Iron Homeostasis in Azotobacter vinelandii.

Iron is an essential nutrient for all life forms. Specialized mechanisms exist in bacteria to ensure iron uptake and its delivery to key enzymes within the cell, while preventing toxicity. Iron uptake and exchange networks must adapt to the different environmental conditions, particularly those that require the biosynthesis of multiple iron proteins, such as nitrogen fixation. In this review, we outline the mechanisms that the model diazotrophic bacterium Azotobacter vinelandii uses to ensure iron nutrition and how it adapts Fe metabolism to diazotrophic growth.

Maternal and Offspring Cardiovascular Function following Pregnancy with Hypertensive Disorder.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) have been associated with increased cardiovascular risk for the mother and her offspring. However, it remains unknown whether cardiovascular changes are present in the postpartum period. METHODS: This was a cross-sectional study of women with singleton pregnancies. We recruited 33 women (20 following preeclampsia and 13 following gestational hypertension) and an equal number of women with uncomplicated pregnancy. Conventional and more advanced echocardiographic modalities such as speckle tracking were used to assess maternal and offspring cardiac function at 3-9 months postpartum. RESULTS: In women with HDP compared to those without, there was higher mean arterial pressure (mean 92.3 (SD 7.3) vs. 86.8 (8.3) mmHg, p = 0.007), left-ventricular mass indexed for body-surface area (64.5 (10.5) vs. 56.8 (10.03), p < 0.003), and E/e' (3.6 (0.8) vs. 3.1 (0.9), p = 0.022). There were no significant differences between groups in maternal left-ventricular systolic-functional indices and in offspring cardiac function between groups. CONCLUSIONS: At 3-9 months postpartum, mothers with HDP had higher blood pressure, higher left-ventricular mass, and reduced left-ventricular diastolic function. However, in their offspring, cardiac function was preserved. These findings suggest that mothers who experienced an HDP would benefit from cardio-obstetric follow-up in the postpartum period.

Forging a symbiosis: transition metal delivery in symbiotic nitrogen fixation.

Symbiotic nitrogen fixation carried out by the interaction between legumes and rhizobia is the main source of nitrogen in natural ecosystems and in sustainable agriculture. For the symbiosis to be viable, nutrient exchange between the partners is essential. Transition metals are among the nutrients delivered to the nitrogen-fixing bacteria within the legume root nodule cells. These elements are used as cofactors for many of the enzymes controlling nodule development and function, including nitrogenase, the only known enzyme able to convert N2 into NH3 . In this review, we discuss the current knowledge on how iron, zinc, copper, and molybdenum reach the nodules, how they are delivered to nodule cells, and how they are transferred to nitrogen-fixing bacteria within.

Sex differences in brain tumor glutamine metabolism reveal sex-specific vulnerabilities to treatment.

BACKGROUND: Brain cancer incidence and mortality rates are greater in males. Understanding the molecular mechanisms that underlie those sex differences could improve treatment strategies. Although sex differences in normal metabolism are well described, it is currently unknown whether they persist in cancerous tissue. METHODS: Using positron emission tomography (PET) imaging and mass spectrometry, we assessed sex differences in glioma metabolism in samples from affected individuals. We assessed the role of glutamine metabolism in male and female murine transformed astrocytes using isotope labeling, metabolic rescue experiments, and pharmacological and genetic perturbations to modulate pathway activity. FINDINGS: We found that male glioblastoma surgical specimens are enriched for amino acid metabolites, including glutamine. Fluoroglutamine PET imaging analyses showed that gliomas in affected male individuals exhibit significantly higher glutamine uptake. These sex differences were well modeled in murine transformed astrocytes, in which male cells imported and metabolized more glutamine and were more sensitive to glutaminase 1 (GLS1) inhibition. The sensitivity to GLS1 inhibition in males was driven by their dependence on glutamine-derived glutamate for α-ketoglutarate synthesis and tricarboxylic acid (TCA) cycle replenishment. Females were resistant to GLS1 inhibition through greater pyruvate carboxylase (PC)-mediated TCA cycle replenishment, and knockdown of PC sensitized females to GLS1 inhibition. CONCLUSION: Our results show that clinically important sex differences exist in targetable elements of metabolism. Recognition of sex-biased metabolism may improve treatments through further laboratory and clinical research. FUNDING: This work was supported by NIH grants, Joshua's Great Things, the Siteman Investment Program, and the Barnard Research Fund.

