The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA).

BACKGROUND: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to 0.2 ng/kg body weight (BW)/day. BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists. Guideline protocols initially formalized in the mid-twentieth century are still used by many regulatory agencies. EFSA used a 21st century approach in its reassessment of BPA and conducted a transparent, but time-limited, systematic review that included both guideline and academic research. The German Federal Institute for Risk Assessment (BfR) opposed EFSA's revision of the TDI for BPA. OBJECTIVES: We identify the flaws in the assumptions that the German BfR, as well as the FDA, have used to justify maintaining the TDI for BPA at levels above what a vast amount of academic research shows to cause harm. We argue that regulatory agencies need to incorporate 21st century science into chemical hazard identifications using the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) nonguideline academic studies in a collaborative government-academic program model. DISCUSSION: We strongly endorse EFSA's revised TDI for BPA and support the European Commission's (EC) apparent acceptance of this updated BPA risk assessment. We discuss challenges to current chemical risk assessment assumptions about EDCs that need to be addressed by regulatory agencies to, in our opinion, become truly protective of public health. Addressing these challenges will hopefully result in BPA, and eventually other structurally similar bisphenols (called regrettable substitutions) for which there are known adverse effects, being eliminated from all food-related and many other uses in the EU and elsewhere. https://doi.org/10.1289/EHP13812.

The association between childhood trauma and motor structure in obsessive-compulsive rituals: An ethological and evolutionary approach.

OBJECTIVE: Ethological models have highlighted a specific motor structure of compulsions in obsessive-compulsive disorder (OCD), based on the rigid repetitions of acts, and with the adaptive significance of facing unpredictable conditions. Such an evolutionary mechanism might explain the robust association between childhood traumatic experiences (CTEs) and OCD. However, a relationship between CTEs and the motor structure of compulsions has not been investigated yet. The first objective of the study was to confirm a specific motor structure of OCD compulsions with respect to control behaviors; the second objective was to assess a possible association between the motor structure of compulsions and CTEs severity. METHOD: Thirty-two OCD outpatients (13 female, Mage = 44.50 years, SE = 19.71) and 27 healthy controls (10 female, Mage = 37.62 years, SE = 16.20), matched for sex and age, provided a videotape of their compulsions and corresponding ordinary acts, respectively. Behavior was scored with the software "Observer." Participants were administered the Yale-Brown Obsessive Compulsive Scale and the Childhood Trauma Questionnaire. A dependent t test was used to compare the motor structure of behavior between the groups; Pearson's correlations to investigate associations between motor parameters and CTEs. RESULTS: Compulsions showed a specific motor structure due to the repetition of functional and nonfunctional acts. CTEs severity was especially associated with the repetition of functional acts, independently from OCD severity. CONCLUSION: Our findings, in confirming a peculiar motor structure for OCD compulsions, hint for the first time at a link between CTEs and compulsive repetition of functional acts, which would represent a plastic developmental response to CTEs unpredictability. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Disembodiment and Language in Schizophrenia: An Integrated Psychopathological and Evolutionary Perspective.

Different hypotheses have flourished to explain the evolutionary paradox of schizophrenia. In this contribution, we sought to illustrate how, in the schizophrenia spectrum, the concept of embodiment may underpin the phylogenetic and developmental pathways linking sensorimotor processes, the origin of human language, and the construction of a basic sense of the self. In particular, according to an embodied model of language, we suggest that the reuse of basic sensorimotor loops for language, while enabling the development of fully symbolic thought, has pushed the human brain close to the threshold of a severe disruption of self-embodiment processes, which are at the core of schizophrenia psychopathology. We adopted an inter-disciplinary approach (psychopathology, neuroscience, developmental biology) within an evolutionary framework, to gain an integrated, multi-perspectival model on the origin of schizophrenia vulnerability. A maladaptive over-expression of evolutionary-developmental trajectories toward language at the expense of embodiment processes would have led to the evolutionary "trade-off" of a hyper-symbolic activity to the detriment of a disembodied self. Therefore, schizophrenia psychopathology might be the cost of long-term co-evolutive interactions between brain and language.

Can we reduce worldwide neonatal mortality?

Worldwide neonatal mortality rate is still very high in many countries, with a sharp difference between developed and developing countries. The difference of interventions to be implemented for reducing neonatal mortality rate  in developing and developed countries will be discussed.

Non-invasive administration of poractant-α in neonatal respiratory distress syndrome via a supraglottic device in the clinical practice in a second level neonatal unit: comparison of LMA® vs iGel® devices.

