Is biochemical pregnancy loss associated with embryo or endometrium? A retrospective cohort study in frozen single embryo transfer of own and donated oocytes.

STUDY QUESTION: Does the use of preimplantation genetic testing for aneuploidies (PGT-A), personalized embryo transfer with endometrial receptivity assay (pET-ERA), or the use of donated oocytes modify the incidence of biochemical pregnancy loss (BPL) in frozen single embryo transfer (FSET)? SUMMARY ANSWER: Following FSET, BPL incidence does not differ between own and donated oocytes, and the use of PGT-A with euploid embryo transfer or pET-ERA results in a similar incidence of BPL compared to cycles without embryo or endometrial analysis. WHAT IS KNOWN ALREADY: BPL occurs frequently after IVF, and many factors have been associated with its incidence. The etiology of BPL is not well known, but the most probable cause seems to be either a low-quality embryo or impaired endometrial maintenance. The impact of techniques diagnosing embryonic ploidy or endometrial receptivity on BPL incidence and the BPL incidence between own and donated oocytes have not been analyzed. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study analyzing the incidence of BPL over 3741 cycles of FSET derived from own (2399 cycles) and donated (1342 cycles) oocytes between January 2013 and January 2022 in 1736 of which PGT-A, pET-ERA, or both were applied. PARTICIPANTS/MATERIALS, SETTING, METHODS: We defined BPL as a pregnancy diagnosed only by serum ß-hCG > 10 UI/l followed by a decrease that does not result in a clinical pregnancy. Clinical pregnancy was defined as the presence of gestational sac on transvaginal ultrasound. We compared BPL rates among patients undergoing 2399 FSETs from own oocytes, which comprised 1310 cycles of embryos analyzed by PGT-A, 950 cycles of untested embryos, 30 cycles of untested embryos with pET-ERA, and a subgroup of 109 cycles analyzed by both PGT-A and pET-ERA. We also included a total of 1342 FSET cycles from donated oocytes comprising 132, 1055, 140, and 15 cycles in the same groups, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In FSET from own oocytes, the overall BPL rate per embryo transfer was 8.2% (95% CI [7.09-9.33]). In untested embryo transfers, the BPL rate was 7.5% [5.91-9.37]. In the PGT-A group, the BPL rate was 8.8% [7.32-10.47]. In the pET-ERA group, the rate was 6.7% [0.82-22.07]. In the PGT-A+ERA group, the rate was 6.5% [2.65-12.90]. No significant differences were found (P = 0.626). A multivariate analysis considering clinically meaningful variables that were significantly different among groups, taking the untested embryos/endometrium group as a reference, showed comparable incidences among groups. For PGT-A, the adjusted odds ratio (AdjOR) was 1.154 [0.768-1.735] (P = 0.49) and for PGT-A+ERA 0.885 [0.330-2.375] (P = 0.808). Because of a low number of registered cases in the pET-ERA group, and to prevent statistical errors and convergence issues, this group was excluded from further analysis. In FSET of donated oocytes, the overall BPL rate per embryo transfer was 4.9% [3.76-6.14]. In the PGT-A group, the BPL rate was 6.8% [3.16-12.55]. In the pET-ERA group, the rate was 5.0% [2.03-10.03]. In untested embryo transfers, the rate was 4.7% [3.46-6.10]. No cases occurred in the PGT-A+ERA group, and no significant differences were found (P = 0.578). The multivariate analysis showed comparable incidences among groups. For PGT-A the AdjOR was 1.669 [0.702-3.972] (P = 0.247) and for pET-ERA 1.189 [0.433-3.265] (P = 0.737). The PGT-A+ERA group was eliminated from the model to prevent statistical errors and convergence issues because no BPL cases were registered in this group. In the multivariate analysis, when the sources of oocytes were compared, own versus donated, no significant differences were found in the incidence of BPL. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective cohort study with potential biases. In addition, we were unable to control differences among groups due to modifications in medical or laboratory protocols during this long time period, which may modify the relationships being addressed. Factors previously associated with BPL, such as immunological conditions other than thyroid autoimmunity, were not considered in this study. Limited sample sizes of some groups may limit the statistical power for finding differences that can be present in the general population. WIDER IMPLICATIONS OF THE FINDINGS: BPL may be related to a mechanism not associated with the chromosomal constitution of the embryo or the transcriptome of the endometrium. More studies are needed to explore the factors associated with this reproductive issue. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was available for this study. None of the authors have a conflict of interest to declare with regard to this study. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov (NCT04549909).

