Is Antipsychotic Drug Use During Pregnancy Associated with Increased Malformation Rates and Worsening of Maternal and Infant Outcomes? A Systematic Review.

There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR "birth defect*" OR "congenital abnormality" OR "congenital abnormalities" OR "brain changes" OR "behavioral abnormalities" OR "behavioral abnormalities") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics, especially the second-generation antipsychotics, were devoid of teratogenic potential, while few studies were inconclusive and recommended replication. Most authoritative articles were from the Boston area, where large databases were implemented to study the malformation potential of psychiatric drugs. Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics are no more related to malformations than the disorders themselves; most studies recommend that there are no reasons to discontinue antipsychotic medications in pregnancy.

Propranolol Promotes Monocyte-to-Macrophage Differentiation and Enhances Macrophage Anti-Inflammatory and Antioxidant Activities by NRF2 Activation.

Adrenergic pathways represent the main channel of communication between the nervous system and the immune system. During inflammation, blood monocytes migrate within tissue and differentiate into macrophages, which polarize to M1 or M2 macrophages with tissue-damaging or -reparative properties, respectively. This study investigates whether the ß-adrenergic receptor (ß-AR)-blocking drug propranolol modulates the monocyte-to-macrophage differentiation process and further influences macrophages in their polarization toward M1- and M2-like phenotypes. Six-day-human monocytes were cultured with M-CSF in the presence or absence of propranolol and then activated toward an M1 pro-inflammatory state or an M2 anti-inflammatory state. The chronic exposure of monocytes to propranolol during their differentiation into macrophages promoted the increase in the M1 marker CD16 and in the M2 markers CD206 and CD163 and peroxisome proliferator-activated receptor É£ expression. It also increased endocytosis and the release of IL-10, whereas it reduced physiological reactive oxygen species. Exposure to the pro-inflammatory conditions of propranolol-differentiated macrophages resulted in an anti-inflammatory promoting effect. At the molecular level, propranolol upregulated the expression of the oxidative stress regulators NRF2, heme oxygenase-1 and NQO1. By contributing to regulating macrophage activities, propranolol may represent a novel anti-inflammatory and immunomodulating compound with relevant therapeutic potential in several inflammatory diseases.

Rapid autopsies to enhance metastatic research: the UPTIDER post-mortem tissue donation program.

Research on metastatic cancer has been hampered by limited sample availability. Here we present the breast cancer post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median of 31 (range: 5-90) metastases and 5-8 liquids per patient from its first 20 patients. In a dedicated experiment, we show the mild impact of increasing time after death on RNA quality, transcriptional profiles and immunohistochemical staining in tumor tissue samples. We show that this impact can be counteracted by organ cooling. We successfully generated ex vivo models from tissue and liquid biopsies from distinct histological subtypes of breast cancer. We anticipate these and future findings of UPTIDER to elucidate mechanisms of disease progression and treatment resistance and to provide tools for the exploration of precision medicine strategies in the metastatic setting.

Keep in mind sex differences when prescribing psychotropic drugs.

Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs. There are inevitable differences in efficacy, side effects and long-term treatment response between men and women. Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects. Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions, to maximize therapeutic effectiveness and to provide personalized management of care.

The Effectiveness of the Third Dose of COVID-19 Vaccine: When Should It Be Performed?

