"Addressing the core trait of bipolar disorder": A concept analysis of mood-stabilizing drugs.

OBJECTIVE: The term "mood stabilizer" is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning. METHODS: We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta-analyses and other sources for drugs used in the treatment of bipolar disorder. RESULTS: Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: "not worsening," "acute effects," "prophylactic effects," and "advanced effects." "Prophylactic effects" were often considered the core aspect of a legitimate mood stabilizer. CONCLUSION: The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long-term outcomes and illness trajectory, instead of simply approaching symptom clusters.

Effects of bisphenol A on murine salivary glands and human tumor cell lines.

Bisphenol A (BPA) is an endocrine-disrupting chemical with a potential role in endocrine cancers. However, the effects of BPA on the salivary glands have been barely explored. We investigated the impact of in vivo sub-chronic exposure to BPA and its in vitro effects on human salivary gland mucoepidermoid carcinoma cell lines. Male and female mice were exposed to BPA (30 mg/kg/day). Sublingual and submandibular salivary glands from an estrogen-deficiency model were also analyzed. BPA concentration in salivary glands was evaluated by gas chromatography coupled to ion trap mass spectrometry. Immunohistochemical analysis using anti-p63 and anti-α-SMA antibodies was performed on mouse salivary gland tissues. Gene expression of estrogen receptors alpha and beta, P63 and α-SMA was quantified in mouse salivary gland and/or mucoepidermoid (UM-HMC-1 and UM-HMC-3A) cell lines. Cell viability, p63 and Ki-67 immunostaining were evaluated in vitro. BPA disrupted the tissue architecture of the submandibular and sublingual glands, particularly in female mice, and increased the expression of estrogen receptors and p63, effects that were accompanied by significant BPA accumulation in these tissues. Conversely, ovariectomy slightly impacted BPA-induced morphological changes. In vitro, BPA did not affect the proliferation of neoplastic cells, but augmented the expression of p63 and estrogen receptors. The present data highlight a potential harmful effect of BPA on salivary gland tissues, particularly in female mice, and salivary gland tumor cells. Our findings suggest that estrogen-dependent pathways may orchestrate the effects of BPA in salivary glands.

Importance of 24 h ambulatory blood pressure monitoring in patients with acromegaly and correlation with cardiac magnetic resonance findings.

INTRODUCTION: Arterial hypertension (AH) is prevalent in acromegaly, but few studies using 24-h ambulatory blood pressure monitoring (24 h-ABPM) suggest that its frequency may be different from office blood pressure (OBP). Left ventricular hypertrophy (LVH) is one of the most frequent cardiac abnormalities. Cardiac magnetic resonance (CMR) is considered the gold standard to evaluate the heart. OBJECTIVES: To compare the frequency of AH when measured by 24 h-ABPM and by OBP and to correlate BP with cardiac mass. METHODS: Patients over 18 years of age with acromegaly underwent OBP evaluation and were later referred to the 24 h-ABPM. Treatment-naïve patients were submitted to CMR. RESULTS: We evaluated 96 patients. From 29 non hypertensive patients by OBP, 9 had AH on 24 h-ABPM. In the group of patients with a previous diagnosis of AH by OBP, 25 had controlled BP and 42 had abnormal BP on 24 h-ABPM, when analyzed by OBP there were 28 with controlled BP. We observed a positive correlation between diastolic BP measured in 24 h-ABPM and IGF-I levels, but we did not observe the same correlation with age, sex, body mass index and GH levels. The CMR was performed in 11 patients. We found a positive correlation of left ventricular mass (LVM) and BP of 24 h-ABPM. In contrast, there was no correlation of OBP with CMR parameters. CONCLUSIONS: We observed, that 24 h-ABPM in acromegaly allows the diagnosis of AH in some patients with normal BP in OBP and also to allow a better treatment. 24 h-ABPM shows a better correlation with VM by CMR.

Lower prevalence of congenital cytomegalovirus infection in Portugal: possible impact of COVID-19 lockdown?

Cytomegalovirus (CMV) is the most frequent cause of congenital infection all over the world. Its prevalence ranges from 0.2 to 2.2%. Transmission from children to their pregnant mothers is a well-known risk factor, particularly if they attend a childcare centre. This study aims to compare the prevalence of CMV congenital infection (CMV_CI) in Portugal (Lisbon) between two studies, performed respectively in 2019 and 2020. In the 2019 study, performed in two hospitals, we found a 0.67% CMV_CI prevalence, using a pool strategy previously tested with saliva samples. In the 2020 study, using the same pool approach in four hospitals (the previous and two additional), and based on 1277 samples, the prevalence was 0.078%.Conclusion: The close temporal coincidence with COVID-19 lockdown suggests that these measures may have had a significant impact on this reduction, although other explanations cannot be ruled-out. What is Known: • Cytomegalovirus is the leading cause of congenital infection. • Behavioural measures decrease cytomegalovirus seroconversion in pregnant women. What is New: • From 2019 to 2020 there was a significant reduction in the prevalence of congenital CMV infection.

