Glucocorticoids promote breast cancer metastasis.

Diversity within or between tumours and metastases (known as intra-patient tumour heterogeneity) that develops during disease progression is a serious hurdle for therapy1-3. Metastasis is the fatal hallmark of cancer and the mechanisms of colonization, the most complex step in the metastatic cascade4, remain poorly defined. A clearer understanding of the cellular and molecular processes that underlie both intra-patient tumour heterogeneity and metastasis is crucial for the success of personalized cancer therapy. Here, using transcriptional profiling of tumours and matched metastases in patient-derived xenograft models in mice, we show cancer-site-specific phenotypes and increased glucocorticoid receptor activity in distant metastases. The glucocorticoid receptor mediates the effects of stress hormones, and of synthetic derivatives of these hormones that are used widely in the clinic as anti-inflammatory and immunosuppressive agents. We show that the increase in stress hormones during breast cancer progression results in the activation of the glucocorticoid receptor at distant metastatic sites, increased colonization and reduced survival. Our transcriptomics, proteomics and phospho-proteomics studies implicate the glucocorticoid receptor in the activation of multiple processes in metastasis and in the increased expression of kinase ROR1, both of which correlate with reduced survival. The ablation of ROR1 reduced metastatic outgrowth and prolonged survival in preclinical models. Our results indicate that the activation of the glucocorticoid receptor increases heterogeneity and metastasis, which suggests that caution is needed when using glucocorticoids to treat patients with breast cancer who have developed cancer-related complications.

Forces required to dynamize sliding screws in gamma nail and selfdynamizable internal fixator.

BACKGROUND: Single limb support phase of the gait-cycle in patients who are treated for a pertrochanteric fracture is characterized by transversal loads acting on the lag screw, tending to block its dynamization. If the simultaneous axial force overcomes transversal loads of the sliding screw, the dynamization can still occur. METHODS: Biomechanical investigation was performed for three types of dynamic implants: Gamma Nail, and two types of Selfdynamizable Internal Fixators (SIF) - SIF-7 (containing two 7 mm non-cannulated sliding screws), and SIF-10 (containing one 10 mm cannulated sliding screw). Contact surface between the stem and the sliding screws is larger in SIF implants than in Gamma Nail, as the stem of Gamma Nail is hollow. A special testing device was designed for this study to provide simultaneous application of a controlled sliding screws bending moment and a controlled transversal load on sliding screws (Qt) without using of weights. Using each of the implants, axial forces required to initiate sliding screws dynamization (Qa) were applied and measured using a tensile testing machine, for several values of sliding screws bending moment. Standard least-squares method was used to present the results through the linear regression model. RESULTS: Positive correlation between Qt and Qa was confirmed (p < 0.05). While performing higher bending moments in all the tested implants, Qa was higher than it could be provided by the body weight. It was the highest in Gamma Nail, and the lowest in SIF-10. CONCLUSIONS: A larger contact surface between a sliding screw and stem results in lower forces required to initiate dynamization of a sliding screw. Patients treated for a pertrochanteric fracture by a sliding screw internal fixation who have longer femoral neck or higher body weight could have different programme of early postoperative rehabilitation than lighter patients or patients with shorter femoral neck.

Are farmers motivated to select for heat tolerance? Linking attitudinal factors, perceived climate change impacts, and social trust to farmers' breeding desires.

