Feasibility and acceptability of a hospital-at-home program for adolescents with eating disorders: Making progress in community/family-based treatments.

OBJECTIVE: To explore the feasibility and acceptability of a novel hospital-at-home (HaH) program for adolescent patients with a severe eating disorder (ED). METHOD: Retrospective description of the program during its first year of activity. The feasibility construct is based on accessibility, recruitment, rate of retention, avoidance of hospital stays, and management of crisis situations. Caregivers completed a satisfaction questionnaire on discharge, including an item on perceived safety. All patients referred to the program were included. RESULTS: Fifty-nine female patients with a mean age of 14.69 years (SD = 1.67) were admitted. The mean stay was 39.14 days (SD = 14.47). On admission, 32.2% of patients presented nonsuicidal self-harm behavior and 47.5% had comorbid mental disorders. All patients were screened in the first 48 h after referral, and the program retention rate was 91.52%. As for use of health services, 2016.03 hospital stays were avoided, and only 16.12% of the 31 calls received for urgent care required emergency department visits. Families gave the program an overall satisfaction score of 4.95/5, and all described it as "very safe." DISCUSSION: The HaH program described is a feasible and acceptable care model in adolescents with severe EDs and comorbidities. Effectiveness studies should be performed. PUBLIC SIGNIFICANCE: Eating disorders are a major concern for public health. The adolescent HaH program presented marks an advance in intensive community treatments for patients with severe EDs and comorbidities.

Variable Intrinsic Expression of Immunoregulatory Biomarkers in Breast Cancer Cell Lines, Mammospheres, and Co-Cultures.

Advances in immunotherapy have increased interest in knowing the role of the immune system in breast cancer (BC) pathogenesis. Therefore, immune checkpoints (IC) and other pathways related to immune regulation, such as JAK2 and FoXO1, have emerged as potential targets for BC treatment. However, their intrinsic gene expression in vitro has not been extensively studied in this neoplasia. Thus, we evaluated the mRNA expression of tumor-cell-intrinsic CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FoXO1 in different BC cell lines, derived mammospheres, and co-cultures with peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction (qRT-PCR). Our results showed that intrinsic CTLA-4, CD274 (PD-L1), and PDCD1LG2 (PD-L2) were highly expressed in triple-negative cell lines, while CD276 was predominantly overexpressed in luminal cell lines. In contrast, JAK2 and FoXO1 were under-expressed. Moreover, high levels of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), and JAK2 were found after mammosphere formation. Finally, the interaction between BC cell lines and peripheral blood mononuclear cells (PBMCs) stimulates the intrinsic expression of CTLA-4, PCDC1 (PD1), CD274 (PD-L1), and PDCD1LG2 (PD-L2). In conclusion, the intrinsic expression of immunoregulatory genes seems very dynamic, depending on BC phenotype, culture conditions, and tumor-immune cell interactions.

Therapeutic effect of α7 nicotinic receptor activation after ischemic stroke in rats.

Nicotinic acetylcholine α7 receptors (α7 nAChRs) have a well-known modulator effect in neuroinflammation. Yet, the therapeutical effect of α7 nAChRs activation after stroke has been scarcely evaluated to date. The role of α7 nAChRs activation with PHA 568487 on inflammation after brain ischemia was assessed with positron emission tomography (PET) using [18F]DPA-714 and [18F]BR-351 radiotracers after transient middle cerebral artery occlusion (MCAO) in rats. The assessment of brain oedema, blood brain barrier (BBB) disruption and neurofunctional progression after treatment was evaluated with T2 weighted and dynamic contrast-enhanced magnetic resonance imaging (T2 W and DCE-MRI) and neurological evaluation. The activation of α7 nAChRs resulted in a decrease of ischemic lesion, midline displacement and cell neurodegeneration from days 3 to 7 after ischemia. Besides, the treatment with PHA 568487 improved the neurofunctional outcome. Treated ischemic rats showed a significant [18F]DPA-714-PET uptake reduction at day 7 together with a decrease of activated microglia/infiltrated macrophages. Likewise, the activation of α7 receptors displayed an increase of [18F]BR-351-PET signal in ischemic cortical regions, which resulted from the overactivation of MMP-2. Finally, the treatment with PHA 568487 showed a protective effect on BBB disruption and blood brain vessel integrity after cerebral ischemia.

