Role of serum-specific immunoglobulin E in egg allergy: a comprehensive study of Portuguese pediatric patients.

INTRODUCTION: Food allergies represent a growing public health concern, particularly among children. This study aims to examine egg allergy in pediatric patients and analyze the value of serum-specific immunoglobulin E (sIgE) levels as predictive biomarkers for oral food challenge (OFC) outcomes. METHODS: Retrospective study, involving pediatric patients with suspected IgE-mediated egg allergy, conducted at a tertiary hospital. RESULTS: Data from 176 pediatric patients were analyzed, revealing a higher male prevalence (59.1%). Most cases (40.3%) presented symptoms in the first year of life, predominantly mucocutaneous symptoms (46%). OFC results varied across various forms of egg presentation, with cooked egg being the most frequently tested food. Positive OFCs were observed in 14.6% (n = 36) of cases. The study identified specific egg protein biomarkers for positive OFC, with ovalbumin for raw egg (sIgE > 1.28 KUA/L; area under the curve [AUC] = 0.917; sensitivity [S] 100%; and specificity [Sp] 92%), ovomucoid for cooked egg (sIgE > 0.99 KUA/L; AUC = 0.788, 95%; S: 79%; and Sp: 74%), and ovomucoid for baked egg (sIgE> 4.63 KUA/L; AUC = 0.870; S: 80%; and Sp: 85%) showing predictive capacities. CONCLUSIONS: The findings underscore the importance of considering various forms of egg presentation in the diagnosis and management of egg allergy. The findings highlight the valuable discriminatory capacity and provided reliable biomarkers, such as ovalbumin for raw egg and ovomucoid for cooked and baked egg in risk assessment, aiding in predicting OFC outcomes and helping clinicians to make informed decisions in diagnosing and managing egg allergies, thus improving patient care and quality of life.

Advances and challenges in the diagnosis and management of left ventricular noncompaction in adults: A literature review.

In the realm of cardiovascular health, isolated left ventricular noncompaction (LVNC) stands out for its distinct morphological features and the clinical challenges it presents, particularly in adults. This literature review explores the intricacies of LVNC, aiming to unravel its epidemiological spread, diagnostic hurdles, and therapeutic strategies. Despite technological advancements in cardiac imaging that have improved the recognition of LVNC, a significant gap persists alongside a fragmented understanding of its pathogenesis. The studies scrutinized reveal a broad spectrum of prevalence rates influenced by diverse diagnostic tools and demographic variables. This variation underscores the complexity of accurately identifying LVNC and the resultant implications for clinical management. The review succinctly addresses the need for precise guidelines to navigate the diagnosis of LVNC and outlines the imperative for tailored clinical management approaches that cater to the wide array of patient presentations, from asymptomatic cases to those with severe cardiac dysfunction. By highlighting the critical gaps in current literature-namely the absence of standardized diagnostic criteria and a comprehensive pathogenic model-the review sets the stage for future research directions. These endeavors are essential for enhancing diagnostic accuracy, refining management protocols, and ultimately improving patient outcomes in this complex subset of cardiomyopathy, thus contributing significantly to the advancement of cardiovascular medicine.

The burden of atopic dermatitis in Portuguese patients: an observational study.

Atopic dermatitis (AD) is a common inflammatory skin condition that significantly affects patients' lives and imposes both economic and non-economic burdens. The precise societal and individual consequences of AD remain incompletely understood. This study aimed to characterize AD in Portuguese patients and assess its personal, familial, and societal implications, including health status and quality of life. The research, conducted from June 2019 to January 2020, involved 204 confirmed AD patients in Portugal, who completed a 70-question questionnaire. Results show that, on average, patients experienced a two-year delay in diagnosis, with two-thirds having allergic comorbidities. Late-onset AD (after age 20) was found to be correlated with worsening symptoms post-diagnosis. Globally, patients reported substantial effects on health, quality of life, and mental well-being. Effects include significant levels of anxiety, frustration and sleep disorders. Severe AD correlated with more suffering and reduced perceived health, indicating a link between disease severity and quality of life. Remarkably, despite questionable effectiveness, 92% of severe AD patients were prescribed antihistamines, while only 19% received biological treatments. In Portugal, delayed AD diagnosis hinders timely treatment, and despite its profound impact and high comorbidity rates, AD patients tend to remain undertreated. Recognizing the personal and societal repercussions is crucial for enhancing care, contributing to improving QoL, social functioning and global well-being.

