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IntroductionTobacco consumption and its impact on health remain high worldwide. Additionally, it is a contentious issue generating significant controversy. Twitter has proven to be a useful platform for evaluating public health topics related to population health behaviors, and tobacco consumption.ObjectiveThe objective of this study is to analyze the content of tweets related to tobacco. Moreover, geolocation data will be considered to understand regional differences.MethodsTweets published between 2018 and 2022, in both English and Spanish, containing the keyword “tobacco,” were analyzed. A total of 56,926 tweets were obtained. The tweets were classified into different categories. 550 tweets were manually analyzed, and an automated and computerized classification was performed for the remaining and largest subset of tweets.ResultsThe analysis yielded 30,812 classifiable tweets. Healthcare professionals were the most frequent contributors to the topic (50.2%), with the most common theme being general information about the toxic effects of tobacco. 57.9% of the tweets discussed the harmful effects of tobacco on health, with fear being the predominant emotion. The largest number of tweets were located in America.ConclusionsOur study revealed a substantial number of tweets highlighting the health risks and negative perceptions of tobacco consumption. Africa showed the lowest percentage of tweets discussing the health risks associated with tobacco, coinciding with the continent having the least developed anti-tobacco policies. Healthcare professionals emerged as the most prominent users discussing the topic, which is encouraging as they play a crucial role in disseminating accurate and scientific health information.

IntroductionCocaine abuse represents a major public health concern. The social perception of cocaine has been changing over the decades, a phenomenon closely tied to its patterns of use and abuse. Twitter is a valuable tool to understand the status of drug use and abuse globally. However, no specific studies discussing cocaine have been conducted on this platform.Methods111,508 English and Spanish tweets containing “cocaine” from 2018 to 2022 were analyzed. 550 were manually studied, and the largest subset underwent automated classification. Then, tweets related to cocaine were analyzed to examine their content, types of Twitter users, usage patterns, health effects, and personal experiences. Geolocation data was also considered to understand regional differences.ResultsA total of 71,844 classifiable tweets were obtained. Among these, 15.95% of users discussed the harm of cocaine consumption to health. Media outlets had the highest number of tweets (35.11%) and the most frequent theme was social/political denunciation (67.88%). Regarding the experience related to consumption, there are more tweets with a negative sentiment. The 9.03% of tweets explicitly mention frequent use of the drug. The continent with the highest number of tweets was America (55.44% of the total).DiscussionThe findings underscore the significance of cocaine as a current social and political issue, with a predominant focus on political and social denunciation in the majority of tweets. Notably, the study reveals a concentration of tweets from the United States and South American countries, reflecting the high prevalence of cocaine-related disorders and overdose cases in these regions. Alarmingly, the study highlights the trivialization of cocaine consumption on Twitter, accompanied by a misleading promotion of its health benefits, emphasizing the urgent need for targeted interventions and antidrug content on social media platforms. Finally, the unexpected advocacy for cocaine by healthcare professionals raises concerns about potential drug abuse within this demographic, warranting further investigation.

BackgroundThere are no studies that measure the prevalence and real comorbidities of neurodevelopmental disorders (NDDs) according to the DSM-5-TR in 6-year-old children in population and clinical samples or studies that measure them as a whole. The data on the prevalence of these disorders are usually disparate because of the estimation methods (direct/indirect), the type of sample (population/clinical/school), and the ages studied.MethodsThe initial sample (289 subjects) was representative of 6-year-old children in the entire population of Menorca, obtained from pediatric primary care services (100% of the sample). The patients were divided into two groups based on the criterion of verification of clinical warning signs. One of the groups represented the clinical or experimental sample (EG) (81 subjects) at risk of NDDs; the other group was considered the control sample (CG) (210 subjects), and they were subjects without risk of suffering NDDs. A direct clinical assessment of the clinical sample was carried out, and they were administered the Wechsler Intelligence Scale for Children (WISC-V), the Clinical Evaluation of Language Fundamentals (CELF-5), the Battery for the evaluation of the processes of revised reading (Batería para la evaluación de los procesos de lectura revisada – PROLEC-R), the Test for the Diagnosis of Basic Mathematical Competences, (TEDI-MATH), and the Developmental Coordination Disorder Questionnaire (DCDQ).ResultsA total of 21.5% of the initial sample suffered from an NDD. A total of 2.4% presented autism spectrum disorder (ASD); 14% presented attention-deficit hyperactivity disorder (ADHD); 0.34% presented mild intellectual disability; 9.54% presented communication disorder (CD) (5.8% language disorder, 3.4% phonological disorder, and 0.34% stuttering); 10% presented learning disorder with reading difficulties; 5.8% presented learning disorder with difficulties in writing; 3.11% presented learning disorder with difficulties in mathematics; 1% presented transitory tic disorder; 0.34% presented chronic tic disorder; 1% presented Tourette syndrome; 2% presented motor coordination disorder (MCD); and 0.34% presented stereotypic movement disorders. Male children were more affected than female children in general, with male/female ORs of 0.14/0.92 for the presence of comorbidities, 0.11/0.88 for combined ADHD, 0.06/0.87 for language disorder, 1.02/1.27 for MCD, and 1.39/1.02 for inattentive ADHD.ConclusionIn disadvantaged contexts, there was a higher prevalence of NDDs and comorbidities, unless the disorder was extreme, in which case only the NDD manifestations were presented. A significant proportion of the sample had not been previously diagnosed (88.6%); therefore, early detection programs are recommended to identify warning signs and develop policies that help and support the most disadvantaged sectors of the population.

Given a sequence of orthogonal polynomials {Ln}n=0∞, orthogonal with respect to a positive Borel ν measure supported on R+, let {Qn}n=0∞ be the the sequence of orthogonal polynomials with respect to the modified measure r(x)dν(x), where r is certain rational function. This work is devoted to the proof of the relative asymptotic formula Qn(d)(z)Ln(d)(z)⇉n∏k=1N1ak+iz+akAk∏j=1N2z+bjbj+iBj, on compact subsets of C∖R+, where ak and bj are the zeros and poles of r, and the Ak, Bj are their respective multiplicities.

