Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors ...involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota.
We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed.
This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease.
ClinicalTrials.gov NCT03885648 , 03/25/2019. Retrospectively registered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fluorometric detection of iodine by MIL-53(Al)-TDC Díaz-Ramírez, Mariana L; Vargas, Brenda; Raziel Álvarez, J ...
Dalton transactions : an international journal of inorganic chemistry,
05/2020, Letnik:
49, Številka:
2
Journal Article
Recenzirano
The fluorescent properties of MIL-53(Al)-TDC are drastically changed due to the presence of iodine, even in small quantities, as a result of an energy transfer process from the host material ...(MIL-53(Al)-TDC) to the guest molecule (I
2
). While MIL-53(Al)-TDC's emission spectrum shows a weak and broad band, after I
2
adsorption, it exhibits well-resolved and long-lasting emission lines, which could be exploited for iodine detection. Density Functional Theory periodical calculations demonstrated that in the most stable MIL-53(Al)-TDC I
2
configuration, the I
2
molecule is bonded mainly by an O-H I hydrogen bond. The QTAIM showed that other non-covalent interactions also provided stability to MIL-53(Al)-TDC I
2
. The electrostatic potential analysis indicated that the I
2
molecule adsorption occurs by a combination of specific interactions with a strong electrostatic contribution and weak interactions. These results postulate fluorescent MIL-53(Al)-TDC as an efficient I
2
detector (potentially for radioactive I
2
), using a simple fluorimetric test.
Low concentrations of I
2
induce severe changes in the luminescence of MIL-53(Al)-TDC. These results postulate fluorescent MIL-53(Al)-TDC as an efficient I
2
detector (potentially for radioactive I
2
), using a simple fluorimetric test.
Background
Opioids are used for the treatment of refractory pain, but their inappropriate use has detrimental consequences for health. Understanding the current experiences and perceptions of ...patients in a spontaneous and colloquial environment regarding the key drugs involved in the opioid crisis is of utmost significance.
Objective
The study aims to analyze Twitter content related to opioids, with objectives including characterizing users participating in these conversations, identifying prevalent topics and gauging public perception, assessing opinions on drug efficacy and tolerability, and detecting discussions related to drug dispensing, prescription, or acquisition.
Methods
In this cross-sectional study, we gathered public tweets concerning major opioids posted in English or Spanish between January 1, 2019, and December 31, 2020. A total of 256,218 tweets were collected. Approximately 27% (69,222/256,218) were excluded. Subsequently, 7000 tweets were subjected to manual analysis based on a codebook developed by the researchers. The remaining databases underwent analysis using machine learning classifiers. In the codebook, the type of user was the initial classification domain. We differentiated between patients, family members and friends, health care professionals, and institutions. Next, a distinction was made between medical and nonmedical content. If it was medical in nature, we classified it according to whether it referred to the drug’s efficacy or adverse effects. In nonmedical content tweets, we analyzed whether the content referred to management issues (eg, pharmacy dispensation, medical appointment prescriptions, commercial advertisements, or legal aspects) or the trivialization of the drug.
Results
Among the entire array of scrutinized pharmaceuticals, fentanyl emerged as the predominant subject, featuring in 27% (39,997/148,335 posts) of the tweets. Concerning user categorization, roughly 70% (101,259/148,335) were classified as patients. Nevertheless, tweets posted by health care professionals obtained the highest number of retweets (37/16,956, 0.2% of their posts received over 100 retweets). We found statistically significant differences in the distribution concerning efficacy and side effects among distinct drug categories (P<.001). Nearly 60% (84,401/148,335) of the posts were devoted to nonmedical subjects. Within this category, legal facets and recreational use surfaced as the most prevalent themes, while in the medical discourse, efficacy constituted the most frequent topic, with over 90% (45,621/48,777) of instances characterizing it as poor or null. The opioid with the greatest proportion of tweets concerning legal considerations was fentanyl. Furthermore, fentanyl was the drug most frequently offered for sale on Twitter, while methadone generated the most tweets about pharmacy delivery.
Conclusions
The opioid crisis is present on social media, where tweets discuss legal and recreational use. Opioid users are the most active participants, prioritizing medication efficacy over side effects. Surprisingly, health care professionals generate the most engagement, indicating their positive reception. Authorities must monitor web-based opioid discussions to detect illicit acquisitions and recreational use.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T ...cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes) versus extrinsic (produced by other cells) components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells). This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular regulatory core and the micro-environment. We discuss the broader use of this approach for other plastic systems and possible therapeutic interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We studied the molecular self‐assembly of commercial and pure‐saturated and pure‐unsaturated phosphatidylcholine (PtdCho) in vegetable (VO) and mineral (MO) oils. The PtdCho self‐assembly was ...monitored through rheology, differential scanning calorimtery (DSC), and polarized light microscopy. The results showed that in the presence of just the constituent water, the PtdCho self‐assembly occurred through the formation of a “liquid structure” stabilized by electrostatic interactions. The DSC measurements did not evidence the development of the “liquid structure.” However, the phase shift angle (δ) measured by rheology closely followed the PtdCho self‐assembly in both oils. The kinetics of the PtdCho self‐assembly and the crystal habit developed depended on the PtdCho solubility in the oil, the PtdCho purity, and the extent of unsaturation. Thus, the saturated PtdCho crystallized in the VO developing an organization of intertwined crystals that resulted in organogels with a true‐gel behavior (G′ of 12.2 × 105 to 16 × 105 Pa). In the MO, the saturated PtdCho crystallized in smaller microstructures developing organogels with higher G′, particularly with the commercial PtdCho (i.e., G′ of 32 × 105 Pa). With the unsaturated PtdCho, the presence of cis unsaturations favored the formation of inverted micelles in the VO and MO organogels. Thus, in contrast to the saturated PtdCho organogels, the unsaturated PtdCho organogels had lower G′ (30 × 102 to 45 × 102 Pa) with a gel‐like behavior.
