Ligilactobacillus salivarius V4II-90 eradicates Group B Streptococcus colonisation during pregnancy: a randomised, double-blind, placebo-controlled trial.

Group B Streptococcus (GBS) is the leading cause of bacterial neonatal sepsis. This study aimed to confirm the effect of Ligilactobacillus salivarius V4II-90 on GBS colonisation during pregnancy. A randomised, multicentre, double-blind, placebo-controlled, parallel-group study was conducted in seven hospitals in Madrid, Spain. The sample was broken down into two groups with 20 participants each (n = 40) in order to show reduced GBS colonisation frequency in the probiotic versus the placebo group. Pregnant participants positive for vaginal-rectal colonisation before or during the 13th week of gestation were randomly assigned to either the placebo or the probiotic group. The probiotic, L. salivarius V4II-90 at 1 × 109 cfu/day was administered for 12 weeks, starting at week 21-23 of gestation. The primary outcome was the percentage of participants with vaginal and/or rectal GBS colonisation at the end of the intervention period (35 weeks of gestation). Secondary outcomes were changes in the microbial composition of vaginal and rectal exudates; premature delivery; premature rupture of membranes; intrapartum antibiotics; new-borns with early or late-onset GBS sepsis; adverse events (AEs); and GBS test results performed at the hospital at week 35 of gestation. Of the 481 participants included, 44 were vaginal-rectal colonised with GBS and randomised. 43 completed the study (20 in the probiotic group and 23 in the placebo group). After intervention, GBS was eradicated in six participants (27%) from the placebo group and in twelve participants (63%) from the probiotic group ( P = 0.030). None of the 185 AEs reported were identified as possibly, probably, or definitely related to the investigational product. In conclusion, oral administration of L. salivarius V4II-90 is a safe and successful strategy to significantly decrease the rates of GBS colonisation at the end of pregnancy and, therefore, to reduce the exposure of subjects and their infants to intrapartum antibiotic prophylaxis. Trial registered at ClinicalTrials.gov: number NCT03669094.

Incidence of venous thromboembolic events in cancer patients receiving immunotherapy: a single-institution experience.

BACKGROUND: Cancer and cancer therapies have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in cancer patients receiving immunotherapy and ascertain its prognostic utility. MATERIALS AND METHODS: We conducted a single-institution retrospective study, including all cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). RESULTS: We selected 229 patients. VTE occurred in 16 of 229 patients (7%). VTE occurred more frequently in patients with lung cancer followed by melanoma. Female sex and melanoma were independently associated with an increased risk of VTE. 12 of 16 VTE (75%) were symptomatic. Progressive disease to immunotherapy [HR 31.60 (95% CI 11.44-87.22), p = 0.00], lung cancer [HR 2.55 (95% CI 1.34-4.86), p = 0.00] and melanoma [HR 2.42 (1.20-4.86), p = 0.01] were independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS [HR 1.33 (95% CI 0.63-2.80), p = 0.44]. CONCLUSIONS: The incidence of VTE in cancer patients receiving immunotherapy in our study appeared to be similar to the incidence previously reported in other series of cancer patients treated with systemic therapies. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions.

Prognostic value of neutrophil-to-lymphocyte ratio in advanced cancer patients receiving immunotherapy.

BACKGROUND: The prognostic value of neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in cancer patients. However, the performance of NLR as an early marker of efficacy of immune checkpoint inhibitors (ICI) is still understudied. We studied the utility of NLR at baseline (bNLR), before the second dose of immunotherapy (NLR2) and the NLR trend for predicting efficacy outcomes. METHODS: We included all patients with advanced cancer treated with ICI from June 2013 to April 2019 at La Paz University Hospital, Madrid (Spain). We examined bNLR, NLR2 and NLR trend and explored the association with progression-free survival (PFS) at 6 months, median PFS and overall survival (OS). RESULTS: We included 211 patients. PFS and OS were significantly longer in the low bNLR group than in the high bNLR group [HR 0.71 (95% CI 0.60-0.84) and HR: 0.66 (95% CI 0.55-0.79), respectively]. Regarding NLR2, patients with low NLR2 had significantly longer PFS and OS than patients with high NLR2 [HR 0.67 (95% CI 0.57-0.79) and HR: 0.60 (95% CI 0.50-0.72), respectively]. Finally, for NLR trend, PFS and OS for patients with NLR trend < 1 were significantly longer than those patients with NLR trend ≥ 1 [HR 0.59 (95% CI 0.43-0.82) and HR 0.63 (95% CI 0.44-0.90), respectively]. At the multivariate analysis for PFS and OS, bNLR, NLR2 and NLR trend were all independent prognostic factors for PFS and OS. CONCLUSIONS: bNLR, NLR2 and NLR trends are independent prognostic factors for survival in patients on immunotherapy. The dynamics of NLR in patients on immunotherapy is a promising marker that needs further investigation.

