Early brain and abdominal oxygenation in extremely low birth weight infants.

BACKGROUND: Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined. METHODS: A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables. RESULTS: In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p < 0.001). CONCLUSION: Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population. IMPACT: Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.

Cognitive function in association with high estradiol levels resulting from fertility treatment.

The putative association between hormones and cognitive performance is controversial. While there is evidence that estradiol plays a neuroprotective role, hormone treatment has not been shown to improve cognitive performance. Current research is flawed by the evaluation of combined hormonal effects throughout the menstrual cycle or in the menopausal transition. The stimulation phase of a fertility treatment offers a unique model to study the effect of estradiol on cognitive function. This quasi-experimental observational study is based on data from 44 women receiving IVF in Zurich, Switzerland. We assessed visuospatial working memory, attention, cognitive bias, and hormone levels at the beginning and at the end of the stimulation phase of ovarian superstimulation as part of a fertility treatment. In addition to inter-individual differences, we examined intra-individual change over time (within-subject effects). The substantial increases in estradiol levels resulting from fertility treatment did not relate to any considerable change in cognitive functioning. As the tests applied represent a broad variety of cognitive functions on different levels of complexity and with various brain regions involved, we can conclude that estradiol does not show a significant short-term effect on cognitive function.

Sexual attraction to visual sexual stimuli in association with steroid hormones across menstrual cycles and fertility treatment.

BACKGROUND: Steroid hormones (i.e., estradiol, progesterone, and testosterone) are considered to play a crucial role in the regulation of women's sexual desire and sexual attraction to sexual stimuli throughout the menstrual cycle. However, the literature is inconsistent, and methodologically sound studies on the relationship between steroid hormones and women's sexual attraction are rare. METHODS: This prospective longitudinal multisite study examined estradiol, progesterone, and testosterone serum levels in association with sexual attraction to visual sexual stimuli in naturally cycling women and in women undergoing fertility treatment (in vitro fertilization, IVF). Across ovarian stimulation of fertility treatment, estradiol reaches supraphysiological levels, while other ovarian hormones remain nearly stable. Ovarian stimulation hence offers a unique quasi-experimental model to study concentration-dependent effects of estradiol. Hormonal parameters and sexual attraction to visual sexual stimuli assessed with computerized visual analogue scales were collected at four time points per cycle, i.e., during the menstrual, preovulatory, mid-luteal, and premenstrual phases, across two consecutive menstrual cycles (n = 88 and n = 68 for the first and second cycle, respectively). Women undergoing fertility treatment (n = 44) were assessed twice, at the beginning and at the end of ovarian stimulation. Sexually explicit photographs served as visual sexual stimuli. RESULTS: In naturally cycling women, sexual attraction to visual sexual stimuli did not vary consistently across two consecutive menstrual cycles. While in the first menstrual cycle sexual attraction to male bodies, couples kissing, and at intercourse varied significantly with a peak in the preovulatory phase, (all p ≤ 0.001), there was no significant variability across the second cycle. Univariable and multivariable models evaluating repeated cross-sectional relationships and intraindividual change scores revealed no consistent associations between estradiol, progesterone, and testosterone and sexual attraction to visual sexual stimuli throughout both menstrual cycles. Also, no significant association with any hormone was found when the data from both menstrual cycles were combined. In women undergoing ovarian stimulation of IVF, sexual attraction to visual sexual stimuli did not vary over time and was not associated with estradiol levels despite intraindividual changes in estradiol levels from 122.0 to 11,746.0 pmol/l with a mean (SD) of 3553.9 (2472.4) pmol/l. CONCLUSIONS: These results imply that neither physiological levels of estradiol, progesterone, and testosterone in naturally cycling women nor supraphysiological levels of estradiol due to ovarian stimulation exert any relevant effect on women's sexual attraction to visual sexual stimuli.

The androgen system across the menstrual cycle: Hormonal, (epi-)genetic and psychometric alterations.