Cerrado and Pantanal fruit flours affect gut microbiota composition in healthy and post-COVID-19 individuals: an in vitro pilot fermentation study.

Cerrado and Pantanal plants can provide fruits with high nutritional value and antioxidants. This study aims to evaluate four fruit flours (from jatobá pulp, cumbaru almond, bocaiuva pulp and bocaiuva almond) and their effects on the gut microbiota in healthy (HD) and post-COVID-19 individuals (PC). An in vitro batch system was carried out, the microbiota was analysed by 16S rRNA amplicon sequencing and the short-chain fatty acids ratio was determined. Furthermore, the effect of jatobá pulp flour oil (JAO) on cell viability, oxidative stress and DNA damage was investigated in a myelo-monocytic cell line. Beyond confirming a microbiota imbalance in PC, we identified flour-specific effects: (i) reduction of Veillonellaceae with jatobá extract in PC samples; (ii) decrease in Akkermansia with jatoba and cumbaru flours; (iii) decreasing trend of Faecalibacterium and Ruminococcus with all flours tested, with the exception of the bocaiuva almond in HD samples for Ruminococcus and (iv) increase in Lactobacillus and Bifidobacterium in PC samples with bocaiuva almond flour. JAO displayed antioxidant properties protecting cells from daunorubicin-induced cytotoxicity, oxidative stress and DNA damage. The promising microbiota-modulating abilities of some flours and the chemopreventive effects of JAO deserve to be further explored in human intervention studies.

Perceptions of preparedness, timing of cancer diagnosis, and objective emergency preparedness among gynecological cancer patients in Puerto Rico before and after Hurricane Maria.

OBJECTIVES: This study investigated the impact of cancer diagnosis status, individual feelings of preparedness, and other covariates on objective emergency preparedness among women diagnosed with gynecological cancers before or after the 2017 Hurricanes Irma and Maria in Puerto Rico. METHODS: This study included 240 women who were interviewed by telephone from 9/2019-11/2020. Objective emergency preparedness was assessed using a list of six items. Subjective emergency preparedness was assessed by asking the women how prepared they felt (well, somewhat, or not at all) to face an emergency. Crude and multivariable logistic regression analyses were conducted to assess the associations (odds ratios [ORs] and 95% confidence intervals [CIs]) between variables of interest and objective preparedness. RESULTS: Before and after the hurricanes, 60% and 66% of women, respectively, were objectively prepared. Before the hurricanes, women reporting feeling well-prepared (vs. not prepared) (OR=9.31, 95%CI:3.96-21.91) and those who were diagnosed before (vs. after) the hurricanes (OR=1.71, 95%CI:0.95-3.09) were more likely to be objectively prepared. After the hurricanes, self-perceived well-preparedness (OR=2.46, 95% CI: 1.10-5.51) was positively associated with emergency preparedness when compared to feeling unprepared. CONCLUSIONS: Perceptions of emergency preparedness and having a cancer diagnosis increased the likelihood of being objectively prepared for an emergency. POLICY SUMMARY: This study demonstrates the need for state, territorial, and federal governments to include emergency preparedness plans for cancer patients in the Comprehensive Cancer Control plans. The study also indicates a need for cancer specific emergency preparedness information to be readily available for patients.

Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet.