Structural origin of the enhanced ionic conductivity upon Nb doping in Sr11Mo4O23 defective double perovskite.

We report a substantial enhancement of the oxide-ion conductivity in Sr11Mo4O23 achieved by Nb doping the Mo sites. This series responds to the formula: Sr11Mo4-xNbxO23-δ (with x = 0.0, 0.5 and 1.0). The original structure can be related to the conventional double perovskite; however, it presents a broken corner sharing connectivity of the octahedral framework, hence leading to a complex and highly defective network. The samples were prepared via citrate precursor method, followed by thermal treatments at 1300 °C for 12 hours in air. The crystal structures were refined from X-ray and neutron powder diffraction (NPD) data. A phase transition from tetragonal to cubic symmetry is identified in a temperature-dependent NPD study, driven by an oxygen delocalization effect. The ionic conductivity measured by impedance spectroscopy is enhanced upon Nb-doping; the x = 1 doped phase exhibits a threefold increase compared to the pristine Sr11Mo4O23 oxide, with conductivity values of 7.6 × 10-3 and 2.7 × 10-2 S·cm-1 at 650 and 800 °C, which are even greater than for YSZ in the 650-800 °C temperature range, and close to those reported for other state-of-the art solid-oxide electrolytes.

TLR2 and TLR4 expression after kidney ischemia and reperfusion injury in mice treated with FTY720.

Ischemia and reperfusion injury (IR) is an antigen independent inflammatory process that causes tissue damage. After IR, kidneys up-regulate leukocyte adhesion molecules and toll-like receptors (TLRs). Moreover, injured kidneys can also secrete factors (i.e. heat shock protein) which bind to TLRs and trigger intracellular events culminating with the increase in the gene expression of inflammatory cytokines. FTY720 is an immunomodulatory compound and protects at least in part kidneys submitted to IR. The mechanisms associated with FTY720's beneficial effects on kidneys after IR remain elusive. We investigated whether FTY720 administration in mice submitted to kidney IR is associated with modulation of TLR2 and TLR4 expression. C57BL/6 mice submitted to 30min of renal pedicles clamp were evaluated for serum parameters (creatinine, urea and nitric oxide), kidney histology, spleen and kidney infiltrating cells expression of TLR2 and TLR4, resident kidney cells expression of TLR2 and TLR4 and IL-6 protein expression in kidney. FTY720-treated mice presented decrease in serum creatinine, urea and nitric oxide, diminished expression of TLR2 and TLR4 both in spleen and kidney infiltrating cells, and reduced kidney IL-6 protein expression in comparison with IR non-treated mice. However, acute tubular necrosis was present both in IR non-treated and IR+FTY720-treated groups. Also, FTY720 did not prevent TLR2 and TLR4 expression in kidney resident cells. In conclusion, FTY720 can promote kidney function recovery after IR by reducing the inflammatory process. Further studies are needed in order to establish whether TLR2 and TLR4 down regulation should be therapeutically addressed as protective targets of renal function and structure after IR.

Effect of the Pb(2+) lone electron pair in the structure and properties of the double perovskites Pb2Sc(Ti0.5Te0.5)O6 and Pb2Sc(Sc0.33Te0.66)O6: relaxor state due to intrinsic partial disorder.

