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Introduction: Pediatricians in training are a population at risk for anxiety and depression: they face long working hours, they are confronted with the suffering and death of a vulnerable population and may have personal characteristics that put them in danger. Nonetheless, few studies have looked at their prevalence and associated factors. We aimed to compare demographic, professional activities, adversities and perfectionism personality features between a group of pediatricians in training with depression and/or anxiety and a group of pediatricians in training without depression nor anxiety and, to identify the variables that increase the probabilities of depression and/or anxiety in pediatricians in training. Methods: Pediatric residents who voluntarily answered an online survey distributed via personal and institutional social media channels from October 2019 to April 2021, as part of a cross-sectional study with medical specialists and residents from Mexico were included. Demographic information, professional activities and adversities, perfectionism personality features (Multidimensional Perfectionism Scale), depression and anxiety (ICD-11 PHC) were evaluated. For comparison purposes Chi-square tests (χ2) and independent sample t-tests were used. A logistic regression analysis was used to identify those variables that increase the probabilities of depression and/or anxiety. Results: 934 pediatric residents answered the survey. 11.6% reported having depression and 20% anxiety. Being single, a history of anxious or depressive episodes, being the resident in charge of a patient who died, aggressions from colleagues and a high concern for errors were associated with current depression and/or anxiety. Discussion: Screening for depressive and anxious symptoms should be routinely performed from entry to the residency to favor early intervention. A shift from promoting perfectionism to a more compassionate training could serve a population facing so many adversities.

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Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

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Dopamine and serotonin receptors and transporters play an essential role in the pathophysiology of schizophrenia; changes in their expression have been reported in neurons and leukocytes. Each antipsychotic induces a unique pattern in leukocyte function and phenotype. However, the use of polytherapy to treat schizophrenia makes it challenging to determine the specific effects of risperidone on peripheral blood mononuclear cells (PBMCs). The aim of this study was to evaluate the changes in the expression of D3, D5, DAT, 5-HT2A, and SERT in PBMCs from healthy volunteers (HV), drug-naive patients with schizophrenia (PWS), drug-free PWS, and PWS treated with risperidone for up to 40 weeks using quantitative PCR. Our study revealed elevated mRNA levels of D3, DAT, 5-HT2A, and SERT in unmedicated PWS. Treatment with risperidone led to a reduction only in the expression of 5-HT2A and SERT. Furthermore, we observed a moderate correlation between 5-HT2A expression and the positive and negative syndrome scale (PANSS), as well as SERT expression and PANSS scale. We also found a moderate correlation between 5-HT2A and SERT expression and the positive subscale. The duration of risperidone consumption had a significant negative correlation with the expression of 5-HT2A and SERT. Our study introduces the measurement of 5-HT2A and SERT expression in PBMCs as a useful parameter for assessing the response to risperidone in PWS.

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The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

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Background: Stressful life events (SLEs) in the development of early psychosis have been little studied in low-income countries. This study examines differences in the prevalence of SLEs in Mexican at clinical high risk (CHR) and those with familial high risk for psychosis who do not meet CHR criteria (non-CHR FHR). We also analyze the association between SLEs and CHR. Methods: Participants included 43 persons with CHR and 35 with non-CHR FHR. CHR criteria were assessed with the Comprehensive Assessment of At-Risk Mental State. SLEs were assessed using the Questionnaire of Stressful Life Events. Results: Participants with CHR reported more SLEs associated with negative academic experiences than those in the non-CHR FHR group. Bullying (OR = 7.77, 95% CI [1.81, 33.32]) and low educational level (OR = 21.25, 95% CI [5.19, 46.90]) were the strongest predictors of CHR, while starting to live with a partner (OR = 0.26, 95% CI [0.10, 0.84]) was associated with a lower risk of CHR. Conclusion: Negative school experiences increase the risk of psychosis, particularly bullying, suggesting that schools may be ideal settings for implementing individual preventive strategies to reduce risk factors and increase protective factors to improve the prognosis of those at risk of developing psychosis. In Latin America, there are multiple barriers to early intervention in psychosis. It is thus crucial to identify risk and protective factors at the onset and in the course of psychosis in order to design effective preventive interventions.

