Molecular gas and a new young stellar cluster in the far outer Galaxy

We investigate the star-formation ocurring in the region towards IRAS07527-3446 in the molecular cloud [MAB97]250.63-3.63, in the far outer Galaxy. We report the discovery of a new young stellar cluster, and describe its properties and those of its parent molecular cloud. Near-infrared JHKS images were obtained with VLT/ISAAC, and millimetre line CO spectra were obtained with the SEST telescope. VLA archive date were also used. The cloud and cluster are located at a distance of 10.3 kpc and a Galactocentric distance of 15.4 kpc, in the far outer Galaxy. Morphologically, IRAS 07527-3446 appears as a young embedded cluster of a few hundred stars seen towards the position of the IRAS source, extending for about 2-4 pc and exhibiting sub-clustering. The cluster contains low and intermediate-mass young reddened stars, a large fraction having cleared the inner regions of their circumstellar discs responsible for (H-Ks) colour excess. The observations are compatible with a < 5 Myr cluster with variable spatial extinction of between Av = 5 and Av = 11. Decomposition of CO emission in clumps, reveals a clump clearly associated with the cluster position, of mass 3.3 x 10^3 M(solar). Estimates of the slopes of the Ks-band luminosity function and of the star-formation efficiency yield values similar to those seen in nearby star-formation sites. These findings reinforce previous results that the distant outer Galaxy continues to be active in the production of new and rich stellar clusters, with the physical conditions required for the formation of rich clusters continuing to be met in the very distant environment of the outer Galactic disc.Comment: 11 pages, 13 figure

Farnesol in combination with N-acetylcysteine against staphylococcus epidermidis planktonic and biofilm cells

Staphylococcus epidermidis is the most frequent cause of nosocomial sepsis and catheter-related infections, in which biofilm formation is considered to be the main virulence mechanism. In biofilm environment, microbes exhibit enhanced resistance to antimicrobial agents. This fact boosted the search of possible alternatives to antibiotics. Farnesol and N-acetylcysteine (NAC) are non-antibiotic drugs that have demonstrated antibacterial properties. In this study, the effect of farnesol and NAC isolated or in combination (farnesol+NAC) was evaluated. NAC at 10 × MIC caused a total cell death in planktonic cells. On the other hand, S. epidermidis biofilms exhibited 4 log reduction in viable cell number after a 24h treatment with NAC at the former concentration. Our results demonstrated that there was a higher CFU log reduction of S. epidermidis planktonic cells when farnesol was combined with NAC at 1 × MIC relatively to each agent alone. However, these results were not relevant because NAC alone at 10 × MIC was always the condition which gave the best results, having a very high killing effect on planktonic cells and a significant bactericidal effect on biofilm cells. This study demonstrated that no synergy was observed between farnesol and NAC. However, the pronounced antibacterial effect of NAC against S. epidermidis, on both lifestyles, indicates the use of NAC as a potential therapeutic agent in alternative to antibiotics.Fernanda Gomes and Pilar Teixeira fully acknowledge the financial support of Fundacao para a Ciencia e Tecnologia (FCT) through the grants SFRH/BD/32126/2006 and SFRH/BPD/26803/2006, respectively

Farnesol antimicrobial role as biofilm cell detachment inducer in S. epidermidis biofilms

Objetives: Farnesol is a naturally-occurring sesquiterpene that was originally isolated from essential oils found in many plants has been described to have antimicrobial potential against several bacteria, including S. epidermidis. However, farnesol mechanism of action is not yet fully understood and some contradictory findings have been reported. We recently described that while farnesol was not efficient at killing biofilm bacteria, a strong reduction on biofilm biomass was detected, and we hypothesize that farnesol could be inducing biofilm detachment. Here, we address this hypothesis. Methods: To test our hypothesis we used 36 representative clinical strains of S. epidermidis from different parts of the world and characterized them in terms of genetic variability, biofilm formation and on the effect of farnesol on biofilm physiology and gene expression. Results: Farnesol had no bactericidal effect on stationary phase populations equal or above 108 CFU/mL. In exponential phase planktonic bacteria, farnesol showed a bacteriostatic effect after cell density reached 108 CFU/mL. In any of the growth phases studied, farnesol was effective in killing above 90% of bacteria in 4 h when cell density was 107 CFU/mL or below. Confocal microscopy and flow citometry analysis confirmed that in biofilms bacteria were not killed by farnesol but nevertheless cell wall integrity was affected. Gene expression studies revealed differential responses to farnesol, depending on the bacterial strain tested. Farnesol cell detachement from biofilms was also straindependent. Conclusions: We found that while farnesol cannot kill high density bacterial communities, such as biofilms, it was nevertheless able to induce biofilm detachment in 50% of the strains that formed biofilm

