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Fusing Bismuth and Mercaptocarboranes: Design and Biological Evaluation of Low-Toxicity Antimicrobial Thiolato Complexes
No full textThis study proposes an innovative strategy to enhance the pharmacophore model of antimicrobial bismuth thiolato complex drugs by substituting hydrocarbon ligand structures with boron clusters, particularly icosahedral closo-dicarbadodecaborane (C2B10H12, carboranes). The hetero- and homoleptic mercaptocarborane complexes BiPh2L (1) and BiL3 (2) (L=9-S-1,2-C2B10H11) were prepared from 9-mercaptocarborane (HL) and triphenylbismuth. Comprehensive characterization using NMR, IR, MS, and XRD techniques confirmed their successful synthesis. Evaluation of antimicrobial activity in a liquid broth microdilution assay demonstrated micromolar to submicromolar minimum inhibitory concentrations (MIC) suggesting high effectiveness against S. aureus and limited efficacy against E. coli. This study highlights the potential of boron-containing bismuth complexes as promising antimicrobial agents, especially targeting Gram-positive bacteria, thus contributing to the advancement of novel therapeutic approaches
Elevated accuracy in recognition of subliminal happy facial expressions in patients with panic disorder after psychotherapy
No full textBackground: Individuals with anxiety disorders (ADs) often display hypervigilance to threat information, although this response may be less pronounced following psychotherapy. This study aims to investigate the unconscious recognition performance of facial expressions in patients with panic disorder (PD) post-treatment, shedding light on alterations in their emotional processing biases.
Methods: Patients with PD (n=34) after (exposure-based) cognitive behavior therapy and healthy controls (n=43) performed a subliminal affective recognition task. Emotional facial expressions (fearful, happy, or mirrored) were displayed for 33 ms and backwardly masked by a neutral face. Participants completed a forced choice task to discriminate the briefly presented facial stimulus and an uncovered condition where only the neutral mask was shown. We conducted a secondary analysis to compare groups based on their four possible response types under the four stimulus conditions and examined the correlation of the false alarm rate for fear responses to non-fearful (happy, mirrored, and uncovered) stimuli with clinical anxiety symptoms.
Results: The patient group showed a unique selection pattern in response to happy expressions, with significantly more correct “happy” responses compared to controls. Additionally, lower severity of anxiety symptoms after psychotherapy was associated with a decreased false fear response rate with non-threat presentations.
Conclusion: These data suggest that patients with PD exhibited a “happy-face recognition advantage” after psychotherapy. Less symptoms after treatment were related to a reduced fear bias. Thus, a differential facial emotion detection task could be a suitable tool to monitor response patterns and biases in individuals with ADs in the context of psychotherapy
Coupling of droplet-on-demand microfluidcs with ESI/MS to study single-cell catalysis
No full textDroplet microfluidics provides an efficient method for analysing reactions within the range of nanoliters to picoliters. However, the sensitive, label-free and versatile detection with ESI/MS poses some difficulties. One challenge is the difficult association of droplets with the MS signal in high-throughput droplet analysis. Hence, a droplet-on-demand system for the generation of a few droplets can address this and other problems such as surfactant concentration or cross-contamination. Accordingly, the system has been further developed for online coupling with ESI/MS. To achieve this, we developed a setup enabling on-demand droplet generation by hydrodynamic gating, with downstream microscopic droplet detection and MS analysis. This facilitated the incorporation of 1–9 yeast cells into individual 1–5 nL droplets and the monitoring of yeast-catalysed transformation from ketoester to ethyl-3-hydroxybutyrate by MS. With our method a mean production rate of 0.035 ± 0.017 fmol per cell per h was observed with a detection limit of 0.30 μM. In conclusion, our droplet-on-demand method is a versatile and advantageous tool for cell encapsulation in droplets, droplet imaging and reaction detection using ESI/MS