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Introduction: Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment. Methods: A systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest. Results: 87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18-2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12-3.22), lurasidone (OR, 2.25; 95% CrI, 1.28-3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06-3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92-14.83), haloperidol (OR, 2.61; 95% CrI, 1.14-5.99), and risperidone (OR, 2.41; 95% CrI, 1.21-4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation. Discussion: Insomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017078052, identifier: PROSPERO 2017 CRD42017078052.

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OBJECTIVES: Clostridioides difficile is a nosocomial pathogen that is associated with the use of antibiotics. One of the most worrying aspects of C. difficile infection is its ability to resist antimicrobial therapies, owing to spore formation. In several bacterial pathogens, proteases of the Clp family participate in phenotypes associated with persistence and virulence. This suggests that these proteins could be involved in virulence-related traits. In this study, we analysed the role of ClpC chaperone-protease of C. difficile in virulence-related traits by comparing the phenotypes of wild-type and mutant strains lacking the clpC gene (ΔclpC). METHODS: We performed biofilm, motility, spore formation, and cytotoxicity assays. RESULTS: Our results show significant differences between the wild-type and ΔclpC strains in all analysed parameters. CONCLUSIONS: Based on these findings, we conclude that clpC plays a role in the virulence properties of C. difficile.

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We report herein the synthesis and characterization of three heterocyclic curcuminoid ligands and their homoleptic metal complexes with magnesium and copper. Thus, N-methyl-2-pyrrolecarboxaldehyde, Furan-2-carboxaldehyde, and 2-Thiophenecarboxaldehyde were condensed with 2,4-pentanedione-boron trioxide complex. The first N-methyl-2-pyrrole curcuminoid and its Mg(II) complex are reported. All curcuminoid ligands and their corresponding metal complexes were characterized by infrared spectroscopy (IR), liquid state nuclear magnetic resonance (LSNMR), electron paramagnetic resonance (EPR), mass spectrometry (MS) and single crystal X-ray diffraction (SCXRD). The ThiopheneCurc-Cu (9) constitutes the first case of a "conformationally-heteroleptic" complex. The unique six-peaks star arrangement for the ThiopheneCurc ligand derived from the supramolecular description is reported. The metal complexes of FuranCurc-Mg (5) and ThiopheneCurc-Cu (9) have a good antioxidant effect (IC50 = 11.26 ± 1.73 and 10.30 ± 0.59 µM), three and two times higher than their free ligands respectively. Additionally, (5) shows remarkable cytotoxicity against colon cancer adenocarcinoma cell line HCT-15, comparable to that of cisplatin, with a negligible toxic effect in vitro towards a healthy monkey kidney cell line (COS-7).

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Background: Psychiatrists are at high risk of developing burnout and mental health problems mainly due to their emotionally demanding jobs, difficult working conditions, long working hours, and poor work-life balance. As leisure activities are associated with better physical and mental health, engaging in these activities has been recommended as a measure to improve the wellbeing of healthcare workers. However, it is unclear the extent of which psychiatrists and trainees are involved in leisure activities, what type of activities they prefer, or how these impact their self-perceived health, stress, confidence in stress management, and satisfaction with their social support. Objective: The aim of this study was to identify differences in self-perceived health, perceived stress, confidence in stress management, and satisfaction with social support, between psychiatrists and trainees who engage in different leisure activities, compared with those who do not. Methods: This was a cross-sectional study, including Mexican psychiatrists (n = 355) and trainees (n = 330) who agreed to participate through an online survey. Results: 73.1% of participants engaged in some leisure activity, being solitary-passive activities the most reported. Those who have a leisure activity reported lower stress, greater confidence in stress management, and more satisfaction with their social support. Passive-solitary activities were associated with less perceived stress and better confidence in stress management, while active-solitary and social activities were associated with better satisfaction with social support. Conclusion: Psychiatrists' and trainees' wellbeing benefits from engagement in leisure activities, which should be part of their daily schedules to reduce stress, and potentially improve their mental health.