In addition to the known metabolic alterations, obesity has consequences at the brain level, driving imbalance in neurotransmitters such as glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA). The consumption of fruits with antioxidant properties, such as the berrycactus Myrtillocactus geometrizans, could have beneficial effects in such an imbalance. The study objective was to evaluate frontal cortex neurotransmitter levels and weight changes in rats fed with a high-fat diet (HFD) and MG. To achieve that, five groups of Wistar rats received different diets for 24 weeks: standard diet (SDt), HFD, HFD + MG extract 150 mg (HMg150), HFD + MG extract 300 mg (HMg300), and HFD + MG extract 450 mg (HMg450); rats received MG extract for the last 4 weeks. Weight and food intake were recorded every week, and also neurotransmitter levels were quantified using high-performance liquid chromatography. Groups fed with HFDs had increased Glu and Gln levels, decreased GABA, and also gained more weight compared to the SDt group; MG extract of 450 mg decreased Glu levels. Concentrations of 300 and 450 mg of MG extract decreased weight compared to the HFD and HMg150 groups. This study reports that HFDs have an impact on neurotransmitter levels and weight, MG extract showed a reduction in Glu concentration and weight.

Cerrado and Pantanal fruit flours affect gut microbiota composition in healthy and post-COVID-19 individuals: an in vitro pilot fermentation study.

Cerrado and Pantanal plants can provide fruits with high nutritional value and antioxidants. This study aims to evaluate four fruit flours (from jatobá pulp, cumbaru almond, bocaiuva pulp and bocaiuva almond) and their effects on the gut microbiota in healthy (HD) and post-COVID-19 individuals (PC). An in vitro batch system was carried out, the microbiota was analysed by 16S rRNA amplicon sequencing and the short-chain fatty acids ratio was determined. Furthermore, the effect of jatobá pulp flour oil (JAO) on cell viability, oxidative stress and DNA damage was investigated in a myelo-monocytic cell line. Beyond confirming a microbiota imbalance in PC, we identified flour-specific effects: (i) reduction of Veillonellaceae with jatobá extract in PC samples; (ii) decrease in Akkermansia with jatoba and cumbaru flours; (iii) decreasing trend of Faecalibacterium and Ruminococcus with all flours tested, with the exception of the bocaiuva almond in HD samples for Ruminococcus and (iv) increase in Lactobacillus and Bifidobacterium in PC samples with bocaiuva almond flour. JAO displayed antioxidant properties protecting cells from daunorubicin-induced cytotoxicity, oxidative stress and DNA damage. The promising microbiota-modulating abilities of some flours and the chemopreventive effects of JAO deserve to be further explored in human intervention studies.

An Explanatory Model of Work-family Conflict and Resilience as Predictors of Job Satisfaction in Nurses: The Mediating Role of Work Engagement and Communication Skills.

BACKGROUND: The Job Demands and Resources (JD-R) model is used to examine predictors of well-being, work engagement, and individual or organizational outcomes. According to the model, work engagement and communication skills play a mediating role between work-family conflict and resilience to job satisfaction in nurses. METHODS: A cross-sectional study was conducted considering 431 Peruvian nurses of mean age (M = 40.31 years; SD = 10.94) ranging from 22 to 68 years working in public hospitals in the Lima region. Data were collected using a self-reported form of the Job Satisfaction Scale, communication skills, work engagement, work-family conflict, and resilience. The theoretical model was evaluated using structural equation modeling (SEM). RESULTS: A theoretical model with adequate fit was obtained [χ2(2) = 6.0, P < .001, CFI = 0.995, RMSEA = 0.068, SRMR = 0.015]. Results indicated an inverse relationship between work-family conflict with communication skills (ß = -.24, P < .001) and work engagement (ß = -.10, P = .003). Likewise, resilience had an influence on communication skills (ß = .55, P < .001) and work engagement (ß = .33, P < .001). In addition, the model explains 71% of job satisfaction. Also, the results indicate the influence of work-family conflict and resilience through the mediating role of work engagement and work-family conflict on job satisfaction. CONCLUSIONS: The model confirmed that work engagement and communication skills are valid moderators to mitigate work-family conflict and strengthen resilience that favors job satisfaction in nurses.

Effects of virtual tour on perioperative pediatric anxiety.