This study provides an understanding of dairy farmers' willingness to include heat tolerance in breeding goals and the modulating effect of sociopsychological factors and farm profile. A survey instrument including a choice experiment was designed to specifically address the trade-off between heat tolerance and milk production level. A total of 122 farmers across cattle, goat, and sheep farms were surveyed face-to-face. The results of the experiment show that most farmers perceive that heat stress and climate change are increasingly important problems, and that farming communities should invest more in generating knowledge and resources on mitigation strategies. However, we found limited initial support for selection for heat tolerance. This attitude changed when farmers were presented with objective information on the benefits and limitations of the different breeding choices, after which most farmers supported selection for heat tolerance, but only if doing so would compromise milk production gains to a small extent. Our results show that farmers' selection choices are driven by the interactions between heat stress risk perception, attitudes toward breeding tools, social trust, the species reared, and farm production level. In general, farmers willing to support selection of heat-tolerant animals are those with positive attitudes toward genetic values and genomic information and a strong perception of climate change and heat stress impacts on farms. On the contrary, negative support for selection for heat tolerance is found among farmers with high milk production levels; high trust in farming magazines, livestock farmers' associations, and veterinarians; and low trust in environmental and animalist groups.

Does the Internet Provide Quality Information on Metoidioplasty? Using the Modified Ensuring Quality Information for Patients Tool to Evaluate Artificial Intelligence-Generated and Online Information on Metoidioplasty.

BACKGROUND: Public interest in gender affirmation surgery has surged over the last decade. This spike in interest, combined with extensive free online medical knowledge, has led many to the Internet for more information on this complicated procedure. This study aimed to evaluate the quality of online information on metoidioplasty. METHODS: Google Trends in searches on "metoidioplasty" from 2004 to present were assessed. "metoidioplasty" was searched on three popular search engines (Google, Yahoo, and Bing), and the first 100 websites from each search were extracted for inclusion (Fig. 1). Exclusion criteria included duplicates, websites requiring fees, photo libraries, and irrelevant websites. Websites were assigned a score (out of 36) using the modified Ensuring Quality Information for Patients (EQIP) instrument, which grades patient materials based on content (18), identification (6), and structure (12). ChatGPT was also queried for metoidioplasty-related information and responses were analyzed using EQIP. RESULTS: Google Trends analysis indicated relative search interest in "metoidioplasty" has more than quadrupled since 2013(Fig. 2). Of the 93 websites included, only 2 received an EQIP score greater than 27 (6%). Website scores ranged from 7 to 33, with a mean of 18.6 ± 4.8. Mean scores were highest for websites made by health departments (22.3) and lowest for those made by encyclopedias and academic institutions (16.0). Websites with the highest frequency were research articles, web portals, hospital websites, and private practice sites, which averaged scores of 18.2, 19.7, 19.0, and 17.8, respectively. Health department sites averaged the highest content points (11.25), and academic institutions averaged the lowest (5.5). The average content point across all websites was 7.9 of 18. ChatGPT scored a total score of 29: 17 content, 2 identification, and 10 structures. The artificial intelligence chatbot scored the second highest score among all included online resources. CONCLUSIONS: Despite the continued use of search engines, the quality of online information on metoidioplasty remains exceptionally poor across most website developers. This study demonstrates the need to improve these resources, especially as interest in gender-affirming surgery continues to grow. ChatGPT and other artificial intelligence chatbots may be efficient and reliable alternatives for those seeking to understand complex medical information.

Applying machine learning in the investigation of the link between the high-velocity streams of charged solar particles and precipitation-induced floods.

This study explores a possible link between solar activity and floods caused by precipitation. For this purpose, discrete blocks of data for 89 separate flood events in Europe in the period 2009-2018 were used. Solar activity parameters with a time lag of 0-11 days were used as input data of the model, while precipitation data in the 12 days preceding the flood were used as output data. The level of randomness of the input and output time series was determined by correlation analysis, while the potential causal relationship was established by applying machine learning classification predictive modeling. A total of 25 distinct machine-learning algorithms and four model ensembles were applied. It was shown that in 81% of cases, the designed model could explain the occurrence or absence of precipitation-induced floods 9 days in advance. Differential proton flux in the 0.068-0.115 MeV and integral proton flux > 2.5 MeV were found to be the most important factors for forecasting precipitation-induced floods. The study confirmed that machine learning is a valuable technique for establishing nonlinear relationships between solar activity parameters and the onset of floods induced by precipitation.