Clinical Outcome Using Different Catheter Interventional Treatment Modalities in High-Risk Pulmonary Artery Embolism
No full textBackground: For patients with high-risk pulmonary artery embolism (PE), catheter-directed therapies pose a viable alternative treatment option to systemic thrombolysis or anticoagulation. Right now, there are multiple devices available which have been proven to be safe and effective in lower-risk settings. There is, however, little data comparing their efficacies in high-risk PE. Methods: We performed a retrospective, single-center study on patients with high-risk PE undergoing catheter interventional treatment. Patients receiving large-bore catheter thrombectomy were compared to patients receiving alternative treatment forms. Results: Of the 20 patients included, 9 received large-bore thrombectomy, and 11 received alternative interventional treatments. While the baseline characteristics were comparable between the two groups, periprocedural and in-hospital mortality tended to be significantly lower with large-bore thrombectomy when compared to other treatment forms (0 vs. 55% and 33 vs. 82%, p = 0.07 and 0.01, respectively). Conclusions: In this small, retrospective study, large-bore thrombectomy was associated with lower mortality as compared to alternative treatment forms. Future prospective research is needed to corroborate these findings
Bilirubin Levels in Infancy and Their Associations with Body Weight, Levels of Iron-Related Parameters and Steroid Hormone Levels
No full textIt is assumed that bilirubin is hormonally regulated and influences weight development by preventing weight gain. However, studies in healthy infants are limited. The present study established reference values for bilirubin and investigated whether bilirubin levels are significantly associated with body weight, levels of ferritin and transferrin as well as steroid hormone levels in a study population of three- and six-month-old healthy infants. Data from a total of 411 study visits from the LIFE Child study (Leipzig, Germany) were analyzed. Associations were examined using linear regression analyses. Besides laboratory parameters, anthropometric data were gathered. We found statistically significant associations between body weight and bilirubin levels. In girls, we observed additional associations between bilirubin levels and both ferritin and transferrin concentrations at three months of age. At six months, steroid hormone levels were significantly associated with concentrations of total and indirect bilirubin, with effects differing by sex. Our study thus confirms associations already reported from animal studies and studies in adult populations. Furthermore, we showed that these associations already exist in the first year of life, are influenced by sex and age and, further, depend on the bilirubin type. Our results provide reference values for bilirubin and assist, therefore, in interpreting bilirubin levels in infancy
Differently increased volumes of multiple brain areas in Npc1 mutant mice following various drug treatments
No full textBackground: Niemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of Npc1−/− displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholesterol storage. Npc1−/− mice receiving a combined therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) showed prevention of Purkinje cell loss, improved motor function and reduced intracellular lipid storage. Although therapy of Npc1−/− mice with COMBI, MIGLU or HPßCD resulted in the prevention of body weight loss, reduced total brain weight was not positively influenced.
Methods: In order to evaluate alterations of different brain areas caused by pharmacotherapy, fresh volumes (volumes calculated from the volumes determined from paraffin embedded brain slices) of various brain structures in sham- and drug-treated wild type and mutant mice were measured using stereological methods.
Results: In the wild type mice, the volumes of investigated brain areas were not significantly altered by either therapy. Compared with the respective wild types, fresh volumes of specific brain areas, which were significantly reduced in sham-treated Npc1−/− mice, partly increased after the pharmacotherapies in all treatment strategies; most pronounced differences were found in the CA1 area of the hippocampus and in olfactory structures.