BackgroundCrisis Resolution Home Treatment (CRHT) seem to offer comparable results to the traditional hospitalization model, at a lower cost and offering greater flexibility and scope. However, in Madrid, its implementation in Mental Health did not occur until the midst of the COVID-19 pandemic. In this work we analysed the effectiveness of a mental health CRHT unit promoted during the COVID-19 pandemic, as well as the degree of satisfaction of patients and their families.Methods90 patients were treated by the CRHT unit in the period between October 2020 and June 2022. All patients met the inclusion criteria: (1) Acute psychopathological decompensation in patients suffering from psychotic disorders, major affective disorder, obsessive compulsive disorder, personality disorder and other severe mental disorders causing functional disability, according to ICD-10 diagnostic criteria; (2) Ages between 18–90 years old; (3) Living in the urban area of Vallecas, Madrid; and (4) Counting with sufficient social and family support. The effectiveness of the intervention was evaluated with the SF-36 health questionnaire, the caregiver burden with the Zarit questionnaire, and patient satisfaction with a survey specifically designed for this work.Results55 (61.1%) patients completed the SF-36 at baseline and at the end of hospitalization. Statistically significant improvements were observed in the 8 dimensions of the SF-36 (p

Abstract Background Few studies have estimated the real prevalence of neurodevelopmental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in Spain and worldwide. However, there are disparate prevalence figures. We consider research in this field essential to improve early detection, secondary prevention, and health planning. Methods The Minikid ADHD and TICS-Mini International Neuropsychiatric Interview for Children and Adolescents, the Autism Spectrum Quotient (Children’s version, AQ- Child) and a protocol of general medical questions were administered for screening purposes. The PROLEXIA battery for children aged from 4 to 6 years was used for direct assessments. Parents provided information on emotional, medical, and school aspects. The final population evaluated using these tools consisted of 291 6-year-old subjects. Results The overall risk of presenting with a neurodevelopmental disorder was 55.4%. A 23.4% risk of presenting with attention-deficit/hyperactivity disorder (ADHD) in any modality (inattentive, hyperactive-impulsive and combined), a 2.8% risk of developing autism spectrum disorder (ASD), a 30.6% risk of presenting with a learning disorder with reading difficulties, a 5.5% risk of tics and a 22.5% risk of language problems (incomprehensible language or minor language problems) were detected in the sample. The most common combination of disorders was learning and language difficulties, accounting for 6.9% of the sample. The second most frequent combination was the presence of learning and language difficulties and ADHD, accounting for 4.5% of the sample. Conclusions The prevalence of risks detected in our sample seems to be consistent with national and international studies. A significant proportion of our sample had never been previously diagnosed (85%), so early detection programs are recommended.

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition well recognized in the pediatric population that can persist into adulthood. The vast majority of patients with ADHD present psychiatric comorbidities that have been suggested to share, to some extent, the pathophysiological mechanism of ADHD. Lisdexamfetamine (LDX) is a stimulant prodrug approved for treating ADHD and, in the US, also for binge eating disorder (BED). Herein, we evaluated, through a systems biology-based in silico method, the efficacy of a virtual model of LDX (vLDX) as ADHD treatment to improve five common ADHD psychiatric comorbidities in adults and children, and we explored the molecular mechanisms behind LDX’s predicted efficacy. After the molecular characterization of vLDX and the comorbidities (anxiety, BED, bipolar disorder, depression, and tics disorder), we created a protein-protein interaction human network to which we applied artificial neural networks (ANN) algorithms. We also generated virtual populations of adults and children-adolescents totaling 2,600 individuals and obtained the predicted protein activity from Therapeutic Performance Mapping System models. The latter showed that ADHD molecular description shared 53% of its protein effectors with at least one studied psychiatric comorbidity. According to the ANN analysis, proteins targeted by vLDX are predicted to have a high probability of being related to BED and depression. In BED, vLDX was modeled to act upon neurotransmission and neuroplasticity regulators, and, in depression, vLDX regulated the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, and glutamatergic excitotoxicity. In conclusion, our modeling results, despite their limitations and although requiring in vitro or in vivo validation, could supplement the design of preclinical and potentially clinical studies that investigate treatment for patients with ADHD with psychiatric comorbidities, especially from a molecular point of view.

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is an impairing psychiatric condition with the stimulants, lisdexamfetamine (LDX), and methylphenidate (MPH), as the first lines pharmacological treatment.MethodsHerein, we applied a novel in silico method to evaluate virtual LDX (vLDX) and vMPH as treatments for ADHD applying quantitative systems pharmacology (QSP) models. The objectives were to evaluate the model’s output, considering the model characteristics and the information used to build them, to compare both virtual drugs’ efficacy mechanisms, and to assess how demographic (age, body mass index, and sex) and clinical characteristics may affect vLDX’s and vMPH’s relative efficacies.Results and DiscussionWe molecularly characterized the drugs and pathologies based on a bibliographic search, and generated virtual populations of adults and children-adolescents totaling 2,600 individuals. For each virtual patient and virtual drug, we created physiologically based pharmacokinetic and QSP models applying the systems biology-based Therapeutic Performance Mapping System technology. The resulting models’ predicted protein activity indicated that both virtual drugs modulated ADHD through similar mechanisms, albeit with some differences. vMPH induced several general synaptic, neurotransmitter, and nerve impulse-related processes, whereas vLDX seemed to modulate neural processes more specific to ADHD, such as GABAergic inhibitory synapses and regulation of the reward system. While both drugs’ models were linked to an effect over neuroinflammation and altered neural viability, vLDX had a significant impact on neurotransmitter imbalance and vMPH on circadian system deregulation. Among demographic characteristics, age and body mass index affected the efficacy of both virtual treatments, although the effect was more marked for vLDX. Regarding comorbidities, only depression negatively impacted both virtual drugs’ efficacy mechanisms and, while that of vLDX were more affected by the co-treatment of tic disorders, the efficacy mechanisms of vMPH were disturbed by wide-spectrum psychiatric drugs. Our in silico results suggested that both drugs could have similar efficacy mechanisms as ADHD treatment in adult and pediatric populations and allowed raising hypotheses for their differential impact in specific patient groups, although these results require prospective validation for clinical translatability.