In this model we use a dynamic and multistable Boolean regulatory network to provide a mechanistic explanation of the lymphopenia and dysregulation of CD4+ T cell subsets in COVID-19 and provide ...therapeutic targets. Using a previous model, the cytokine micro-environments found in mild, moderate, and severe COVID-19 with and without TGF-β and IL-10 was we simulated. It shows that as the severity of the disease increases, the number of antiviral Th1 cells decreases, while the the number of Th1-like regulatory and exhausted cells and the proportion between Th1 and Th1R cells increases. The addition of the regulatory cytokines TFG-β and IL-10 makes the Th1 attractor unstable and favors the Th17 and regulatory subsets. This is associated with the contradictory signals in the micro-environment that activate SOCS proteins that block the signaling pathways. Furthermore, it determined four possible therapeutic targets that increase the Th1 compartment in severe COVID-19: the activation of the IFN-γ pathway, or the inhibition of TGF-β or IL-10 pathways or SOCS1 protein; from these, inhibiting SOCS1 has the lowest number of predicted collateral effects. Finally, a tool is provided that allows simulations of specific cytokine environments and predictions of CD4 T cell subsets and possible interventions, as well as associated secondary effects.
The proximal tubule is a target of subchronic exposure to fluoride (F) in the kidney. Early markers are used to classify kidney damage, stage, and prognosis. MicroRNAs (miRNAs) are small sequences of ...non-coding single-stranded RNA that regulate gene expression and play an essential role in developing many pathologies, including renal diseases. This study aimed to evaluate the expression of Cytokine-Chemokine molecules (IL-1α/1β/4/6/10, INF-γ, MIP-1α, MCP-1, RANTES, and TGF β1/2/3) and inflammation-related miRNAs to evidence the possible renal mechanisms involved in subchronic exposure to F. Total protein and miRNAs were obtained from the renal cortex of male Wistar rats exposed to 0, 15 and 50 mg NaF/L through drinking water during 40 and 80 days. In addition, cytokines-chemokines were analyzed by multiplexing assay, and a panel of 77 sequences of inflammatory-related miRNAs was analyzed by qPCR. The results show that cytokines-chemokines expression was concentration- and time-dependent with F, where the 50 mg NaF/L were the main altered groups. The miRNAs expression resulted in statistically significant differences in thirty-four miRNAs in the 50 mg NaF/L groups at 40 and 80 days.
Furthermore, a molecular interaction network analysis was performed. The relevant pathways modified by subchronic exposure to fluoride were related to extracellular matrix-receptor interaction, Mucin type O-glycan biosynthesis, Gap junction, and miRNAs involved with renal cell carcinoma. Thus, F-induced cytokines-chemokines suggest subchronic inflammation; detecting miRNAs related to cancer and proliferation indicates a transition from renal epithelium to pathologic tissue after fluoride exposure.
•Fluoride altered cytokine-chemokines in the kidney.•F modified the tissular miRNAs profile related to renal inflammation.•Renal EMT and cancer pathways were induced after exposure to fluoride.
The two-step model for plant root microbiomes considers soil as the primary microbial source. Active selection of the plant’s bacterial inhabitants results in a biodiversity decrease toward roots. We ...collected sixteen samples of
in situ
ruderal plant roots and their soils and used these soils as the main microbial input for single genotype tomatoes grown in a greenhouse. Our main goal was to test the soil influence in the structuring of rhizosphere microbiomes, minimizing environmental variability, while testing multiple plant species. We massively sequenced the 16S rRNA and shotgun metagenomes of the soils,
in situ
plants, and tomato roots. We identified a total of 271,940 bacterial operational taxonomic units (OTUs) within the soils, rhizosphere and endospheric microbiomes. We annotated by homology a total of 411,432 (13.07%) of the metagenome predicted proteins. Tomato roots did follow the two-step model with lower α-diversity than soil, while ruderal plants did not. Surprisingly, ruderal plants are probably working as a microenvironmental oasis providing moisture and plant-derived nutrients, supporting larger α-diversity. Ruderal plants and their soils are closer according to their microbiome community composition than tomato and its soil, based on OTUs and protein comparisons. We expected that tomato β-diversity clustered together with their soil, if it is the main rhizosphere microbiome structuring factor. However, tomato microbiome β-diversity was associated with plant genotype in most samples (81.2%), also supported by a larger set of enriched proteins in tomato rhizosphere than soil or ruderals. The most abundant bacteria found in soils was the Actinobacteria
Solirubrobacter soli
, ruderals were dominated by the Proteobacteria
Sphingomonas
sp. URGHD0057, and tomato mainly by the Bacteroidetes
Ohtaekwangia koreensis
,
Flavobacterium terrae, Niastella vici
, and
Chryseolinea serpens.