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Background/Objectives: Individuals with disabilities (IWD) have a higher risk of potentially traumatic events (PTEs) either in childhood or adulthood, increasing the risk of suicide attempts, mental disorders, and substance use disorder. The aim of this study was to explore the association between substance use, psychiatric symptoms and suicidal behavior with PTEs. A Multisite cross-sectional study was conducted. Materials and methods: The sample includes 1,098 participants with any type of disability (motor, intellectual, visual, and mixed) located in Mexico City. Traumatic events, violence, discrimination, addictive disorders, and psychiatric disorders were examined. Multivariate logistic regression models were conducted. Data was collected between September-October 2014. Results: People with motor or visual disability have a higher prevalence in nicotine use disorder (NUD), generalize anxiety disorder (GAD), mayor depression disorder (MDD), want to be dead, and lifetime suicide attempts. Intellectual disability group only presents GAD and MDD. All disability groups have a high prevalence of PTEs. Verbal violence in childhood, sexual abuse, discrimination and serious accidents had a strong impact in the development of NUD, psychiatric symptoms and suicidal behavior. Conclusion: These findings show the relevance of develop specific tools for detection, referral and treatment, in order to improve the mental health of people with disabilities.

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Few studies have explored the differences in clinical psychopathology between youth at high risk for psychosis and those at familial high risk for psychosis. This study seeks to describe and compare the sociodemographic, clinical, and functional characteristics of At-Risk Mental State (ARMS) for psychosis youth and those with a first- or second-degree relative with psychosis (Familial High-Risk: FHR) in a Mexican sample. Twenty-one ARMS individuals and 21 with FHR were evaluated for sociodemographic characteristics, psychopathological symptoms, and functional impairment. ARMS individuals were significantly younger, had fewer years of schooling, and were more likely to be male than those in the FHR group. Groups did not differ as regards marital status or occupation. The ARMS group showed greater severity of prodromal symptoms, schizotypal personality traits, and general psychopathology than the FHR group. In addition, they reported more premorbid adjustment deficit from early adolescence than the FHR group. Current overall social and role functioning was significantly lower in the ARMS group. Findings are consistent with ARMS studies from other countries. First- or second-degree relatives of patients with psychosis should be considered a vulnerable group as they display several symptoms of general psychopathology and may experience social adjustment problems in their adult lives. The lack of early detection and intervention psychosis programs in Mexico underlines the need to prioritize the development of preventive strategies to help close the care gap.

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BACKGROUND: Evidence suggests that schizophrenia (SCZ), schizoaffective disorder (SAD) and bipolar disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. GWAS and candidate gene studies have reported association between the rs1344706 A allele with SCZ, SAD and BPD in European and Asian populations. In Mexican patients, no studies have specifically analyzed ZNF804A gene variants with these disorders. The aim of the study was to analyze the rs1344706 and identify common and rare variants in a targeted region of the ZNF804A gene in Mexican patients with SCZ, BPD and SAD compared with a control group. METHODS: We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. Also, an additional sample of 167 patients with these disorders and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene. RESULTS: Association analysis of rs1344706 observed a higher frequency of A allele in the patients compared with the control group; however, did not show statistical differences after Bonferronís correction (χ2 = 5.3, p = 0.0208). In the sequence analysis, we did not identify rare variants; however, we identified three common variants: rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between patients and controls did not show statistical differences (p > 0.0125). Finally, haplotype analysis did not show statistical differences between SCZ, SAD and BPD and controls. CONCLUSIONS: Our findings did not support the evidence suggesting that ZNF804A gene participates in the etiology of SCZ, SAD and BPD. Future studies are needed in a larger sample size to identify the effect of this gene in psychiatric disorders.

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The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF2 group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al2O3) or silica (SiO2) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms "click" and "unclick" applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80-92% yield), in pure form and excellent yields.