Abstract Objective To interpret the current evidence on the prevalence of neurodevelopmental disorders (NDDs) through a systematic review based on both DSM-5 (2013) and PRISMA criteria. Method Empirical studies complying with the PRISMA guidelines were identified from four databases (PubMed, Scopus, Science Direct, and ProQuest) and systematically reviewed. In total, 17 articles were selected for the study. Results In the scientific literature, there have been only a few studies measuring the prevalence of NDDs according to the DSM-5 (2013) criteria in people under 18 years old. The reported prevalence rates were as follows: intellectual disability (ID), 0.63%; attention-deficit/hyperactivity disorder (ADHD), 5–11%; autism spectrum disorder (ASD), 0.70–3%; specific learning disorder (SLD), 3–10%; communication disorders (CDs), 1–3.42%; and motor disorders (MDs), 0.76–17%. Although there is extensive literature on specific disorders, NDDs have rarely been assessed as a whole. All of the reviewed studies support the idea that such disorders can be considered chronic, heterogeneous, underdiagnosed conditions and that comorbidity of multiple NDDs is the norm. Likewise, it is estimated that the prevalence of the most studied disorders, such as ADHD, ASD and SLD, remains stable over time and is consistent in different cultures, ages, ethnicities and sexes. Conclusion The studies reviewed lead us to conclude that the prevalence rate of NDDs fluctuates globally between 4.70 and 88.50%; these variations depend on methodological aspects such as estimation procedures, as well as on sociocontextual phenomena. It is also important to consider that the prevalence found is probably highly influenced by the activity of the countries in the diagnosis and training of professionals who care for children and adolescents. Hence, there is a need for a secondary intervention in the fields of public health and education to minimize socioemotional consequences, prevent academic failure, and reduce the economic cost to society.

We study the sequence of monic polynomials {Sn}n⩾0, orthogonal with respect to the Jacobi-Sobolev inner product ⟨f,g⟩s=∫−11f(x)g(x)dμα,β(x)+∑j=1N∑k=0djλj,kf(k)(cj)g(k)(cj), where N,dj∈Z+, λj,k⩾0, dμα,β(x)=(1−x)α(1+x)βdx, α,β>−1, and cj∈R∖(−1,1). A connection formula that relates the Sobolev polynomials Sn with the Jacobi polynomials is provided, as well as the ladder differential operators for the sequence {Sn}n⩾0 and a second-order differential equation with a polynomial coefficient that they satisfied. We give sufficient conditions under which the zeros of a wide class of Jacobi-Sobolev polynomials can be interpreted as the solution of an electrostatic equilibrium problem of n unit charges moving in the presence of a logarithmic potential. Several examples are presented to illustrate this interpretation.

In recent years, the incidence of different types of cancer and patient survival have been rising, as well as their prevalence. The increase in survival in recent years exposes the patients to a set of stressful factors such as more rigorous follow-up and more aggressive therapeutic regimens that, added to the diagnosis of the disease itself, cause an increase in the incidence of depressive disorders. These alterations have important consequences for the patients, reducing their average survival and quality of life, and for these reasons, special emphasis has been placed on developing numerous screening tests and early recognition of depressive symptoms. Despite that cancer and major depressive disorder are complex and heterogeneous entities, they also share many critical pathophysiological mechanisms, aiding to explain this complex relationship from a biological perspective. Moreover, a growing body of evidence is supporting the relevant role of lifestyle habits in the prevention and management of both depression and cancer. Therefore, the present study aims to perform a thorough review of the intricate relationship between depression and cancer, with a special focus on its biological links, clinical management, challenges, and the central role of lifestyle medicine as adjunctive and preventive approaches to improve the quality of life of these patients.

Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.

Objective To measure plasma levels of malondialdehyde (MDA), a marker of oxidative stress (OS), in patients with major depressive disorder (MDD) compared with healthy control (HC) subjects in order to determine if it is a possible biomarker of depression. Methods This prospective cross-sectional study enrolled patients with MDD and HC subjects. The plasma levels of MDA were measured using a commercially-available colorimetric assay. Results A total of 30 patients with MDD and 20 HC subjects with similar sex, age and body mass index distribution were enrolled in the study. Patients with MDD had significantly higher plasma levels of MDA than the HC subjects. Receiver operating characteristic curve analysis for plasma MDA levels in patients with MDD demonstrated an area under the curve of 0.9767. Conclusion The findings of this current study provide further evidence of the role pathophysiological relevance of OS and MDA in MDD. This study provides the basis for the use of MDA as a biomarker for MDD.

Major depressive disorder (MDD) is a complex psychiatric disorder that, presented alone or with other comorbidities, requires different adjustments of antidepressant treatments. Some investigations have demonstrated that psychoactive drugs, such as serotonin and norepinephrine reuptake inhibitors (SNRIs), can exert more effective and faster antidepressant effects than other common medications used, such as serotonin selective reuptake inhibitors (SSRIs), although these differences are still controversial. During the last five years, the SNRI duloxetine has shown favorable results in clinical practice for the treatment of MDD, anxiety, and fibromyalgia. Through an online self-completed survey, in the present article, we collected information from 163 psychiatrists regarding the use of duloxetine and its comparison with other psychiatric drugs, concerning psychiatrists’ knowledge and experience, as well as patients’ preferences, symptoms, and well-being. We discussed and contrasted physicians’ reports and the scientific literature, finding satisfactory concordances, and finally concluded that there is agreement regarding the use of duloxetine, not only due to its tolerability and effectiveness but also due to the wide variety of situations in which it can be used (e.g., somatic symptoms in fibromyalgia, diabetes) as it relieves neuropathic pain as well.