We calculated a metagenomic tomato root core of 51 bacterial genera and 2,762 proteins, which could be the basis for microbiome-oriented plant breeding programs. We attributed a larger diversity in ruderal plants roots exudates as an effect of the moisture and nutrient acting as a microbial harbor. The tomato and ruderal metagenomic differences are probably due to plant domestication trade-offs, impacting plant-bacteria interactions.
BACKGROUND:In the treatment for severe acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19), the World Health Organization (WHO) recommends prone positioning (PP) ...during mechanical ventilation for periods of 12–16 h/d to potentially improve oxygenation and survival. In this prospective observational study, we evaluated the ability of long PP sessions to improve oxygenation in awake intensive care unit (ICU) patients with moderate or severe ARDS due to COVID-19.
METHODS:The study was approved by the ethics committee of Galicia (code No. 2020-188), and all patients provided informed consent. In this case series, awake patients with moderate or severe ARDS by COVID-19 admitted to the ICU at University Hospital of Santiago from March 21 to April 5, 2020 were prospectively analyzed. Patients were instructed to remain in PP as long as possible until the patient felt too tired to maintain that position. Light sedation was administered with dexmedetomidine. The following information was collectednumber and duration of PP sessions; tissue O2 saturation (StO2) and blood gases before, during, and following a PP session; need of mechanical ventilation; duration of ICU admission; and ICU outcome. Linear mixed-effects models (LMM) were fit to estimate changes from baseline with a random effect for patient.
RESULTS:Seven patients with moderate or severe ARDS by COVID-19 were included. All patients received at least 1 PP session. A total of 16 PP sessions were performed in the 7 patients during the period study. The median duration of PP sessions was 10 hours. Dexmedetomidine was used in all PP sessions. Oxygenation increased in all 16 sessions performed in the 7 patients. The ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FIO2) significantly increased during PP (change from baseline 110 with 97.5% confidence interval CI, 19-202) and, after PP, albeit not significantly (change from baseline 38 with 97.5% CI, −9.2 to 85) compared with previous supine position. Similarly, tissue oxygenation underwent a small improvement during PP (change from baseline 2.6% with 97.5% CI, 0.69-4.6) without significant changes after PP. Two patients required intubation. All patients were discharged from the ICU.
CONCLUSIONS:We found that PP improved oxygenation in ICU patients with COVID-19 and moderate or severe ARDS. PP was relatively well tolerated in our patients and may be a simple strategy to improve oxygenation trying to reduce the number of patients in mechanical ventilation and the length of stay in the ICU, especially in COVID-19 pandemic.
The partial functionalisation of MIL-101(Cr) with fluorine was successfully achieved, for the first time, with 2,3,5,6-tetrafluoro-1,4-benzenedicarboxylate (BDC-4F) affording MIL-101(Cr)-4F(1%). As a ...result of the functionalisation the acidity of the metal centres for MIL-101(Cr)-4F(1%) was enhanced, which was measured by cyclic voltammetry. The resulting adsorption properties of the new material were explored and compared to those of MIL-101(Cr). H
2
O sorption experiments demonstrated an augmented hydrophobicity of the material due to the incorporation of fluorine atoms. CO
2
adsorption experiments exhibited an augmented CO
2
interaction energy (Δ
H
) for MIL-101(Cr)-4F(1%). The diffusion time constant
for CO
2
showed a higher CO
2
mobility inside the pores of MIL-101(Cr) than in MIL-101(Cr)-4F(1%), which was also associated with a higher selectivity (
α
) of MIL-101(Cr)-4F(1%) towards CO
2
. O
2
sorption isotherms of MIL-101(Cr)-4F(1%), at a high pressure (up to 90 bar), demonstrated O
2
uptakes among the highest values reported for a MOF material. H
2
adsorption isotherms exhibited, at low pressures, higher H
2
uptakes for the fluorine functionalised material. This was attributed to dipolar interactions of H
2
molecules with the fluorine atoms and corroborated by the calculation of Δ
H
for H
2
.
129
Xe NMR experiments were used to investigate the atypical pore-surface electron density of MIL-101(Cr)-4F(1%), demonstrating a huge effect of the polarising power of the fluorine atoms on the highly polarisable Xe atoms. Finally, the capture of I
2
and H
2
S on MIL-101(Cr)-4F(1%) showed considerably higher values in comparison to MIL-101(Cr). This was attributed to the high dipolarity and polarisability of the fluorinated pores.
Partial fluorine functionalisation of MIL-101(Cr) was successfully achieved.
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