Of adenosine and the blues: the adenosinergic system in the pathophysiology and treatment of major depressive disorder

© 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Major depressive disorder (MDD) is the foremost cause of global disability, being responsible for enormous personal, societal, and economical costs. Importantly, existing pharmacological treatments for MDD are partially or totally ineffective in a large segment of patients. As such, the search for novel antidepressant drug targets, anchored on a clear understanding of the etiological and pathophysiological mechanisms underpinning MDD, becomes of the utmost importance. The adenosinergic system, a highly conserved neuromodulatory system, appears as a promising novel target, given both its regulatory actions over many MDD-affected systems and processes. With this goal in mind, we herein review the evidence concerning the role of adenosine as a potential player in pathophysiology and treatment of MDD, combining data from both human and animal studies. Altogether, evidence supports the assertions that the adenosinergic system is altered in both MDD patients and animal models, and that drugs targeting this system have considerable potential as putative antidepressants. Furthermore, evidence also suggests that modifications in adenosine signaling may have a key role in the effects of several pharmacological and non-pharmacological antidepressant treatments with demonstrated efficacy, such as electroconvulsive shock, sleep deprivation, and deep brain stimulation. Lastly, it becomes clear from the available literature that there is yet much to study regarding the role of the adenosinergic system in the pathophysiology and treatment of MDD, and we suggest several avenues of research that are likely to prove fruitful.This work was supported by project funding from Fundação para a Ciência e para a Tecnologia (FCT) to SHV (PTDC/BTM-SAL/32147/2017) and AMS (PTDC/MED-FAR/30933/2017). This project has received funding from H2020-WIDESPREAD-05-2017-Twinning (EpiEpinet) under grant agreement No. 952455. MF-F (SFRH/BD/147505/2019), JG-R (PD/BD/150342/2019), and NR (PD/BD/113463/2015) are supported by PhD fellowships from FCT.info:eu-repo/semantics/publishedVersio

The comparative effect of farnesol and antibiotics against Staphylococcus epidermidis

Introduction: Staphylococcus epidermidis is one of the main causes of medical device-related infections owing to its adhesion and biofilm-forming abilities on biomaterial surfaces. Farnesol is a sesquiterpenoid produced by many organisms, and also found in several essential oils. Studies revealed that farnesol affect the growth of a number of bacteria and fungi, pointing to a potential role as an antimicrobial agent. In this work we evaluated the role of farnesol on S. epidermidis growth and compared the effect of farnesol with the effect of various antibiotics on planktonic and biofilm cells of S. epidermidis. Methods: A 24 h kinetic study was performed using vancomycin, tetracycline and rifampicin at the peak serum concentration and farnesol at concentrations of 30, 100, 200 and 300 microM. The growth inhibition effect of the antimicrobial agents on planktonic and biofilm cells of S. epidermidis were assessed by XTT (the reduction of this tetrazolium salt is a measure of cellular activity and is easily assessed by colorimetry), Crystal Violet (only for biofilms), which measures total biomass of biofilm and Colony forming units (CFU). The biofilm cells were also analysed by confocal laser scanning microscopy after being stained with Live/Dead. Results: On planktonic cells, 300 microM of farnesol seems to have an inhibitory effect after 8 hours of agent exposition causing a reduction of 1.5 log on CFU. However after 24 hours the planktonic cells seem to recover. Over time, tetracycline and vancomycin caused a progressive reduction of CFU of 2 and 3 log, respectively. Rifampicin caused a reduction of 0.5 log after 6 hours. After that the CFU increase gradually until 24 hours. In comparation with the antibiotics tested, after 8 hours of exposition to the antimicrobial agents, 300 microM of farnesol has a similar effect of vancomycin and tetracycline. Rifampicin was the antimicrobial agent less effective against those cells. After 24 hours farnesol is less effective than vancomycin and tetracycline, but more effective than rifampicin. On biofilms, vancomycin and tetracycline do not have any effect on CFU. After 24 hours, rifampicin provoked a reduction on CFU of 1 log. 300 microM of farnesol provoked a gradual increase of CFU until 8hours. After that and until 24 hours, farnesol caused a reduction of CFU of 2 log. Until 8 hours farnesol has a similar effect of vancomycin and tetracycline. After 24 hours farnesol seems to be more effective than the former antibiotics and as effective as rifampicin. Conclusions: Since antibiotics are usually administrated every 8-12 hours, farnesol may be used as an alternative to antibiotics in the treatment of S. epidermidis systemic infections. It can also be used in chronic infection provoked by biofilm cells because farnesol is as or more effective than the antibiotics tested