Psychosis is a complex clinical syndrome resulting in a loss of contact with reality and alterations in behavior and sensorial and motor functions. Although the onset of psychosis can be related to any medical condition, most cases of psychosis are not fully understood. Psychosis may manifest for the first time during pregnancy, which is detrimental to maternofetal well-being. The impact of having a first episode of psychosis during pregnancy on the placenta has not yet been explored. Oxidative stress is thought to take part in the etiopathogenesis of this complex disorder, and this condition can also affect the placenta as it is highly sensitive to changes in the maternal environment. In this sense, the aim of the present work was to study the gene and protein expression through RT–qPCR and immunohistochemistry, respectively, of oxidative stress markers (NOX-1, NOX-2, iNOS, eNOS and PARP) in the placental tissue of women who underwent a first episode of psychosis during pregnancy (FE-PW) in comparison to healthy pregnant women. Our results showed augmented gene and protein expression of NOX-1, NOX-2, iNOS and PARP in the placental tissue of FE-PW. For the first time, we demonstrated that oxidative stress may have an important pathophysiological role in this tissue, aiding in explaining the impact of psychosis on pregnancy and the need for future studies in this field to guide better clinical management of these patients.

Psychosis is a complex entity characterized by psychological, behavioral, and motor alterations resulting in a loss of contact with reality. Although it is not common, pregnancy can be a period in which a first episode of psychosis can manifest, entailing detrimental consequences for both the fetus and the mother. The pathophysiological basis and study of maternofetal wellbeing need to be further elucidated. Lipid peroxidation and ferroptosis are two phenomena that are tightly linked to the placental dysfunction commonly observed in different complications of pregnancy. In the present study, we aim to explore the histopathological and gene expression of different markers of lipid peroxidation and ferroptosis in the placentas of women who underwent a first episode of psychosis during their pregnancy (n = 22). The aim is to then compare them with healthy pregnant women (n = 20). In order to achieve this goal, iron deposits were studied using Prussian Blue staining. In addition, the protein/gene expression of a transferrin receptor (TFRC), as well as an acyl-CoA synthetase long-chain family member 4 (ACSL-4), arachidonate lipoxygenase-5 (ALOX-5), malondialdehyde (MDA), and glutathione peroxidase 4 (GPX4) were all analyzed through gene expression (RT-qPCR) and immunohistochemical procedures. Our results demonstrate an increased presence of iron deposits that are accompanied by a further expression of TFRC, ACSL-4, ALOX-5, MDA, and GPX4—all of which are observed in the placenta tissue of women who have suffered from a first episode of psychosis. Therefore, in our study, a histopathological increase in lipid peroxidation and ferroptosis markers in the affected women is suggested. However, further studies are needed in order to validate our results and to establish possible consequences for the reported alterations.

Psychotic episodes represent one of the most complex manifestations of various mental illnesses, and these encompass a wide variety of clinical manifestations that together lead to high morbidity in the general population. Various mental illnesses are associated with psychotic episodes; in addition, although their incidence and prevalence rates have been widely described in the general population, their correct identification and treatment is a challenge for health professionals in relation to pregnancy. In pregnant women, psychotic episodes can be the consequence of the manifestation of a previous psychiatric illness or may begin during the pregnancy itself, placing not only the mother, but also the fetus at risk during the psychotic episode. In addition, we cannot forget that both pharmacological and nonpharmacological management are complex given the different teratogenic effects of various neuroleptic drugs or mood stabilizers; moreover, the recommendation is that patients should be followed together with different specialists to maintain close contact during puerperium given the high incidence of recurrence of psychotic episodes. In addition, we cannot forget that a large portion of these patients for whom the onset times of such episodes are during pregnancy have a greater probability of an unpredictable psychiatric illness that requires a postpartum follow up, in addition to the postpartum psychotic episodes, at some point in their lives. Therefore, the purpose of this review is to summarize the epidemiology of psychotic breaks during pregnancy related to the main mental illnesses that affect this population and to summarize the main pharmacological treatments available for their clinical management.

BackgroundCognitive stimulation therapy appears to show promising results in the rehabilitation of impaired cognitive processes in attention deficit hyperactivity disorder. ObjectiveEncouraged by this evidence and the ever-increasing use of technology and artificial intelligence for therapeutic purposes, we examined whether cognitive stimulation therapy implemented on a mobile device and controlled by an artificial intelligence engine can be effective in the neurocognitive rehabilitation of these patients. MethodsIn this randomized study, 29 child participants (25 males) underwent training with a smart, digital, cognitive stimulation program (KAD_SCL_01) or with 3 commercial video games for 12 weeks, 3 days a week, 15 minutes a day. Participants completed a neuropsychological assessment and a preintervention and postintervention magnetoencephalography study in a resting state with their eyes closed. In addition, information on clinical symptoms was collected from the child´s legal guardians. ResultsIn line with our main hypothesis, we found evidence that smart, digital, cognitive treatment results in improvements in inhibitory control performance. Improvements were also found in visuospatial working memory performance and in the cognitive flexibility, working memory, and behavior and general executive functioning behavioral clinical indexes in this group of participants. Finally, the improvements found in inhibitory control were related to increases in alpha-band power in all participants in the posterior regions, including 2 default mode network regions of the interest: the bilateral precuneus and the bilateral posterior cingulate cortex. However, only the participants who underwent cognitive stimulation intervention (KAD_SCL_01) showed a significant increase in this relationship. ConclusionsThe results seem to indicate that smart, digital treatment can be effective in the inhibitory control and visuospatial working memory rehabilitation in patients with attention deficit hyperactivity disorder. Furthermore, the relation of the inhibitory control with alpha-band power changes could mean that these changes are a product of plasticity mechanisms or changes in the neuromodulatory dynamics. Trial RegistrationISRCTN Registry ISRCTN71041318; https://www.isrctn.com/ISRCTN71041318

