Introduction
Air pollution is a current major health issue. The burden of airborne pollutants and aeroallergen levels varies throughout the year, as well as their interaction and consequences. ...Prenatal exposure during pregnancy has been associated with adverse perinatal outcomes. The aim of this study was to evaluate the impact of air pollutants on perinatal outcomes in patients with or without respiratory allergy.
Material and methods
Nested case–control retrospective study on 3006 pregnant women. Correlations between concentrations of common pollutants in each trimester of pregnancy and on average during the whole pregnancy and both gestational age at delivery and birthweight were studied. Pearson's correlation coefficient and binary logistic regression were used.
Results
In general, pollutants correlated more strongly with birthweight than with gestational age at delivery. Nine‐month NO2, SO2, CO, and benzene, and second‐trimester CO negatively correlated with birthweight, whereas only first‐trimester NO2 showed a very mild correlation with gestational age at delivery. Negative correlations between pollutants and birthweight were much stronger in the respiratory allergy group (n = 43; 1.4%) than in the non‐allergic group. After adjustments, the most significant predictive pollutant of birthweight was SO2 in both groups. The best predictive model was much stronger in the allergic group for third‐trimester SO2 (R2 = 0.12, p = 0.02) than in the non‐allergic group for total SO2 (R2 = 0.002, p = 0.02). For each unit that SO2 increased, birthweight reduced by 3.22% vs. 1.28% in each group, respectively.
Conclusions
Air pollutant concentrations, especially SO2, negatively influenced birthweight. The impact of this association was much stronger and more relevant in the group of women with respiratory allergies.
Exposure to air pollutants, especially SO2, negatively influenced birthweight. These associations were much stronger and relevant in the respiratory allergy group, although other inflammatory mechanisms cannot be ruled out.
Breast cancer is a complex and heterogeneous disease with a high mortality rate due to non-specific cytotoxicity, low intratumoral accumulation and drug resistance associated with the ineffectiveness ...of chemotherapy. In recent years, all efforts have been focused on finding new markers and therapeutic targets, protein kinase MNK1b being a promising candidate. Recently, an aptamer known as apMNK2F showed a highly specific interaction with this protein kinase, leading to a significant reduction in tumour cell proliferation, migration and colony formation. However, as aptamers are unable to penetrate the cell membrane and reach the target, these small biomolecules need to be conjugated to suitable vectors that can transport and protect them inside the cells. In this work, covalent conjugation between biocompatible and non-harmful nanoemulsions of vitamin E and sphingomyelin and the aptamer was performed to facilitate intracellular delivery of the therapeutic aptamer apMNK2F. All strategies employed were based on 2-step bioconjugation and optimized to get the simplest and most reproducible vehicle with the highest association efficiency (about 70% in all cases). The ability of the nanosystems to successfully deliver the conjugated therapeutic aptamer was demonstrated and compared to other commercial transfection agents such as Lipofectamine 2000, leading to an effective decrease of breast cancer cell proliferation in the MDA-MB-231 cell line. The proliferation inhibition of the aptamer nanoconjugates compared to the non-conjugated aptamer provides evidence that the antitumoral capacity derived from kinase interaction is improved in a dose-dependent manner. Furthermore, various experiments including cell migration and colony formation assays, along with apoptosis induction experiments, emphasize the significant antitumoral potential. Overall, the obtained results indicate that the developed formulation could be a promising therapy for the treatment of breast cancer.
Food addiction is linked to obesity and eating disorders and is characterized by a loss of behavioral control and compulsive food intake. Here, using a food addiction mouse model, we report that the ...lack of cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents the development of food addiction-like behavior, which is associated with enhanced synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc). In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking. Transcriptomic analysis and genetic manipulation identified that increased dopamine D2 receptor expression in the mPFC-NAc pathway promotes the addiction-like phenotype. Our study unravels a new neurobiological mechanism underlying resilience and vulnerability to the development of food addiction, which could pave the way towards novel and efficient interventions for this disorder.