ATP-P2X7 signaling mediates brain pathology while contributing to viral control in perinatal Zika virus infection.

Zika virus (ZIKV), the causative agent of Zika fever, is a flavivirus transmitted by mosquitoes of the Aedes genus. Zika virus infection has become an international concern due to its association with severe neurological complications such as fetal microcephaly. Viral infection can induce the release of ATP in the extracellular environment, activating receptors sensitized by extracellular nucleotides, such as the P2X7 receptor. This receptor is the primary purinergic receptor involved in neuroinflammation, neurodegeneration, and immunity. In this work, we investigated the role of ATP-P2X7 receptor signaling in Zika-related brain abnormalities. Wild-type mice (WT) and P2X7 receptor-deficient (P2X7-/-) C57BL/6 newborn mice were subcutaneously inoculated with 5 × 106plaque-forming units of ZIKV or mock solution. P2X7 receptor expression increased in the brain of Zika virus-infected mice compared to the mock group. Comparative analyses of the hippocampi from WT and P2X7-/-mice revealed that the P2X7 receptor increased hippocampal damage in CA1/CA2 and CA3 regions. Doublecortin expression decreased significantly in the brains of ZIKV-infected mice. WT ZIKV-infected mice showed impaired motor performance compared to P2X7-/- infected mice. WT ZIKV-infected animals showed increased expression of glial markers GFAP (astrocytes) and IBA-1 (microglia) compared to P2X7-/- infected mice. Although the P2X7 receptor contributes to neuronal loss and neuroinflammation, WT mice were more efficient in controlling the viral load in the brain than P2X7 receptor-deficient mice. This result was associated with higher induction of TNF-α, IFN-ß, and increased interferon-stimulated gene expression in WT mice than P2X7-/-ZIKV-infected. Finally, we found that the P2X7 receptor contributes to inhibiting the neuroprotective signaling pathway AKT/mTOR while stimulating the caspase-3 activation, possibly two distinct pathways contributing to neurodegeneration. These findings suggest that ATP-P2X7 receptor signaling contributes to the antiviral response in the brain of ZIKV-infected mice while increasing neuronal loss, neuroinflammation, and related brain abnormalities.

Tumour-infiltrated cortex participates in large-scale cognitive circuits.

The extent to which tumour-infiltrated brain tissue contributes to cognitive function remains unclear. We tested the hypothesis that cortical tissue infiltrated by diffuse gliomas participates in large-scale cognitive circuits using a unique combination of intracranial electrocorticography (ECoG) and resting-state functional magnetic resonance (fMRI) imaging in four patients. We also assessed the relationship between functional connectivity with tumour-infiltrated tissue and long-term cognitive outcomes in a larger, overlapping cohort of 17 patients. We observed significant task-related high gamma (70-250 Hz) power modulations in tumour-infiltrated cortex in response to increased cognitive effort (i.e., switch counting compared to simple counting), implying preserved functionality of neoplastic tissue for complex tasks probing executive function. We found that tumour locations corresponding to task-responsive electrodes exhibited functional connectivity patterns that significantly co-localised with canonical brain networks implicated in executive function. Specifically, we discovered that tumour-infiltrated cortex with larger task-related high gamma power modulations tended to be more functionally connected to the dorsal attention network (DAN). Finally, we demonstrated that tumour-DAN connectivity is evident across a larger cohort of patients with gliomas and that it relates to long-term postsurgical outcomes in goal-directed attention. Overall, this study contributes convergent fMRI-ECoG evidence that tumour-infiltrated cortex participates in large-scale neurocognitive circuits that support executive function in health. These findings underscore the potential clinical utility of mapping large-scale connectivity of tumour-infiltrated tissue in the care of patients with diffuse gliomas.

Muscle abnormalities worsen after post-exertional malaise in long COVID.

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Predicting post-discharge complications in cardiothoracic surgery: A clinical decision support system to optimize remote patient monitoring resources.