Regulatory agencies encourage computer modeling and simulation to reduce the time and cost of clinical trials. Although still not classified in formal guidelines, system biology-based models represent a powerful tool for generating hypotheses with great molecular detail. Herein, we have applied a mechanistic head-to-head in silico clinical trial (ISCT) between two treatments for attention-deficit/hyperactivity disorder, to wit lisdexamfetamine (LDX) and methylphenidate (MPH). The ISCT was generated through three phases comprising (i) the molecular characterization of drugs and pathologies, (ii) the generation of adult and children virtual populations (vPOPs) totaling 2,600 individuals and the creation of physiologically based pharmacokinetic (PBPK) and quantitative systems pharmacology (QSP) models, and (iii) data analysis with artificial intelligence methods. The characteristics of our vPOPs were in close agreement with real reference populations extracted from clinical trials, as did our PBPK models with in vivo parameters. The mechanisms of action of LDX and MPH were obtained from QSP models combining PBPK modeling of dosing schemes and systems biology-based modeling technology, i.e., therapeutic performance mapping system. The step-by-step process described here to undertake a head-to-head ISCT would allow obtaining mechanistic conclusions that could be extrapolated or used for predictions to a certain extent at the clinical level. Altogether, these computational techniques are proven an excellent tool for hypothesis-generation and would help reach a personalized medicine.

Background: Antipsychotic medications are the first-line treatment for schizophrenia. However, non-adherence is frequent despite its negative impact on the course of the illness. In response, we aimed to investigate social media posts about antipsychotics to better understand the online environment in this regard.Methods: We collected tweets containing mentions of antipsychotic medications posted between January 1st 2019 and October 31st 2020. The content of each tweet and the characteristics of the users were analyzed as well as the number of retweets and likes generated.Results: Twitter users, especially those identified as patients, showed an interest in antipsychotic medications, mainly focusing on the topics of sexual dysfunction and sedation. Interestingly, paliperidone, despite being among one of the newest antipsychotics, accounted for a low number of tweets and did not generate much interest. Conversely, retweet and like ratios were higher in those tweets asking for or offering help, in those posted by institutions and in those mentioning cognitive complaints. Moreover, health professionals did not have a strong presence in tweet postings, nor did medical institutions. Finally, trivialization was frequently observed.Conclusion: This analysis of tweets about antipsychotic medications provides insights into experiences and opinions related to this treatment. Twitter user perspectives therefore constitute a valuable input that may help to improve clinicians' knowledge of antipsychotic medications and their communication with patients regarding this treatment.

BackgroundAntiobesity drugs are prescribed for the treatment of obesity in conjunction with healthy eating, physical activity, and behavior modification. However, poor adherence rates have been reported. Attitudes or beliefs toward medications are important to ascertain because they may be associated with patient behavior. The analysis of tweets has become a tool for health research. ObjectiveThe aim of this study is to investigate the content and key metrics of tweets referring to antiobesity drugs. MethodsIn this observational quantitative and qualitative study, we focused on tweets containing hashtags related to antiobesity drugs between September 20, 2019, and October 31, 2019. Tweets were first classified according to whether they described medical issues or not. Tweets with medical content were classified according to the topic they referred to: side effects, efficacy, or adherence. We additionally rated it as positive or negative. Furthermore, we classified any links included within a tweet as either scientific or nonscientific. Finally, the number of retweets generated as well as the dissemination and sentiment score obtained by the antiobesity drugs analyzed were also measured. ResultsWe analyzed a total of 2045 tweets, 945 of which were excluded according to the criteria of the study. Finally, 320 out of the 1,100 remaining tweets were also excluded because their content, although related to drugs for obesity treatment, did not address the efficacy, side effects, or adherence to medication. Liraglutide and semaglutide accumulated the majority of tweets (682/780, 87.4%). Notably, the content that generated the highest frequency of tweets was related to treatment efficacy, with liraglutide-, semaglutide-, and lorcaserin-related tweets accumulating the highest proportion of positive consideration. We found the highest percentages of tweets with scientific links in those posts related to liraglutide and semaglutide. Semaglutide-related tweets obtained the highest probability of likes and were the most disseminated within the Twitter community. ConclusionsThis analysis of posted tweets related to antiobesity drugs shows that the interest, beliefs, and experiences regarding these pharmacological treatments are heterogeneous. The efficacy of the treatment accounts for the majority of interest among Twitter users.

Major Depressive Disorder (MDD) is a growing disabling condition affecting around 280 million people worldwide. This complex entity is the result of the interplay between biological, psychological, and sociocultural factors, and compelling evidence suggests that MDD can be considered a disease that occurs as a consequence of an evolutionary mismatch and unhealthy lifestyle habits. In this context, diet is one of the core pillars of health, influencing multiple biological processes in the brain and the entire body. It seems that there is a bidirectional relationship between MDD and malnutrition, and depressed individuals often lack certain critical nutrients along with an aberrant dietary pattern. Thus, dietary interventions are one of the most promising tools to explore in the field of MDD, as there are a specific group of nutrients (i.e., omega 3, vitamins, polyphenols, and caffeine), foods (fish, nuts, seeds fruits, vegetables, coffee/tea, and fermented products) or dietary supplements (such as S-adenosylmethionine, acetyl carnitine, creatine, amino acids, etc.), which are being currently studied. Likewise, the entire nutritional context and the dietary pattern seem to be another potential area of study, and some strategies such as the Mediterranean diet have demonstrated some relevant benefits in patients with MDD; although, further efforts are still needed. In the present work, we will explore the state-of-the-art diet in the prevention and clinical support of MDD, focusing on the biological properties of its main nutrients, foods, and dietary patterns and their possible implications for these patients.

Immune-mediated inflammatory diseases (IMIDs) represent a large group of diseases (Crohn’s, ulcerative colitis, psoriasis, lupus, and rheumatoid arthritis) evidenced by systemic inflammation and multiorgan involvement. IMIDs result in a reduced quality of life and an economic burden for individuals, health care systems, and countries. In this brief descriptive review, we will focus on some of the common biological pathways of these diseases from the point of view of psychoneuroimmunoendocrinology (PNIE). PNIE consists of four medical disciplines (psychology, nervous system, immune system, and endocrine system), which are key drivers behind the health–disease concept that a human being functions as a unit. We examine these drivers and emphasize the need for integrative treatments that addresses the disease from a psychosomatic point of view.