Pre-pubertal obesity compromises ovarian oxidative stress, DNA repair and chemical biotransformation.

Obesity in adult females impairs fertility by altering oxidative stress, DNA repair and chemical biotransformation. Whether prepubertal obesity results in similar ovarian impacts is under-explored. The objective of this study was to induce obesity in prepubertal female mice and assess puberty onset, follicle number, and abundance of oxidative stress, DNA repair and chemical biotransformation proteins basally and in response to 7,12-dimethylbenz(a)anthracene (DMBA) exposure. DMBA is a polycyclic aromatic hydrocarbon that has been shown to be ovotoxic. Lactating dams (C57BL6J) were fed either a normal rodent containing 3.5% kCal from fat (lean), or a high fat diet comprised of 60% kCal from fat, and 9% kCal from sucrose. The offspring were weaned onto the diet of their dam and exposed at postnatal day 35 to either corn oil or DMBA (1 mg/kg) for 7 d via intraperitoneal injection. Mice on the HFD had reduced (P < 0.05) age at puberty onset as measured by vaginal opening but DMBA did not impact puberty onset. Heart, spleen, kidney, uterus and ovary weight were increased (P < 0.05) by obesity and liver weight was increased (P < 0.05) by DMBA exposure in obese mice. Follicle number was largely unaffected by obesity or DMBA exposure, with the exception of primary follicle number, which were higher (P < 0.05) in lean DMBA exposed and obese control relative to lean control mice. There were also greater numbers (P < 0.05) of corpora lutea in obese relative to lean mice. In lean mice, DMBA exposure reduced (P < 0.05) the level of CYP2E1, EPHX1, GSTP1, BRCA1, and CAT but this DMBA-induced reduction was absent in obese mice. Basally, obesity reduced (P < 0.05) the abundance of CYP2E1, EPHX1, GSTP1, BRCA1, SOD1 and CAT. There was greater (P < 0.05) fibrotic staining in obese DMBA-exposed ovaries and PPP2CA was decreased (P < 0.05) in growing follicles by both obesity and DMBA exposure. Thus, prepubertal obesity alters the capacity of the ovary to respond to DNA damage, ovotoxicant exposure and oxidative stress.

Exposure to 7,12-dimethylbenz[a]anthracene impacts ovarian DNA damage sensing and repair proteins differently in lean and obese female mice and weight loss may mitigate obesity-induced ovarian dysfunction.

Obesity impairs oocyte quality, fertility, pregnancy maintenance, and is associated with offspring birth defects. The model ovotoxicant, 7,12-dimethylbenz[a]anthracene (DMBA), causes ovarian DNA damage and follicle loss. Both DMBA-induced chemical biotransformation and the DNA damage response are partially attenuated in obese relative to lean female mice but whether weight loss could improve the DNA damage response to DMBA exposure has not been explored. Thus, at six weeks of age, C57BL/6 J female mice were divided in three groups: 1) Lean (L; n = 20) fed a chow diet for 12 weeks, 2) obese (O; n = 20) fed a high fat high sugar (HFHS) diet for 12 weeks and, 3) slim-down (S; n = 20). The S group was fed with HFHS diet for 7 weeks until attaining a higher body relative to L mice on week 7.5 and switched to a chow diet for 5 weeks to achieve weight loss. Mice then received either corn oil (CT) or DMBA (D; 1 mg/kg) for 7 d via intraperitoneal injection (n = 10/treatment). Obesity increased (P < 0.05) kidney and spleen weight, and DMBA decreased uterine weight (P < 0.05). Ovarian weight was reduced (P < 0.05) in S mice, but DMBA exposure increased ovary weight in the S mice. LC-MS/MS identified 18, 64, and 7 ovarian proteins as altered (P < 0.05) by DMBA in the L, S and O groups, respectively. In S and O mice, 24 and 8 proteins differed, respectively, from L mice. These findings support weight loss as a strategy to modulate the ovarian genotoxicant response.