BACKGROUND: COVID-19 vaccination is the most significant step toward the long-term mitigation of SARS-CoV-2-related complication, avoiding disease and death and decreasing virus spread. This study aimed to evaluate, in a real-world setting, booster dose effectiveness to reduce COVID-19 risk considering the amount of time after the end of the two-dose vaccination cycle. A sub-analysis was conducted to adjust the booster dose effect for occupational and demographic factors. METHODS: About 16,000 COVID-19-vaccinated HCWs of three University Hospital Networks in Milan (HN1/HN2/HN3) were included in the study. Data were collected by Occupational Health Physicians of the HNs within specific computerized databases. RESULTS: In univariable analysis, booster dose administration displayed a slightly higher risk of infection with respect to not receiving it, OR = 1.18, with 95% confidence interval (C.I) [0.99, 1.41]. When the model was adjusted with the modulating effect of time from the completion of the vaccination cycle on booster dose administration, the latter resulted in strong protective effect against infection, OR = 0.43, 95% CI [0.26, 0.74]. However, considering the modifying influence of time from the vaccination cycle's completion, the administration of booster doses appeared to have a protective effect against infection. In HN1, students and resident physicians displayed lower odds of infection with respect to physicians. Lastly, a non-linear effect of age was reported. CONCLUSIONS: Our findings suggest that the correct timing in vaccine scheduling and administration is critical to vaccine effectiveness. These findings, applicable to all vaccinations, should help in setting up more effective vaccination strategies.

Is peripartum anhedonia a missing target?

The perinatal period is an extremely delicate phase that can involve a high risk for onset of depressive disorders. The Edinburgh Postnatal Depression Scale (EPDS) is a widely validated instrument for assessing perinatal depressive symptoms, including the dimension of anhedonia. There are studies suggesting that the neural mechanism underlying the occurrence of anhedonia in patients with major depressive disorder (MDD) and bipolar depression (BD) might be distinct. Anhedonia seems to represent a more stable and frequent symptom in women with postpartum bipolar relative to unipolar depressive disorder and is associated with significantly higher depressive symptom severity. Perinatal medicine is an important component of women's health. Treatment of anhedonia can be challenging, and the most effective treatment can be a combination of psychotherapy and medication, but the screening of anhedonia in peripartum women can prevent the development of other psychiatric disorders and maladaptive behaviors.

Long-term effects of SARS-CoV-2 infection in hospitalized children: findings from an Italian single-center study.

BACKGROUND: Limited evidence exists regarding the association between COVID-19 and Long COVID manifestations in children, particularly concerning variants of concern (VOCs). We aimed to characterize a cohort of pediatric patients hospitalized with confirmed acute SARS-CoV-2 and monitor them for Long COVID symptoms. Additionally, it seeks to explore any potential correlations between VOCs and clinical symptoms. METHODS: We conducted a prospective study involving children hospitalized from November 2021 to March 2023, with confirmed acute SARS-CoV-2 infection. A telephone survey was conducted at 3-6-12 months after discharge. RESULTS: We included 167 patients (77 F/90 M). Upon hospital admission, 95.5% of patients presented as symptomatic. Regarding patients for whom it was feasible to determine the SARS-CoV-2 variant (n = 51), the Delta variant was identified in 11 children (21.6%) and Omicron variant in the remaining 40 patients (78.4%: 27.5% BA.1 variant; 15% BA.2 variant; 57.5% BA.5 variant). 19 patients (16.5%) reported experiencing at least one symptom indicative of Long COVID (weight loss 31.6%, inappetence 26.3%, chronic cough 21.1%, fatigue 21.1%, and sleep disturbances, wheezing, abdominal pain and mood disorders 15.8%). In only 4 patients with Long COVID we could identified a specific SARS-CoV-2 variant (3 Omicron: 2 BA.1 and 1 BA.2; 1 Delta). CONCLUSIONS: this study underscores that long COVID is a significant concern in the pediatric population. Our data reinforce the importance of continuously monitoring the impact of long-COVID in infants, children, and adolescents. A follow-up following SARS-CoV-2 infection is therefore advisable, with symptom investigation tailored to the patient's age.

Lorcaserin: Worthy of Further Insights? Results from Recent Research.