Cardiac surgery patients are highly prone to severe complications post-discharge. Close follow-up through remote patient monitoring can help detect adverse outcomes earlier or prevent them, closing the gap between hospital and home care. However, equipment is limited due to economic and human resource constraints. This issue raises the need for efficient risk estimation to provide clinicians with insights into the potential benefit of remote monitoring for each patient. Standard models, such as the EuroSCORE, predict the mortality risk before the surgery. While these are used and validated in real settings, the models lack information collected during or following the surgery, determinant to predict adverse outcomes occurring further in the future. This paper proposes a Clinical Decision Support System based on Machine Learning to estimate the risk of severe complications within 90 days following cardiothoracic surgery discharge, an innovative objective underexplored in the literature. Health records from a cardiothoracic surgery department regarding 5 045 patients (60.8% male) collected throughout ten years were used to train predictive models. Clinicians' insights contributed to improving data preparation and extending traditional pipeline optimization techniques, addressing medical Artificial Intelligence requirements. Two separate test sets were used to evaluate the generalizability, one derived from a patient-grouped 70/30 split and another including all surgeries from the last available year. The achieved Area Under the Receiver Operating Characteristic curve on these test sets was 69.5% and 65.3%, respectively. Also, additional testing was implemented to simulate a real-world use case considering the weekly distribution of remote patient monitoring resources post-discharge. Compared to the random resource allocation, the selection of patients with respect to the outputs of the proposed model was proven beneficial, as it led to a higher number of high-risk patients receiving remote monitoring equipment.

Plant-derived Durvalumab variants show efficient PD-1/PD-L1 blockade and therapeutically favourable FcR binding.

Immune checkpoint blocking therapy targeting the PD-1/PD-L1 inhibitory signalling pathway has produced encouraging results in the treatment of a variety of cancers. Durvalumab (Imfinzi®) targeting PD-L1 is currently used for immunotherapy of several tumour malignancies. The Fc region of this IgG1 antibody has been engineered to reduce FcγR interactions with the aim of enhancing blockade of PD-1/PD-L1 interactions without the depletion of PD-L1-expressing immune cells. Here, we used Nicotiana benthamiana to produce four variants of Durvalumab (DL): wild-type IgG1 and its 'Fc-effector-silent' variant (LALAPG) carrying further modifications to increase antibody half-life (YTE); IgG4S228P and its variant (PVA) with Fc mutations to decrease binding to FcγRI. In addition, DL variants were produced with two distinct glycosylation profiles: afucosylated and decorated with α1,6-core fucose. Plant-derived DL variants were compared to the therapeutic antibody regarding their ability to (i) bind to PD-L1, (ii) block PD-1/PD-L1 inhibitory signalling and (iii) engage with the neonatal Fc receptor (FcRn) and various Fcγ receptors. It was found that plant-derived DL variants bind to recombinant PD-L1 and to PD-L1 expressed in gastrointestinal cancer cells and are able to effectively block its interaction with PD-1 on T cells, thereby enhancing their activation. Furthermore, we show a positive impact of Fc amino acid mutations and core fucosylation on DL's therapeutic potential. Compared to Imfinzi®, DL-IgG1 (LALAPG) and DL-IgG4 (PVA)S228P show lower affinity to CD32B inhibitory receptor which can be therapeutically favourable. Importantly, DL-IgG1 (LALAPG) also shows enhanced binding to FcRn, a key determinant of serum half-life of IgGs.

Long-term recruitment of peripheral immune cells to brain scars after a neonatal insult.

Although brain scars in adults have been extensively studied, there is less data available regarding scar formation during the neonatal period, and the involvement of peripheral immune cells in this process remains unexplored in neonates. Using a murine model of neonatal hypoxic-ischemic encephalopathy (HIE) and confocal microscopy, we characterized the scarring process and examined the recruitment of peripheral immune cells to cortical and hippocampal scars for up to 1 year post-insult. Regional differences in scar formation were observed, including the presence of reticular fibrotic networks in the cortex and perivascular fibrosis in the hippocampus. We identified chemokines with chronically elevated levels in both regions and demonstrated, through a parabiosis-based strategy, the recruitment of lymphocytes, neutrophils, and monocyte-derived macrophages to the scars several weeks after the neonatal insult. After 1 year, however, neutrophils and lymphocytes were absent from the scars. Our data indicate that peripheral immune cells are transient components of HIE-induced brain scars, opening up new possibilities for late therapeutic interventions.

Histopathological characterization of cerebral small vessel disease in epilepsy patients with temporal lobe epilepsy submitted to surgery: A case-control study.