Non-invasive pulmonary surfactant (SF) administration for neonatal respiratory distress syndrome (NRDS) is a development of administration of SF. Administration of SF via a supraglottic device (SGD) has been shown to be effective. Here the results of administration of SF in NRDS in infants requiring oxygen and nasal-CPAP (n-CPAP) via two types of SGDs, LMA® vs iGel®, in a second level Neonatal Unit are reported in a retrospective study. Results - Fourteen infants in the LMA®Group were matched with 21 comparable infants in the iGel® Group (g.a. ≥30 wks and b.w. ≥ 1,500 gr) presenting NRDS with fraction of inspired oxygen (FiO2) ≥ 0.25 - 0.6, requiring n-CPAP. All infants presented a significant improvement of PaO2/FiO2 ratio that was seen earlier in the iGel® Group vs the LMA® Group. There was no severe adverse effect during the maneuver with both SGDs. No baby died, No.2 required endotracheal intubation for a second dose of SF as by protocol, and No. 1 was transferred to a higher level of care. Conclusion - Non-invasive SF administration via SGD has been done effectively at a second level Neonatal Unit and very early in the course of the disease therefore limiting transfer of the baby without complications with both SGDs. Improvement in gas exchange was more rapid in the iGel®Group. This result needs confirmation. In our experience iGel® was easier to use than LMA®.

Quo Vadis Psychiatry? Why It Is Time to Endorse Evolutionary Theory.

ABSTRACT: In recent decades, psychiatry and the neurosciences have made little progress in terms of preventing, diagnosing, classifying, or treating mental disorders. Here we argue that the dilemma of psychiatry and the neurosciences is, in part, based on fundamental misconceptions about the human mind, including misdirected nature-nurture debates, the lack of definitional concepts of "normalcy," distinguishing defense from defect, disregarding life history theory, evolutionarily uninformed genetic and epigenetic research, the "disconnection" of the brain from the rest of the body, and lack of attention to actual behavior in real-world interactions. All these conceptual difficulties could potentially benefit from an approach that uses evolutionary theory to improve the understanding of causal mechanisms, gene-environment interaction, individual differences in behavioral ecology, interaction between the gut (and other organs) and the brain, as well as cross-cultural and across-species comparison. To foster this development would require reform of the curricula of medical schools.

The motor profile of obsessive-compulsive rituals: psychopathological and evolutionary implications.

BACKGROUND: Studies investigating obsessive-compulsive disorder from an ethological approach have highlighted a specific motor pattern of compulsive rituals with respect to corresponding ordinary behaviors. Particularly, compulsive motor profile is built through the repetition of acts, with prevalence of nonfunctional ones and redirection of attention to its basic structural units. These formal features would characterize ritual behavior throughout evolution, from nonhuman animals to human cultures. However, no study to date has investigated a possible relationship between such motor profile and underlying psychopathology. Therefore, the first objective of the study was to confirm previous findings on a larger sample size of obsessive patients; the second objective was to elucidate whether motor profile might be associated with obsessive-compulsive psychopathology and/or prepsychotic symptoms of schizophrenia. METHODS: Twenty-one obsessive-compulsive outpatients provided a videotape of their rituals. An equal number of healthy controls, matched for sex and age, were registered for corresponding ordinary acts. Obsessive patients were administered the Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Hamilton Rating Scale for Depression, and the Frankfurt Complaint Questionnaire. RESULTS: The results of the present study confirm that ritual compulsions present a specific motor structure characterized by repetition of both functional and nonfunctional acts and their longer duration. Such a motor pattern is independent from obsessive-compulsive psychopathology, whereas it results specifically associated with prepsychotic symptoms of schizophrenia. CONCLUSIONS: We argue that this association may reflect the adaptive significance of ritual behavior across evolution, that is, its homeostatic function in conditions of unpredictability.

Conditional Inactivation of Limbic Neuropeptide Y-1 Receptors Increases Vulnerability to Diet-Induced Obesity in Male Mice.

NPY and its Y1 cognate receptor (Y1R) have been shown to be involved in the regulation of stress, anxiety, depression and energy homeostasis. We previously demonstrated that conditional knockout of Npy1r gene in the excitatory neurons of the forebrain of adolescent male mice (Npy1rrfb mice) decreased body weight growth and adipose tissue and increased anxiety. In the present study, we used the same conditional system to examine whether the targeted disruption of the Npy1r gene in limbic areas might affect susceptibility to obesity and associated disorders during adulthood in response to a 3-week high-fat diet (HFD) regimen. We demonstrated that following HFD exposure, Npy1rrfb male mice showed increased body weight, visceral adipose tissue, and blood glucose levels, hyperphagia and a dysregulation of calory intake as compared to control Npy1r2lox mice. These results suggest that low expression of Npy1r in limbic areas impairs habituation to high caloric food and causes high susceptibility to diet-induced obesity and glucose intolerance in male mice, uncovering a specific contribution of the limbic Npy1r gene in the dysregulation of the eating/satiety balance.