BACKGROUND: There is a high incidence of perioperative anxiety in the pediatric population, with adverse side effects, such as emergency delirium and maladaptive postoperative behaviors. AIMS: The study's objective was to compare the level of preoperative anxiety in children after standard preparation plus a virtual tour of the operating room vs. standard preparation alone. PATIENTS/METHODS: This was a prospective single-center, randomized, controlled, blinded trial with parallel assignment, registered as NCT04043663. Eligible subjects were healthy children (ASA I-II) aged 4-12, scheduled for outpatient surgery. Five visits were conducted during the study, two at the hospital and three over the phone. Variables assessed were child's anxiety through the modified Yale Perioperative Anxiety Scale, demographic data, cooperation with induction through the Induction Compliance Checklist, preoperative parental anxiety through the State-Trait Anxiety Inventory and Anxiety Visual Analog Scale, the postoperative delirium degree through the Pediatric Anesthesia Emergence Delirium Scale, the presence of behavioral changes through the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery, and the overall parental satisfaction. RESULTS: A total of 125 participants were included; 61 (48.8%) of them were randomized to the Virtual Tour Group (VT+) and 64 (51.2%) to the Non-virtual Tour Group (VT-). Yale Preoperative Anxiety Scale results in VT+ vs. VT- were mean 27.26 vs. 32.57, and median 23.4 (CI 95% 23.4-23.4) vs. 23.4 (CI 95% 23.4-33.4), (p = .0086). In the VT+ group, satisfaction was higher for questions one (p = .0213), three (p = <.0001), and four (p = .0130). Throughout the study, we observed a significant reduction in perioperative anxiety in the VT+ group, facilitating anesthetic induction in perfect (p = .018) and moderate compliance (p = .0428). The other variables did not show statistically significant differences. CONCLUSION: Our study confirms previous studies that found virtual tours for perioperative patients may reduce perioperative anxiety and improve satisfaction. We found no impact on longer-term outcomes.

Synergistic effect of environmental food pollutants: Pesticides and marine biotoxins.

Emerging marine biotoxins such as ciguatoxins and pyrethroid compounds, widely used in agriculture, are independently treated as environmental toxicants. Their maximum residue levels in food components are set without considering their possible synergistic effects as consequence of their interaction with the same cellular target. There is an absolute lack of data on the possible combined cellular effects that biological and chemical pollutants, may have. Nowadays, an increasing presence of ciguatoxins in European Coasts has been reported and these toxins can affect human health. Similarly, the increasing use of phytosanitary products for control of food plagues has raised exponentially during the last decades due to climate change. The lack of data and regulation evaluating the combined effect of environmental pollutants with the same molecular target led us to analyse their in vitro effects. In this work, the effects of ciguatoxins and pyrethroids in human sodium channels were investigated. The results presented in this study indicate that both types of compounds have a profound synergistic effect in voltage-dependent sodium channels. These food pollutants act by decreasing the maximum peak inward sodium currents and hyperpolarizing the sodium channels activation, effects that are boosted by the simultaneous presence of both compounds. A fact that highlights the need to re-evaluate their limits in feedstock as well as their potential in vivo toxicity considering that they act on the same cellular target. Moreover, this work sets the cellular basis to further apply this type of studies to other water and food pollutants that may act synergistically and thus implement the corresponding regulatory limits taking into account its presence in a healthy diet.

Clinical and technical insights of tumour mutational burden in non-small cell lung cancer.

Despite the durable responses provided by the introduction of checkpoint inhibitors in advanced Non-Small Cell Lung Cancer (NSCLC) without actionable targets in a subset of patients, a large proportion of them will progress after immunotherapy. Programmed Death Ligand 1 (PD-L1) was the first biomarker approved for immunotherapy, although it has multiple limitations, thus the development of novel biomarkers is an urgent need. Tumour Mutational Burden (TMB) is an emerging biomarker defined as the total number of mutations per coding area of tumour genome. Targeted gene panels have emerged as a cost-effective approach to estimate TMB. However, there is still an unmet need to fully standardize sample requirements, panel size, and bioinformatic pipelines to ensure that TMB is calculated appropriately. In addition, researchers are also evaluating TMB calculation in liquid biopsy. In this work, we summarize the relevant advances and the clinical utility of TMB in NSCLC.