Cellular trafficking is the set of processes of distributing different macromolecules by the cell. This process is highly regulated in cells, involving a system of organelles (endomembranous system), among which are a great variety of vesicles that can be secreted from the cell, giving rise to different types of extracellular vesicles (EVs) that can be captured by other cells to modulate their function. The cells of the immune system are especially sensitive to this cellular traffic, producing and releasing different classes of EVs, especially in disease states. There is growing interest in this field due to the therapeutic and translational possibilities it offers. Different ways of taking advantage of the understanding of cell trafficking and EVs are being investigated, and their use as biomarkers or therapeutic targets is being investigated. The objective of this review is to collect the latest results and knowledge in this area with a specific focus on immune-mediated diseases. Although some promising results have been obtained, further knowledge is still needed, at both the basic and translational levels, to understand and modulate cellular traffic and EVs for better clinical management of these patients.

Background: Major Depressive Disorder (MDD) is associated with both proinflammatory and adaptive immune response abnormalities. Regulatory T lymphocytes (Tregs), a subtype of CD4+ T cells, are relevant for maintaining immune-inflammatory system homeostasis and control of inflammation such as the kind potentially induced by the interactions between the intestinal microbiome and gut mucosa. We investigated the Treg population and its distribution along their stages of differentiation/activation, as well as its function in MDD patients without concomitant diseases. We also studied the potential association between Treg alterations, intestinal barrier damage, and bacterial translocation.Methods: 30 MDD patients and 20 healthy controls were studied. The levels of circulating CD25FoxP3+ Tregs and their distribution on the naïve (TN), effector (TE), central (TCM), and effector memory(TEM) differentiation/activation stages were analyzed using polychromatic flow cytometry. Chemokine receptors (CCR) 2, 5, and 6, and the intracytoplasmic IL-10 expression by the Tregs were also analyzed. The serum IL-10 was measured using Luminex. The serum levels of zonulin and the intestinal fatty acid-binding protein (I-FABP), both markers of gut barrier function, and the LPS-binding protein (LBP), a marker of bacterial translocation, were measured using an enzyme-linked immunosorbent assay.Results: MDD patients had increased number of circulating Tregs cells with enhanced number of Tregs at the TN, TE, TCM, and TEM stages. The percentage of Tregs cells at TN stage was significantly higher in MDD patients. The percentage of Tregs that expressed CCR2 and CCR6 was increased as well as those expressing IL-10. MDD patients had significantly increased levels of circulating I-FABP and LBP. MDD patients with high LBP levels had a significant reduction in the number of circulating Tregs compared to normal-LBP MDD patients.Conclusions: MDD patients showed an expansion of circulating Tregs and their CD25highFoxP3+ and CD25lowFoxP3+ subsets throughout the different stages of CD4+ T lymphocyte differentiation/activation. Tregs also showed an increased frequency of cells expressing CCR6 and CCR2. IL-10 Treg production was also enhanced in MDD patients that concurrently had increased serum IL-10 levels. However, this Treg expansion was blunted in MDD patients with gut barrier damage and increased bacterial translocation.

Background: current findings in the etiopathogenesis of eating disorders (ED) do not allow the formulation of a unique causal model. Currently, the main hypotheses about the etiopathogenesis are based on a multifactorial approach, considering both genetic and environmental factors. The aim of this study is to analyze the relationship between sociodemographic and behavioral factors, as well as self-esteem, in students of the first cycle of middle school and the probability of belonging to the risk group of eating disorders (ED) measured through the EAT-26 scale. Methods: The study target population consists of students of the first cycle of middle school. The instruments applied to the population consisted in: (1) a survey of sociodemographic data and behavioral variables; (2) Rosenberg’s self-esteem test; and (3) EAT Test (Eating Attitudes Test 26). Results: Of a total of 656 students belonging to eight educational centers in Madrid who were offered to participate in the study, 88.6% (n = 579) answered the whole questionnaire. The mean age of the participants was 13.7 years old. Of the participating adolescents, 57.3% were male and the remaining 42.7% (n = 260) were female. A significant relationship was observed between self-esteem and belonging to an ED risk group, with an OR = 0.910 (CI 95% 0.878–0.943). Hence, each one-point increase on the self-esteem dimension decreased the risk of belonging to an ED risk group by 9.5%. In the variables considered in the area of dysfunctional feeding patterns, the variables ‘number of meals’ (p < 0.01), ‘dieting’ (p < 0.01), and ‘drug consumption to lose weight’ (p < 0.01) were found to be related to the risk of belonging to the ED group. Conclusions: The results obtained in our research can help to establish explanatory models that include the understanding of the interaction of the different factors that influence the appearance and development of EDs. Therefore, these should be taken into consideration when developing ED preventive programs.

Major depressive disorder (MDD) is an incapacitating condition characterized by loss of interest, anhedonia and low mood, which affects almost 4% of people worldwide. With rising prevalence, it is considered a public health issue that affects economic productivity and heavily increases health costs alone or as a comorbidity for other pandemic non-communicable diseases (such as obesity, cardiovascular disease, diabetes, inflammatory bowel diseases, etc.). What is even more noteworthy is the double number of women suffering from MDD compared to men. In fact, this sex-related ratio has been contemplated since men and women have different sexual hormone oscillations, where women meet significant changes depending on the age range and moment of life (menstruation, premenstruation, pregnancy, postpartum, menopause…), which seem to be associated with susceptibility to depressive symptoms. For instance, a decreased estrogen level promotes decreased activation of serotonin transporters. Nevertheless, sexual hormones are not the only triggers that alter neurotransmission of monoamines and other neuropeptides. Actually, different dietary habits and/or nutritional requirements for specific moments of life severely affect MDD pathophysiology in women. In this context, the present review aims to descriptively collect information regarding the role of malnutrition in MDD onset and course, focusing on female patient and especially macro- and micronutrient deficiencies (amino acids, ω3 polyunsaturated fatty acids (ω3 PUFAs), folate, vitamin B12, vitamin D, minerals…), besides providing evidence for future nutritional intervention programs with a sex-gender perspective that hopefully improves mental health and quality of life in women.

