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Exploration of Rhenium Bisquinoline Tricarbonyl Complexes for their Antibacterial Properties.
No full textMetal complexes have emerged as a promising source for novel classes of antibacterial agents to combat the rise of antimicrobial resistance around the world. In the exploration of the transition metal chemical space for novel metalloantibiotics, the rhenium tricarbonyl moiety has been identified as a promising scaffold. Here we have prepared eight novel rhenium bisquinoline tricarbonyl complexes and explored their antibacterial properties. Significant activity against both Gram-positive and Gram-negative bacteria was observed. However, all complexes also showed significant toxicity against human cells, putting into question the prospects of this specific rhenium compound class as metalloantibiotics. To better understand their biological effects, we conduct the first mode of action studies on rhenium bisquinoline complexes and show that they are able to form pores through bacterial membranes. Their straight-forward synthesis and tuneability suggests that further optimisation of this compound class could lead to compounds with enhanced bacterial specificity
Environmental Homeopathy: Homeopathic Potencies Regulate the Toxicity and Growth of Raphidiopsis raciborskii (cyanobacteria) and can be Tracked Physico-Chemically. Part 1: Biological Results.
No full textINTRODUCTION
Cyanobacteria are microorganisms found in many parts of the world and several genera, such as Raphidiopsis raciborskii, are producers of cyanotoxins. Homeopathic potencies have been found to modulate toxicity in different biological models, and the present study endeavors to discover whether this might also be the case with cyanobacteria.
OBJECTIVES
Our objective was to investigate the possible effects of homeopathic potencies on the resilience of Artemia franciscana (brine shrimp) embryos to saxitoxin (STX; cyanotoxin) and on controlling the growth of R. raciborskii in vitro.
METHOD
A. franciscana cysts were cultivated in seawater in 96-well plates to evaluate the hatching rate and vitality, plus the gene expression of heat shock proteins (HSPs), after being challenged with R. raciborskii extract containing 2.5 µg/L of STX and treated with different homeopathic potencies. Untreated wells were used as controls ("base-line"). Potencies were chosen from a screening process based on seven selected homeopathic preparations according to the similitude of STX symptoms (Sulphur, Zincum metallicum, Nitric acidum, Plumbum metallicum, Mercurius solubilis, Phosphoric acidum, Isotherapic from R. raciborskii extract; all at 6cH, 30cH and 200cH). Cultures of R. raciborskii maintained in an artificial seawater medium were equally treated with screened homeopathic potencies selected from the same list but specifically for their growth control as a function of time.
RESULTS
A 15% lower rate of hatching of A. franciscana cysts was observed after treatment with Nitric acidum 6cH in comparison with baseline (p = 0.05). A complete toxicity reversal was seen after treatment with Isotherapic 200cH, with a 23-fold increase of Hsp 26 gene expression (p = 0.023) and a 24-fold increase of p26 gene expression (p ≤ 0.001) in relation to baseline. Nitric acidum 200cH and Mercurius solubilis 30cH limited the exponential growth of cyanobacteria up to 95% and 85% respectively (p ≤ 0.003) in relation to baseline. Succussed water presented only a transitory 50% inhibition effect.
CONCLUSION
Isotherapic 200cH improved A. franciscana bioresilience to STX; Nitric acidum 200cH and Mercurius solubilis 30cH showed the optimal performance on limiting R. raciborskii growth. The results point to the potential of homeopathic potencies to mitigate environmental problems related to water quality
Transient brain structure changes after high phenylalanine exposure in adults with phenylketonuria.