Discussion: Volumes of brain areas of Npc1−/− mice were not specifically changed in terms of functionality after administering COMBI, MIGLU, or HPßCD. Measurements of fresh volumes of brain areas in Npc1−/− mice could monitor region-specific changes and response to drug treatment that correlated, in part, with behavioral improvements in this mouse model
Modular Chip-Based nanoSFC−MS for Ultrafast Separations
No full textThis study presents the development of a miniaturized device for
supercritical fluid chromatography coupled with mass spectrometry. The chip-based,
modular nanoSFC approach utilizes a particle-packed nanobore column embedded
between two monolithically structured glass chips. A microtee in the pre-column section
ensures picoliter sample loads onto the column, while a microcross chip structure
fluidically controls the column backpressure. The restrictive emitter and the minimal post-
column volume of 16 nL prevent mobile phase decompression and analyte dilution,
maintaining chromatographic integrity during transfer to the atmospheric pressure MS
interface. This facilitates high-speed chiral separations in less than 80 s with high
reproducibility
Canon clásico y academia hispanohablante: patrones de canonización en textos académicos del siglo XXI
No full textImpaired Modulation of the Autonomic Nervous System in Adult Patients with Major Depressive Disorder
No full textPatients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS) indicated by a reduced vagal tone and a (relative) sympathetic hyperactivity. However, in most studies, heart rate variability (HRV) was only examined while resting. So far, it remains unclear whether the dysbalance of the ANS in patients with MDD is restricted to resting or whether it is also evident during sympathetic and parasympathetic activation. The aim of this study was to compare the responses of the ANS to challenges that stimulated the sympathetic and, respectively, the parasympathetic nervous systems in patients with MDD. Forty-six patients with MDD (female 27 (58.7%), mean age 44 ± 17 years) and 46 healthy controls (female 26 (56.5%), mean age 44 ± 20 years) underwent measurement of time- and frequency-dependent domains of HRV at rest, while standing (sympathetic challenge), and during slow-paced breathing (SPB, vagal, i.e., parasympathetic challenge). Patients with MDD showed a higher heart rate, a reduced HRV, and a diminished vagal tone during resting, standing, and SPB compared to controls. Patients with MDD and controls responded similarly to sympathetic and vagal activation. However, the extent of modulation of the ANS was impaired in patients with MDD, who showed a reduced decrease in the vagal tone but also a reduced increase in sympathetic activity when switching from resting to standing. Assessing changes in the ANS during sympathetic and vagal activation via respective challenges might serve as a future biomarker and help to allocate patients with MDD to therapies like HRV biofeedback and psychotherapy that were recently found to modulate the vagal tone
Immunohistochemical Detection of Indoleamine 2,3-Dioxygenase in Spontaneous Mammary Carcinomas of 96 Pet Rabbits
No full textMammary carcinomas have been diagnosed with increasing frequency in pet
rabbits. Prognostic biomarkers are limited, and the only available treatment is surgical excision.
Additional treatment options are needed, e.g., for animals in which metastases to internal organs
preclude complete tumor removal. Human breast cancer may express the immunosuppressive
enzyme indoleamine 2,3-dioxygenase 1 (IDO1), that represents a prognostic biomarker and a possible
therapeutic target. Since previous studies revealed similarities between human breast cancer and
pet rabbit mammary carcinomas, this study investigated IDO1 immunostaining in 96 mammary
carcinomas of 96 pet rabbits with an average age of 5.5 years. All rabbits with reported sex were
female. Variable percentages of IDO1-positive tumor cells were detected in 90 (94%) carcinomas.
Furthermore, IDO1 immunostaining was observed in the secretory epithelial cells of the adjacent
non-neoplastic mammary tissue. This study provides further information on the molecular features
of mammary carcinomas in rabbits. It also shows similarities in IDO1 expression between rabbit
mammary carcinomas and human breast cancer. These findings can have a mutual benefit. They
could lead the development of novel treatment options for rabbits with mammary carcinomas. In
addition, they further support the value of rabbits with mammary carcinomas for breast cancer
research.For mammary carcinomas in pet rabbits, prognostic biomarkers are poorly defined, and
treatment is limited to surgical excision. Additional treatment options are needed for rabbit patients
for which surgery is not a suitable option. In human breast cancer, the immunosuppressive enzyme
indoleamine 2,3-dioxygenase 1 (IDO1) represents a prognostic biomarker and possible therapeutic
target. This retrospective immunohistochemical study examined IDO1 in 96 pet rabbit mammary
carcinomas with known mitotic count, hormone receptor status, and percentage of stromal tumor
infiltrating lymphocytes (TILs). Tumors were obtained from 96 pet rabbits with an average of
5.5 years. All rabbits with reported sex (n = 88) were female or female-spayed. Of the carcinomas,
94% expressed IDO1, and 86% had sparse TILs consistent with cold tumors. Statistically significant
correlations existed between a higher percentage of IDO1-positive tumor cells, lower mitotic counts,
and increased estrogen receptor expression. The threshold for significance was IDO1 staining in >10%
of tumor cells. These results lead to the assumption that IDO1 expression contributes to tumorigenesis
and may represent a prognostic biomarker and possible therapeutic target also in pet rabbit mammary
carcinomas. They also support the value of rabbits for breast cancer research