Sex-biased impact of endocrine disrupting chemicals on behavioral development and vulnerability to disease: Of mice and children.

Sex is a fundamental biological characteristic that influences many aspects of an organism's phenotype, including neurobiological functions and behavior as a result of species-specific evolutionary pressures. Sex differences have strong implications for vulnerability to disease and susceptibility to environmental perturbations. Endocrine disrupting chemicals (EDCs) have the potential to interfere with sex hormones functioning and influence development in a sex specific manner. Here we present an updated descriptive review of findings from animal models and human studies regarding the current evidence for altered sex-differences in behavioral development in response to early exposure to EDCs, with a focus on bisphenol A and phthalates. Overall, we show that animal and human studies have a good degree of consistency and that there is strong evidence demonstrating that EDCs exposure during critical periods of development affect sex differences in emotional and cognitive behaviors. Results are more heterogeneous when social, sexual and parental behaviors are considered. In order to pinpoint sex differences in environmentally-driven disease vulnerabilities, researchers need to consider sex-biased developmental effects of EDCs.

Proximate and ultimate causes of ritual behavior.

Ritual behaviour, intended as a specific, repetitive and rigid form of action flow, appears both in social and non-social environmental contexts, representing an ubiquitous phenomenon in animal life including human individuals and cultures. The purpose of this contribution is to investigate an evolutionary continuum in proximate and ultimate causes of ritual behavior. A phylogenetic homology in proximal mechanisms can be found, based on the repetition of genetically programmed and/or epigenetically acquired action patterns of behavior. As far as its adaptive significance, ethological comparative studies show that the tendency to ritualization is driven by the unpredictability of social or ecological environmental stimuli. In this perspective, rituals may have a "homeostatic" function over unpredictable environments, as further highlighted by psychopathological compulsions. In humans, a circular loop may have occurred among ritual practices and symbolic activity to deal with a novel culturally-mediated world. However, we suggest that the compulsion to action patterns repetition, typical of all rituals, has a genetically inborn motor foundation, thus precognitive and pre-symbolic. Rooted in such phylogenetically conserved motor structure (proximate causes), the evolution of cognitive and symbolic capacities have generated the complexity of human rituals, though maintaining the original adaptive function (ultimate causes) to cope with unpredictable environments.

Effects of Prenatal Exposure to a Low-Dose of Bisphenol A on Sex Differences in Emotional Behavior and Central Alpha2-Adrenergic Receptor Binding.

Prenatal exposure to bisphenol A (BPA) influences the development of sex differences neurologically and behaviorally across many species of vertebrates. These effects are a consequence of BPA's estrogenic activity and its ability to act as an endocrine disrupter even, at very low doses. When exposure to BPA occurs during critical periods of development, it can interfere with the normal activity of sex steroids, impacting the fate of neurons, neural connectivity and the development of brain regions sensitive to steroid activity. Among the most sensitive behavioral targets of BPA action are behaviors that are characterized by a sexual dimorphism, especially emotion and anxiety related behaviors, such as the amount of time spent investigating a novel environment, locomotive activity and arousal. Moreover, in some species of rodents, BPA exposure affected males' sexual behaviors. Interestingly, these behaviors are at least in part modulated by the catecholaminergic system, which has been reported to be a target of BPA action. In the present study we investigated the influence of prenatal exposure of mice to a very low single dose of BPA on emotional and sexual behaviors and on the density and binding characteristics of alpha2 adrenergic receptors. Alpha2 adrenergic receptors are widespread in the central nervous system and they can act as autoreceptors, inhibiting the release of noradrenaline and other neurotransmitters from presynaptic terminals. BPA exposure disrupted sex differences in behavioral responses to a novel environment, but did not affect male mice sexual behavior. Importantly, BPA exposure caused a change in the binding affinity of alpha2 adrenergic receptors in the locus coeruleus and medial preoptic area (mPOA) and it eliminated the sexual dimorphism in the density of the receptors in the mPOA.

The biological origins of rituals: An interdisciplinary perspective.