The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of the organism, affecting the health and disease status of the individuals. There is continuous and bidirectional communication between gut microbiota and the host, conforming to a unique entity known as “holobiont”. Among these crosstalk mechanisms, the gut microbiota synthesizes a broad spectrum of bioactive compounds or metabolites which exert pleiotropic effects on the human organism. Many of these microbial metabolites can cross the blood–brain barrier (BBB) or have significant effects on the brain, playing a key role in the so-called microbiota-gut-brain axis. An altered microbiota-gut-brain (MGB) axis is a major characteristic of many neuropsychiatric disorders, including major depressive disorder (MDD). Significative differences between gut eubiosis and dysbiosis in mental disorders like MDD with their different metabolite composition and concentrations are being discussed. In the present review, the main microbial metabolites (short-chain fatty acids -SCFAs-, bile acids, amino acids, tryptophan -trp- derivatives, and more), their signaling pathways and functions will be summarized to explain part of MDD pathophysiology. Conclusions from promising translational approaches related to microbial metabolome will be addressed in more depth to discuss their possible clinical value in the management of MDD patients.

Background: Antidepressants are the foundation of the treatment of major depressive disorders. Despite the scientific evidence, there is still a sustained debate and concern about the efficacy of antidepressants, with widely differing opinions among the population about their positive and negative effects, which may condition people’s attitudes towards such treatments. Our aim is to investigate Twitter posts about antidepressants in order to have a better understanding of the social consideration of antidepressants. Methods: We gathered public tweets mentioning antidepressants written in English, published throughout a 22-month period, between 1 January 2019 and 31 October 2020. We analysed the content of each tweet, determining in the first place whether they included medical aspects or not. Those with medical content were classified into four categories: general aspects, such as quality of life or mood, sleep-related conditions, appetite/weight issues and aspects around somatic alterations. In non-medical tweets, we distinguished three categories: commercial nature (including all economic activity, drug promotion, education or outreach), help request/offer, and drug trivialization. In addition, users were arranged into three categories according to their nature: patients and relatives, caregivers, and interactions between Twitter users. Finally, we identified the most mentioned antidepressants, including the number of retweets and likes, which allowed us to measure the impact among Twitter users. Results: The activity in Twitter concerning antidepressants is mainly focused on the effects these drugs may have on certain health-related areas, specifically sleep (20.87%) and appetite/weight (8.95%). Patients and relatives are the type of user that most frequently posts tweets with medical content (65.2%, specifically 80% when referencing sleep and 78.6% in the case of appetite/weight), whereas they are responsible for only 2.9% of tweets with non-medical content. Among tweets classified as non-medical in this study, the most common subject was drug trivialization (66.86%). Caregivers barely have any presence in conversations in Twitter about antidepressants (3.5%). However, their tweets rose more interest among other users, with a ratio 11.93 times higher than those posted by patients and their friends and family. Mirtazapine is the most mentioned antidepressant in Twitter (45.43%), with a significant difference with the rest, agomelatine (11.11%). Conclusions: This study shows that Twitter users that take antidepressants, or their friends and family, use social media to share medical information about antidepressants. However, other users that do not talk about antidepressants from a personal or close experience, frequently do so in a stigmatizing manner, by trivializing them. Our study also brings to light the scarce presence of caregivers in Twitter.

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in childhood (5.3% to 7.1% worldwide prevalence), with substantial overall financial burden to children/adolescents, their families, and society. The aims of this study were to describe the clinical characteristics of children and adolescents with ADHD in Spain, estimate the associated direct/indirect costs of the disorder, and assess whether the characteristics and financial costs differed between children/adolescents adequately responding to currently available pharmacotherapies compared with children/adolescents for whom pharmacotherapies failed. Methods This was a multicenter, cross-sectional, descriptive analysis conducted in 15 health units representative of the overall Spanish population. Data on demographic characteristics, socio-occupational status, social relationships, clinical variables of the disease, and pharmacological and non-pharmacological treatments received were collected in 321 children and adolescents with ADHD. Direct and indirect costs were estimated over one year from both a health care system and a societal perspective. Results The estimated average cost of ADHD per year per child/adolescent was €5733 in 2012 prices; direct costs accounted for 60.2% of the total costs (€3450). Support from a psychologist/educational psychologist represented 45.2% of direct costs and 27.2% of total costs. Pharmacotherapy accounted for 25.8% of direct costs and 15.5% of total costs. Among indirect costs (€2283), 65.2% was due to caregiver expenses. The total annual costs were significantly higher for children/adolescents who responded poorly to pharmacological treatment (€7654 versus €5517; P = 0.024), the difference being mainly due to significantly higher direct costs, particularly with larger expenses for non-pharmacological treatment (P = 0.012). Conclusions ADHD has a significant personal, familial, and financial impact on the Spanish health system and society. Successful pharmacological intervention was associated with lower overall expenses in the management of the disorder.

Major Depressive Disorder (MDD) represents a major global health concern, a body-mind malady of rising prevalence worldwide nowadays. The complex network of mechanisms involved in MDD pathophysiology is subjected to epigenetic changes modulated by microRNAs (miRNAs). Serum free or vesicles loaded miRNAs have starred numerous publications, denoting a key role in cell-cell communication, systematically and in brain structure and neuronal morphogenesis, activity and plasticity. Upregulated or downregulated expression of these signaling molecules may imply the impairment of genes implicated in pathways of MDD etiopathogenesis (neuroinflammation, brain-derived neurotrophic factor (BDNF), neurotransmitters, hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, circadian rhythms...). In addition, these miRNAs could serve as potential biomarkers with diagnostic, prognostic and predictive value, allowing to classify severity of the disease or to make decisions in clinical management. They have been considered as promising therapy targets as well and may interfere with available antidepressant treatments. As epigenetic malleable regulators, we also conclude emphasizing lifestyle interventions with physical activity, mindfulness and diet, opening the door to new clinical management considerations.

