+ regulated membrane binding protein that can induce lipid domain formation and plays a role in exocytosis and endocytosis. To better understand the mode of annexin-membrane interaction, we analyzed membrane-bound AnxA2 assemblies by employing a novel 3-armed chemical crosslinker and specific AnxA2 mutant proteins. Our data show that AnxA2 forms crosslinkable oligomers upon binding to membranes containing negatively charged phospholipids. AnxA2 mutants with amino acid substitutions in residues predicted to be involved in lateral protein-protein interaction show compromised oligomer formation, albeit still being capable of binding to negatively charged membranes in the presence of Ca2+. These results suggest that lateral protein-protein interactions are involved in the formation of AnxA2 clusters on a biological membrane.

Controlled Cellular Delivery of Amphiphilic Cargo by Redox-Responsive Nanocontainers.

The specific transport of amphiphilic compounds such as fluorescently labeled phospholipids into cells is a prerequisite for the analysis of highly dynamic cellular processes involving these molecules, e.g., the intracellular distribution and metabolism of phospholipids. However, cellular delivery remains a challenge as it should not affect the physiological integrity and morphology of the cell membrane. To address this, polymer nanocontainers based on redox-responsive cyclodextrin (CD) amphiphiles are prepared, and their potential to deliver fluorescently labeled phospholipids to intracellular membrane compartments is analyzed. It is shown that mixtures of reductively degradable cyclodextrin amphiphiles and different phospholipids form liposome-like vesicles (CD-lipid vesicles, CSSLV) with a homogeneous distribution of each lipid. Host-guest-mediated self-assembly of a cystamine-crosslinked polymer shell on these CSSLV produces polymer-shelled liposomal vesicles (PSSCSSLV) with the unique feature of a redox-sensitive CSSLV core and reductively degradable polymer shell. PSSCSSLV show high stability and a redox-sensitive release of the amphiphilic cargo. Live cell experiments reveal that the novel PSSCSSLV are readily internalized by primary human endothelial cells and that the reductive microenvironment of the cells' endosomes triggers the release of the amphiphilic cargo into the cytosol. Thus, PSSCSSLV represent a highly efficient system to transport lipid-like amphiphilic cargo into the intracellular environment.

Diagnósticos de enfermagem do domínio segurança e proteção em pacientes críticos / Diagnósticos de enfermería del dominio seguridad y protección en pacientes críticos / Nursing Diagnosis within the Domain Safety and Protection in Critically-ill Patients

RESUMO Introdução: A clientela crítica encontra-se exposta à riscos. Assim, compreender as relações entre os elementos que envolvem a segurança e proteção torna-se fundamental. Objetivo: verificar a associação entre os diagnósticos de enfermagem do domínio segurança e proteção da NANDA Internacional com seus componentes em pacientes críticos internados em unidade de terapia intensiva. Métodos: estudo transversal, realizado com 86 pacientes críticos de um hospital no Nordeste do Brasil, por meio do formulário. Na análise estatística, foram aplicados os testes de Qui-quadrado e exato de Fisher. Resultados: O diagnóstico Risco de resposta adversa ao meio de contraste com iodo apresentou associação estatística com os componentes: Propriedades físicas e químicas dos meios de contraste, Ansiedade, Uso concomitante de medicamentos, Veias fragilizadas, Doença subjacente e Extremos de idade. O diagnóstico Risco de desequilíbrio na temperatura corporal associou-se à taxa metabólica alterada, extremos de idade e sedação. Conclusão: Esses achados proporcionam avanço científico para a enfermagem ao fornecerem auxílio na inferência diagnóstica, na previsão dos cuidados e na tomada de decisão do enfermeiro(AU)