Ritual behavior is ubiquitous, marking animal motor patterns, normal and psychopathological behavior in human individuals as well as every human culture. Moreover, formal features of rituals appear to be highly conserved along phylogeny and characterized by a circular and spatio-temporal structure typical of habitual behavior with internal repetition of non-functional acts and redirection of attention to the "script" of the performance. A continuity, based on highly conserved cortico-striatal loops, can be traced from animal rituals to human individual and collective rituals with psychopathological compulsions at the crossing point. The transition from "routinization" to "ritualization" may have been promoted to deal with environmental unpredictability in non-social contexts and, through motor synchronization, to enhance intra-group cohesion and communication in social contexts. Ultimately, ritual, following its biological constraints exerts a "homeostatic" function on the environment (social and non-social) under conditions of unpredictability.

Back to Stir It Up: Erectile Dysfunction in an Evolutionary, Developmental, and Clinical Perspective.

In this review, we analyze erectile dysfunction (ED) in the context of sexual selection. We highlight that ED is a specific human male characteristic linked to the loss of the baculum or penile bone and results from a range of physical and psychological factors. We discuss evolutionary interpretations that consider dysfunctional penile erection as an honest signal of a low-quality male. We further emphasize the importance of considering psychosocial context and early attachment dynamics for understanding the etiology of some types of ED. Finally, we suggest that the integration of developmental factors for understanding the emergence of this sexual disorder is instrumental for the calibration of more effective therapies.

Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting.

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.

What is stressful for females? Differential effects of unpredictable environmental or social stress in CD1 female mice.

Stressful life events are a major factor in the etiology of several diseases, such as cardiovascular, inflammatory and psychiatric disorders (i.e., depression and anxiety), with the two sexes greatly differing in vulnerability. In humans and other animals, physiological and behavioral responses to stress are strongly dependent on gender, and conditions that are stressful for males are not necessarily stressful for females. Hence the need of an animal model of social chronic stress specifically designed for females. In the present study we aimed to compare the effects of two different chronic stress procedures in female mice, by investigating the impact of 4weeks of nonsocial unpredictable, physical stress by the Chronic Mild Stress paradigm (CMS; Exp.1) or of Social Instability Stress (SIS; Exp.2) on physiological, endocrine and behavioral parameters in adult female mice. CMS had a pronounced effect on females' response to novelty (i.e., either novel environment or novel social stimulus), body weight growth and hormonal profile. Conversely, 4weeks of social instability did not alter females' response to novelty nor hormonal levels but induced anhedonia. Our findings thus showed that female mice were more sensitive to nonsocial stress due to unpredictable physical environment than to social instability stressors. Neither of these stress paradigms, however, induced a consistent behavioral and physiological stress response in female mice comparable to that induced by chronic stress procedures in male mice, thus confirming the difficulties of developing a robust and validated model of chronic psychosocial stress in female mice.

Correction to: Parma consensus statement on metabolic disruptors.

CORRECTION: After publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".

How does sex matter? Behavior, stress and animal models of neurobehavioral disorders.

Many aspects of brain functioning exhibit important sex differences that affect behavior, mental health and mental disorders. However, most translational neuroscience research related to animal models of neurobehavioral disorders are carried out in male animals only. Based on published data from our laboratory on the House mouse, we discuss the following issues: (1) sex differences in social behavior of wild-derived mice; (2) artificial selection of laboratory strains and its consequences on social and reproductive competition; (3) sex-dependent effects of common experimental procedures; (4) differential effects of developmental events: the case of endocrine disruption; (5) implications for female models of stress and neurobehavioral disorders. Altogether, this review of data outline the marked differences of male and female responses to different social challenges and evinces the current lack of a relevant female mouse model of social stress. Whilst animal modelling is an important approach towards understanding mechanisms of neurobehavioral disorders, it is evident that data obtained in males may be irrelevant for inferring psychopathology and efficacy of pharmacological treatments for females.

Successful breastfeeding: a global intervention for a physiological process.

In our perinatal unit we applied the ten steps of WHO/UNICEF for Baby Friendly Hospital Initiative and evaluated the percentage of exclusive (EBF) or complementary breastfeeding (CBF), and of formula fed (FF) healthy full-term infants (HFI) at hospital discharge (HD). HFI performing EBF at HD were 85.3%, a quite high value. At the age of 3 mths EBF percentage ranged between 59-62.4%, and at 6 mths it decreased to 51.7-37.7%. Customer satisfaction questionnaire at HD ranked "good" to "very good" in 92.8%. Causes of breastfeeding reduction with time and comparison with previous and actual situation in Italy and civilized countries are discussed.