Embryonal rhabdomyosarcoma of the uterine cervix: a rare case report

Embryonal rhabdomyosarcoma of the female genital tract is a rare tumour. It tends to occur during childhood in the vagina and, rarely, it can arise in the uterine cervix, with a peak incidence in the second decade. We report a case of a 18-year-old female with an embryonal rhabdomyosarcoma (sarcoma botryoides) presenting himself as a cervical polyp. This tumour consisted of rhabdomyoblasts with miscellaneous differentiation surrounded by a loose, myxoid stroma. The patient was successfully treated with cervical conization and adjuvant chemotherapy. She is now disease-free at the 28th month follow-up. Awareness of this uncommon lesion in the cervix and its clinical implications is important to prevent misdiagnosis. Therapy has recently inclined to conservative and fertility-sparing treatment

Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior

© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).Chronic adolescent cannabinoid receptor agonist exposure has been shown to lead to persistent increases in depressive-like behaviors. This has been a key obstacle to the development of cannabinoid-based therapeutics. However, most of the published work has been performed with only three compounds, namely Δ9-tetrahydrocannabinol, CP55,940 and WIN55,212-2. Hypothesizing that different compounds may lead to distinct outcomes, we herein used the highly potent CB1R/CB2R full agonist HU-210, and first aimed at replicating cannabinoid-induced long-lasting effects, by exposing adolescent female Sprague-Dawley rats to increasing doses of HU-210, for 11 days and testing them at adulthood, after a 30-day drug washout. Surprisingly, HU-210 did not significantly impact adult anxious- or depressive-like behaviors. We then tested whether chronic adolescent HU-210 treatment resulted in short-term (24h) alterations in depressive-like behavior. Remarkably, HU-210 treatment simultaneously induced marked antidepressant- and prodepressant-like responses, in the modified forced swim (mFST) and sucrose preference tests (SPT), respectively. Hypothesizing that mFST results were a misleading artifact of HU-210-induced behavioral hyperreactivity to stress, we assessed plasmatic noradrenaline and corticosterone levels, under basal conditions and following an acute swim-stress episode. Notably, we found that while HU-210 did not alter basal noradrenaline or corticosterone levels, it greatly augmented the stress-induced increase in both. Our results show that, contrary to previously studied cannabinoid receptor agonists, HU-210 does not induce persisting depressive-like alterations, despite inducing marked short-term increases in stress-induced reactivity. By showing that not all cannabinoid receptor agonists may induce long-term negative effects, these results hold significant relevance for the development of cannabinoid-based therapeutics.Work was supported by project funding from Fundação para a Ciência e para a Tecnologia (FCT) (PTDC/MED-FAR/30933/2017 and PTDC/MED-FAR/4834/2021) and by H2020-WIDESPREAD-05-2017-Twinning (EpiEpinet) under grant agreement No. 952455. MF-F (SFRH/BD/147505/2019), NR (PD/BD/113463/2015), JF-G (PD/BD/114441/2016) and CM-L (SFRH/BD/118238/2016) are supported by PhD fellowships from FCT. The funding sources had no involvement in study design, preparation of the manuscript, or decision regarding its submission.info:eu-repo/semantics/publishedVersio