Single-cell Analysis Reveals Inter- and Intratumour Heterogeneity in Metastatic Breast Cancer.

Metastasis is the leading cause of cancer-related deaths of breast cancer patients. Some cancer cells in a tumour go through successive steps, referred to as the metastatic cascade, and give rise to metastases at a distant site. We know that the plasticity and heterogeneity of cancer cells play critical roles in metastasis but the precise underlying molecular mechanisms remain elusive. Here we aimed to identify molecular mechanisms of metastasis during colonization, one of the most important yet poorly understood steps of the cascade. We performed single-cell RNA-Seq (scRNA-Seq) on tumours and matched lung macrometastases of patient-derived xenografts of breast cancer. After correcting for confounding factors such as the cell cycle and the percentage of detected genes (PDG), we identified cells in three states in both tumours and metastases. Gene-set enrichment analysis revealed biological processes specific to proliferation and invasion in two states. Our findings suggest that these states are a balance between epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial transitions (MET) traits that results in so-called partial EMT phenotypes. Analysis of the top differentially expressed genes (DEGs) between these cell states revealed a common set of partial EMT transcription factors (TFs) controlling gene expression, including ZNF750, OVOL2, TP63, TFAP2C and HEY2. Our data suggest that the TFs related to EMT delineate different cell states in tumours and metastases. The results highlight the marked interpatient heterogeneity of breast cancer but identify common features of single cells from five models of metastatic breast cancer.

Metasurfaces integrated with a single-mode waveguide array for off-chip wavefront shaping.

Integration of metasurfaces and SOI (silicon-on-insulator) chips can leverage the advantages of both metamaterials and silicon photonics, enabling novel light shaping functionalities in planar, compact devices that are compatible with CMOS (complementary metal-oxide-semiconductor) production. To facilitate light extraction from a two-dimensional metasurface vertically into free space, the established approach is to use a wide waveguide. However, the multi-modal feature of such wide waveguides can render the device vulnerable to mode distortion. Here, we propose a different approach, where an array of narrow, single-mode waveguides is used instead of a wide, multi-mode waveguide. This approach tolerates nano-scatterers with a relatively high scattering efficiency, for example Si nanopillars that are in direct contact with the waveguides. Two example devices are designed and numerically studied as demonstrations: the first being a beam deflector that deflects light into the same direction regardless of the direction of input light, and the second being a light-focusing metalens. This work shows a straightforward approach of metasurface-SOI chip integration, which could be useful for emerging applications such as metalens arrays and neural probes that require off-chip light shaping from relatively small metasurfaces.

Evaluation of outdoor thermal comfort conditions: evidence from the Serbian major ski resort over the last 30 years.

The study aims to present reliable information about thermal conditions and their impacts on visitors to ski travel destinations. Mountain tourism areas are specific since high altitudes affect the ambient weather conditions which can affect different types of human activities. In this paper, the thermal comfort and its changes in Kopaonik Mountain, the most popular ski resort in Serbia over the last 30 years, have been evaluated. Information about thermal comfort is presented by using the Universal Thermal Climate Index (UTCI), physiologically equivalent temperature (PET), and modified physiologically equivalent temperature (mPET) in 3-h resolution for the period 1991-2020. The results indicate prevailing cold stress all year round. Days with moderate, strong, and very strong heat stress were not recorded. Strong and extreme cold stress prevailed during winter, while slight and moderate cold stress prevailed during summer. Transitional seasons were very cold, but autumn was more comfortable than spring. The occurrence of days with neutral and slightly warm/cool conditions is concentrated in the summer months. However, summer is not used enough for tourism because the choice of tourists to stay at Kopaonik is not primarily based on favorable bioclimatic conditions, but on resources for winter tourism. With global warming, the annual number of thermally favorable days has been increasing, while the number of days with extreme and strong cold stress is decreasing. Continuing this trend can significantly influence tourism in the future, and therefore, new strategies in ski resorts will be required to adapt to the changing climate.