C≡N and N≡O Bond Cleavages of Acetonitrile and Nitrosyl Ligands at a Dimolybdenum Center to Render Ethylidyne and Acetamidinate Ligands.

Extended reduction of [Mo2Cp2(µ-Cl)(µ-PtBu2)(NO)2] (1) with Na(Hg) in acetonitrile (MeCN) at room temperature resulted in an unprecedented full cleavage of the C≡N bond of a coordinated MeCN molecule to yield the vinylidene derivative Na[Mo2Cp2(µ-PtBu2)(µ-CCH2)(NO)2], which upon protonation with (NH4)PF6 gave the ethylidyne complex [Mo2Cp2(µ-PtBu2)(µ-CMe)(NO)2] [Mo1-Mo2 = 2.9218(2) Å] in a selective and reversible way. Controlled reduction of 1 at 273 K yielded instead, after protonation, the 30-electron acetamidinate complex [Mo2Cp2(µ-PtBu2)(µ-κN:κN'-HNCMeNH)(µ-NO)]PF6 [Mo1-Mo2 = 2.603(2) Å], in a process thought to stem from the paramagnetic MeCN-bridged intermediate [Mo2Cp2(µ-PtBu2)(µ-NCMe)(NO)2], followed by a complex sequence of elementary steps including cleavage of the N≡O bond of a nitrosyl ligand.

Effect of long-term oral administration of the flavonoid quercetin on the antioxidant profile of young and adult reproductive rabbit does.

In industrialized farms, rabbit does undergo intensive production rhythms which overlap lactation and gestation, leading to a high energy mobilization and increasing oxidative stress. Accordingly, we hypothesize that administration of the flavonoid quercetin (QUR) may improve the antioxidant status of young and adult rabbit reproductive females. In this study, the effect of daily oral administration of 300 mg/kg QUR for 8 weeks was assessed on the antioxidant profile of 24 New Zealand × Californian rabbit does, assigned to 4 experimental groups: rearing young (8-16 weeks old) and adult does at the end of their reproductive life (12-14 months old, with at least 3-4 reproductive cycles) treated (YQ and AQ) or not (YC and AC) with QUR, respectively. Plasma glutathione (GSH), as well as serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured during the experimental period. To assess the health status of the animals, a physical examination was also performed. GSH plasma concentrations were significantly higher in young does at weeks 1 and 4, but not at week 8 of the experiment, irrespectively of QUR administration. An increase in GSH plasma concentration was observed during the 8-week experiment in both AQ and AC groups. Furthermore, QUR administration did not alter either SOD or MDA serum activity and concentration in any group during the experimental period. Physical examination revealed no differences between the experimental groups. In conclusion, under our experimental conditions, QUR did not modify the general clinical or the antioxidant profile of young and adult reproductive rabbit females.

Impact of wildfire recurrence on soil properties and organic carbon fractions.

The recurrence and severity of wildfire is on the rise due to factors like global warming and human activities. Mediterranean regions are prone to significant wildfire events, which cause extensive damage to ecosystems and soil properties. This study focuses on the municipality of Allande in south-western Asturias (Spain), a region highly affected by recurrent wildfires. In this regard, we sought to examine how the recurrence of such fires influences soil organic carbon fractionation and other soil parameters, such as nitrogen fractionation, pH, and cation exchange capacity. The study involved six sampling plots with between varying fire recurrence levels, from 0 to 4 events between 2005 and 2022. The results revealed some significant effects of wildfires recurrence on soil texture, inorganic elemental composition and CEC, but not on pH and CE. In soil affected by recurrent fires, labile carbon fractions (cold-water extractable & hot-water extractable), and fulvic acid concentrations decreased by up to 36%, 5%, and 45%, respectively in comparison with undisturbed soil. In contrast, humic acid concentration remained stable or increased in soils damaged by fire. Additionally, nitrogen species in soil were observed to decrease significantly in high recurrence scenarios, especially nitrate. On the basis of our findings, we conclude that wildfires impact the distinct fractions of organic carbon and nitrogen in soils and that this effect is aggravated by increasing recurrence.