Lorcaserin is a 3-benzazepine that binds 5-HT2C serotonin receptors in the hypothalamus, where it mediates lack of hunger and/or satiety, and in the ventral tegmental area, the site of origin of the mesolimbic and mesocortical dopaminergic projections, which mediate pleasure and reward. The drug has been first developed for the treatment of obesity, where it has shown efficacy, and subsequently trialed to counter substance use (mostly cocaine, cannabis, opioids, and nicotine) and craving, but showed inconsistent effects. Since 2020, the US Food and Drug Administration obtained that the drug was voluntarily withdrawn from the US market on the grounds that its long-term use was found to be associated with a greater incidence of some types of cancer. Provided it can show to be free from cancerogenic effects, ongoing research suggests that lorcaserin may have therapeutic potential for a variety of disorders and conditions beyond obesity. Since 5-HT2C receptors are involved in many diversified physiological functions (mood, feeding, reproductive behavior, neuronal processes related to impulsiveness, and modulating reward-related mechanisms) this drug has the potential to treat different central nervous system conditions, such as depression and schizophrenia.

The Italian registry of therapeutic apheresis in SISTRA: Year of activity 2022.

Therapeutic apheresis refers to a group of extracorporeal blood processing procedures used in the treatment of a variety of systemic diseases. These complex procedures are burdened by adverse reactions related to both procedures and underlying medical conditions. Given the importance of centralizing the collection and the analysis of information on therapeutic apheresis, the Italian National Blood Center (NBC), at the request of the Italian Scientific Society of Hemapheresis and Cell Manipulation (SIdEM), implemented the Italian Registry of Therapeutic Apheresis (IRTA) including it in the Information System of Transfusion Services (SISTRA), coordinated by the NBC. In 2022, a total of 34,702 therapeutic apheresis procedures was carried out in 8,781 patients, including paediatric patients, with an average of 3.9 procedures per patient. The 2022 IRTA data indicate that the patient with hematological and/or neurological disorders mainly turns to the apheresis centers. These results confirm the IRTA data from years 2020 and 2021. In the hematological field, the apheresis centers supply hematopoietic stem cells collection for autologous transplantation as well as mononuclear cell collection for extracorporeal photopheresis. With regard to the neurological field, myasthenia, chronic inflammatory demyelinating polyneuropathy and Guillain-Barré syndrome along with other neurological pathologies related to immune disorders are the most treated. In conclusion, this manuscript presents 2022 activity data of IRTA providing institutions and scientific societies with a wide range of information including type and number of therapeutic procedures, adverse events and patients' outcome.

Unveiling the Dark Nexus: A systematic review on the interplay of mental health, substance abuse, and socio-cultural factors in femicide.

A shared definition of femicide would help to distinguish it from the murder of a woman and understand its root causes favoring prevention. We conducted a Systematic Literature Review (SLR) to assess how (and if) femicide cases were related to mental disorders. Articles papers that explicitly define or discuss femicides or articles that, albeit not expressly mention femicides, thoroughly compare generic homicides and homicides with female victims. We analyse 3546 articles were retrieved from the databases, and 75 studies fulfilled the eligibility criteria and were included in the SLR. Many forms of femicide emerge worldwide as people's values, beliefs, attitudes, and behaviours evolve (intimate partner femicide, femicide-suicide, religious femicide, honour, revolt femicide) and state of vulnerability. A tiny percentage of femicides occur at the hands of subjects with diagnosed mental disorders, and controversies exist regarding the possible link between femicide and the use of drugs and/or alcohol and other factors. The complex problem of violence against women must be addressed with a transdisciplinary approach and targeted interventions for both the victims and the perpetrators. The present SLR shows that it is not possible to link femicides to mental disorders and that socio and cultural factors appear to be more relevant. Further quantitative research is warranted to disentangle the root causes of this heinous phenomenon plaguing our times. Our studies show that using the proposed definition of feminicide would help to delimit and adequately recognise violence in courtrooms, promote the culture of equality, and identify adequate policy strategies for prevention.

Gut microbiota in women: The secret of psychological and physical well-being.