Early dissemination seeds metastasis in breast cancer.

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation, but the mechanisms of early metastatic spread have not yet been addressed. Here, by studying metastasis in a HER2-driven mouse breast cancer model, we show that progesterone-induced signalling triggers migration of cancer cells from early lesions shortly after HER2 activation, but promotes proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by increased HER2 expression and tumour-cell density involving microRNA-mediated progesterone receptor downregulation, and was reversible. Cells from early, low-density lesions displayed more stemness features, migrated more and founded more metastases than cells from dense, advanced tumours. Notably, we found that at least 80% of metastases were derived from early disseminated cancer cells. Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination.

Gaia as Solaris: An Alternative Default Evolutionary Trajectory.

Now that we know that Earth-like planets are ubiquitous in the universe, as well as that most of them are much older than the Earth, it is justified to ask to what extent evolutionary outcomes on other such planets are similar, or indeed commensurable, to the outcomes we perceive around us. In order to assess the degree of specialty or mediocrity of our trajectory of biospheric evolution, we need to take into account recent advances in theoretical astrobiology, in particular (i) establishing the history of habitable planets' formation in the Galaxy, and (ii) understanding the crucial importance of "Gaian" feedback loops and temporal windows for the interaction of early life with its physical environment. Hereby we consider an alternative macroevolutionary pathway that may result in tight functional integration of all sub-planetary ecosystems, eventually giving rise to a true superorganism at the biospheric level. The blueprint for a possible outcome of this scenario has been masterfully provided by the great Polish novelist Stanislaw Lem in his 1961 novel Solaris. In fact, Solaris offers such a persuasive and powerful case for an "extremely strong" Gaia hypothesis that it is, arguably, high time to investigate it in a discursive astrobiological and philosophical context. In addition to novel predictions in the domain of potentially detectable biosignatures, some additional cognitive and heuristic benefits of studying such extreme cases of functional integration are briefly discussed.

Chemometric Approach to the Composition of Flavonoid Compounds and Phenolic Acids and Antioxidant Potential of Artemisia Species from Different Habitats.

Four Artemisia species from Serbia were selected for the study: A. annua L., A. absinthium L., A. vulgaris L. and A. scoparia Waldst. et Kit. because of the proven excellent action in treating certain medical conditions and diseases. A. absinthium L., A. vulgaris L., A. annua L. and A. scoparia Waldst. et Kit. collected from different habitats across Serbia (48 samples in total) were studied from the statistical aspect considering the phenolic and flavonoid contents, compositions, and antioxidant activities of methanol extracts in correlation with the soil type. The components were identified using HPLC (High Performance Liquid Chromatography), while antioxidant activities were determined by seven assays (TP (Total phenolic content), TF (Total flavonoid content), DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-based, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical cation-based, FRAP (Ferric Reducing Antioxidant Power), TRP (Total Reducing Power), and CUPRAC (Cupric Reducing Antioxidant Capacity). The results were processed using five statistical methods (PCA (Principal Component Analysis), ANOVA (Analysis of Variance), MANOVA (Multivariate analysis of variance), DA (Discriminant analysis), and AHC (Agglomerative Hierarchical Clustering)). Principal component analysis enabled very well separation of the analyzed Artemisia species based on the content of total phenolics, total flavonoids, and the values obtained from antioxidant tests, but not on the individual compounds identified and quantified by HPLC. The MANOVA analyses showed that for A. scoparia and A. annua there was a significant effect of soil type on the total phenolics, total flavonoids, and antioxidant tests. In contrast, for A. vulgaris and A. absinthium, that effect was not significant. Additional MANOVA analyses showed a significant effect of soil type on phenolic and flavonoid compounds in the case of A. vulgaris, A. annua, and A. absinthium. The overall correct classification rate of all samples of four investigated Artemisia species by the discriminant analysis was 81.25 % using the training sample and 72.92 % the cross-validation results based on TP, TF, and antioxidant tests, but a much lower based on selected compounds identified and quantified by HPLC. MANOVA analyses based on particular Artemisia species show that soil is a significant factor affecting the measurable variables.