Association between COMMD1 gene polymorphism rs11125908 and rheumatoid arthritis in the Cuban population.

OBJECTIVE: To evaluate the association of the rs11125908 polymorphism in the COMMD1 gene in the Cuban population with rheumatoid arthritis (RA). METHODS: In this case-control study, 161 RA patients and 150 control subjects were genotyped for rs11125908 by the allele-specific polymerase chain reaction method. DNA sequencing was used to verify the assignation of the polymorphism. The odds ratios (OR) and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and RA using the SNPStats software. RESULTS: An association of the single nucleotide polymorphism with the disease was found in the overdominant model (p=0.025; OR=1.91) for the AG genotype. Our analyses revealed an association between rs11125908 and the subgroup of patients with swollen joints < median under the codominant model for AG (p=0.034; OR=2.30) and GG genotype (p=0.034; OR=0.82) and with the overdominant model (p=0.01; OR=2.38). The subgroup of patients with an age of onset lower than the mean and AG genotype showed an association in the overdominant model (p=0.027; OR=2.27). Disease activity score 28 with erythrocyte sedimentation rate and disease duration variables were not associated with the rs11125908 polymorphism. CONCLUSIONS: rs11125908 was associated with RA and with the number of swollen joints and age of onset subgroup analyses. We provide concepts for treatments for RA, based on pharmacological management of COMMD1 expression.

B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

Hepatic and ovarian effects of perfluorooctanoic acid exposure differ in lean and obese adult female mice.

Obesity and overweight cause poor oocyte quality, miscarriage, infertility, polycystic ovarian syndrome, and offspring birth defects and affects 40% and 20% of US women and girls, respectively. Perfluorooctanoic acid (PFOA), a per- and poly-fluoroalkyl substance (PFAS), is environmentally persistent and has negative female reproductive effects including endocrine disruption, oxidative stress, altered menstrual cyclicity, and decreased fertility in humans and animal models. PFAS exposure is associated with non-alcoholic fatty liver disease which affects ∼24-26% of the US population. This study investigated the hypothesis that PFOA exposure impacts hepatic and ovarian chemical biotransformation and alters the serum metabolome. At 7 weeks of age, female lean, wild type (KK.Cg-a/a) or obese (KK.Cg-Ay/J) mice received saline (C) or PFOA (2.5 mg/Kg) per os for 15 d. Hepatic weight was increased by PFOA exposure in both lean and obese mice (P < 0.05) and obesity also increased liver weight (P < 0.05) compared to lean mice. The serum metabolome was also altered (P < 0.05) by PFOA exposure and differed between lean and obese mice. Exposure to PFOA altered (P < 0.05) the abundance of ovarian proteins with roles in xenobiotic biotransformation (lean - 6; obese - 17), metabolism of fatty acids (lean - 3; obese - 9), cholesterol (lean - 8; obese - 11), amino acids (lean - 18; obese - 19), glucose (lean - 7; obese - 10), apoptosis (lean - 18; obese - 13), and oxidative stress (lean - 3; obese - 2). Use of qRT-PCR determined that exposure to PFOA increased (P < 0.05) hepatic Ces1 and Chst1 in lean but Ephx1 and Gstm3 in obese mice. Also, obesity basally increased (P < 0.05) Nat2, Gpi and Hsd17b2 mRNA levels. These data identify molecular changes resultant from PFOA exposure that may cause liver injury and ovotoxicity in females. In addition, differences in toxicity induced by PFOA exposure occurs in lean and obese mice.

Scrambled eggs-Negative impacts of heat stress and chemical exposures on ovarian function in swine.

Exposure to environmental toxicants and hyperthermia can hamper reproduction in female mammals including swine. Phenotypic manifestations include poor quality oocytes, endocrine disruption, infertility, lengthened time to conceive, pregnancy loss, and embryonic defects. The ovary has the capacity for toxicant biotransformation, regulated in part by the phosphatidylinositol-3 kinase signaling pathway. The impacts of exposure to mycotoxins and pesticides on swine reproduction and the potential for an emerging chemical class of concern, the per- and polyfluoroalkylated substances, to hamper porcine reproduction are reviewed. The negative impairments of heat stress (HS) on swine reproductive outcomes are also described and the cumulative effect of environmental exposures, such as HS, when present in conjunction with a toxicant is considered.