No full textPhenylketonuria is a rare metabolic disease resulting from a deficiency of the enzyme phenylalanine hydroxylase. Recent cross-sectional evidence suggests that early-treated adults with phenylketonuria exhibit alterations in cortical grey matter compared to healthy peers. However, the effects of high phenylalanine exposure on brain structure in adulthood need to be further elucidated. In this double-blind, randomised, placebo-controlled crossover trial, we investigated the impact of a four-week high phenylalanine exposure on the brain structure and its relationship to cognitive performance and metabolic parameters in early-treated adults with phenylketonuria. Twenty-eight adult patients with early-treated classical phenylketonuria (19-48 years) underwent magnetic resonance imaging before and after the four-week phenylalanine and placebo interventions (four timepoints). Structural T1-weighted images were preprocessed and evaluated using DL+DiReCT, a deep-learning-based tool for brain morphometric analysis. Cortical thickness, white matter volume, and ventricular volume were compared between the phenylalanine and placebo periods. Brain phenylalanine levels were measured using 1H spectroscopy. Blood levels of phenylalanine, tyrosine, and tryptophan were assessed at each of the four timepoints, along with performance in executive functions and attention. Blood phenylalanine levels were significantly higher after the phenylalanine period (1441µmol/L) than after the placebo period (873µmol/L, P<0.001). Morphometric analyses revealed a statistically significant decrease in cortical thickness in 17 out of 60 brain regions after the phenylalanine period compared to placebo. The largest decreases were observed in the right pars orbitalis (point estimate=-0.095mm, P<0.001) and the left lingual gyrus (point estimate=-0.070mm, P<0.001). Bilateral white matter and ventricular volumes were significantly increased after the phenylalanine period. However, the structural alterations in the Phe-placebo group returned to baseline measures following the washout and placebo period. Additionally, elevated blood and brain phenylalanine levels were related to increased bilateral white matter volume (rs=0.43 to 0.51, P≤0.036) and decreased cortical thickness (rs=-0.62 to -0.39, not surviving FDR correction) after the phenylalanine and placebo periods. Moreover, decreased cortical thickness was correlated with worse cognitive performance after both periods (rs=-0.54 to -0.40, not surviving FDR correction). These findings provide evidence that a four-week high phenylalanine exposure in adults with phenylketonuria results in transient reductions of the cortical grey matter and increases in white matter volume. Further research is needed to determine the potential long-term impact of high phenylalanine levels on brain structure and function in adults with phenylketonuria
Short-term air pollution exposure and mortality in Brazil: Investigating the susceptible population groups.
No full textThis is the first study to examine the association between ambient air pollution (PM2.5, O3, and NO2) and mortality (in different population groups by sex and age) based on a nationwide death record across Brazil over a 15-year period (2003-2017). We used a time-series analytic approach with a distributed lag model. Our study population includes 2,872,084 records of deaths in Brazil between 2003 and 2017. Men accounted for a higher proportion of deaths, with 58% for all-cause mortality, 54% for respiratory mortality, and 52% for circulatory mortality. Most individuals were over 65 years of age. Our results suggest an association between air pollution and mortality in Brazil. The direction, statistical significance, and effect size of these associations varied considerably by type of air pollutant, region, and population group (sex and age group). In particular, the older population group (>65 years) was most affected. The national meta-analysis for the entire data set (without stratification by sex and age) showed that for every 10 μg/m3 increase in PM2.5 concentration, the risk of death from respiratory diseases increased by 2.93% (95%CI: 1.42; 4.43). For every 10 ppb increase in O3, there is a 2.21% (95%CI: 0.59; 3.83) increase in the risk of all-cause mortality for the group of all people between 46 and 65 years old, and a 3.53% (95%CI: 0.34; 6.72) increase in the risk of circulatory mortality for the group of women, all ages. For every 10 ppb increase in NO2, the risk of respiratory mortality increases by 17.56% (95%CI: 4.44; 30.64) and the risk of all-cause mortality by 5.63% (95%CI: 1.83; 9.44). The results of our study provide epidemiological evidence that air pollution is associated with a higher risk of cardiorespiratory mortality in Brazil. Given the lack of nationwide studies on air pollution in Brazil, our research is an important contribution to the local and international literature that can provide better support to policymakers to improve air quality and public health
Real-World Evidence of the Cambridge Hybrid Closed-Loop App With a Novel Real-Time Continuous Glucose Monitoring System.