The menstrual cycle is characterized by various hormonal alterations and associations with mental and physical conditions have been postulated. Among endocrine factors, the androgen system has been a target of major interest in males and to a lesser extent in females and may influence emotion, cognition, behavior and somatic factors. Only few studies investigated alterations of these parameters throughout the menstrual cycle and there is a lack of studies exploring a link towards epigenetic and genetic regulation. This multisite longitudinal study examines behavioral parameters including affectivity, stress perception and various diary parameters of mental and physical well-being in conjunction with testosterone and LH plasma levels in 87 menstruating women. Additionally, Cysteine-Adenenine-Guanin (CAG) repeat length and methylation of the androgen receptor gene collected at four time points across two cycles comprising the menstrual, pre-ovulatory, mid-luteal and premenstrual phase were assesed. There was a significant increase of LH and testosterone plasma levels during the pre-ovulatory phase as well as a decrease of methylation of the androgen receptor at mid-luteal phase. Subjective ratings of physical condition and sexual interest peaked during the pre-ovulatory phase and the former correlated negatively with the androgen receptor gene methylation level. This longitudinal study shows alterations of the androgen system including epigenetic measurements throughout the menstrual cycle. While a link between peripheral testosterone and sexual activity and between increased physical condition and an upregulation of testosterone receptor protein expression can be assumed, the majority of parameters remained unchanged. These initial findings need validation by subsequent studies.

Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants: A Secondary Near-Infrared Spectroscopy Study of the Transfusion of Prematures Randomized Clinical Trial (TOP NIRS).

Importance: Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes. Objective: To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age. Design, Setting, and Participants: This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022. Interventions: Near-infrared spectroscopy monitoring of Csat and Msat. Main Outcomes and Measures: Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score <85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment. Results: A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower-hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher-hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs -0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03). Conclusions and Relevance: In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia. Trial Registration: ClinicalTrials.gov Identifier: NCT01702805.

The impact of machine learning in predicting risk of violence: A systematic review.

Background: Inpatient violence in clinical and forensic settings is still an ongoing challenge to organizations and practitioners. Existing risk assessment instruments show only moderate benefits in clinical practice, are time consuming, and seem to scarcely generalize across different populations. In the last years, machine learning (ML) models have been applied in the study of risk factors for aggressive episodes. The objective of this systematic review is to investigate the potential of ML for identifying risk of violence in clinical and forensic populations. Methods: Following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a systematic review on the use of ML techniques in predicting risk of violence of psychiatric patients in clinical and forensic settings was performed. A systematic search was conducted on Medline/Pubmed, CINAHL, PsycINFO, Web of Science, and Scopus. Risk of bias and applicability assessment was performed using Prediction model Risk Of Bias ASsessment Tool (PROBAST). Results: We identified 182 potentially eligible studies from 2,259 records, and 8 papers were included in this systematic review. A wide variability in the experimental settings and characteristics of the enrolled samples emerged across studies, which probably represented the major cause for the absence of shared common predictors of violence found by the models learned. Nonetheless, a general trend toward a better performance of ML methods compared to structured violence risk assessment instruments in predicting risk of violent episodes emerged, with three out of eight studies with an AUC above 0.80. However, because of the varied experimental protocols, and heterogeneity in study populations, caution is needed when trying to quantitatively compare (e.g., in terms of AUC) and derive general conclusions from these approaches. Another limitation is represented by the overall quality of the included studies that suffer from objective limitations, difficult to overcome, such as the common use of retrospective data. Conclusion: Despite these limitations, ML models represent a promising approach in shedding light on predictive factors of violent episodes in clinical and forensic settings. Further research and more investments are required, preferably in large and prospective groups, to boost the application of ML models in clinical practice. Systematic review registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022310410].

Food preferences throughout the menstrual cycle - A computer-assisted neuro-endocrino-psychological investigation.