Granulomatosis with Polyangiitis-Mimicking Advanced Gynecological Cancer: A Case Report and Systematic Review of the Literature.

(1) Background: Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis that mimics gynecologic cancer. In GPA patients, the genitourinary system is affected in <1%. The objective of the study was to provide a systematic review of the literature of GPA patients with gynecological involvement. (2) Methods: PubMed and Embase were searched from inception to July 2021 for GPA patients with gynecological involvement Medical Subject Headings (MeSH) and free-text terms. Exclusion criteria were other language, review articles, pregnancy, fertility, or male patients. Data were extracted on clinical evolution, symptoms, examinations findings, diagnosis delay, treatment, outcome, patient status, and follow-up. (3) Results: Seventeen studies included data from patients with GPA and primary or relapsed gynecological involvement. 68% of the authors of this review thought the patient had cancer. The main gynecological symptom is bleeding, but exclusive gynecologic symptomatology is rare (ENT: 63%, lungs: 44%, kidneys-urinary tract: 53%). GPA could affect all areas of the genital tract, but the most frequent location is the uterine cervix. Medical treatment for GPA is effective. (4) Conclusions: GPA of the female genital tract must be considered when biopsies of an ulcerated malignant-appearing cervical or vaginal mass are negative for malignancy even when they are unspecific. Rheumatology consultation is indicated.

Poder pronóstico de mortalidad a corto plazo delreceptor soluble activador del plasminógeno tipo uroquinasa (suPAR) en los pacientes atendidos en urgencias por infección / Prognostic power of soluble urokinase plasminogen activator receptor (suPAR) for short-term mortality in patients seen in Emergency Departments due to infections

Objetivos. Analizar y comparar el poder predictivo de mortalidad a 30 días de varios biomarcadores (proteína C reactiva, procalcitonina, lactato y suPAR) en los pacientes que acuden al servicio de urgencias (SU) por un episodio de infección. Y, secundariamente, si estos mejoran la capacidad pronóstica de los criterios de sepsis (síndrome de respuesta inflamatoria sistémica-SRIS- y del quick Sepsis-related Organ Failure Assessment –qSOFA-). Métodos. Estudio observacional, prospectivo y analítico. Se incluyó consecutivamente a pacientes atendidos en un SU por un proceso infeccioso. Se analizaron 32 variables independientes (epidemiológicas, de comorbilidad, funcionales, clínicas y analíticas) que pudieran influir en la mortalidad a corto plazo (30 días). Resultados. Se incluyó a 347 pacientes, de los que 54 (15,6%) habían fallecido a los 30 días tras su consulta en el SU. El suPAR es el biomarcador que consigue la mayor área bajo la curva (ABC)-ROC para predecir mortalidad a los 30 días de 0,836 [IC 95%: 0,765-0,907; p< 0,001] con sensibilidad de 53% y especificidad de 89%. El modelo combinado (suPAR > 10 ng/ml con qSOFA ≥ 2) mejora el ABC-ROC a 0,853 [IC 95%: 0,790-0,916; p<0,001] y ofrece el mejor rendimiento pronóstico con una sensibilidad de 39%, especificidad del 97% y un valor predictivo negativo de 90%. Conclusiones. En los pacientes que acuden al SU por un episodio de infección, suPAR presenta una capacidad pronóstica de mortalidad a los 30 días superior al resto de biomarcadores, la qSOFA obtiene mayor rendimiento que los criterios de SRIS, y el modelo combinado qSOFA ≥ 2 con suPAR > 10 ng/ mL mejora el poder predictivo de qSOFA. (AU)