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Background: Previous studies in Mexico undertaken at residential facilities for treating substance use disorders (SUDs) reported that the prevalence of Dual Disorders (DDs) is over 65%. DDs pose a major challenge for the Mexican health system, particularly for community-based residential care facilities for SUDs, due to the shortage of certified professionals to diagnose and treat these patients. Moreover, the lack of standardized algorithms for screening for and evaluating DDs to refer patients to specialized services (whether private or public) hinders timely care, delaying the start of integrated treatment. The use of new technologies provides a strategic opportunity for the timely detection of DDs through the development of standardized digital applications for the timely detection of DDs. Objective: To develop an app to screen for DDs, which will contribute to referral to specialized services in keeping with the level of severity of psychiatric and addictive symptomatology, and be suitable for use by community-based residential care facilities for SUDs. Method: The research project was implemented in two stages. Stage 1 involved obtaining the psychometric properties of the Dual Diagnosis Screening Interview (DDSI). Stage 2 consisted of two steps to test the Beta version of the app and the quality of version 1.0. Results: The DDS obtained sensitivity and specificity scores above 85%. The app and its algorithm to screen for and refer DDs proved to be efficient and easy to apply with satisfactory community acceptance. Conclusion: The app promises to be a useful screening tool at residential addiction treatment centers.

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Among the insect pests that affect crucifer crops in Mexico are Delia planipalpis (Meigen) and D. platura (Stein). They are a threat to the production of these vegetables since the damage they cause directly and indirectly affects yield, quality, and commercialization of these crops. Nevertheless, the existence of natural enemies of these dipterans is still unknown. It is fundamental to determine which parasitoids or predators can be considered possible biological control agents in an integrated pest management program. The sampling sites were located in Guanajuato, Puebla, and the State of Mexico, where plants of Brassica oleracea L. var. italica Plenk and capitata L., B. napus L., and Raphanus sativus L. infested with Delia spp. were selected. The symptoms observed were wilting, yellowish, flaccid leaves and individuals less developed than the rest of the crop. These plants were extracted with their root and the surrounding soil. Also, wild crucifers were collected, such as Raphanus raphanistrum L., Brassica campestris L., and Sisymbrium irio L. The first records of Aphaereta pallipes Say (Hymenoptera, Braconidae), Trybliographa rapae (Westwood) (Hymenoptera, Figitidae), and Aleochara bimaculata Gravenhorst (Coleoptera, Staphylinidae) are reported parasitizing the puparia of these anthomyiid flies on cultivated and wild crucifers. This represents only a starting point for the continuous study of these parasitoids, which is needed to consider them useful for the biological control of D. planipalpis and D. platura.

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No large-scale genome-wide association studies (GWASs) of psychosis have been conducted in Mexico or Latin America to date. Schizophrenia and bipolar disorder in particular have been found to be highly heritable and genetically influenced. However, understanding of the biological basis of psychosis in Latin American populations is limited as previous genomic studies have almost exclusively relied on participants of Northern European ancestry. With the goal of expanding knowledge on the genomic basis of psychotic disorders within the Mexican population, the National Institute of Psychiatry Ramón de la Fuente Muñiz (INPRFM), the Harvard T.H. Chan School of Public Health, and the Broad Institute's Stanley Center for Psychiatric Research launched the Neuropsychiatric Genetics Research of Psychosis in Mexican Populations (NeuroMex) project to collect and analyze case-control psychosis samples from 5 states across Mexico. This article describes the planned sample collection and GWAS protocol for the NeuroMex study. The 4-year study will span from April 2018 to 2022 and aims to recruit 9,208 participants: 4,604 cases and 4,604 controls. Study sites across Mexico were selected to ensure collected samples capture the genomic diversity within the Mexican population. Blood samples and phenotypic data will be collected during the participant interview process and will contribute to the development of a local biobank in Mexico. DNA extraction will be done locally and genetic analysis will take place at the Broad Institute in Cambridge, MA. We will collect extensive phenotypic information using several clinical scales. All study materials including phenotypic instruments utilized are openly available in Spanish and English. The described study represents a long-term collaboration of a number of institutions from across Mexico and the Boston area, including clinical psychiatrists, clinical researchers, computational biologists, and managers at the 3 collaborating institutions. The development of relevant data management, quality assurance, and analysis plans are the primary considerations in this protocol article. Extensive management and analysis processes were developed for both the phenotypic and genetic data collected. Capacity building, partnerships, and training between and among the collaborating institutions are intrinsic components to this study and its long-term success.