Purpose
Patients suffering from recurrent and residual grade 2 (WHO) meningiomas after subtotal excision should be considered as high-risk groups with an uncertain prognosis. Adjuvant radiotherapy ...seems to be the best approach to reduce disease progression. The primary aim of this phase II explorative, monocentric, single arm study was to evaluate the safety of adjuvant multisession radiosurgery (mRS) in this group of patients; the efficacy in terms of tumour local control was the secondary endpoint.
Methods
Patients recruited from April 2017 to May 2019 were over 18 years old, had a histologically-documented intracranial recurrent or residual Grade 2 meningioma (WHO 2016) and a KPS > 70. Patients with NF2, concomitant neoplasm or pregnancy were excluded. Descriptive statistics were provided for categorical variables. Progression free survival (PFS) was modelled using the Kaplan–Meier method.
Results
Twenty-four patients were enrolled. All 24 patients underwent mRS: twenty-two patients received 28 Gy in 4 fractions, 2 patients received 24 Gy in 4 Treatment related adverse events (CTCAE 4.3) were limited to grade 2 in 1 patient (4.1%). At a median follow-up of 28 months, 8 patients (33.3%) had disease progression, either out-of-field or infield, compared with the planning target volume. Considering both infield and out-of-field progressions, 3-year PFS was 47% (95% confidence interval, CI, 22–69%); considering only the infield ones, 3-year PFS was 86% (95% CI 55–96%), and local control at last follow-up was 92%.
Conclusion
mRS provides good local control of the tumour volume (TV) and is associated with a low rate of toxicity. These results call for further investigation to confirm favourable outcomes in patients with high-risk meningioma.
Trial information
NCT05081908, October 18, 2021, retrospectively registered.
The genus Pestivirus, family Flaviviridae, includes four historically accepted species, i.e., bovine viral diarrhea virus (BVDV)-1 and -2, classical swine fever virus (CSFV), and border disease virus ...(BDV). A large number of new pestivirus species were identified in recent years. A common feature of most members is the presence of two unique proteins, Npro and Erns, that pestiviruses evolved to regulate the host’s innate immune response. In addition to its function as a structural envelope glycoprotein, Erns is also released in the extracellular space, where it is endocytosed by neighboring cells. As an endoribonuclease, Erns is able to cleave viral ss- and dsRNAs, thus preventing the stimulation of the host’s interferon (IFN) response. Here, we characterize the basic features of soluble Erns of a large variety of classified and unassigned pestiviruses that have not yet been described. Its ability to form homodimers, its RNase activity, and the ability to inhibit dsRNA-induced IFN synthesis were investigated. Overall, we found large differences between the various Erns proteins that cannot be predicted solely based on their primary amino acid sequences, and that might be the consequence of different virus-host co-evolution histories. This provides valuable information to delineate the structure-function relationship of pestiviral endoribonucleases.
The dramatic spread of SARS-CoV-2 infections calls for reliable, inexpensive tools to quickly identify patients with a poor prognosis. In this study, acute respiratory distress syndrome (ARDS) was ...assessed within 72 h after admission of each of 153 consecutive, SARS-CoV-2 infected, adult patients to either of two hospitals in Tenerife, Spain, using suitable routine laboratory tests for lymphocyte counts, as well as ferritin, lactate dehydrogenase (LDH), and C-reactive protein levels. Results were correlated with the patients' respiratory function, defined through their pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2) ratio.
Within 72 h from admission, criteria matched ARDS (SpO2/FiO2 < 235) in 13.1% of cases. We found a significant, negative correlation between SpO2/FiO2 ratios and D-dimer, ferritin, and LDH levels (- 0.31, - 0.32, and - 0.41; p = 0.004, 0.004, and < 0.0001, respectively). In patients with ARDS, the mean LDH was 373 U/L (CI
: 300.6-445.3), but only 298 U/L (CI
: 274.7-323.1) when they did not develop the syndrome (p = 0.015). None of the additionally evaluated biomarkers correlated with the SpO2/FiO2 ratios. Serum LDH levels in patients hospitalised for COVID-19 correlate with ARDS, as defined by their SpO2/FiO2 ratio, and might help to predict said complication.