No full textWe evaluated the performance of the interoperable Cambridge hybrid closed-loop app with FreeStyle Libre 3 glucose sensor, and YpsoPump insulin pump in a real-world setting. Data from 100 users (63 adults [mean ± SD age 41.9 ± 14.0 years], 15 children [8.6 ± 5.2 years)] and 22 users of unreported age) for a period of 28 days were analyzed. Time in range (3.91- 10.0mmol/L) was 72.6 ± 11.1% overall. Time below range (<3.9mmol/L) was 3.1% (1.4-5.1) (median [interquartile range]). Auto-mode was active for 95.8% (91.8-97.9) of time. This real-world analysis suggests that the performance of Cambridge hybrid closed-loop app with this glucose sensor is comparable to other commercially available hybrid closed-loop systems
The central role of borderline personality disorder in imprisoned people: a network analysis of mental disorder diagnoses.
No full textMultiple comorbid mental disorders have been reported in prison populations worldwide. This study aimed to assess the interrelatedness of comorbid mental disorders in imprisoned people. We surveyed 427 consecutively imprisoned people at intake to the prison system in the Greater Metropolitan Region of Santiago, Chile, using the Mini Neuropsychiatric Interview. In addition, we used the Structured Clinical Interview for DSM-IV (SCID-II) to assess borderline personality disorder (BPD). We conducted network analyses using R 4.3.1 (package bootnet version 1.5.3) with 11 variables representing the diagnostic entities agoraphobia, alcohol use disorder, antisocial personality disorder, BPD, illicit drug use disorder, major depression, obsessive-compulsive disorder, panic disorder, psychotic disorder, posttraumatic stress disorder (PTSD), and social anxiety disorder. BPD had a central position in a network of nine interrelated diagnoses and showed the highest levels of connectedness (strength, closeness, and betweenness) among personality, anxiety, mood, and substance use disorders. Psychotic disorders and PTSD were not connected with the other diagnoses. In sensitivity analyses stratified by sex, BPD remained in a central position and psychotic disorders were unconnected, while PTSD was connected with different nodes in each sex. BPD has a central role in the complex comorbidity of imprisoned people, which needs consideration for intervention development
Environmental Homeopathy: Homeopathic Potencies Regulate the Growth and Toxicity of Raphidiopsis raciborskii (cyanobacteria) and Can be Tracked Physico-Chemically. Part 2: Physico-chemical Results.
No full textINTRODUCTION
The control of cyanobacterial toxicity and growth by homeopathic potencies was described in Part 1 of this two-part report. Here, a parallel approach characterized the physico-chemical features of the potencies used and the liquid media treated with them, correlating these results with their respective biological effects.
OBJECTIVES
Our objective was to establish if physico-chemical parameters can track homeopathic potencies in seawater or artificial seawater medium (ASM)-1 and to discover whether these parameters correlate with previously described biological effects.
METHOD
Artemia franciscana (brine shrimp) cysts were cultivated in seawater challenged with Raphidiopsis raciborskii extract and treated with different homeopathic potencies chosen from a screening process. Cultures of R. raciborskii maintained in ASM-1 were also treated with previously screened homeopathic potencies, and their growth was monitored as a function of time. The physico-chemical properties of the treated media (seawater or ASM-1) were evaluated by their interaction with solvatochromic dyes and changes in pH, conductivity and temperature.
RESULTS
Coumarin 7 was found to be a marker for Nitric acidum 6cH and Isotherapic (R. raciborskii extract) 200cH in seawater (analysis of variance [ANOVA], p = 0.0015). Nile red was found to be a marker for Nitric acidum 200cH and Mercurius solubilis 30cH in ASM-1 (ANOVA, p ≤ 0.001). An increase in pH of ASM-1 and endothermic effects were observed after these treatments (two-way ANOVA, p = 0.0001). Seawater and ASM-1 to which potencies had been added were also subjected to a constant unidirectional 2,400 Gauss static magnetic field and found to have enhanced effects on the solvatochromic dyes tested.