The gut microbiota works in unison with the host, promoting its health. In particular, it has been shown to exert protective, metabolic and structural functions. Recent evidence has revealed the influence of the gut microbiota on other organs such as the central nervous system, cardiovascular and the endocrine-metabolic systems and the digestive system. The study of the gut microbiota is outlining new and broader frontiers every day and holds enormous innovation potential for the medical and pharmaceutical fields. Prevention and treatment of specific women's diseases involves the need to deepen the function of the gut as a junction organ where certain positive bacteria can be very beneficial to health. The gut microbiota is unique and dynamic at the same time, subject to external factors that can change it, and is capable of modulating itself at different stages of a woman's life, playing an important role that arises from the intertwining of biological mechanisms between the microbiota and the female genital system. The gut microbiota could play a key role in personalized medicine.

Effect of Modified Cow Dung Fibers on Strength and Autogenous Shrinkage of Alkali-Activated Slag Mortar.

Alkali-activated slag (AAS) presents a promising alternative to ordinary Portland cement due to its cost effectiveness, environmental friendliness, and satisfactory durability characteristics. In this paper, cow dung waste was recycled as a renewable natural cellulose fiber, modified with alkali, and then added to AAS mortar. The physico-chemical characteristics of raw and modified cow dung fibers were determined through Fourier transform infrared (FTIR), X-ray diffraction (XRD), and Scanning electron microscope (SEM). Investigations were conducted on the dispersion of cow dung fibers in the AAS matrix, as well as the flowability, strength, and autogenous shrinkage of AAS mortar with varying cow dung fiber contents. The results indicated that modified fiber has higher crystallinity and surface roughness. The ultrasonic method showed superior effectiveness compared to pre-mixing and after-mixing methods. Compared with raw cow dung fibers, modified fibers led to an increase of 11.3% and 36.3% of the 28 d flexural strength and compressive strength of the AAS mortar, respectively. The modified cow dung fibers had a more significant inhibition on autogenous shrinkage, and the addition of 2 wt% cow dung fibers reduced the 7 d autogenous shrinkage of the AAS paste by 52.8% due to the "internal curing effect." This study provides an alternative value-added recycling option for cow dung fibers as a potential environmentally friendly and sustainable reinforcing raw material for cementitious materials, which can be used to develop low autogenous shrinkage green composites.

A Flexible Regression Modeling Approach Applied to Observational Laboratory Virological Data Suggests That SARS-CoV-2 Load in Upper Respiratory Tract Samples Changes with COVID-19 Epidemiology.

(1) Background. Exploring the evolution of SARS-CoV-2 load and clearance from the upper respiratory tract samples is important to improving COVID-19 control. Data were collected retrospectively from a laboratory dataset on SARS-CoV-2 load quantified in leftover nasal pharyngeal swabs (NPSs) collected from symptomatic/asymptomatic individuals who tested positive to SARS-CoV-2 RNA detection in the framework of testing activities for diagnostic/screening purpose during the 2020 and 2021 winter epidemic waves. (2) Methods. A Statistical approach (quantile regression and survival models for interval-censored data), novel for this kind of data, was applied. We included in the analysis SARS-CoV-2-positive adults >18 years old for whom at least two serial NPSs were collected. A total of 262 SARS-CoV-2-positive individuals and 784 NPSs were included: 193 (593 NPSs) during the 2020 winter wave (before COVID-19 vaccine introduction) and 69 (191 NPSs) during the 2021 winter wave (all COVID-19 vaccinated). We estimated the trend of the median value, as well as the 25th and 75th centiles of the viral load, from the index episode (i.e., first SARS-CoV-2-positive test) until the sixth week (2020 wave) and the third week (2021 wave). Interval censoring methods were used to evaluate the time to SARS-CoV-2 clearance (defined as Ct < 35). (3) Results. At the index episode, the median value of viral load in the 2021 winter wave was 6.25 log copies/mL (95% CI: 5.50-6.70), and the median value in the 2020 winter wave was 5.42 log copies/mL (95% CI: 4.95-5.90). In contrast, 14 days after the index episode, the median value of viral load was 3.40 log copies/mL (95% CI: 3.26-3.54) for individuals during the 2020 winter wave and 2.93 Log copies/mL (95% CI: 2.80-3.19) for those of the 2021 winter wave. A significant difference in viral load shapes was observed among age classes (p = 0.0302) and between symptomatic and asymptomatic participants (p = 0.0187) for the first wave only; the median viral load value is higher at the day of episode index for the youngest (18-39 years) as compared to the older (40-64 years and >64 years) individuals. In the 2021 epidemic, the estimated proportion of individuals who can be considered infectious (Ct < 35) was approximately half that of the 2020 wave. (4) Conclusions. In case of the emergence of new SARS-CoV-2 variants, the application of these statistical methods to the analysis of virological laboratory data may provide evidence with which to inform and promptly support public health decision-makers in the modification of COVID-19 control measures.