Neuromotor activity inhibition in zebrafish early-life stages after exposure to environmental relevant concentrations of caffeine.

Caffeine (CAF), a neuroactive compound, has been found in surface waters at concentrations ranging from few nanograms up to micrograms and may induce adverse effects in aquatic vertebrates. Thus, the aim of this study was to evaluate the potential of CAF in affecting fish early-life stages in a wide concentration range, including occurring levels in surface waters. Specimens of zebrafish in early-life stages were exposed to CAF for 168 h and survival, developmental alterations, locomotor activity and acetylcholinesterase activity were evaluated. CAF induced mortality in embryos unable to hatch or in larvae after hatching (LC50 - 168 h = 283.2 mg/L). Tail deformities were observed in organisms exposed to concentrations ≥ 40 mg/L, while edemas were found at concentrations of 100 mg/L. CAF also decreased the total swimming time and distance moved of exposed organisms (LOEC = 0.0006 mg/L). Locomotor inhibition may be associated with an acetylcholinesterase inhibition observed at concentration ≥ 0.0088 mg/L. Therefore, the hazard of CAF for fish populations deserves further attention since unexpected effects on neuro-behavioral parameters occurs at concentrations often detected in natural aquatic ecosystems.

Promiscuous RNA binding ensures effective encapsidation of APOBEC3 proteins by HIV-1.

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins are cell-encoded cytidine deaminases, some of which, such as APOBEC3G (A3G) and APOBEC3F (A3F), act as potent human immunodeficiency virus type-1 (HIV-1) restriction factors. These proteins require packaging into HIV-1 particles to exert their antiviral activities, but the molecular mechanism by which this occurs is incompletely understood. The nucleocapsid (NC) region of HIV-1 Gag is required for efficient incorporation of A3G and A3F, and the interaction between A3G and NC has previously been shown to be RNA-dependent. Here, we address this issue in detail by first determining which RNAs are able to bind to A3G and A3F in HV-1 infected cells, as well as in cell-free virions, using the unbiased individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) method. We show that A3G and A3F bind many different types of RNA, including HIV-1 RNA, cellular mRNAs and small non-coding RNAs such as the Y or 7SL RNAs. Interestingly, A3G/F incorporation is unaffected when the levels of packaged HIV-1 genomic RNA (gRNA) and 7SL RNA are reduced, implying that these RNAs are not essential for efficient A3G/F packaging. Confirming earlier work, HIV-1 particles formed with Gag lacking the NC domain (Gag ΔNC) fail to encapsidate A3G/F. Here, we exploit this system by demonstrating that the addition of an assortment of heterologous RNA-binding proteins and domains to Gag ΔNC efficiently restored A3G/F packaging, indicating that A3G and A3F have the ability to engage multiple RNAs to ensure viral encapsidation. We propose that the rather indiscriminate RNA binding characteristics of A3G and A3F promote functionality by enabling recruitment into a wide range of retroviral particles whose packaged RNA genomes comprise divergent sequences.

Does collateral retrospective information about childhood attention-deficit/hyperactivity disorder symptoms assist in the diagnosis of attention-deficit/hyperactivity disorder in adults? Findings from a large clinical sample.

OBJECTIVES: In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder. METHODS: Adult patients with attention-deficit/hyperactivity disorder (n = 449) and non-attention-deficit/hyperactivity disorder subjects (n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement (n = 277) and disagreement (n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms. RESULTS: Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta(2) < 0.05). CONCLUSION: Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings.

Severity but not comorbidities predicts response to methylphenidate in adults with attention-deficit/hyperactivity disorder: results from a naturalistic study.