RESUMEN Introducción: Los pacientes en estado crítico, internados en una unidad de terapia intensiva, se encuentran expuestos a riesgos. Así, comprender las relaciones entre los elementos que involucran su seguridad y su protección se vuelve fundamental. Objetivo: Verificar la asociación entre los diagnósticos de enfermería del dominio seguridad y protección de la NANDA Internacional con sus componentes en pacientes críticos internados en unidad de terapia intensiva. Métodos: Estudio transversal, realizado con 86 pacientes críticos de un hospital en el Nordeste de Brasil, a través del formulario. En el análisis estadístico, se aplicaron las pruebas de Qui-cuadrado y exacto de Fisher. Resultados: El diagnóstico Riesgo de respuesta adversa al medio de contraste con yodo presentó asociación estadística con los componentes: Propiedades físicas y químicas de los medios de contraste, Ansiedad, Uso concomitante de medicamentos, Venas fragilizadas, Enfermedad subyacente y Extremos de edad. El diagnóstico Riesgo de desequilibrio en la temperatura corporal se asoció a la tasa metabólica alterada, extremos de edad y sedación. Conclusión: Estos hallazgos proporcionan avances científicos para la enfermería al proporcionar ayuda en la inferencia diagnóstica, en la previsión de los cuidados y en la toma de decisión del personal de enfermería(AU)

ABSTRACT Introduction: Critically-ill patients, admitted to an intensive care unit, are exposed to risks. Therefore, understanding the relationships between the elements involving their safety and protection becomes fundamental. Objective: To verify the association between the nursing diagnoses within the domain safety and protection of NANDA (North American Nursing Diagnosis Association) International with its components in critically-ill patients hospitalized in an intensive care unit. Methods: Cross-sectional study carried out through a form conducted on 86 critically-ill patients of a hospital in the northeast of Brazil. The chi-square and Fisher's exact tests were applied in the statistical analysis. Results: The diagnosis of the risk of adverse response to the contrast medium with iodine presented statistical association with the components: physical and chemical properties of the contrast media, anxiety, concomitant use of medications, fragile veins, underlying disease, and age extremes. The diagnosis of the risk of imbalance in body temperature was associated with the altered metabolic rate, age extremes, and sedation. Conclusion: These findings provide scientific advances for nursing by providing help in diagnostic inference, in the anticipation of care, and in the decision-making by the nursing staff(AU)

Necessity of transnasal gastroscopy in routine diagnostics: a patient-centred requirement analysis.

INTRODUCTION: Numerous indications require regular upper gastrointestinal endoscopy (oesophagogastroduodenoscopy; EGD) in outpatients. In most cases, peroral gastroscopy is performed. The aim of this study was to evaluate the need of transnasal gastroscopy (nEGD) in outpatients. METHODS: A questionnaire was used to assess patients' preferred choice of method, previous experience with EGD, psychological aspects and sociodemographic data. Furthermore, patient satisfaction with and potentially perceived discomfort during the examination as well as preference for a method in regard to future examinations was evaluated. RESULTS: From September 2016 to March 2017, a total of 283 outpatients at endoscopy of the University Hospital of Leipzig were approached to participate in the study. 196 patients were eligible, of whom 116 (60%) chose nEGD. For 87 patients (87/283, 31%) nEGD had to be excluded for medical reasons. The average age in the total sample was 53 (±17) years. 147 (77%) have had previous experience with peroral EGD (oEGD). Of the nEGD examined patients 83% were fairly up to extremely satisfied with the procedure. Satisfaction significantly predicted the choice of future EGD examinations. Nasal pain experienced during nEGDs was associated with rejection of nEGD in further EGD examinations (p<0.01). Patients who did choose a specific procedure were more likely to select the same procedure as their future preference (χ²= 73.6, df=1, p<0.001); this preference was unaffected by the procedure that had been chosen previously (reselecting nEGD: 84%, oEGD: 89%, p=0.874). CONCLUSION: nEGD without sedation is a viable alternative. Patient satisfaction with nEGD is high, and reselection rate for nEGD is similar to that for oEGD. As a result of this study nEGD is now offered as a routine procedure at the University of Leipzig. TRIAL REGISTRATION NUMBER: NCT03663491.