Environmental and Lifestyle Cancer Risk Factors: Shaping Extracellular Vesicle OncomiRs and Paving the Path to Cancer Development.

Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information transfer between cells. Furthermore, they respond not only to internal stimuli but also to environmental and lifestyle factors. Identifying EV-borne oncomiRs, a subset of miRNAs implicated in cancer development, could revolutionize our understanding of how environmental and lifestyle exposures contribute to oncogenesis. To investigate this, we studied the plasma levels of EV-borne oncomiRs in a population of 673 women and 238 men with a body mass index > 25 kg/m2 (SPHERE population). The top fifty oncomiRs associated with the three most common cancers in women (breast, colorectal, and lung carcinomas) and men (lung, prostate, and colorectal carcinomas) were selected from the OncomiR database. Only oncomiRs expressed in more than 20% of the population were considered for statistical analysis. Using a Multivariate Adaptive Regression Splines (MARS) model, we explored the interactions between environmental/lifestyle exposures and EV oncomiRs to develop optimized predictor combinations for each EV oncomiR. This innovative approach allowed us to better understand miRNA regulation in response to multiple environmental and lifestyle influences. By uncovering non-linear relationships among variables, we gained valuable insights into the complexity of miRNA regulatory networks. Ultimately, this research paves the way for comprehensive exposome studies in the future.

Standardization of canine meningioma grading: Validation of new guidelines for reproducible histopathologic criteria.

Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of this study was to validate the new guidelines for canine meningiomas. To evaluate the inter-observer agreement, 5 veterinary surgical pathologists graded 158 canine meningiomas following the human grading system alone or with the new guidelines. The inter-observer agreement for histologic grade and each of the grading criteria (mitotic grade, invasion, spontaneous necrosis, macronucleoli, small cells, hypercellularity, pattern loss and anaplasia) was evaluated using the Fleiss kappa index. The diagnostic accuracy (sensitivity and specificity) was assessed by comparing the diagnoses obtained with the 2 grading systems with a consensus grade (considered the reference classification). The consensus histologic grade was obtained by agreement between 4 experienced veterinary neuropathologists following the guidelines. Compared with the human grading alone, the canine-specific guidelines increased the inter-observer agreement for: histologic grade (κ = 0.52); invasion (κ = 0.67); necrosis (κ = 0.62); small cells (κ = 0.36); pattern loss (κ = 0.49) and anaplasia (κ = 0.55). Mitotic grade agreement remained substantial (κ = 0.63). The guidelines improved the sensitivity in identifying grade 1 (95.6%) and the specificity in identifying grade 2 (96.2%) meningiomas. In conclusion, the new grading guidelines for canine meningiomas are associated with an overall improvement in the inter-observer agreement and higher diagnostic accuracy in diagnosing grade 1 and grade 2 meningiomas.

NOx degradation ability of S-g-C3N4/MgAl-CLDH nanocomposite and its potential application in cement-based materials.