Although the identification of reliable predictors of methylphenidate response in adults with attention-deficit/hyperactivity disorder (ADHD) is necessary to guide treatment decisions, very few data exist on this issue. Here, we assessed the predictors of clinical response to immediate-release methylphenidate hydrochloride (IR-MPH) in a naturalistic setting by analyzing the influence of demographic factors, severity, and a wide range of comorbid psychiatric disorders. Two hundred fifty adult patients with ADHD were evaluated and completed a short-term treatment with IR-MPH. Mental health diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria through the use of standard structured interviews. The Swanson, Nolan, and Pelham Rating Scale, version 4, adapted to adults was used to assess the severity of ADHD. In the linear regression model, only higher severity of ADHD was associated to a better IR-MPH response (b = 0.770; P < 0.001). Treatment of comorbidities in a subsample (n = 62) did not modify this pattern. Our findings suggest that in clinical settings, patients with more severe ADHD symptoms have a good response to treatment independently from the presence of mild or stabilized comorbidities and their treatments. For adults with ADHD, differently from other common psychiatric disorders such as depression and anxiety, higher severity is associated with better treatment response.

Automatic control of the NMB level in general anaesthesia with a switching total system mass control strategy.

This paper presents a model based switching control strategy to drive the neuromuscular blockade (NMB) level of patients undergoing general anesthesia to a predefined reference. A single-input single-output Wiener system with only two parameters is used to model the effect of two different muscle relaxants, atracurium and rocuronium, and a switching controller is designed based on a bank of total system mass control laws. Each of such laws is tuned for an individual model from a bank chosen to represent the behavior of the whole population. The control law to be applied at each instant corresponds to the model whose NMB response is closer to the patient's response. Moreover a scheme to improve the reference tracking quality based on the analysis of the patient's response, as well as, a comparison between the switching strategy and the Extended Kalman Kilter (EKF) technique are presented. The results are illustrated by means of several simulations, where switching shows to provide good results, both in theory and in practice, with a desirable reference tracking. The reference tracking improvement technique is able to produce a better reference tracking. Also, this technique showed a better performance than the (EKF). Based on these results, the switching control strategy with a bank of total system mass control laws proved to be robust enough to be used as an automatic control system for the NMB level.

Safety-promoting interventions for the older person with hip fracture on returning home: A systematic review.

BACKGROUND: Older adults with a prior history of falls that results in hip fractures have difficulties in regaining pre-fracture functional capacity. Scientific evidence has shown benefits of the implementation of multidimensional rehabilitation programs, but this evidence is not systematized with regard to continuity of care after hospital discharge. OBJECTIVE: To identify interventions that promote safety and functional recovery of older adults with hip fractures after hospital discharge. METHOD: A systematic review was carried out according to Cochrane methodology. The research strategy was predefined for the MEDLINE and CINAHL databases. The identified articles were screened according to the eligibility criteria by two independent reviewers. The articles included in the bibliographic sample were evaluated for risk of bias. RESULTS: Of the 10,036 articles found, 10 were included in this systematic review. The safety-promoting interventions identified were: exercise training, occupational therapy/activities of daily living training, transfer and gait training, strengthening exercises, education on assistive device use, fall prevention education, nutritional assessment, environmental modifications/adjustments at home, use of an app, medication, self-care education, and support and counseling. CONCLUSIONS: In eight studies analyzed, exercise training emerged as the most effective intervention for promoting the safety of older adults after hip fractures on returning home. Three studies associated two or more interventions, which focused on exercise training, occupational therapy/training of activities of daily living, and conventional postoperative rehabilitation with transfer and gait training, strengthening exercises, education on assistive device use and discharge planning, aiming to achieve muscle strengthening and safe gait, associated with the performance of activities of daily living.

Oral cancer and oral potentially malignant disorders in patients with Fanconi anemia - A systematic review.

The purpose of the present study was to perform a systematic review focusing on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) in Fanconi anemia (FA) individuals. Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature. Case reports and/or cases series were included. The searches yielded 55 studies describing 112 cases of OSCC (n = 107) and/or OPMD (n = 5) in FA individuals. The mean age at diagnosis of OSCC/OPMD was 27.1 (±9.6) years, and females (51.8 %) were slightly more affected. Ulcer (n = 37) or mass (n = 25) were described as clinical presentations for OSCC and OPMD. White lesions (n = 4) were the most common manifestation in OPMD. Tongue (47.2 %) was the most frequent location. Sixty-one (54.5 %) individuals underwent HSCT. Surgical resection (n = 75) was the main treatment adopted. The estimated rate of OPMD malignant transformation was 1.8 % and recurrences following OSCC excision occurred in 26.8 % of individuals. Overall, at 60 months of follow-up, the probability of survival fell to 25.5 % and at 64 months the probability of recurrence increased to 63.2 %. The present data support the need for strict surveillance of patients with FA, even in the absence of OPMD, for early OSCC detection and reduction of mortality.

Hb Plasencia [α125(H8)Leu→Arg (α2)] is a frequent cause of α+-thalassemia in the Portuguese population.