Recent Advances in Electrochemical Sensors for Caffeine Determination.

The determination of target analytes at very low concentrations is important for various fields such as the pharmaceutical industry, environmental protection, and the food industry. Caffeine, as a natural alkaloid, is widely consumed in various beverages and medicines. Apart from the beneficial effects for which it is used, caffeine also has negative effects, and for these reasons it is very important to determine its concentration in different mediums. Among numerous analytical techniques, electrochemical methods with appropriate sensors occupy a special place since they are efficient, fast, and entail relatively easy preparation and measurements. Electrochemical sensors based on carbon materials are very common in this type of research because they are cost-effective, have a wide potential range, and possess relative electrochemical inertness and electrocatalytic activity in various redox reactions. Additionally, these types of sensors could be modified to improve their analytical performances. The data available in the literature on the development and modification of electrochemical sensors for the determination of caffeine are summarized and discussed in this review.

Indigo Carmine in a Food Dye: Spectroscopic Characterization and Determining Its Micro-Concentration through the Clock Reaction.

Indigo carmine is a commonly used industrial blue dye. To determine its concentration in a commercially available food dye composed of a mixture of indigo carmine and D-glucose, this paper characterizes it through (ATR, KBr) FTIR micro-Raman as well as UV/Vis and clock: Briggs-Rauscher (BR) oscillatory reaction methods. The indigo carmine was detected in the bulk food dye only by applying micro-Raman spectroscopy, indicating a low percentage of the indigo carmine present. This research provides an improvement in the deviations from the experimental Raman spectrum as calculated by the B97D/cc-pVTZ level of theory one, resulting in a better geometrical optimization of the indigo carmine molecule compared to data within the literature. The analytical curves used to determine indigo carmine concentrations (and quantities) in an aqueous solution of food dye were applied by means of UV/Vis and BR methods. BR yielded significantly better analytical parameters: 100 times lower LOD and LOQ compared to commonly used UV/Vis. The remarkable sensitivity of the BR reaction towards indigo carmine suggests that not only does indigo carmine react in an oscillatory reaction but also its decomposition products, meaning that the multiple oxidation reactions have an important role in the BR's indigo carmine mechanism. The novelty of this research is the investigation of indigo carmine using a clock BR reaction, opening new possibilities to determine indigo carmine in other complex samples (pharmaceutical, food, etc.).

Commercial insurance delays direct-acting antiviral treatment for hepatitis C kidney transplantation into uninfected recipients.

INTRODUCTION: The advent of direct-acting antivirals (DAAs) has created an avenue for transplantation of hepatitis C virus (HCV)-infected donors into uninfected recipients (D+/R-). The donor transmission of HCV is then countered by DAA administration during the post-operative period. However, initiation of DAA treatment is ultimately dictated by insurance companies. METHODS: A retrospective chart review of 52 D+/R- kidney recipients who underwent DAA treatment post-transplant was performed. Patients were grouped according to their prescription coverage plans, managed by either commercial or government pharmacy benefit managers (PBMs). RESULTS: Thirty-nine patients had government PBMs and 13 had commercial PBMs. Demographics were similar between the two groups. All patients developed HCV viremia, but cleared the virus after treatment with DAA. Patients with government PBMs were treated earlier compared to those with commercial PBMs (11 days vs 26 days, P = .01). Longer time to DAA initiation resulted in higher peak viral loads (ß = 0.39, R2  = .15, P = .01) and longer time to HCV viral load clearance (ß = 0.41, R2  = .17, P = .01). CONCLUSIONS: D+/R- transplantation offers patients an alternative strategy to increase access. However, treatment can be profoundly delayed by a third-party payer authorization process that may be subjecting patients to unnecessary risks and worsened outcomes.