Reactions of Heterometallic Phosphinidene-Bridged MoMn and MoRe Complexes with Sulfur and Selenium: From Chalcogenophosphinidene- to Trithiophosphonate-Bridged Derivatives.

Reactions of [MoReCp(µ-PR*)(CO)6] with S8 were strongly dependent on experimental conditions (R* = 2,4,6-C6H2tBu3). When using 1 equiv of sulfur, complex [MoReCp(µ-η2:κ1S-SPR*)(CO)6] was slowly formed at 313 K, with a thiophosphinidene ligand unexpectedly bridging the dimetal center in the novel µ-κ1S:η2 coordination mode, as opposed to the µ-κ1P:η2 mode usually found in related complexes. The latter underwent fast decarbonylation at 363 K to give [MoReCp(µ-η2:η2-SPR*)(CO)5], with a six-electron donor thiophosphinidene ligand rearranged into the rare µ-η2:η2 coordination mode. Depending on reaction conditions, reactions with excess sulfur involved the addition of two or three S atoms to the phosphinidene ligand to give new complexes identified as the dithiophosphinidene-bridged complex [MoReCp(µ-η2:κ2S,S'-S2PR*)(CO)5], its dithiophosphonite-bridged isomer [MoReCp(µ-κ2S,S':κ2S,S'-S2PR*)(CO)5], or the trithiophosphonate-bridged derivative [MoReCp(µ-κ2S,S':κ2S,S'-S3PR*)(CO)5], all of them displaying novel coordination modes of their PRS2 and PRS3 ligands, as determined by X-ray diffraction studies. In contrast, the related MoMn complex yielded [MoMnCp(µ-η2:η2-SPR*)(CO)5] under most conditions. A similar output was obtained in reactions with gray selenium for either MoRe or MoMn phosphinidene complexes, which under different conditions only gave the pentacarbonyl complexes [MoMCp(µ-η2:η2-SePR*)(CO)5] (M = Re, Mn), these providing a new coordination mode for selenophosphinidene ligands.

Nicotiana hairy roots for recombinant protein expression, where to start? A systematic review.

BACKGROUND: Hairy roots are a plant-tissue culture raised by Rhizobium rhizogenes infection (formerly known as Agrobacterium rhizogenes). Nowadays, these roots have been gaining more space in biotechnology due to their benefits for the recombinant expression of valuables proteins; it includes simplified downstream processing, protein rhizosecretion, and scalability in bioreactors. However, due to methodological inconsistency among reports, the tissue platform is still a promising technology. METHODS AND RESULTS: In the current paper, we propose the first step to overcome this issue through a systematic review of studies that employ Nicotiana hairy roots for recombinant expression. We conducted a qualitative synthesis of 36 out of 387 publications initially selected. Following the PRISMA procedure, all papers were assessed for exclusion and inclusion criteria. Multiple points of root culture were explored, including transformation methods, root growth curve, external additives, and scale-up with bioreactors to determine which approaches performed best and what is still required to achieve a robust protocol. CONCLUSION: The information presented here may help researchers who want to work with hairy roots in their laboratories trace a successful path to appraisal the literature status.

Portion control tableware differentially impacts eating behaviour in women with and without overweight.