Gestational diabetes prevalence and outcomes in women undergoing assisted reproductive techniques (ART).

Infertility affects millions worldwide and use of assisted reproductive techniques (ART) is in high demand. AIMS: To investigate whether women that underwent ART at our hospital had a higher incidence of GDM than women who conceived spontaneously, if the ART subtype affects the GDM rate and to study obstetrical outcomes in women with GDM in both groups. METHODS: This was a retrospective analysis of prospectively collected data of singleton pregnancies attended at Hospital Universitari Dexeus between 2008 and 2019. Age<18 years, pregestational diabetes, metformin prior to pregnancy and multiple pregnancies were excluded. RESULTS: A total of 29,529 patients were included. Pregnancy was achieved by ART in 2596 (8.8%): in vitro fertilisation (IVF/ICSI) 32.8%, frozen embryo transfer (FET) 37.7%, oocyte donor receptors (ODR) 17.2% and insemination 12.2%. The GDM rate was 8.9% (12.7% in ART vs 8.5% in non-ART, p<0.001). The GDM was 11.2% in IVF/ICSI, 17.7% in ODR, 13% in FET and 9.1% in the insemination group (p=0.001). In a multivariable analysis adjusting for age, parity and BMI, ART was not associated with GDM [OR 1.03 (0.90-1.19)], nor was type of ART. Pregnancy outcomes in GDM patients were similar in both groups except for C-section rates (30.0% in ART vs 15.9% in non-ART (p<0.001). CONCLUSIONS: Despite a higher prevalence of GDM in ART pregnancies, ART was not associated with an increased risk of GDM when adjusting for age, parity and BMI. The prognosis of GDM in ART and non-ART was similar except for C-section rates.

Functional responses of key marine bacteria to environmental change - toward genetic counselling for coastal waters.

Coastal ecosystems deteriorate globally due to human-induced stress factors, like nutrient loading and pollution. Bacteria are critical to marine ecosystems, e.g., by regulating nutrient cycles, synthesizing vitamins, or degrading pollutants, thereby providing essential ecosystem services ultimately affecting economic activities. Yet, until now bacteria are overlooked both as mediators and indicators of ecosystem health, mainly due to methodological limitations in assessing bacterial ecosystem functions. However, these limitations are largely overcome by the advances in molecular biology and bioinformatics methods for characterizing the genetics that underlie functional traits of key bacterial populations - "key" in providing important ecosystem services, being abundant, or by possessing high metabolic rates. It is therefore timely to analyze and define the functional responses of bacteria to human-induced effects on coastal ecosystem health. We posit that categorizing the responses of key marine bacterial populations to changes in environmental conditions through modern microbial oceanography methods will allow establishing the nascent field of genetic counselling for our coastal waters. This requires systematic field studies of linkages between functional traits of key bacterial populations and their ecosystem functions in coastal seas, complemented with systematic experimental analyses of the responses to different stressors. Research and training in environmental management along with dissemination of results and dialogue with societal actors are equally important to ensure the role of bacteria is understood as fundamentally important for coastal ecosystems. Using the responses of microorganisms as a tool to develop genetic counselling for coastal ecosystems can ultimately allow for integrating bacteria as indicators of environmental change.

Neurophysiological Findings in Critical COVID-19 Patients With Peripheral Nervous System Manifestations.