Objectives. To analyse and compare 30-day mortality prognostic power of several biomarkers (C-reactive protein, procalcitonin, lactate and suPAR) in patients seen in emergency departments (ED) due to infections. Secondly, if these could improve the accuracy of systemic inflammatory response syndrome (SIRS) and quick Sepsis-related Organ Failure Assessment (qSOFA). Methods. A prospective, observational and analytical study was carried out on patients who were treated in an ED of one of the eight participating hospitals. An assessment was made of 32 independent variables that could influence mortality at 30 days. They covered epidemiological, comorbidity, functional, clinical and analytical factors. Results. The study included 347 consecutive patients, 54 (15.6%) of whom died within 30 days of visiting the ED. SUPAR has got the best biomarker area under the curve (AUC)-ROC to predict mortality at 30 days of 0.836 (95% CI: 0.765-0.907; P < .001) with a cut-off > 10 ng/mL who had a sensitivity of 70% and a specificity of 86%. The score qSOFA ≥ 2 had AUC-ROC of 0.707 (95% CI: 0.621-0.793; P < .001) with sensitivity of 53% and a specificity of 89%. The mixed model (suPAR > 10 ng/mL plus qSOFA ≥ 2) has improved the AUC-ROC to 0.853 [95% CI: 0.790-0.916; P < .001] with the best prognostic performance: sensitivity of 39% and a specificity of 97% with a negative predictive value of 90%. Conclusions. suPAR showed better performance for 30- day mortality prognostic power from several biomarkers in the patients seen in ED due to infections. Score qSOFA has better performance that SRIS and the mixed model (qSOFA ≥ 2 plus suPAR > 10 ng/mL) increased the ability of qSOFA. (AU)

Cardiac troponin and COVID-19 severity: Results from BIOCOVID study.

BACKGROUND: Myocardial injury is a common finding in COVID-19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated cardiac troponin, in a large population of COVID-19 patients, and further evaluated separately the role of troponin T and I. METHODS: This is a multicentre, retrospective observational study enrolling patients with laboratory-confirmed COVID-19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex-specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty-day mortality was defined as endpoint. RESULTS: A total of 1280 COVID-19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut-off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex-specific cut-off was used. This prevalence was significantly higher (42.9% vs 21.9%; P < .001) in patients in whom troponin T was measured in comparison with troponin I. Sex-specific elevated troponin levels were significantly associated with 30-day mortality, with adjusted odds ratios (ORs) of 3.00 for total population, 3.20 for cardiac troponin T and 3.69 for cardiac troponin I. CONCLUSION: In this multicentre study, myocardial injury was a common finding in COVID-19 patients. Its prevalence increased when a sex-specific cut-off and cardiac troponin T were used. Elevated troponin was an independent predictor of 30-day mortality, irrespective of cardiac troponin assay and cut-offs to detect myocardial injury. Hence, the early measurement of cardiac troponin may be useful for risk stratification in COVID-19.

Medicago truncatula Ferroportin2 mediates iron import into nodule symbiosomes.

Iron is an essential cofactor for symbiotic nitrogen fixation, required by many of the enzymes involved, including signal transduction proteins, O2 homeostasis systems, and nitrogenase itself. Consequently, host plants have developed a transport network to deliver essential iron to nitrogen-fixing nodule cells. Ferroportin family members in model legume Medicago truncatula were identified and their expression was determined. Yeast complementation assays, immunolocalization, characterization of a tnt1 insertional mutant line, and synchrotron-based X-ray fluorescence assays were carried out in the nodule-specific M. truncatula ferroportin Medicago truncatula nodule-specific gene Ferroportin2 (MtFPN2) is an iron-efflux protein. MtFPN2 is located in intracellular membranes in the nodule vasculature and in inner nodule tissues, as well as in the symbiosome membranes in the interzone and early-fixation zone of the nodules. Loss-of-function of MtFPN2 alters iron distribution and speciation in nodules, reducing nitrogenase activity and biomass production. Using promoters with different tissular activity to drive MtFPN2 expression in MtFPN2 mutants, we determined that expression in the inner nodule tissues is sufficient to restore the phenotype, while confining MtFPN2 expression to the vasculature did not improve the mutant phenotype. These data indicate that MtFPN2 plays a primary role in iron delivery to nitrogen-fixing bacteroids in M. truncatula nodules.