Portion control tableware has been described as a potentially effective approach for weight management, however the mechanisms by which these tools work remain unknown. We explored the processes by which a portion control (calibrated) plate with visual stimuli for starch, protein and vegetable amounts modulates food intake, satiety and meal eating behaviour. Sixty-five women (34 with overweight/obesity) participated in a counterbalanced cross-over trial in the laboratory, where they self-served and ate a hot meal including rice, meatballs and vegetables, once with a calibrated plate and once with a conventional (control) plate. A sub-sample of 31 women provided blood samples to measure the cephalic phase response to the meal. Effects of plate type were tested through linear mixed-effect models. Meal portion sizes (mean ± SD) were smaller for the calibrated compared with the control plate (served: 296 ± 69 vs 317 ± 78 g; consumed: 287 ± 71 vs 309 ± 79 g respectively), especially consumed rice (69 ± 24 vs 88 ± 30 g) (p < 0.05 for all comparisons). The calibrated plate significantly reduced bite size (3.4 ± 1.0 vs 3.7 ± 1.0 g; p < 0.01) in all women and eating rate (32.9 ± 9.5 vs 33.7 ± 9.2 g/min; p < 0.05), in lean women. Despite this, some women compensated for the reduced intake over the 8 h following the meal. Pancreatic polypeptide and ghrelin levels increased post-prandially with the calibrated plate but changes were not robust. Plate type had no influence on insulin, glucose levels, or memory for portion size. Meal size was reduced by a portion control plate with visual stimuli for appropriate amounts of starch, protein and vegetables, potentially because of the reduced self-served portion size and the resulting reduced bite size. Sustained effects may require the continued use of the plate for long-term impact.

P-C, P-N, and M-N Bond Formation Processes in Reactions of Heterometallic Phosphinidene-Bridged MoMn and MoRe Complexes with Diazoalkanes and Organic Azides to Build Three- to Five-Membered Phosphametallacycles.

Reactions of the heterometallic MoRe complex [MoReCp(µ-PR*)(CO)6] and its MoMn analogue with some small molecules having N-N multiple bonds, such as diazoalkanes and organic azides, were investigated (R* = 2,4,6-C6H2tBu3). Reactions with excess ethyl diazoacetate proceeded slowly and with concomitant denitrogenation to give complexes [MoMCp(µ-η2P,C:κ2P,O-PR*CHCO2Et)(CO)5], which display a bridging phosphaalkene ligand in a novel µ-η2:κ2 coordination mode, while reactions with other diazoalkanes resulted only in the decomposition of the organic reagent. The MoRe complex reacted with benzyl- or p-tolyl azide at room temperature to give the green complexes [MoReCp(µ-η2P,N:κP,N'2-PR*N3R)(CO)6] [R = Bn, p-tol], which display bridging phosphatriazadiene ligands in a novel 6-electron donor coordination mode as a result of a formal [2 + 1] cycloaddition of the terminal N atom of the azide to the Mo-P double bond of the parent complex, followed by coordination of the distal NR nitrogen to the rhenium center. Denitrogenation was only observed for the p-tolyl azide derivative, which upon heating at 333 K yielded [MoReCp{µ-κP:κN-PR*N(p-tol)}(CO)6], a molecule displaying a bridging phosphaimine ligand in a rare κP:κN coordination mode. Analogous reactions of the MoMn phosphinidene complex proceeded similarly at 273 K to give the phosphatriazadiene-bridged derivatives [MoMnCp(µ-η2P,N:κ2P,N'-PR*N3R)(CO)6], but these were thermally unstable and degraded at room temperature to give the mononuclear triazenylphosphanyl complexes [Mn2(κP,N-PR*NHNNR)(CO)3] as major products, along with small amounts of the phosphaimine-bridged complex [MoMnCp{µ-κP:κN-PR*N(p-tol)}(CO)6] in the case of the p-tolyl azide derivative. The structure of the new complexes was analyzed in light of spectroscopic data and single-crystal diffraction studies on selected examples of each type of complex.

Chemistry of a Nitrosyl Ligand κ:η-Bridging a Ditungsten Center: Rearrangement and N-O Bond Cleavage Reactions.