INTRODUCTION: Coronavirus disease 2019 patients hospitalized in intensive care units develop neuromuscular manifestations. However, to our knowledge, a study describing the neurophysiological findings in these patients has not been reported. The objective of this study was to diagnose the cause of neuromuscular deficit in severe coronavirus disease 2019 patients, through neurophysiological examination. METHODS: This is a retrospective, observational case series. Data were collected from April 13, 2020, to May 31, 2020. Twenty-two coronavirus disease 2019 patients with generalized neuromuscular deficit during intensive care unit hospitalization were studied. Neurophysiological examinations included motor and sensory peripheral nerve conductions, needle electromyography, F waves, and repetitive nerve stimulation. RESULTS: The subjects were 14 men (63.6%) and eight women, ranged from 35 to 74 years old (58.0, interquartile ranges 50.7-66.2). Intensive care unit hospitalization time ranged from 14 to 82 days (median 37.5, interquartile ranges 22.7-55.0). Through neurophysiological examination, myopathy was diagnosed in 17 patients (77.3%) and polyneuropathy in four (18.2%). Focal neuropathies were diagnosed in 12 patients (54.6%), with a total of 19 affected nerves. Common peroneal nerve lesions at the fibular head (68.4%) and ulnar nerve lesions at the elbow level (21.1%) were the most frequent locations. No significant differences were established between neurophysiological findings and clinical or analytical data. CONCLUSIONS: In critical coronavirus disease 2019 patients with neuromuscular complaints, neurophysiological examination provides an accurate diagnosis-useful to select treatment measures and establish the prognosis of recovery. Neurophysiological findings are similar to those described for critical illness neuromuscular disease, with myopathy being the most frequent diagnosis.

Ultrastructural Characterization of Human Gingival Fibroblasts in 3D Culture.

Cell spheroids are applied in various fields of research, such as the fabrication of three-dimensional artificial tissues in vitro, disease modeling, stem cell research, regenerative therapy, and biotechnology. A preclinical 3D culture model of primary human gingival fibroblasts free of external factors and/or chemical inducers is presented herein. The ultrastructure of the spheroids was characterized to establish a cellular model for the study of periodontal tissue regeneration. The liquid overlay technique was used with agarose to generate spheroids. Fibroblasts in 2D culture and cell spheroids were characterized by immunofluorescence, and cell spheroids were characterized by optical and scanning electron microscopy, energy-dispersive X-ray spectroscopy, backscattered electrons, and Fourier transform infrared spectroscopy. Ostegenic related genes were analyzed by RT-qPCR. Gingival fibroblasts formed spheroids spontaneously and showed amorphous calcium phosphate nanoparticle deposits on their surface. The results suggest that human gingival fibroblasts have an intrinsic potential to generate a mineralized niche in 3D culture.

Do reproductive history and information given through genetic counselling influence patients' decisions on mosaic embryo transfer?

OBJECTIVE: To assess patients' and embryonic characteristics that may have an influence on the decision to transfer a mosaic embryo. METHOD: Single centre retrospective cohort study including 1247 PGT-A cycles. Demographic and clinical factors associated with a decision to transfer a mosaic embryo were studied. Female age, number of previous cycles, previous availability of euploid embryos, history of miscarriages and parity as well as percentage of mosaicism, type of anomaly and chromosome risk were studied in relation to decision-making. Outcomes after mosaic embryo transfer were assessed. RESULTS: To date, in 7.9% of cycles (99/1247), patients have had to make a decision on the fate of their mosaic embryos. In 23.2% of cycles (23/99), patients decided to transfer. In most cases (79.8%; 79/99), patients underwent genetic counselling before the decision. None of the variables analysed were associated with the patients' decision, although parity and the high-degree mosaicism (>50%) seemed to be negatively associated with the decision to transfer (18.2% vs. 29.8%, p = 0.294; 10% vs. 32.2%, p = 0.052). CONCLUSIONS: Neither reproductive history nor information on mosaic embryo characteristics through counselling seems to be determinative for patients when deciding to transfer a mosaic embryo. Promising and increasing data on clinical outcomes after mosaic embryo transfer will be of utmost importance to soften risk perception regarding mosaic embryos and give a better, simplified and more evidence-based counselling.

Seasonal Dynamics in Carbon Cycling of Marine Bacterioplankton Are Lifestyle Dependent.