Yeasts of the
species complex are widespread in nature and can be isolated from a variety of sources, from the environment to arthropods to hospital patients. To date, the species complex comprises ...the thoroughly studied and versatile
, the hard to distinguish
, and
Here we report the whole genome sequencing and
assembly of four
isolates, identified with the most recent molecular techniques, derived from four Diptera species. The four novel assemblies present reduced fragmentation and comparable metrics (genome size, gene content) to the available genomes belonging to the species complex. We performed a phylogenomic analysis comprising all known members of the species complex, to investigate evolutionary relationships within this clade. Our results show a compact phylogenetic structure for the complex and indicate the presence of a sizable core set of genes. Furthermore,
, despite a broad literature on the difficulties of discerning it from
, seems to be more closely related to
Finally, we believe that there is evidence for considering these four genomes to be the first published for the species
Raw reads and assembled contigs have been made public to further the study of these organisms.
In order to explore the potential of helical Tomotherapy in the treatment of head and neck cancers (HNC), a planning study comparing our routinely delivered IMRT technique (dynamic MLC Varian 600CD ...Linac, inversely optimised by the Helios/Eclipse system) against two different Tomotherapy planning approaches was performed.
In the first Tomotherapy plan (TOMO-a), we merely applied the same constraints used for the IMRT-Linac technique; in the second one (TOMO-b), we tried to stress the sparing of parotids and mandible while keeping PTV coverage and spinal cord
D
max similar to their values in the TOMO-a plan. Five patients with locally advanced oropharinx (
n=3), hypopharinx (
n=1) and larynx (
n=1) cancer were considered. For each patient, CTV1 including neck nodes and the tumour was defined and was expanded with a margin of 0.5
cm (PTV1); then, CTV2 including high risk nodes and CTV3 including only T were defined and the corresponding PTV2/PTV3 were defined by a 0.5
cm expansion. IMRT and Tomotherapy planning were optimised to deliver 54
Gy in 30 fractions on PTV1 and 16.2
Gy in 9 fractions on PTV3; in the case a PTV2 was defined, 15
Gy were concomitantly delivered while delivering 16.2
Gy on PTV3. Separated plans for the two phases (Phase 1: first 30 fractions; Phase 2: last 9 fractions) were compared in terms of dose–volume histograms (DVH) and dose statistics on PTVs and OARs.
When considering Phase 1, Tomotherapy improved the homogeneity of the dose distribution within PTV1 while delivering the same prescribed dose (assessed to be the median dose to PTV): the fraction of PTV1 receiving more than 95% of the prescribed dose (V95%) increased from 90% (IMRT) to 96–97% for Tomotherapy plans.
D
max within PTV1 decreased from 60.3
Gy (IMRT) to 57.4
Gy (TOMO-a) and 58.7
Gy (TOMO-b). Spinal cord
D
max decreased from 31.6
Gy (IMRT) to 26.5
Gy (TOMO-a) and 24.6
Gy (TOMO-b). No attempts to further reduce spinal cord
D
max were done. Mean dose to the parotids decreased from 26.1
Gy (IMRT) to 25.1
Gy (TOMO-a) and 20.8
Gy (TOMO-b). Mandible was significantly better spared with Tomotherapy: mean dose decreased from 34.9
Gy (IMRT) to 34.0
Gy (TOMO-a) and 30.7
Gy (TOMO-b).When considering phase 2, the average gains (TOMO-b vs IMRT) were more modest and depended on the location of PTV2/PTV3.
Preliminary findings obtained in a sequential approach for HNC suggest that Tomotherapy has the potential to significantly improve the therapeutic ratio with respect to a conventional IMRT delivery method.
VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of ...synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved residues within the C terminus of the VAMP2 SNARE motif. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene in human brain development and function.
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