Study of the putative fusion regions of the preS domain of hepatitis B virus.

In a previous study, it was shown that purified preS domains of hepatitis B virus (HBV) could interact with acidic phospholipid vesicles and induce aggregation, lipid mixing and leakage of internal contents which could be indicative of their involvement in the fusion of the viral and cellular membranes (Núñez, E. et al. 2009. Interaction of preS domains of hepatitis B virus with phospholipid vesicles. Biochim. Biophys. Acta 17884:417-424). In order to locate the region responsible for the fusogenic properties of preS, five mutant proteins have been obtained from the preS1 domain of HBV, in which 40 amino acids have been deleted from the sequence, with the starting point of each deletion moving 20 residues along the sequence. These proteins have been characterized by fluorescence and circular dichroism spectroscopy, establishing that, in all cases, they retain their mostly non-ordered conformation with a high percentage of ß structure typical of the full-length protein. All the mutants can insert into the lipid matrix of dimyristoylphosphatidylglycerol vesicles. Moreover, we have studied the interaction of the proteins with acidic phospholipid vesicles and each one produces, to a greater or lesser extent, the effects of destabilizing vesicles observed with the full-length preS domain. The ability of all mutants, which cover the complete sequence of preS1, to destabilize the phospholipid bilayers points to a three-dimensional structure and/or distribution of amino acids rather than to a particular amino acid sequence as being responsible for the membrane fusion process.

Spectroscopic characterization and fusogenic properties of preS domains of duck hepatitis B virus.

In order to shed light on the hepatitis B virus fusion mechanism and to explore the fusogenic capabilities of preS regions, a recombinant duck hepatitis B virus (DHBV) preS protein (DpreS) containing six histidines at the carboxy-terminal end has been obtained. The DpreS domain, which has an open and mostly nonordered conformation as indicated by fluorescence and circular dichroism spectroscopies, has the ability to interact with negatively charged phospholipid vesicles. The observed interaction differences between neutral and acidic phospholipids can be interpreted in terms of an initial ionic interaction between the phospholipid polar headgroup and the protein followed by the insertion of probably the N-terminal region in the cellular membrane. Fluorescence polarization studies detect a decrease of the transition enthalpy together with a small modification of the transition temperature, typical effects of integral membrane proteins. The interaction of the protein with acidic phospholipid vesicles induces aggregation, lipid mixing, and leakage of internal contents, properties that have been ascribed to membrane destabilizing proteins. The fact that the preS domains of the hepadnaviruses have little similarity but share a very similar hydrophobic profile points to the importance of the overall three-dimensional structure as well as to its conformational flexibility and the distribution of polar and apolar amino acids on the expression of their destabilizing properties rather than to a particular amino acid sequence. The results presented herein argue for the involvement of DpreS in the initial steps of DHBV infection. Taken together with previously reported results, the conclusion that both S and preS regions participate in the fusion process of the hepadnaviridae family may be drawn.

Interaction of preS domains of hepatitis B virus with phospholipid vesicles.