Although free-living (FL) and particle-attached (PA) bacteria are recognized as ecologically distinct compartments of marine microbial food-webs, few, if any, studies have determined their dynamics in abundance, function (production, respiration and substrate utilization) and taxonomy over a yearly cycle. In the Baltic Sea, abundance and production of PA bacteria (defined as the size-fraction >3.0 µm) peaked over 3 months in summer (6 months for FL bacteria), largely coinciding with blooms of Chitinophagales (Bacteroidetes). Pronounced changes in the growth efficiency (range 0.05-0.27) of FL bacteria (defined as the size-fraction <3.0 µm) indicated the magnitude of seasonal variability of ecological settings bacteria experience. Accordingly, 16S rRNA gene analyses of bacterial community composition uncovered distinct correlations between taxa, environmental variables and metabolisms, including Firmicutes associated with elevated hydrolytic enzyme activity in winter and Verrucomicrobia with utilization of algal-derived substrates during summer. Further, our results suggested a substrate-controlled succession in the PA fraction, from Bacteroidetes using polymers to Actinobacteria and Betaproteobacteria using monomers across the spring to autumn phytoplankton bloom transition. Collectively, our findings emphasize pronounced seasonal changes in both the composition of the bacterial community in the PA and FL size-fractions and their contribution to organic matter utilization and carbon cycling. This is important for interpreting microbial ecosystem function-responses to natural and human-induced environmental changes.

Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles.

STUDY QUESTION: Is there any difference in the mean number of euploid embryos following luteal phase start (LS) and follicular phase start (FS) of ovarian stimulation? SUMMARY ANSWER: The mean number of euploid blastocysts is equivalent independent of whether the inseminated oocytes are derived from FS or LS. WHAT IS KNOWN ALREADY: Starting ovarian stimulation at any time of the cycle ('random-start') is commonly used for emergency fertility preservation in cancer patients. A few retrospective studies have been published evaluating LS in women undergoing ovarian stimulation in the context of IVF, but there is a lack of robust data on the comparative efficacy of LS versus FS.Although 'random start' is commonly used in cancer survivors, few retrospective and uncontrolled studies have been published evaluating luteal phase stimulation in women undergoing ovarian stimulation in the context of IVF. Owing to this evident lack of robust data on the efficacy of LS, guidelines typically recommend the LS approach only for medical reasons and not in the context of IVF. STUDY DESIGN, SIZE, DURATION: This is a prospective, equivalence study, with repeated stimulation cycles, conducted between May 2018 and December 2021. Overall, 44 oocyte donors underwent two identical consecutive ovarian stimulation cycles, one initiated in the FS and the other in the LS. The primary outcome of the study was to evaluate whether FS and LS in the same patient would result in equivalent numbers of euploid embryos following fertilization of oocytes with the same sperm sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 44 oocyte donors underwent two consecutive ovarian stimulation protocols with 150 µg corifollitropin alpha followed by 200 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. The only difference between the two cycles was the day of initiation of ovarian stimulation, which was in the early follicular phase (FS) in one cycle, and in the luteal phase (LS) in the other. Forty-four oocyte recipients participated in the study receiving a mean of six metaphase II (MII) oocytes from each stimulation cycle (FS and LS). All MIIs were inseminated with the corresponding recipient's partner sperm (which had been previously frozen) or donor sperm, in order to safeguard the use of the same sample for either the FS or LS. Following fertilization and blastocyst culture, all generated embryos underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuploidy). MAIN RESULTS AND THE ROLE OF CHANCE: FS resulted in a significantly shorter duration of ovarian stimulation (difference between means (DBM) -1.05 (95% CI -1.89; -0.20)) and a lower total additional dose of daily rFSH was needed (DBM -196.02 (95% CI -319.92; -72.12)) compared with LS. The donors' hormonal profile on the day of trigger was comparable between the two stimulation cycles, as well as the mean number of oocytes (23.70 ± 10.79 versus 23.70 ± 8.81) (DBM 0.00 (95% CI -3.03; 3.03)) and MII oocytes (20.27 ± 9.60 versus 20.73 ± 8.65) (DBM -0.45 (95% CI -2.82; 1.91)) between FS and LS cycles, respectively. Following fertilization, the overall blastocyst formation rate was 60.70% with a euploid rate of 57.1%. Comparisons between the two stimulation cycles did not reveal any significance differences in terms of fertilization rates (71.9% versus 71.4%), blastocyst formation rates (59.4% versus 62%) and embryo euploidy rates (56.9 versus 57.3%) for the comparison of FS versus LS, respectively. The mean number of euploid blastocysts was equivalent between the FS (1.59 ± 1.30) and the LS (1.61 ± 1.17), (DBM -0.02 (90%CI -0.48; 0.44)). LIMITATIONS, REASONS FOR CAUTION: The study was performed in young, potentially fertile oocyte donors who are patients with high blastocyst euploidy rates. Although results may be extrapolated to young infertile women with good ovarian reserve, caution is needed prior to generalizing the results to infertile women of older age. WIDER IMPLICATIONS OF THE FINDINGS: The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by an unrestricted grant from MSD/Organon. N.P.P. has received Research grants and honoraria for lectures from: Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins Intenational, Roche Diagnostics, IBSA, Theramex, Gedeon Richter. F.M., E.C., M.R. and S.G. declared no conflict of interests. TRIAL REGISTRATION NUMBER: The study was registered at Clinical Trials Gov (NCT03555942).