Hb Plasencia is a thalassemic hemoglobin (Hb) mutation caused by a leucine to arginine replacement at residue 125 of the α2-globin chain (HBA2:c.377T>G). This variant was first described in the heterozygous state in association with a very mild α-thalassemic phenotype in three members of a Spanish family from Plasencia, Western Spain. Reviewing the molecular characterization of 308 Portuguese individual suspected of having α-thalassemia (α-thal) we found Hb Plasencia to be the second most frequent mutation after the -α(3.7) deletion.

Pooling Saliva Sample as an Effective Strategy for the Systematic CMV Screening of Newborns-A Multicentric Prospective Study.

BACKGROUND: Cytomegalovirus is the most common cause of congenital infections worldwide. Screening all newborns in the first 2 weeks of life is the only way to detect all cases of congenital infection, allowing the monitoring of children with asymptomatic infection at birth and early intervention. AIM: In this multicenter study, we aimed to evaluate the feasibility of using a saliva pool strategy for mass screening in 7 Portuguese hospitals, and to estimate the current prevalence of this congenital infection in these hospitals. METHODS: A total of 7033 newborns were screened between June 2020 and June 2022, and 704 pools of 10 saliva samples were analyzed by polymerase chain reaction (PCR). RESULTS: Of the 704 pools analyzed, 685 were negative and 19 had positive PCR results for cytomegalovirus. After individual PCR testing, 26 newborns had positive saliva results, of which 15 were confirmed by urine testing. Thus, this study's prevalence of congenital infection was 0.21% (95% confidence interval: 0.12%-0.35%). CONCLUSIONS: In this study, the pooling strategy proved to be effective for the systematic screening of newborns, although this low prevalence raises questions regarding the cost-effectiveness of implementing universal screening. However, this prevalence is probably the result of the control measures taken during the pandemic; therefore, the rates are expected to return to prepandemic values, but only a new study after the pandemic will be able to confirm this.

Inhibitory effects of resveratrol analogs on mushroom tyrosinase activity.

Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC(50) = 28.66 µg/mL), two times more active than resveratrol (IC(50) = 57.05 µg/mL), followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity.

Safety-Promoting Interventions for the Older Person with Hip Fracture on Returning Home: A Protocol for a Systematic Review.

Ageing and physical frailty associated with decrease in muscle and bone mass lead to the older persons' vulnerability and increased risk of falling. It is estimated that one in every ten falls in this age group results in a fracture, leading to a downward spiral in their health status, causing greater dependence, with a progressive functional decline that makes it difficult to return to their functional and social status prior to the fracture. The aim of this study is to identify the available evidence on the interventions that promote the safety of older people with hip fracture after hospital discharge. A search will be performed in MEDLINE and CINAHL databases. Randomised and controlled studies that focus on functional assessment, performance in activities of daily living, level of concern about falls, risk and prevalence of falls, injuries secondary to falls, re-fracture rate and health-related quality of life in hip fracture patients will be included. Two authors will perform the study selection, data extraction, and quality assessment independently. Any disagreements will be resolved through discussion with a third researcher. Methodological quality of the included trials will be evaluated by the Cochrane risk-of-bias criteria, and the Standards for Reporting Interventions in Controlled Trials.

Description of a safe doppler ultrasound-guided technique for hyaluronic acid filler in the face-A method to avoid adverse vascular events.

BACKGROUND: Knowledge of facial anatomy is essential for professionals intending to inject hyaluronic acid (HA) into that region, but due to the considerable anatomical variations in region, it does not guarantee the complete safety of the procedure. Similarly, procedures widely disseminated among professionals, such as aspiration and the use of cannulas, do not ensure total safety against vascular occlusion events caused by the filler. OBJECTIVES: This article describes a technique for injecting hyaluronic acid into the face guided by Doppler ultrasonography (DUS) in order to ensure greater safety against vascular occlusion events secondary to the procedure. METHODS: We describe a Doppler ultrasound-guided filling technique, with an 18 MHZ transducer, consisting of three steps: arterial mapping, real-time ultrasound-guided filling, and assessing the perfusion. RESULTS: The described technique was performed in 480 patients and can be adopted in the routine of professionals who inject hyaluronic acid, especially in areas at high risk for vascular events. Its use results in greater safety against vascular occlusion events secondary to the procedure, without the need for prior aspiration. We conclude that there is a local vasodilation right after the filling that makes it difficult the possibility of extrinsic compression exerted by the filler on the vessel. Furthermore, the product moves to deep planes even with the bevel facing up (toward the epidermis). CONCLUSIONS: We believe that in the future the use of Doppler ultrasound-guided filling technique will be mandatory for professionals who intend to perform HA injection, to both ensure patient safety and provide legal protection for the professional.