We describe the preparation, the crystal structure refined from neutron powder diffraction (NPD) data, and study of the permittivity of two related double perovskites, Pb2Sc(Ti0.5Te0.5)O6 and Pb2Sc(Sc0.33Te0.66)O6. These compounds were synthesized by standard ceramic procedures; Rietveld refinements from room temperature NPD data show that the crystal structures are well defined in a cubic unit cell (space group Fm3m) with double parameter, a = 2a0 ≈ 8 Å. They contain a completely ordered array of ScO6 and (B,Te)O6 (B = Sc, Ti) octahedra sharing corners; the PbO12 polyhedra present an off-center displacement of the lead atoms along the [1 1 1] directions, due to the electrostatic repulsion between the Pb(2+) 6 s electron lone-pair and the Pb-O bonds of the cuboctahedron. Both compounds present a low temperature, highly dispersive maximum in permittivity, the position of which follows the Vogel-Fulcher relation with freezing temperatures of 156 and 99 K for Pb2Sc(Ti0.5Te0.5)O6 and Pb2Sc(Sc0.33Te0.66)O6, respectively, exhibiting a typical phenomenology of relaxors.

Three-dimensional ultrasound in the diagnosis of Müllerian duct anomalies and concordance with magnetic resonance imaging.

OBJECTIVES: To demonstrate the value of three-dimensional (3D) ultrasound in the diagnosis of uterine malformations and its concordance with magnetic resonance imaging (MRI). METHODS: This study included 286 women diagnosed with uterine malformation by 3D ultrasound, having been referred to our clinics on suspicion of uterine malformation following clinical and/or conventional two-dimensional ultrasound examination. With the exception of three with intact hymen, patients underwent both bimanual examination and speculoscopy before and/or after sonography. MRI was performed in 65 cases. We analyzed the diagnostic concordance between the techniques in the study of uterine malformations. RESULTS: Using 3D ultrasound we diagnosed: one case with uterine agenesis; 10 with unicornuate uterus, four of which also underwent MRI; six with didelphic uterus, one of which had MRI; 45 with bicornuate uterus, 12 of which had MRI; 125 with septate uterus (18 with two cervices), 42 of which had MRI (six with two cervices); 96 with arcuate uterus, three of which had MRI; and three with diethylstilbestrol (DES) iatrogenic uterine malformations, all of which had MRI. Among the 65 which underwent MRI, the diagnosis was: four cases with unicornuate uterus, 10 with bicornuate uterus (two with two cervices), 45 with septate uterus (five with two cervices), three with arcuate uterus and three with DES-related uterine malformations. The concordance between 3D ultrasound and MRI was very good (kappa index, 0.880 (95% CI, 0.769-0.993)). Discrepancies in diagnosis between the two techniques occurred in four cases. There was very good concordance in the diagnosis of associated findings (kappa index, 0.878 (95% CI, 0.775-0.980)), this analysis identifying differences in two cases. CONCLUSIONS: There is a high degree of concordance between 3D ultrasound and MRI in the diagnosis of uterine malformations, the relationship between cavity and fundus being visualized equally well with both techniques. 3D ultrasound should be complemented by careful gynecological exploration in order to identify any alterations in the cervix.

Retronasal triangle: a sonographic landmark for the screening of cleft palate in the first trimester.

OBJECTIVES: To describe a new first-trimester sonographic landmark, the retronasal triangle, which may be useful in the early screening for cleft palate. METHODS: The retronasal triangle, i.e. the three echogenic lines formed by the two frontal processes of the maxilla and the palate visualized in the coronal view of the fetal face posterior to the nose, was evaluated prospectively in 100 consecutive normal fetuses at the time of routine first-trimester sonographic screening at 11 + 0 to 13 + 6 weeks' gestation. In a separate study of five fetuses confirmed postnatally as having a cleft palate, ultrasound images, including multiplanar three-dimensional views, were analyzed retrospectively to review the retronasal triangle. RESULTS: None of the fetuses evaluated prospectively was affected by cleft lip and palate. During their first-trimester scan, the retronasal triangle could not be identified in only two fetuses. Reasons for suboptimal visualization of this area included early gestational age at scanning (11 weeks) and persistent posterior position of the fetal face. Of the five cases with postnatal diagnosis of cleft palate, an abnormal configuration of the retronasal triangle was documented in all cases on analysis of digitally stored three-dimensional volumes. CONCLUSIONS: This study demonstrates the feasibility of incorporating evaluation of the retronasal triangle into the routine evaluation of the fetal anatomy at 11 + 0 to 13 + 6 weeks' gestation. Because fetuses with cleft palate have an abnormal configuration of the retronasal triangle, focused examination of the midface, looking for this area at the time of the nuchal translucency scan, may facilitate the early detection of cleft palate in the first trimester.