BACKGROUND: Cerebrovascular disease (CVD) is a major contributor to epilepsy; however, patients with epilepsy also have a significantly increased risk of stroke. The way in which epilepsy contributes to the increased risk of stroke is still uncertain and is ill-characterized in neuropathological studies. A neuropathological characterization of cerebral small vessel disease (cSVD) in patients with chronic epilepsy was performed. METHODS: Thirty-three patients with refractory epilepsy and hippocampal sclerosis (HS) submitted to epilepsy surgery from a reference center were selected between 2010 and 2020 and compared with 19 autopsy controls. Five randomly selected arterioles from each patient were analyzed using a previously validated scale for cSVD. The presence of CVD disease imaging markers in pre-surgical brain magnetic resonance imaging (MRI) was studied. RESULTS: There were no differences in age (43.8 vs. 41.6 years; p = 0.547) or gender distribution (female gender 60.6% vs. male gender 52.6%; p = 0.575) between groups. Most CVD findings in brain MRI were mild. Patients had a mean time between the epilepsy onset and surgery of 26 ± 14.7 years and were medicated with a median number of three antiseizure medication (ASMs) [IQR 2-3]. Patients had higher median scores in arteriolosclerosis (3 vs. 1; p < 0.0001), microhemorrhages (4 vs. 1; p < 0.0001) and total score value (12 vs. 8.9; p = 0.031) in comparison with controls. No correlation was found between age, number of years until surgery, number of ASMs or cumulative defined daily dosage of ASM. CONCLUSION: The present study provides evidence supporting the increased burden of cSVD in the neuropathological samples of patients with chronic epilepsy.

A Combination of Ex Vivo and In Vivo Strategies for Evaluating How Much New Oral Anticoagulants Exacerbate Experimental Intracerebral Bleeding.

Background Intracerebral hemorrhage is the most serious complication of anticoagulant therapy but the effects of different types of oral anticoagulants on the expansion of these hemorrhages are still unclear. Clinical studies have revealed controversial results; more robust and long-term clinical evaluations are necessary to define their outcomes. An alternative is to test the effect of these drugs in experimental models of intracerebral bleeding induced in animals. Aims To test new oral anticoagulants (dabigatran etexilate, rivaroxaban, and apixaban) in an experimental model of intracerebral hemorrhage induced by collagenase injection into the brain striatum of rats. Warfarin was used for comparison. Methods Ex vivo anticoagulant assays and an experimental model of venous thrombosis were employed to determine the doses and periods of time required for the anticoagulants to achieve their maximum effects. Subsequently, volumes of brain hematoma were evaluated after administration of the anticoagulants, using these same parameters. Volumes of brain hematoma were evaluated by magnetic resonance imaging, H&E (hematoxylin and eosin) staining, and Evans blue extravasation. Neuromotor function was assessed by the elevated body swing test. Results and Conclusions The new oral anticoagulants did not increase intracranial bleeding compared with control animals, while warfarin markedly favored expansion of the hematomas, as revealed by magnetic resonance imaging and H&E staining. Dabigatran etexilate caused a modest but statistically significant increase in Evans blue extravasation. We did not observe significant differences in elevated body swing tests among the experimental groups. The new oral anticoagulants may provide a better control over a brain hemorrhage than warfarin.

The effect of non-pharmaceutical interventions on COVID-19 outcomes: A heterogeneous age-related generalisation of the SEIR model.

Successive generalisations of the basic SEIR model have been proposed to accommodate the different needs of the organisations handling the SARS-CoV-2 epidemic and the assessment of the public health measures adopted and named under the common umbrella of Non-Pharmaceutical Interventions (NPIs). So far, these generalisations have not been able to assess the ability of these measures to avoid infection by the SARS-CoV-2 and thus their contribution to contain the spread of the disease. This work proposes a new generalisation of SEIR model and includes a heterogeneous and age-related generation of infections that depends both on a probability that a contact generates the transmission of the disease and a contact rate. The results show (1) thanks to the universal wearing of facial coverings, the probability that a contact provokes the transmission of the disease was reduced by at least 50% and (2) the impact of the other NPI is so significant that otherwise Portugal would have gone into a non-sustainable situation of having 80% of its population infected in the first 300 days of the pandemic. This situation would have led to a number of deaths almost twenty times higher than the number that was actually recorded by December 26th, 2020. Moreover, the results suggest that even if the requirement of universal wearing of facial coverings was adopted sooner jointly with closing workplaces and resorting to teleworking would have postponed the peak of the incidence, altought the epidemic path would have result in a number of infections hardly managed by the National Health System. Complementary, results confirm that (3) the health authorities adopted a conservative approach on the criteria to consider an infected individual not infective any longer; and (4) the most effective NPIs and stringency levels either impacting on self-protection against infection or reducing the contacts that would eventually result in infection are, in decreasing order of importance, the use of Facial coverings, Workplace closing and Stay at home requirements.