Angiogenic factors assessment in pre-eclampsia high risk population for the prediction of small-for-gestational age neonates: A prospective longitudinal study.

OBJECTIVE: The authors aimed to compare cross-sectional versus longitudinal models for prediction of small-for-gestational age (SGA) neonates among pregnancies with high risk of early pre-eclampsia (PE). METHODS: A prospective longitudinal study was performed in Hospital Universitari Dexeus, Barcelona. The study population included 390 pregnancies with a high risk of early PE according to the first trimester algorithm. Cross-sectional models combining first trimester risk plus placental growth factor and FMS-like tyrosine kinase 1/placental growth factor ratio, respectively, were created at 19-22, 24-26, and 27-30 weeks and compared with a model assessing longitudinal changes of these parameters. Models adding mean uterine artery pulsatility index and abdominal circumference were evaluated. SGA neonates were defined as having a birth weight less than the tenth centile. RESULTS: The predictive performance of a model assessing longitudinal changes of angiogenic factors was similar to that of single evaluations at the second and early third trimesters. The performance of the models combining angiogenic factors with mean uterine artery pulsatility index and abdominal circumference was better than those using only biochemical markers. However, the longitudinal evaluation of biochemical and biophysical parameters did not perform better than cross-sectional evaluations. CONCLUSIONS: Evaluation of angiogenic factors are useful for prediction of SGA neonates in a high-risk population for early PE. However, longitudinal models do not increase their predictive capacity.

Relationship between handgrip strength and endogenous hormones in postmenopausal women.

OBJECTIVES: This study aimed to evaluate the endogenous hormonal factors related to dominant handgrip strength (HGS) in postmenopausal women. METHODS: A cross-sectional study was performed on 402 postmenopausal women aged 47 to 83 years. The following variables were recorded: age, age at menopause, smoking status, adiposity, HGS, and physical activity. Hormonal parameters (follicle-stimulating hormone, estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate, Δ4 androstenedione, insulin-like growth factor-1 [IGF-1], vitamin D, and parathormone levels) were measured and results reported as odds ratios (ORs), ß coefficients and 95% confidence interval (95% CI). A directed acyclic graph was used to identify potential confounding variables and was adjusted in the regression model to assess associations between endogenous hormones and HGS. RESULTS: The mean dominant HGS was 22.8 ± 3.7 kg, and 25.6% of women had dynapenia. There were significant differences in plasma levels of follicle-stimulating hormone (OR, 0.99; 95% CI, 0.98-1.00), cortisol (OR, 1.07; 95% CI, 1.02-1.12), and dehydroepiandrosterone sulfate (OR, 0.99; 95% CI, 0.98-1.00) between women with normal HGS and those who presented with dynapenia. After adjusting for confounding variables, no significant association was found between endogenous hormones and HGS. CONCLUSIONS: Our results showed that studied ovarian steroids, adrenal hormones, IGF-1, parathormone, and vitamin D were not associated with HGS.