Major depressive disorder (MDD) is a complex and common disorder, with many factors involved in its onset and development. The clinical management of this condition is frequently based on the use of some pharmacological antidepressant agents, together with psychotherapy and other alternatives in most severe cases. However, an important percentage of depressed patients fail to respond to the use of conventional therapies. This has created the urgency of finding novel approaches to help in the clinical management of those individuals. Nutraceuticals are natural compounds contained in food with proven benefits either in health promotion or disease prevention and therapy. A growing interest and economical sources are being placed in the development and understanding of multiple nutraceutical products. Here, we summarize some of the most relevant nutraceutical agents evaluated in preclinical and clinical models of depression. In addition, we will also explore less frequent but interest nutraceutical products which are starting to be tested, also evaluating future roads to cover in order to maximize the benefits of nutraceuticals in MDD.

We focused on tweets containing hashtags related to ADHD pharmacotherapy between 20 September and 31 October 2019. Tweets were classified as to whether they described medical issues or not. Tweets with medical content were classified according to the topic they referred to: side effects, efficacy, or adherence. Furthermore, we classified any links included within a tweet as either scientific or non-scientific. We created a dataset of 6568 tweets: 4949 (75.4%) related to stimulants, 605 (9.2%) to non-stimulants and 1014 (15.4%) to alpha-2 agonists. Next, we manually analyzed 1810 tweets. In the end, 481 (48%) of the tweets in the stimulant group, 218 (71.9%) in the non-stimulant group and 162 (31.9%) in the alpha agonist group were considered classifiable. Stimulants accumulated the majority of tweets. Notably, the content that generated the highest frequency of tweets was that related to treatment efficacy, with alpha-2 agonist-related tweets accumulating the highest proportion of positive consideration. We found the highest percentages of tweets with scientific links in those posts related to alpha-2 agonists. Stimulant-related tweets obtained the highest proportion of likes and were the most disseminated within the Twitter community. Understanding the public view of these medications is necessary to design promotional strategies aimed at the appropriate population.

Background: We have investigated the distribution of the Th1, Th2 and Th17 subsets in circulating CD4+ T lymphocytes and their naïve (TN), effector (TE), central (TCM) and effector memory (TEM) activation/differentiation stages in patients with major depressive disorder (MDD). Methods: Thirty MDD patients and 30 healthy controls were studied. The counts of circulating CD4+ T lymphocytes and their distribution on the TN, TE, TCM and TEM activation/differentiation stages were analyzed by polychromatic flow cytometry. The intracytoplasmic interferon gamma (IFNγ), interleukin (IL)-4, IL-17A and tumor necrosis factor alpha (TNF-alpha) and membrane CD28 expression were also measured. The serum IFNγ, IL-4, Il-17A and TNF-alpha were measured by Luminex, respectively. Results: MDD patients had normal counts of CD4+ T lymphocytes and of their TN, TCM and TEM subsets but increased number and percentage of TE CD4+ subset. CD4+ T lymphocytes had significantly enhanced percentage of cells that express IL-17 and TNF-alpha explained by the expansions found in the TN, TCM and, TEM and TCM, TEM and TE activation/differentiation stages, respectively. A selective increase in the percentages of TCM and TEM expressing IFNγ was also observed. We found a significant correlation between the percentages of CD4+ T lymphocytes expressing IFNγ and TNF-alpha in these patients. MDD patients showed increased serum levels of IL-17 and TNF-alpha, but normal IFNγ and IL-4 concentration. Limitations: the cross-sectional nature of the study could be considered a limitation. Conclusions: MDD patients have abnormal circulating CD4+ T lymphocytes with expansion of the IL-17 and TNF-alpha expressing cells as well as increased levels of circulating IL-17 and TNF-alpha.

A principios de los años 70 de la centuria pasada, en un contexto de imperialismo, guerras, dictaduras, utópicos proyectos políticos y, por supuesto, crisis económicas expresadas en frases como la del director de Le monde diplomatique en castellano, Ignacio Ramonet, “se privatizan las ganancias y se socializan las pérdidas”, ocurrieron una serie de debates protagonizados por prestigiosos intelectuales, a quienes, por la manera de articular una vasta cantidad de información, se les suponía aptos para enfrentar el complejo panorama. Uno de estos debates se realizó en Holanda, específicamente en la Universidad de Ámsterdam, y en él participaron el lingüista norteamericano N. Chomsky y el filósofo francés M. Foucault. Dicho debate fue posteriormente traducido y publicado en un volumen por la editorial argentina Katz bajo el nombre de La naturaleza humana: justicia versus poder (2006). Allí Foucault expuso un contundente argumento que me servirá de exordio para presentar la hipótesis expuesta por el médico Yidi Páez Casadiegos en su libro Cosmovisiones de la Medicina: Una aproximación crítico-hermenéutica, trabajo que se encuentra en un contexto de lectura nada alejado de los citados años 70. El argumento de Foucault era el siguiente: Me parece que la verdadera tarea política, en una sociedad como la nuestra, es realizar una crítica al funcionamiento de las instituciones que parecen neutrales e independientes; hacer Psicogente, 12 (21): pp. 236-240. Junio, 2009. Universidad Simón Bolívar. Barranquilla, Colombia. ISSN: 0124-0137 EISSN 2027-212Xhttp://www.unisimonbolivar.edu.co/rdigital/psicogente/index.php/psicogente237una crítica y atacarlas de modo tal de desenmascarar la violencia política que se ha ejercido a través de estas de manera oculta, para que podamos combatirlas... Si no logramos reconocer estos puntos de apoyo del poder de clases, corremos el riesgo de permitir la continuidad de su existencia y de ver a este poder de clase reconstituirse a sí mismo, incluso luego de un aparente proceso revolucionario. (La naturaleza humana: justicia versus poder, pp. 59-60).