In this study a new photocatalytic nanocomposite, S-g-C3N4/MgAl-CLDH, was synthesized and implemented into cement mortar by internal mixing or coating. The photocatalytic NOx degradation efficiency of the S-g-C3N4/MgAl-CLDH and photocatalytic mortar was investigated. The NOx degradation efficiency and photoluminescence spectra of S-g-C3N4/MgAl-CLDH after being immersed in the simulated concrete pore solution were evaluated to assess its chemical stability. The results show that compared with S-g-C3N4, the S-g-C3N4/MgAl-CLDH exhibits a narrower bandgap (2.45 eV), a lower photogenerated electron-hole pair recombination rate and a higher specific surface area (36.86 m2 g-1). After 21 min of visible light irradiation, the NOx degradation rate of S-g-C3N4/MgAl-CLDH achieves 100% as compared to merely 81.5% of S-g-C3N4. After being submerged in simulated concrete pore solution, the S-g-C3N4/MgAl-CLDH exhibits only a slight decrease of 5% in degradation rate after 12 min of irradiation, confirming a good compatibility and stability in cement-based materials. The NOx degradation ability of the internally mixed mortar is enhanced with an increase in the dosage of S-g-C3N4/MgAl-CLDH. For coated mortar, in contrast, a decline in NOx degradation rate is observed after 5 layers of coating owing to the lower porosity of mortar after excessive coating.

Resilience and Attachment in Patients with Major Depressive Disorder and Bipolar Disorder.

BACKGROUND: Resilience represents one of the fundamental elements of attachment and has often been investigated in mood disorders. This study aims to investigate possible correlations between attachment and resilience in patients with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: 106 patients (51 MDD, 55 BD) and 60 healthy controls (HCs) were administered the 21-item Hamilton Depression Rating Scale (HAM-D-21), the Hamilton Anxiety Rating Scale (HAM-A), the Young Mania Rating Scale (YMRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Barratt Impulsiveness Scale-11 (BIS-11), the Toronto Alexithymia Scale (TAS), the Connor-Davidson Resilience Scale (CD-RISC), and Experiences in Close Relationship (ECR). RESULTS: MDD and BD patients did not significantly differ from each other according to the HAM-D-21, HAM-A, YMRS, SHAPS, and TAS, while they scored higher than HCs on all these scales. Patients in the clinical group scored significantly lower on CD-RISC resilience than HCs (p < 0.01). A lower proportion of secure attachment was found among patients with MDD (27.4%) and BD (18.2%) compared to HCs (90%). In both clinical groups, fearful attachment prevailed (39.2% patients with MDD; 60% BD). CONCLUSIONS: Our results highlight the central role played by early life experiences and attachment in participants with mood disorders. Our study confirms the data from previous research showing a significant positive correlation between the quality of attachment and the development of resilience capacity, and supports the hypothesis that attachment constitutes a fundamental aspect of resilience capacity.

[Parole chiave. Appropriatezza prescrittiva, consumi farmaceutici, emofilia, fattori della coagulazione, malattia di von Willebrand, malattie emorragiche congenite.] / Strategie terapeutiche per il trattamento delle malattie emorragiche congenite.

Therapeutic strategies for the treatment of congenital bleeding disorders. Congenital hemorrhagic diseases (CHDs) are a group of rare disorders caused by quantitative or qualitative deficiency of one or more coagulation factors. Haemophilia A, Haemophilia B, and von Willebrand disease are the most common congenital bleeding disorders. Over the past decades, the evolution of CHDs treatments has resulted in an increase in the average life expectancy of patients and in an improvement in their quality of life; it has also enabled the prevention of bleeding complications much more effectively than in the past. This has been possible, especially for haemophilia, mainly because of earlier diagnosis, introduction of recombinant factors, especially long-acting factors, and availability of new non-substitutive therapies. In 2021, there was an increase in the overall expenditure and consumption of coagulation factors in Italy; the increase concerned especially the long-acting recombinant factors used in the treatment of Haemophilia A and B and the monoclonal antibody emicizumab. Waiting for innovative therapies that can enable individually tailored therapies, special attention must be paid to prescriptive appropriateness and to identify the best diagnostic and therapeutic care pathways for patients.