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ABSTRACT The complete genome sequence of Desulfovibrio piger FI11049 was determined. The genome consists of a single circular chromosome of 2,807,531 bp encoding seven rRNA operons, 76 tRNA genes, and 2,535 coding genes.

In a previous study, lactic acid bacteria were isolated from meconium obtained from healthy neonates born by cesarean section. Such a finding suggested that term fetuses are not completely sterile, and that a mother-to-child efflux of commensal bacteria may exist. Therefore, presence of such bacteria in umbilical cord blood of healthy neonates born by elective cesarean section was investigated. The blood samples were submitted to an enrichment step and then inoculated onto agar plates. All the identified isolates belonged to the genus Enterococcus, Streptococcus, Staphylococcus, or Propionibacterium. Later, a group of pregnant mice were orally inoculated with a genetically labeled E. faecium strain previously isolated from breast milk of a healthy woman. The labeled strain could be isolated and polymerase chain reaction detected from the amniotic fluid of the inoculated animals. In contrast, it could not be detected in the samples obtained from a noninoculated control group.

We developed a semi-automated tool to assess mammographic density (MD), a phenotype risk marker for breast cancer (BC), in full-field digital images and evaluated its performance testing its reproducibility, comparing our MD estimates with those obtained by visual inspection and using Cumulus, verifying their association with factors that influence MD, and studying the association between MD measures and subsequent BC risk. Three radiologists assessed MD using DM-Scan, the new tool, on 655 processed images (craniocaudal view) obtained in two screening centers. Reproducibility was explored computing pair-wise concordance correlation coefficients (CCC). The agreement between DM-Scan estimates and visual assessment (semi-quantitative scale, 6 categories) was quantified computing weighted kappa statistics (quadratic weights). DM-Scan and Cumulus readings were compared using CCC. Variation of DM-Scan measures by age, body mass index (BMI) and other MD modifiers was tested in regression mixed models with mammographic device as a random-effect term. The association between DM-Scan measures and subsequent BC was estimated in a case–control study. All BC cases in screening attendants (2007–2010) at a center with full-field digital mammography were matched by age and screening year with healthy controls (127 pairs). DM-Scan was used to blindly assess MD in available mammograms (112 cases/119 controls). Unconditional logistic models were fitted, including age, menopausal status and BMI as confounders. DM-Scan estimates were very reliable (pairwise CCC: 0.921, 0.928 and 0.916). They showed a reasonable agreement with visual MD assessment (weighted kappa ranging 0.79-0.81). DM-Scan and Cumulus measures were highly concordant (CCC ranging 0.80-0.84), but ours tended to be higher (4%-5% on average). As expected, DM-Scan estimates varied with age, BMI, parity and family history of BC. Finally, DM-Scan measures were significantly associated with BC (p-trend=0.005). Taking MD<7% as reference, OR per categories of MD were: OR 7%-17% =1.32 (95% CI=0.59-2.99), OR 17%-28% =2.28 (95% CI=1.03-5.04) and OR >=29% =3.10 (95% CI=1.35-7.14). Our results confirm that DM-Scan is a reliable tool to assess MD in full-field digital mammograms.

Glucosinolate (GSL) hydrolysis is mediated by the enzyme myrosinase which together with specifier proteins can give rise to isothiocyanates (ITCs), thiocyanates, and nitriles (NITs) in cruciferous plants. However, little is known about the metabolism of GSLs by the human gut flora. The aim of the work was to investigate the metabolic fates of sinigrin (SNG), glucotropaeolin (GTP), gluconasturtiin (GNT), and their corresponding desulfo-GSLs (DS-GSLs). Three human gut bacterial strains, Enterococcus casseliflavus CP1, Lactobacillus agilis R16, and Escherichia coli VL8, were chosen for this study. GNT was metabolized to completion within 24 h to phenethyl ITC and phenethyl NIT (PNIT) by all bacteria, except for L. agilis R16 which produced only PNIT. At least 80 % of GTP and SNG were metabolized by all bacteria within 24 h to the corresponding ITCs and NITs. The pH of media over time gradually became acidic for both L. agilis R16 and E. coli VL8, while for E. casseliflavus CP1 the media became slightly alkaline with NIT and ITC production occurring between pH 3.0 and 7.5. ITC production peaked between 4 and 10 h in most cases and gradually declined while NIT production increased and remained relatively constant over time. The total percentage products accounted for 3–53 % of the initial GSL. NITs were produced from DS-GSLs suggesting an alternative metabolism via desulfation for the food based GSLs. The metal ion dependency for NIT production for GNT and its DS form was investigated where it was shown that Fe 2+ increased NIT production, while Mg 2+ stimulated the formation of ITC.

Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds.

Following its emergence in late 2019, the spread of SARS-CoV-2 1 , 2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail 3 – 5 . Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. Analysis of the spread of the 20E (EU1) variant of SARS-CoV-2 through Europe suggests that international travel and insufficient containment, rather than increased transmissibility, led to a resurgence of infections.

Cerebrovascular complications are frequent in pneumococcal meningitis and are associated with poor functional outcomes. Among these complications, the incidence of cerebral vasculitis (CV) has been increasingly reported, but neither its pathogenesis nor its relationship with cortisone treatment have been conclusively established. We wanted to describe cerebrospinal fluid (CSF) metalloprotease (MMP) levels, which are linked to cerebral damage and vasculitis (MMP-2, MMP-9, and the antagonist TIMP-1), and differences in microbiological serotypes or virulence factors that could be associated to the development of this complication. A prospective multicenter cohort study was performed from January 2019 to August 2022. All adult patients diagnosed with pneumococcal meningitis and for whom CSF samples from the initial lumbar puncture were available were included and followed up for six months after discharge. Streptococcus pneumoniae strains isolated from CSF or blood were assessed including whole genome sequencing and CSF levels of MMP-2, MMP-9, and TIMP-1 were measured. CV developed in three of 21 patients (14.3%). The serotypes of those who developed CV were 3, 9 N, and 35 F, with no microbiological differences with respect to the non-CV group. The CV group had higher CSF levels of MMP-9 (13.2 vs. 9.8 ng/L) and TIMP-1 (699 vs. 318 ng/L), but lower CSF levels of MMP-2 (5689 vs. 10,484 ng/L) compared with the non-CV group. Although no patients with CV died, they had worse clinical outcomes than the non-CV group. CV is a frequent complication of pneumococcal meningitis that may be associated with worse outcomes. No differences in microbiological serotypes or virulence factors were detected. Further analyses should be carried out to confirm whether CSF MMP levels may be markers of CV development.

Abstract Context Medical treatment of acromegaly is currently performed through a trial-and-error approach using first-generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. Objective Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated. Methods This was a prospective trial (21 university hospitals) comparing the effectiveness and time-to-control of 2 treatment protocols during 12 months: (A) a personalized protocol in which the first options were fgSRLs as monotherapy or in combination with pegvisomant, or pegvisomant as monotherapy depending on the short acute octreotide test (sAOT) results, tumor T2 magnetic resonance (MRI) signal or immunostaining for E-cadherin; and (B) a control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control. Results Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, P < .05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI, 1.30-4.80). Patients from the personalized arm were controlled in a shorter period of time (P = .01). Conclusion Personalized medicine is feasible using a relatively simple protocol, and it allows a higher number of patients to achieve control in a shorter period of time.

Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH3SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH3SeH. The fifteen compounds follow Lipinski’s Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G2/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase.

Amyotrophic lateral sclerosis (ALS), a devastating progressive neurodegenerative disease, has no effective treatment. Recent evidence supports a strong metabolic component in ALS pathogenesis. Indeed, metabolic abnormalities in ALS correlate to disease susceptibility and progression, raising additional therapeutic targets against ALS. Ozone (O 3 ), a natural bioactive molecule, has been shown to elicit beneficial effects to reduce metabolic disturbances and improved motor behavior in TDP-43 A315T mice. However, it is fundamental to determine the mechanism through which O 3 acts in ALS. To characterize the association between O 3 exposure and disease-associated weight loss in ALS, we assessed the mRNA and protein expression profile of molecular pathways with a main role in the regulation of the metabolic homeostasis on the hypothalamus and the brown adipose tissue (BAT) at the disease end-stage, in TDP-43 A315T mice compared to age-matched WT littermates. In addition, the impact of O 3 exposure on the faecal bacterial community diversity, by Illumina sequencing, and on the neuromuscular junctions (NMJs), by confocal imaging, were analysed. Our findings suggest the effectiveness of O 3 exposure to induce metabolic effects in the hypothalamus and BAT of TDP-43 A315T mice and could be a new complementary non-pharmacological approach for ALS therapy.