Three-dimensional ultrasound diagnosis of cleft palate: 'reverse face', 'flipped face' or 'oblique face'--which method is best?

OBJECTIVES: To compare the performance of three sonographic techniques, the 'reverse-face', 'flipped-face' and 'oblique-face' methods, for visualizing the hard and soft palate in diagnosing cleft lip and palate (CLP). METHODS: A total of 60 fetuses (10 with CLP) with a gestational age ranging from 20 to 33 weeks were examined. We compared visualization of the secondary palate with the previously described reverse-face and flipped-face methods (the latter modified by us) and the oblique-face method developed by us using Oblique View imaging technology. RESULTS: Among the 10 fetuses with CLP the defect involved the lip, alveolus and secondary palate in seven, and the primary palate only in the remaining three. The upper lip and alveolar ridge were well visualized in all cases with all three methods. Involvement of the hard palate was diagnosed correctly in 71% (5/7) of the cases using the reverse-face view, in 86% (6/7) with the flipped-face view, and in 100% (7/7) with the oblique-face view; the hard palate was correctly found to be intact in 78%, 84% and 86%, respectively, of the 50 normal fetuses examined with each view. Involvement of the soft palate was diagnosed correctly in only one of the seven fetuses with defects of the secondary palate in flipped-face and oblique-face views, and was correctly considered intact in only 16% of normal fetuses in flipped-face view and in 26% in oblique-face images. CONCLUSIONS: Accurate visualization of the soft palate requires an excellent initially acquired volume, fluid between the fetal tongue and palate, and curving of the plane to follow the structure of the palate. The oblique-face or flipped-face views make it possible to visualize the soft palate well in selected cases.

Crystal and magnetic structure of the double perovskite Sr2CoUO6: a neutron diffraction study.

Sr2CoUO6 double perovskite has been prepared as a polycrystalline powder by solid-state reaction, in air. This material has been studied by X-ray, neutron powder diffraction (NPD) and magnetic measurements. At room temperature, the crystal structure is monoclinic, space group P2(1)/n, Z= 2, with a= 5.7916(2), b= 5.8034(2), c= 8.1790(3) A, beta= 90.1455(6)degrees. The perovskite lattice consists of a completely ordered array of CoO6 and UO6 octahedra, which exhibit an average tilting angle phi= 11.4 degrees. Magnetic and neutron diffraction measurements indicate an antiferromagnetic ordering below TN = 10 K. The low-temperature magnetic structure was determined by NPD, selected among the possible magnetic solutions compatible with the P2(1)/n space group, according with the group theory representation. The propagation vector is k= 0. A canted antiferromagnetic structure is observed below TN = 10 K, which remains stable down to 3 K, with an ordered magnetic moment of 2.44(7)mu(B) for Co2+ cations. The magnetic moment calculated from the Curie-Weiss law at high temperatures (5.22 mu(B)/f.u.) indicates that the orbital contribution is unquenched at high temperatures, which is consistent with high-spin Co2+((4)T(1g) ground state) in a quasi-regular octahedral environment. Magnetic and structural features are consistent with an electronic configuration Co2+[3d(7)]-U6+[Rn].

Removal of oxovanadium(IV) from aqueous solutions by using commercial crystalline calcium hydroxyapatite.

The interaction of oxovanadium(IV) (VO(2+)) in aqueous solution with commercial calcium hydroxyapatite (CAP) has been studied. VO(2+) ions are adsorbed on the surface of CAP by coordination to OH groups, without modification of the crystalline lattice. The extent of the adsorption is followed by chemical analysis, ESR and IR spectroscopy. Results are compared with those obtained for VO(2+)/synthetic calcium hydroxyapatite (HAP), reported by us in previous works. The uptake is better than the observed for HAP. The maximum adsorption is observed at pH 3.5 and 288 K. We conclude that VO(2+) is indeed adsorbed on CAP and the extent of adsorption depends on the pH and temperature.