The novel nitrosyl-bridged complex [W2Cp2(µ-PtBu2)(µ-κ:η-NO)(CO)(NO)](BAr4) [Ar = 3,5-C6H3(CF3)2] was prepared in a multistep procedure starting from the hydride [W2Cp2(µ-H)(µ-PtBu2)(CO)4] and involving the new complexes [W2Cp2(µ-PtBu2)(CO)4](BF4), [W2Cp2(µ-PtBu2)(CO)2(NO)2](BAr4), and [W2(µ-κ:η5-C5H4)Cp(µ-PtBu2)(CO)(NO)2] as intermediates, which follow from reactions with HBF4·OEt2, NO, and Me3NO·2H2O, respectively. The nitrosyl-bridged cation easily added chloride upon reaction with [N(PPh3)2]Cl, with concomitant NO rearrangement into the terminal coordination mode, to give [W2ClCp2(µ-PtBu2)(CO)(NO)2], and underwent N-O and W-W bond cleavages upon the addition of CNtBu to give the mononuclear phosphinoimido complex [WCp(NPtBu2)(CNtBu)2](BAr4). Another N-O bond cleavage was induced upon photochemical decarbonylation at 243 K, which gave the oxo- and phosphinito-bridged nitrido complex [W2Cp2(N)(µ-O)(µ-OPtBu2)(NO)](BAr4), likely resulting from a N-O bond cleavage step following decarbonylation.

Electrocatalytic activity of calcined manganese ferrite solid nanospheres in the oxygen reduction reaction.

In this study, we synthesized MnFe2O4 solid nanospheres (MSN) calcined at different temperatures (200-500 °C) and MSN-based materials mixed with carbon black, for their use as electrocatalysts in the oxygen reduction reaction (ORR) in alkaline medium (0.1 M KOH). It was demonstrated that the calcination temperature of MSN material determined its chemical surface composition and microstructure and it had an important effect on the electrocatalytic properties for ORR, which in turn was reflected in the performance of MSN/CB-based electrocatalysts. The study revealed that the presence of Mn species plays a key role in the ORR activity. Among tested, MSN200/CB and MSN350/CB exhibited the best electrochemical performances together with outstanding stability.

Onset of Nut Allergy in a Pediatric Cohort: Clinical and Molecular Patterns in the AFRUSEN Study.

BACKGROUND AND OBJECTIVE: Nut allergy is a growing problem, yet little is known about its onset in children. Objective: To characterize the onset of nut allergy in children in southern Europe. METHODS: The study population comprised consecutive patients up to 14 years of age who visited allergy departments with an initial allergic reaction to peanut, tree nut, or seed. The allergy work-up included a clinical history, food challenge, skin prick testing, determination of whole-extract sIgE, and ImmunoCAP ISAC-112 assay. RESULTS: Of the 271 children included, 260 were first diagnosed with nut allergy at a mean age of 6.5 years and at a mean (SD) of 11.8 (21.2) months after the index reaction. The most common culprit nuts at onset were walnut (36.5%), peanut (28.5%), cashew (10.4%), hazelnut (8.5%), pistachio (5.4%), and almond (5%). Onset of peanut allergy was more frequent in children ≤6 years and walnut in those aged >6 years (P=.032). In 65% of cases, the allergic reaction occurred the first time the patient consumed the nut, and 35% of reactions were anaphylactic. Overall, polysensitization to nuts was detected by skin prick testing in 64.9% of patients, although this rate was lower among walnut-allergic children (54.7%) and peanut-allergic children (54.1%) (P<.0001). Sensitization to 2S albumins was predominant (75%), especially Jug r 1 (52.8%), whereas sensitization to lipid transfer proteins was less relevant (37%). CONCLUSION: In the population we assessed, the onset of nut allergy occurred around 6 years of age, slightly later than that reported in English-speaking countries. Walnut was the main trigger, followed by peanut. 2S albumin storage proteins, especially Jug r 1, were the most relevant allergens. This study will help guide management and may contribute to preventive strategies in pediatric nut allergy.

Genetic and phenotypic characteristics of Clostridium (Clostridioides) difficile from canine, bovine, and pediatric populations.