The role of preS domains of the hepatitis B virus (HBV) envelope proteins in the first steps of viral infection has been restricted to their implication in virus attachment to a putative hepatocyte receptor. In order to explore a fusion activity in these regions, we used recombinant preS domains to characterize their interaction with liposomes. Binding experiments carried out with NBD-labeled proteins indicated that preS were able to interact in a monomeric way with acidic phospholipid vesicles, being the partition coefficient similar to that described for peptides which can insert deeply into bilayers. Fluorescence depolarization of DPH-labeled vesicles confirmed the specificity for negative charged phospholipids. Upon interaction the proteins induced aggregation, lipid mixing and release of internal contents of acidic vesicles at both acid and neutral pH in a concentration-dependent manner. Taken together, all these data indicate that preS domains are able to insert into the hydrophobic core of the bilayer. Moreover, the insertion resulted in a protein conformational change which increased the helical content. Therefore all these results suggest that, besides their participation in the recognition of a cellular receptor, the preS domains could be involved in the fusion mechanism of HBV with the plasma membrane of target cells.

On-line monitoring of pH junctions in capillary electrophoresis using Fourier transform infrared spectrometry.

Fourier transform mid-infrared spectroscopic detection is proposed as an on-line detection technique for the study of on-line preconcentration processes in capillary electrophoresis (CE). The molecule-specific information contained in mid-IR spectra can be used to directly determine the chemical compositions of individual zones and their boundaries. This paper reports on pH junctions employed in myoglobin analysis. On-line mid-IR detection allowed the shape of the sample peak to be monitored as well as the chemical compositions of the surrounding zones. From this information it was possible to obtain detailed insights into the actual chemical compositions of the individual zones governing the efficiency of the preconcentration technique applied. The principle of measurement outlined here can therefore also be regarded as a promising one for investigating other on-line preconcentration techniques, like stacking, sweeping, and pH junction-sweeping among others.

Pancreatitis de repetición en colecistectomizada / Recurrent pancreatitis after cholecystectomy

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[On the ownership of Medical Records]. / A quien pertenece la Ficha Clínica?

It is not clear if medical records belong to the physician, the institution or the patient. There is a bill being discussed in the Chilean Congress that establishes that "the patient, personally or through a representative, has the right to access and review his medical record. In case of death, this right may be exerted by his inheritors". In this article we postulate that this bill infringes a number of legal norms in force and universally accepted ethical principles. We distinguish between patient's advocacy to be informed and their free access to medical records. The main ethical principles violated are those of beneficence and non maleficence.

Insuficiencia renal cronica: casuistica 1987-1988 / Chronic renal failure: 1987-1988

Siendo la I.R.C. una afección frecuente, con alta morbi-mortalidad y teniendo cantidad suficiente de portadores de esta patológica en nuestro servício, revisando fichas clínicas encontramos que en el periodo 1987-88 fueron internadas 131 pacientes, y las causas mas frecuentes fueron: nefropatia diabética , glomerulonefritis y le siguen la uropatía hipertensiva, poliquistosis. El sexo mas afectado es el masculino 63.3%. La distribución de patologías por edad es la siguiente: Glomerulonefritis edad promedio 30 años. Nefropatía diabética - 60 años. Uropatías obstructivas (Ad. de Prost.) - 70 años. Pielonefritis crónica sin preferencia por la edad. Nefropatías hipertensivas - 55 años. poliquistois - 50 años. Muchas veces no se llegó a Dx por fallecimiento rapido, o por encontrarse riñones escleroatroficos y sin antecedentes que guién. Fueron realizadas 31 biopsias renales, cuyos informes abarcaban; 26 - glomerulonefritis. 3 - pielonefritis crónica. 1 - glomeruloesclerosis difusa. 1 - nefritis intersticial crónica (hiperuricemía.). Un paciente jóven, hipertenso revelde, luego de la biópsia renal presentó hematuria grave por lo que fué nefréctomizado, su informe indico G.N.M.P. La biopsia renal establece un Dx histológico definitivo, a condición de que se practique antes que la enfermedad haya progresado a tal grado que la única interpretación morfológica posible sea "renopatía en fase terminal". La biopsia renal está indicada en un numero reducido de pacientes. No se acostumbra ...