CONCLUSION
Homeopathic potencies were specifically traceable in aqueous media using solvatochromic dyes, especially when the samples were subjected to a magnetic field. Results from monitoring other physical parameters, such as pH and temperature, were less specific in relation to potency tracking. However, potency-induced endothermic effects might provide valuable thermodynamic data relating to the nature of potencies
Lower Trapezius and Latissimus Dorsi Transfer relieve Teres Minor Activity into the Physiological Range in Collin D Irreparable Posterosuperior Massive Rotator Cuff Tears: A Biomechanical Analysis.
No full textBACKGROUND
Tendon transfers are established techniques to regain external rotation mobility in patients suffering from an irreparable, posterosuperior massive rotator cuff tear (MRCT). Posterosuperior MRCT with intact teres minor (Type D MRCT) can lead to excessive teres minor loading to maintain external rotation. We hypothesize that tendon transfers are effective in relieving teres minor loading in Type D MRCTs. Our aim was to biomechanically assess muscle synergism with latissimus dorsi (LD-Transfer) and lower trapezius (LT-Transfer) tendon transfer during external rotation at different abduction heights.
METHODS
Using musculoskeletal modeling, we analyzed and compared the moment arm, muscle torque and muscle activity between a healthy and Type D MRCT pathological model with and without the LD- or LT-Transfer at infraspinatus and teres minor insertion sites. Output measures were analyzed during external rotation at different abduction angles and 10 to 50N resistance against external rotation. We assessed its impact on teres minor loading in a Type D MRCT. Morphological variations were parameterized using the critical shoulder angle and the acromiohumeral distance to address variations among patients.
RESULTS
Both transfer types reduced teres minor torque and activity significantly, reaching physiological state at 40N external resistance (p<0.001), with insertion to infraspinatus site being more effective than teres minor site (p<0.001). External rotation moment arms of LD-Transfer were larger than LT-Transfer at 90° abduction (25.1±0.8mm vs. 21.2±0.6mm, p<0.001) and vice versa at 0° abduction (17.4±0.5mm vs. 24.0±0.2mm, p<0.001). While the healthy infraspinatus was the main external rotator in all abduction angles (50-70% torque), a Type D MRCT resulted in a 70-90% increase of teres minor torque and an up to sevenfold increase in its activity leading to excessive loadings beyond 10N resistance against external rotation. Varying the critical shoulder angle and the acromiohumeral distance led to minor variations in muscle moment arm and muscle activity.
CONCLUSION
We identified biomechanical efficacy of both tendon transfers in Type D MRCT regarding teres minor load relieve and superior performance of the transfers at the infraspinatus insertion site
Electrodermal and respiratory synchrony in couple therapy in distinct therapeutic subsystems and reflection periods.
No full textObjective Synchrony in the multi-person context of systemic therapy is a complex and understudied phenomenon. We analyzed respiratory and electrodermal synchronies within a couple therapy system with two therapists to determine whether dyadic subsystems between each client and therapist synchronized differently. We also studied synchrony in reflection periods, in which the therapists discussed the therapy process with clients listening. Finally, we examined the association of synchronies with alliance and outcome.Method: A sample of 22 therapy sessions in which electrodermal activity (EDA) and respiration were recorded were analyzed. Self-report measures of session alliance and outcome were obtained. Synchrony computation was based on windowed cross-correlation using surrogate synchrony and segment-wise shuffling of physiological time series.Results: The results supported the presence of EDA synchrony for the client-therapist and therapist-therapist dyads but not client-client dyads across entire sessions. No significant synchronies were found for respiration behavior. A similar picture was found in reflection periods. Clients' well-being as well as therapists' alliance ratings were significant predictors of client-client EDA synchrony.Conclusion: Our results point to the relational meaning of synchrony and its importance for understanding couple psychotherapy, particularly the reflection periods. Challenges involved in extending synchrony computation to multi-person settings were highlighted
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