Influence of coronavirus disease 2019 pandemic state of emergency in orthopaedic fracture surgical treatment.

PURPOSE: After the appearance of first COVID-19 cases in Serbia, state of emergency was declared on 15 March 2020 and lasted for 54 days. The aim of this report is to compare orthopaedic fracture frequencies in this period, when the walk was limited at the home mostly, with those during the same part in the previous year with regular state, thus to examine staying at home as a factor influencing the frequency of different fracture types. METHODS: There were 86 patients during the state of emergency in year 2020 and 106 patients during the same part of year 2019 with a regular state, having orthopaedic trauma surgery. Number of fractures, gender distribution, and age of patients have been compared between these periods. RESULTS: Total number of fractures decreased for about 19% during the state of emergency. There was nonsignificant difference in fracture frequency for all skeletal areas (p > 0.05), except for distal femoral fractures which occurred more often during the state of emergency (p < 0.05). Female ratio was higher during state of emergency than in regular state for femoral neck fractures. CONCLUSION: Restricted going outside the home for 54 days has the influence in total number of fractures and gender distribution in femoral neck fractures. The method of external fixation used could be assumed as a reducing factor of intraoperative virus pandemic propagation among medical staff.

Prediction of tropospheric ozone concentration using artificial neural networks at traffic and background urban locations in Novi Sad, Serbia.

In this paper, we described generation and performances of feedforward neural network models that could be used for a day ahead predictions of the daily maximum 1-h ozone concentration (1hO3) and 8-h average ozone concentration (8hO3) at one traffic and one background station in the urban area of Novi Sad, Serbia. The six meteorological variables for the day preceding the forecast and forecast day, ozone concentrations in the day preceding the forecast, the number of the day of the year, and the number of the weekday for which ozone prediction was performed were utilized as inputs. The three-layer perceptron neural network models with the best performance were chosen by testing with different numbers of neurons in the hidden layer and different activation functions. The mean bias error, mean absolute error, root mean squared error, correlation coefficient, and index of agreement or Willmott's Index for the validation data for 1hO3 forecasting were 0.005 µg m-3, 12.149 µg m-3, 15.926 µg m-3, 0.988, and 0.950, respectively, for the traffic station (Dnevnik), and - 0.565 µg m-3, 10.101 µg m-3, 12.962 µg m-3, 0.911, and 0.953, respectively, for the background station (Liman). For 8hO3 forecasting, statistical indicators were - 1.126 µg m-3, 10.614 µg m-3, 12.962 µg m-3, 0.910, and 0.948 respectively for the station Dnevnik and - 0.001 µg m-3, 8.574 µg m-3, 10.741 µg m-3, 0.936, and 0.966, respectively, for the station Liman. According to the Kolmogorov-Smirnov test, there is no significant difference between measured and predicted data. Models showed a good performance in forecasting days with the high values over a certain threshold.

Silicon erasable waveguides and directional couplers by germanium ion implantation for configurable photonic circuits.

A novel technique for realization of configurable/one-time programmable (OTP) silicon photonic circuits is presented. Once the proposed photonic circuit is programmed, its signal routing is retained without the need for additional power consumption. This technology can potentially enable a multi-purpose design of photonic chips for a range of different applications and performance requirements, as it can be programmed for each specific application after chip fabrication. Therefore, the production costs per chip can be reduced because of the increase in production volume, and rapid prototyping of new photonic circuits is enabled. Essential building blocks for the configurable circuits in the form of erasable directional couplers (DCs) were designed and fabricated, using ion implanted waveguides. We demonstrate permanent switching of optical signals between the drop port and through the port of the DCs using a localized post-fabrication laser annealing process. Proof-of-principle demonstrators in the form of generic 1×4 and 2×2 programmable switching circuits were fabricated and subsequently programmed.