Contagem de microrganismos indicadores em queijo cozido produzido em Salinas-MG / Indicator microorganisms count in cooked cheese produced in the city of Salinas-MG

Na região de Salinas, assim como no estado de Minas Gerais inteiro, a fabricação e comercialização de queijo artesanal é um hábito cultural. A venda de queijo em feira comercial ou em residências é uma prática tradicional que oferece sustento para muitos produtores da cidade mineira. O presente estudo aborda a qualidade de queijo cozido produzido por produtores da região de Salinas-MG. Foram coletadas amostras de queijos já prontos para consumo, de 10 produtores escolhidos aleatoriamente no Mercado Municipal da cidade. As amostras foram analisadas no laboratório de microbiologia do Instituto Federal do Norte de Minas Gerais (IFNMG) - Campus Salinas. Nas análises realizadas foi possível notar uma alta contagem de mesófilos e psicrotróficos, e baixa contagem de coliformes totais e termotolerantes, com três amostras fora dos padrões legais. Sugere -se ações de capacitação e regulamentação pelo poder público para melhorar a qualidade final do produto.

Dissipative Microgravimetry to Study the Binding Dynamics of the Phospholipid Binding Protein Annexin A2 to Solid-supported Lipid Bilayers Using a Quartz Resonator.

The dissipative quartz crystal microbalance technique is a simple and label-free approach to measure simultaneously the mass uptake and viscoelastic properties of the absorbed/immobilized mass on sensor surfaces, allowing the measurements of the interaction of proteins with solid-supported surfaces, such as lipid bilayers, in real-time and with a high sensitivity. Annexins are a highly conserved group of phospholipid-binding proteins that interact reversibly with the negatively charged headgroups via the coordination of calcium ions. Here, we describe a protocol that was employed to quantitatively analyze the binding of annexin A2 (AnxA2) to planar lipid bilayers prepared on the surface of a quartz sensor. This protocol is optimized to obtain robust and reproducible data and includes a detailed step-by-step description. The method can be applied to other membrane-binding proteins and bilayer compositions.

Phosphorescent cationic iridium(iii) complexes dynamically bound to cyclodextrin vesicles: applications in live cell imaging.

We report cationic Ir(iii) complexes functionalized with adamantyl groups designed to bind to ß-cyclodextrin vesicles (CDV) with high affinity (K a = 1 × 106 M-1). The emission of the complexes is tuned by changing the nature of the cyclometalating ligands. The host-guest adduct of CDV and Ir(iii) complexes shows increased and significantly blue-shifted emission due to the lower mobility of the Ir(iii)-complexes residing in the less polar environment of the vesicle surface. Ir(iii)-decorated CDV are efficiently taken up by cells and can be used in live cell imaging. The CDV act as carriers to transport the phosphorescent complexes into cells where they selectively stain mitochondria.

Development and characterization of an inducible mouse model for glycogen storage disease type Ib.

BACKGROUND AND AIMS: Glycogen storage disease type Ib (GSD1b) is a rare metabolic and immune disorder caused by a deficiency in the glucose-6-phosphate transporter (G6PT) and characterized by impaired glucose homeostasis, myeloid dysfunction, and long-term risk of hepatocellular adenomas. Despite maximal therapy, based on a strict diet and on granulocyte colony-stimulating factor treatment, long-term severe complications still develop. Understanding the pathophysiology of GSD1b is a prerequisite to develop new therapeutic strategies and depends on the availability of animal models. The G6PT-KO mouse mimics the human disease but is very fragile and rarely survives weaning. We generated a conditional G6PT-deficient mouse as an alternative model for studying the long-term pathophysiology of the disease. We utilized this conditional mouse to develop an inducible G6PT-KO model to allow temporally regulated G6PT deletion by the administration of tamoxifen (TM). METHODS: We generated a conditional G6PT-deficient mouse utilizing the CRElox strategy. Histology, histochemistry, and phenotype analyses were performed at different times after TM-induced G6PT inactivation. Neutrophils and monocytes were isolated and analyzed for functional activity with standard techniques. RESULTS: The G6PT-inducible KO mice display the expected disturbances of G6P metabolism and myeloid dysfunctions of the human disorder, even though with a milder intensity. CONCLUSIONS: TM-induced inactivation of G6PT in these mice leads to a phenotype which mimics that of human GSD1b patients. The conditional mice we have generated represent an excellent tool to study the tissue-specific role of the G6PT gene and the mechanism of long-term complications in GSD1b.