Impact of umbilical cord mesenchymal stromal/stem cell secretome and cord blood serum in prostate cancer progression.

Prostate cancer (PCa) is the second most common malignancy in men, and the fifth leading cause of death worldwide. Mesenchymal stromal/stem cells (MSC) have been identified in PCa, although contradictory effects in malignant transformation and tumor progression have been described. Since umbilical cord (UC) MSC and cord blood serum (CBS) are rich in numerous growth and anti-inflammatory factors, UC-MSC secretome and CBS are able to modulate tumor cell proliferation and survival as well as immunity and angiogenesis. In the present study, we address this relationship and investigate the influence of UC-MSC secretome and CBS on two human PCa cell lines (PC3 and LNCaP) and a normal epithelial prostate cell line (HPEpiC). Our results disclosed that upon exposure to UC-MSC-conditioned medium or CBS, both PC3 and LNCaP cells exhibited reduced viability, proliferation, and motility while non-malignant epithelial prostate cells were unaffected. These findings were corroborated by expression analysis of AKT/PI3K signaling pathway, p53 and interleukin genes. UC-MSC and CBS factors decreased the expression of growth-stimulating AKT and PI3K effectors and simultaneously up-regulated the expression of tumor-suppressor p53. Moreover, a more anti-inflammatory expression profile was found in both malignant PCa cell lines. Altogether, these results shed light into possible mechanisms by which UC-MSC and CBS reduce PCa progression, further reinforcing their potential use as novel therapeutic agents in PCa.

High gamma activity distinguishes frontal cognitive control regions from adjacent cortical networks.

Though the lateral frontal cortex is broadly implicated in cognitive control, functional MRI (fMRI) studies suggest fine-grained distinctions within this region. To examine this question electrophysiologically, we placed electrodes on the lateral frontal cortex in patients undergoing awake craniotomy for tumor resection. Patients performed verbal tasks with a manipulation of attentional switching, a canonical control demand. Power in the high gamma range (70-250 Hz) distinguished electrodes based on their location within a high-resolution fMRI network parcellation of the frontal lobe. Electrodes within the canonical fronto-parietal control network showed increased power in the switching condition, a result absent in electrodes within default mode, language and somato-motor networks. High gamma results contrasted with spatially distributed power decreases in the beta range (12-30 Hz). These results confirm the importance of fine-scale functional distinctions within the human frontal lobe, and pave the way for increased precision of functional mapping in tumor surgeries.

Malignant Primary and Metastatic Cardiac Tumors: A Single-Center 27-Year Case Review.

BACKGROUND: Malignant primary cardiac tumors are exceedingly rare, and despite surgical exeresis or chemotherapy, their prognosis remains poor. Cardiac invasion by metastatic tumors, while more common, also entails an unsatisfactory outcome. This study aimed to review patients diagnosed with malignant primary and secondary cardiac tumors in a tertiary center between 1995 and 2022. METHODS: Clinical data, echocardiographic, computed tomography, and magnetic resonance assessments of tumor location and morphology, histology, treatment, and survival were retrospectively analyzed. RESULTS: Sixty malignant cardiac tumors were diagnosed: 17 primary (A) and 43 metastatic (B) tumors. A: the most common types were angiosarcoma (41%), undifferentiated sarcoma (23%), and fibrosarcoma (18%). Patients with primary tumors were younger than patients with metastatic tumors (41 ± 13 years vs. 57 ± 18 years, p = 0.001), with no significant gender difference. The most frequent presentations were heart failure (59%) and arrhythmia (23%). The most prevalent tumor location was the right heart chambers (71%), mostly in the right atrium (35%). 47% were submitted to tumor resection, and 29% received chemotherapy. The mortality rate was 82% with a median survival of 6.0 (interquartile range: 1.0-11.8) months after diagnosis (minimum of 12 days and maximum of 19 years). One patient with fibrosarcoma underwent heart transplantation and was still alive and well after 19 years. B: regarding metastatic cardiac invasion, the most common primary tumor sites were lung carcinomas (38%), thymomas (17%), and lymphomas (14%). Presentation with pericardial effusion was common (33%). The mortality rate was 72%, with a median survival of 3.6 (1.0-13.4) months (minimum of 7 days, maximum of 5 years). CONCLUSION: Diagnosis of metastatic cardiac tumors was more common than that of malignant primary tumors, both with a dismal prognosis. When radical exeresis is not possible, heart transplantation can be an option with a favorable outcome in carefully selected patients with sarcomas.