OBJECTIVES: Carriage of Clostridioides difficile by different species of animals has led to speculation that animals could represent a reservoir of this pathogen for human infections. The objective of this study was to compare C. difficile isolates from humans, dogs, and cattle from a restricted geographic area. METHODS: C. difficile isolates from 36 dogs and 15 dairy calves underwent whole genome sequencing, and phenotypic assays assessing growth and virulence were performed. Genomes of animal-derived isolates were compared to 29 genomes of isolates from a pediatric population as well as 44 reference genomes. RESULTS: Growth rates and relative cytotoxicity of isolates were significantly higher and lower, respectively, in bovine-derived isolates compared to pediatric- and canine-derived isolates. Analysis of core genes showed clustering by host species, though in a few cases, human strains co-clustered with canine or bovine strains, suggesting possible interspecies transmission. Geographic differences (e.g., farm, litter) were small compared to differences between species. In an analysis of accessory genes, the total number of genes in each genome varied between host species, with 6.7% of functional orthologs differentially present/absent between host species and bovine-derived strains having the lowest number of genes. Canine-derived isolates were most likely to be non-toxigenic and more likely to carry phages. A targeted study of episomes identified in local pediatric strains showed sharing of a methicillin-resistance plasmid with dogs, and historic sharing of a wide range of episomes across hosts. Bovine-derived isolates harbored the widest variety of antibiotic-resistance genes, followed by canine CONCLUSIONS: While C. difficile isolates mostly clustered by host species, occasional co-clustering of canine and pediatric-derived isolates suggests the possibility of interspecies transmission. The presence of a pool of resistance genes in animal-derived isolates with the potential to appear in humans given sufficient pressure from antibiotic use warrants concern.

Development and validation of a new methodological platform to measure behavioral, cognitive, and physiological responses to food interventions in real time.

To fully understand the causes and mechanisms involved in overeating and obesity, measures of both cognitive and physiological determinants of eating behavior need to be integrated. Effectively synchronizing behavioral measures such as meal micro-structure (e.g., eating speed), cognitive processing of sensory stimuli, and metabolic parameters, can be complex. However, this step is central to understanding the impact of food interventions on body weight. In this paper, we provide an overview of the existing gaps in eating behavior research and describe the development and validation of a new methodological platform to address some of these issues. As part of a controlled trial, 76 men and women self-served and consumed food from a buffet, using a portion-control plate with visual stimuli for appropriate amounts of main food groups, or a conventional plate, on two different days, in a random order. In both sessions participants completed behavioral and cognitive tests using a novel methodological platform that measured gaze movement (as a proxy for visual attention), eating rate and bite size, memory for portion sizes, subjective appetite and portion-size perceptions. In a sub-sample of women, hormonal secretion in response to the meal was also measured. The novel platform showed a significant improvement in meal micro-structure measures from published data (13 vs. 33% failure rate) and high comparability between an automated gaze mapping protocol vs. manual coding for eye-tracking studies involving an eating test (ICC between methods 0.85; 90% CI 0.74, 0.92). This trial was registered at Clinical Trials.gov with Identifier NCT03610776.

Obesity alters the ovarian proteomic response to zearalenone exposure†.

Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, is detrimental to female reproduction. Altered chemical biotransformation, depleted primordial follicles and a blunted genotoxicant response have been discovered in obese female ovaries, thus, this study investigated the hypothesis that obesity would enhance ovarian sensitivity to ZEN exposure. Seven-week-old female wild-type nonagouti KK.Cg-a/a mice (lean) and agouti lethal yellow KK.Cg-Ay/J mice (obese) received food and water ad libitum, and either saline or ZEN (40 µg/kg) per os for 15 days. Body and organ weights, and estrous cyclicity were recorded, and ovaries collected posteuthanasia for protein analysis. Body and liver weights were increased (P < 0.05) in the obese mice, but obesity did not affect (P > 0.05) heart, kidney, spleen, uterus, or ovary weight and there was no impact (P > 0.05) of ZEN exposure on body or organ weight in lean or obese mice. Obese mice had shorter proestrus (P < 0.05) and a tendency (P = 0.055) for longer metestrus/diestrus. ZEN exposure in obese mice increased estrus but shortened metestrus/diestrus length. Neither obesity nor ZEN exposure impacted (P > 0.05) circulating progesterone, or ovarian abundance of EPHX1, GSTP1, CYP2E1, ATM, BRCA1, DNMT1, HDAC1, H4K16ac, or H3K9me3. Lean mice exposed to ZEN had a minor increase in γH2AX abundance (P < 0.05). In lean and obese mice, LC-MS/MS identified alterations to proteins involved in chemical metabolism, DNA repair and reproduction. These data identify ZEN-induced adverse ovarian modes of action and suggest that obesity is additive to ZEN-induced ovotoxicity.