Transplantation of viral-positive hepatitis C-positive kidneys into uninfected recipients offers an opportunity to increase organ access.

The advent of direct-acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus-positive donors into uninfected recipients (D+/R-). Thirty D+/R- patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12 weeks after treatment. An age-matched cohort of uninfected donor and recipient pairs (D-/R-) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R- patients was 100%. The initial median viral load was 531 copies/µL (range: 10-1 × 108 copies/µL) with a median peak viral load of 3.4 × 105 copies/µL (range: 804-1.0 × 108 copies/µL). DAAs were initiated on median POD 9 (range: 5-41 days). All 30 patients had confirmed SVR12. During a median follow-up of 10 months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R- patients as compared to the age-matched cohort (27% vs 60%; P = .01). D+/R- transplantation offers patients an alternative strategy to increase access.

The effects of glyphosate and AMPA on the mediterranean mussel Mytilus galloprovincialis and its microbiota.

Glyphosate, the most widely used herbicide worldwide, targets the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme in the shikimate pathway found in plants and some microorganisms. While the potential for glyphosate to induce a broad range of biological effects in exposed organisms has been demonstrated, the global molecular mechanisms of toxicity and potential effects in bacterial symbionts remain unclear, in particular for ecologically important marine species such as bivalve molluscs. Here, the effects of glyphosate (GLY), its degradation product aminomethylphosphonic acid (AMPA), and a mixture of both (MIX) on the mussel M. galloprovincialis were assessed in a controlled experiment. For the first time, next generation sequencing (RNA-seq and 16S rRNA amplicon sequencing) was used to evaluate such effects at the molecular level in both the host and its respective microbiota. The results suggest that the variable capacity of bacterial species to proliferate in the presence of these compounds and the impairment of host physiological homeostasis due to AMPA and GLY toxicity may cause significant perturbations to the digestive gland microbiota, as well as elicit the spread of potential opportunistic pathogens such as Vibrio spp.. The consequent host-immune system activation identified at the molecular and cellular level could be aimed at controlling changes occurring in the composition of symbiotic microbial communities. Overall, our data raise further concerns about the potential adverse effects of glyphosate and AMPA in marine species, suggesting that both the effects of direct toxicity and the ensuing changes occurring in the host-microbial community must be taken into consideration to determine the overall ecotoxicological hazard of these compounds.

Anxiety and depression in patients with vocal fold nodules, edema and polyps.

PURPOSE: To compare the prevalence and severity of depression and anxiety among patients with vocal fold (VF) nodules, polyps and edema. At the same time the aim was to analyse association between severity of distress and the level of vocal handicap as well as to identify other factors related to severity of depression and anxiety in these patients. METHODS: To all participants were given five questionnaires: (1) questionnaire on socio-demographic and some other characteristics of patient; (2) Beck's Depression Inventory (BDI); (3) State-Trait Anxiety Inventory (STAI) 1 (State Anxiety); (4) STAI 2 (Trait Anxiety); and (5) Voice Handicap Index (VHI)-10. RESULTS: A total of 205 patients were included in this study. Mild-to-severe depression, according to BDI was present in 79 (38.6%) patients. Mild-to-severe state anxiety and trait anxiety were present in 199 (97.1%) and 200 (97.6%) patients, respectively. Only 10 patients had VHI-10 score ≤ 11. Multivariate analyses showed that there were no significant differences in the level of depression and anxiety between patients with VF nodules, polyps and edema. The VHI-10 score was significantly higher in patients with VF edema in comparison with VF nodule patients (p = 0.001), as well as in comparison with VF polyp patients (p = 0.001). CONCLUSION: The present study identified a high prevalence of psychological and vocal distress among patients with vocal disorders. Severity of depression and anxiety did not differ between patients with VF nodules, polyps and edema, and it was not related to the level of vocal handicap.