Young People Awareness of Sexually Transmitted Diseases and Contraception: A Portuguese Population-Based Cross-Sectional Study.

Adolescents and young adults are an important target concerning reducing health-risk behavior adoption, including sexual health. Studying their knowledge concerning sexuality and their main counsellors, can be an important step in targeting an updated health promotion approach. This study characterized adolescents and young adults' knowledge and attitudes about sexually transmitted diseases (STDs), and contraception, prospecting for their main trusted counseling sources. We conducted a cross-sectional, population-based, self-report survey of 746 individuals aged between 14 and 24 years from Paredes, Portugal. The questionnaire included many dimensions, as demographic characteristics, youth behavior, currently sexually active status, main counselors concerning health topics, awareness, and knowledge about STDs and contraception. Mean age of the participants was 18.3 years, 50.5% of them had started their sexual activity. Males present themselves as more sexually active, starting earlier, and have more sexual partners than females. Participants reported an adequate knowledge perception about STDs and contraception methods, however we found different patterns on specific STDs and contraceptive methods, according to gender, age, and sexually active status. Our results help design specific interventions to reach youth, community, and healthcare providers, pointing out the value of bringing people to the center of health policies.

Diversity of Nematoda and Digenea from different species of characiform fishes from Tocantins River, Maranhão, Brazil.

During a survey of the helminth fauna of characiform fishes from the Tocantins River, Brazil, 185 fish specimens from 22 species were studied. Twelve species of Nematoda and nine species of Digenea were collected. Some of these helminth species were reported for the first time in their hosts, thus representing new host records: Procamallanus (Spirocamallanus) sp. in Bivibranchia notata, Brycon pesu, Chalceus macrolepidotus, Hemiodus microlepis and Hemiodus unimaculatus; Procamallanus (Spirocamallanus) inopinatus in Triportheus elongatus; Goezia sp. (larva) in Boulengerella cuvieri; Rhabdochona acuminata in Brycon pesu and Triportheus trifurcatus; Raphidascaris sp. (larva) in Caenotropus labyrinthicus; Cosmoxynema vianai in Cyphocharax gouldingi; Rondonia rondoni in Leporinus fasciatus and Mylesinus paucisquamatus; Klossinemella iheringi in Mylesinus paucisquamatus; Cucullanidae gen. sp. in Myloplus rubripinnis; Rhabdochona sp. in Triportheus elongatus; Alphamphistoma sp. in Myleus setiger; Chalcinotrema sp. in Cyphocharax gouldingi; Pacudistoma guianense in Hemiodus unimaculatus and Myleus torquatus; Pseudocladorchis cylindricus in Hemiodus unimaculatus; Dadaytrema oxycephala in Mylesinus paucisquamatus; Travassosinia dilatata in Myloplus asterias; and Genarchella genarchella in Raphiodon vulpinus. Studies identifying new hosts and new localities for parasites have contributed to the knowledge of local biodiversity. A list of previous records of helminths included in the present study, providing hosts, localities, and references, is presented here.

Correction: Validation of the Unesp-Botucatu composite scale to assess acute postoperative abdominal pain in sheep (USAPS).

[This corrects the article DOI: 10.1371/journal.pone.0239622.].

Placental model as an important tool to study maternal-fetal interface.

The placenta is a temporary organ that plays critical roles at the maternal-fetal interface. Normal development and function of the placenta is dependent on hormonal signaling pathways that make the placenta a target of endocrine disrupting chemical (EDC) action. Studies showing association between prenatal exposure, hormone disruption, and reproductive damage indicate that EDCs are developmentally toxic and can impact future generations. In this context, new placental models (trophoblast-derived cell lines, organotypic or 3D cell models, and physiologically based kinetic models) have been developed in order to create new approach methodology (NAM) to assess and even prevent such disastrous toxic harm in future generations. With the widespread discouragement of conducting animal studies, it has become irrefutable to develop in vitro models that can serve as a substitute for in vivo models. The goal of this review is to discuss the newest in vitro models to understand the maternal-fetal interface and predict placental development, physiology, and dysfunction generated by failures in molecular hormone control mechanisms, which, consequently, may change epigenetic programming to increase susceptibility to metabolic and other disorders in the offspring. We summarize the latest placental models for developmental toxicology studies, focusing mainly on three-dimensional (3D) culture models.