Randomized trial of the efficacy of trial-based cognitive therapy for obsessive-compulsive disorder: preliminary findings.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is the fourth most prevalent mental disorder and is a disabling condition. OCD is associated with anatomical and functional changes in the brain, in addition to dysfunctional cognitions. The treatments of choice are selective serotonin reuptake inhibitors, cognitive-behavioral therapy (CBT), and exposure and response prevention (ERP). Trial-based cognitive therapy (TBCT) is a recent and empirically validated psychotherapy with a focus on restructuring dysfunctional negative core beliefs (CBs). The objective of this study was to evaluate the efficacy of TBCT relative to ERP for treatment of OCD. METHOD: A randomized, single-blind clinical trial was conducted, randomizing 26 patients for individual treatment with TBCT (n = 12) or ERP (n = 14). The groups were evaluated at baseline, at the end of 3 months (12 sessions), and at 3, 6, and 12-month follow-ups. RESULTS: Both approaches reduced the severity of symptoms with large effect sizes. These results were maintained at the 12-month follow-up assessment. CONCLUSION: TBCT may be a valid and promising treatment for this disorder.

Psiquiatras e psicotrópicos: o uso de substâncias psicoativas pela terapêutica psiquiátrica na década de 1950 em São Paulo / Psychiatrists and psychotropic drugs: the use of psychoactive substances in psychiatric therapy in the 1950s in São Paulo

Considerando o campo de estudos incipiente sobre história das drogas, a presente pesquisa busca compreender qual a formação social e histórica da dinâmica prescritiva de psicofármacos em contraposição a intensificação da restrição de outras drogas no processo de incorporação de substâncias psicoativas na terapêutica psiquiátrica entre os anos 1950 e 1964 em São Paulo. A proposta investigativa aborda a complexa relação entre o uso de drogas na psiquiatria paulista e a historiografia sobre o tema, destacando a necessidade de uma abordagem multidisciplinar e crítica e que considera como fundamentais os contextos sociais, econômicos, políticos e culturais. Articulando uma história das drogas com a história da psiquiatria, buscou-se entender de que forma foram assimiladas e incorporadas as primeiras drogas psiquiátricas e quais foram seus impactos na classe médica e no tecido social. Partindo do materialismo histórico e da história "vista de baixo", a ideia é romper com uma historiografia acritica e linear e construir uma história para além da oficialidade, que considera as relações e contextos em suas multideterminações e busca identificar rupturas, continuidades, diálogos, resistências e negociações entre os distintos atores sociais. Nesse sentido, as fontes documentais e clínicas são ferramentas potentes na promoção de uma perspectiva crítica e multidisciplinar nos estudos históricos e sociais sobre o uso de drogas e psicofármacos e sua regulação na psiquiatria e na sociedade em geral.

Considering the incipient field of studies on the history of drugs, this research aims to understand the social and historical formation of the prescriptive dynamics of psychotropic drugs as opposed to the intensification of restrictions on other drugs in the process of incorporating psychoactive substances into psychiatric therapy between the 1950s and 1964 in São Paulo. The investigative proposal addresses the complex relationship between drug use in psychiatry in São Paulo and the historiography about this topic, highlighting the need for a multidisciplinary and critical approach that considers social, economic, political and cultural contexts as fundamental. Articulating a history of drugs with the history of psychiatry, this study seeks to understand how the first psychiatric drugs were assimilated and incorporated such as their impacts on the medical profession and the social context. Starting from historical materialism and the history itself "seen from below", the idea is to break with an uncritical and linear historiography and build a history beyond officialdom, considering relationships and contexts in their multiple determinations and seeks to identify ruptures, continuities, dialogues, resistance and negotiations between different social players. In this sense, documentary and clinical sources are powerful tools in promoting a critical and multidisciplinary perspective in historical and social studies on the use of drugs and psychotropic drugs and their regulation in psychiatry and society in general.