BACKGROUND: As eating behavior changes in relation to the menstrual cycle and weight changes with menopausal transition, ovarian hormones appear to be involved in regulating eating behavior. However, observations are contradictory and are difficult to compare, due to methodological problems related to nutritional epidemiology. To better understand the relationship between ovarian steroid hormones and eating behavior, our study evaluates women's responses to visual food cues at different points in the menstrual cycle with their specific serum estrogen/progesterone levels and women's responses in the case of strong estrogen changes in the context of fertility treatments. METHODS: We collected data from 129 women, 44 of whom received in vitro fertilization (IVF) at the Department of Reproductive Endocrinology, University Hospital Zurich. A total of 85 women with natural cycles were recruited at the University Hospital Zurich (n = 37) and at the Hannover Medical School (n = 48). Our observational study used 4 different measurement time points across the natural cycle and 2 measurement time points in women with supraphysiological estradiol levels during fertility treatments. Using a second cycle, we then tested our results for replication. At these predefined time points, women were shown pictures of 11 categories of food, with 4 items for each category and blood samples for measurement of hormone levels were taken. Food preferences registered at the time of the investigation were indicated on a visual analogue scale (0-100). RESULTS: We did not find any statistically significant association between women's serum hormone levels and the rating of visually presented food, either during the menstrual cycle or during fertility treatments after controlling for multiple testing (all p > 0.005). Ratings for fruits, vegetables, and carbohydrates showed a significant linear decline throughout the first menstrual cycle (p < 0.01), which did not replicate in the second cycle (p > 0.05). In contrast, the ratings for sweets showed a significant linear decline in both cycles (both p < 0.01), with a mean rating of 54.2 and 48.8 in the menstrual phase of the first and second cycle, respectively, to a mean rating of 47.7 and 43.4 in the premenstrual phase of the first and second cycle, respectively. During fertility treatments, no food rating showed a significant change (all p > 0.05). Mood such as negative and positive affects did not influence ratings for visual food cues neither throughout the menstrual cycles nor during fertility treatment. CONCLUSIONS: Serum levels of estradiol and progesterone do not correlate with food ratings in women, even when estradiol levels are above the physiological level of a natural menstrual cycle. Since, except for sweets, significant changes in food ratings in a first cycle did not replicate in a second menstrual cycle, significant findings from the literature based on animal or human studies focusing on a single-cycle have to be interpreted with caution.

Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation.

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts ("waves") of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.

Associations Between Natural Physiological and Supraphysiological Estradiol Levels and Stress Perception.

Stress is a risk factor for impaired general, mental, and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We, therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception, and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle, and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization (IVF) at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The German version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phases were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasizes the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment. Clinical trial registration: ClinicalTrials.gov # NCT02098668.

Negative affect is unrelated to fluctuations in hormone levels across the menstrual cycle: Evidence from a multisite observational study across two successive cycles.

BACKGROUND: Female sex hormones may play a crucial role in the occurrence of cycle-related mood disorders. However, the literature is inconsistent and methodologically stringent observational studies on the relationship between sex hormones and negative affect are lacking. METHODS: In this longitudinal multisite study from Hannover, Germany, and Zurich, Switzerland, we examined oestrogen, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone serum levels in association with negative affect as measured with the Positive and Negative Affect Schedule (PANAS). Negative affect and hormone assays were collected at four consecutive time points comprising menstrual, pre-ovulatory, mid-luteal and premenstrual phase across two cycles (n=87 and n=67 for the first and second cycles). The Beck Depression Inventory (BDI) was assessed once prior to the first cycle and included as a secondary measure. RESULTS: Mean negative affect scores did not significantly fluctuate across both cycles and there was in particular no symptom increase premenstrually. No sex hormone consistently related to repeated measures of negative affect across two consecutive cycles. The BDI sum-score assessed at baseline was not related to hormone levels across the first cycle. CONCLUSIONS: This is the first multisite longitudinal study on the association between negative affect and sex hormone levels encompassing two consecutive menstrual cycles. Negative affect did not fluctuate across the cycle and there was no direct and uniform association between sex hormones and self-reported negative affect. These findings suggest that moderators such as personality traits and epigenetics should be considered in future research.

Lack of Associations between Female Hormone Levels and Visuospatial Working Memory, Divided Attention and Cognitive Bias across Two Consecutive Menstrual Cycles.

Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability. Methods: This observational multisite study comprised data of n = 88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n = 68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consecutive time-points across both cycles. In addition to inter-individual differences we examined intra-individual change over time (i.e., within-subject effects). Results: Estrogen, progesterone and testosterone did not relate to inter-individual differences in cognitive functioning. There was a significant negative association between intra-individual change in progesterone and change in working memory from pre-ovulatory to mid-luteal phase during the first cycle, but that association did not replicate in the second cycle. Intra-individual change in testosterone related negatively to change in cognitive bias from menstrual to pre-ovulatory as well as from pre-ovulatory to mid-luteal phase in the first cycle, but these associations did not replicate in the second cycle. Conclusions: There is no consistent association between women's hormone levels, in particular estrogen and progesterone, and attention, working memory and cognitive bias. That is, anecdotal findings observed during the first cycle did not replicate in the second cycle, suggesting that these are false-positives attributable to random variation and systematic biases such as practice effects. Due to methodological limitations, positive findings in the published literature must be interpreted with reservation.