A low temperature infrared study of the coordinated water in calcium malonate dihydrate.

The infrared spectra of calcium malonate dihydrate in the polycrystalline state, both normal and with different degrees of deuteration, were obtained at low temperatures in order to obtain information about the crystalline environment of the hydration water molecules. The study showed that both water molecules are non-equivalent and non-symmetric. That result is indicative of a non-symmetric space group for the crystal, in agreement with one out of three different crystallographic studies made on the substance.

Bis(diethylenetriamine-kappa3N)nickel(II) 5-amino-1,3,4-thiadiazole-2-sulfonamidate chloride monohydrate.

In the X-ray crystal structure of the title complex, [Ni(C(4)H(13)N(3))(2)](C(2)H(3)N(4)O(2)S(2))Cl.H(2)O, the coordination polyhedron is composed of non-centrosymmetric [Ni(diethylenetriamine)(2)](2+) cations in which the triamine ligands coordinate to the metal centre as tridentate ligands in a facial position. The Ni(II) ions are linked to six N atoms in an octahedral arrangement, slightly compressed in one extreme. The sulfonamide behaves as a counter-ion instead of as a ligand. Important information about the deprotonated sulfonamide group conformation has been obtained.

A novel heterocyclic sulfonamide: N-benzyl-5-[N-benzyl-N-(tert-butyloxycarbonyl)amino]-N-(tert-butyloxycarbonyl)-1,3,4-thiadiazole-2-sulfonamide.

The title compound, C(26)H(32)N(4)O(6)S(2), is a heterocyclic sulfonamide which is a 1,3,4-thiadiazole derivative. Structural data for this compound are compared with those of related compounds.

Anticonvulsant activity of analogues of acetazolamide.

The anticonvulsant activity of 5-tertbutyloxycarbonylamido-1,3,4-thiadiazole-2-sulfonamide (B-H2ats) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (Hats) was compared in mice, to that of acetazolamide (H2acm). These compounds exhibit potent anticonvulsant activity and low minimal motor impairment.

A potentiometric and spectrophotometric study on acid-base equilibria in ethanol-aqueous solution of acetazolamide and related compounds.

Acid-base equilibria in ethanol-aqueous solution of 5-acetamido-1,3,4-thiadiazole-2-sulfonamide (acetazolamide, H(2)acm), 5-tertbutyloxycarbonylamido-1,3,4-thiadiazole-2-sulfonamide (B-H(2)ats), 5-amino-1,3,4-thiadiazole-2-sulfonamide (Hats) and 5-amino-1,3,4-thiadiazole-2-thiol (Hatm) at 25 degrees C, 0.15 mol dm(-3) ionic strength (NaNO(3)), have been investigated by potentiometry and UV spectrophotometry. The ionization constants were calculated with SUPERQUAD program from potentiometric measurements and by a method according to Edsall et al. using the mole fractions determined by complementary tri-stimulus colorimetry (CTS). The constants obtained by potentiometry were: B-H(2)ats, pk(a(1))=7.33(3) and pk(a(2))=9.27(1); Hats, pk(a(1))=2.51(3) and pk(a(2))=8.49(1); Hatm, pk(a(1))=1.92(1) and pk(a(2))=6.81(1); whereas the constants determined by spectrophotometry were: H(2)acm, pk(a(1))=7.78(1) and pk(a(2))=9.57(2); B-H(2)ats, pk(a(1))=7.71(2) and pk(a(2))=9.61(2); Hats, pk(a(1))=2.19(3) and pk(a(2))=8.61(2); Hatm, pk(a(2))=6.90(2). Theoretical calculations using MO semiempirical and ab-initio RHF/6-31G* computations for the compounds were also performed. It was possible to clarify the preferred deprotonation mechanism of acetazolamide and B-H(2)ats in which the first deprotonation takes place at the carbonamido group.