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Salmonella Typhimurium is a facultative, intracellular pathogen whose products range from self-limited gastroenteritis to systemic diseases. Food ingestion increases biomolecules' concentration in the intestinal lumen, including amino acids such as cysteine, which is toxic in a concentration-dependent manner. When cysteine's intracellular concentration reaches toxic levels, S. Typhimurium expresses a cysteine-inducible enzyme (CdsH), which converts cysteine into pyruvate, sulfide, and ammonia. Despite this evidence, the biological context of cdsH's role is not completely clear, especially in the infective cycle. Since inside epithelial cells both cdsH and its positive regulator, ybaO, are overexpressed, we hypothesized a possible role of cdsH in the intestinal phase of the infection. To test this hypothesis, we used an in vitro model of HT-29 cell infection, adding extra cysteine to the culture medium during the infective process. We observed that, at 6 h post-invasion, the wild type S. Typhimurium proliferated 30% more than the ΔcdsH strain in the presence of extra cysteine. This result shows that cdsH contributes to the bacterial replication in the intracellular environment in increased concentrations of extracellular cysteine, strongly suggesting that cdsH participates by increasing the bacterial fitness in the intestinal phase of the S. Typhimurium infection.

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Soil pests of cruciferous crops in Mexico have been gaining importance in recent years; such is the case of Delia spp. (Robineau-Desvoidy) (Diptera, Anthomyiidae), of which, to date, there are no studies on the correct identification of associated species, as well as the range of hosts. In an integrated pest management program, it is essential to know this information to design and implement adequate phytosanitary measures. Plants infested by Delia spp. were collected in the states of Guanajuato, Puebla, and Mexico from June to November 2017 and March to December 2018 in commercial plantations of cruciferous crops (Brassica oleracea L. var. italica, botrytis and capitata), B. napus L., and Raphanus sativus L.) as well as some cruciferous weeds (R. raphanistrum L., Sisymbrium irio L., B. campestris L., Capsella bursa-pastoris L., and Lepidium virginicum L.) in the edges of these crops. The two species found in this study, Delia planipalpis (Stein) and Delia platura (Meigen), identified using male genitalia was corroborated by molecular techniques. Both species emerged from all the sampled hosts, except for C. bursa-pastoris and L. virginicum. The association of the two species in cruciferous crops and weeds, provides valuable information for the management of these insects not only in cruciferous crops but other ones that are strongly attacked by D. platura.

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BACKGROUND: Paliperidone palmitate is a long-acting, second-generation antipsychotic (SGA) indicated for the treatment of acute exacerbations and maintenance treatment of adults with schizophrenia. This study addressed the response to paliperidone palmitate in Latin American patients with acute symptoms and recently diagnosed schizophrenia. OBJECTIVE: Explore the efficacy and tolerability of paliperidone palmitate administered once a month for 4 months in patients with acute phase and recent diagnosis (within 1-6 years) of schizophrenia in 3 Latin American countries. METHODS: This was a non-randomized, open-label, multicenter study with paliperidone palmitate injected intramuscularly in the deltoid muscle at an initial loading dose of 150 mg eq. (234 mg) on day 1 and 100 mg eq. (156 mg) on day 8 (± 4 days). The recommended maintenance dose was 75 mg eq. (117 mg) from day 36 to day 92. Efficacy was evaluated with PANSS and CGI-S. The last observation carried forward (LOCF) was used for efficacy analysis for imputation of missing data; no adjustments were made for multiplicity. Adverse events were evaluated during treatment. RESULTS: The patient retention rate was 84.0% (144 patients received study drug; 121 finished the study). The percentage of patients with a reduction of at least 30% in PANSS total score compared to baseline gradually increased during the study, and at the end, 78.4% of patients showed response. The PANSS total score and CGI-S scores decreased significantly from baseline to LOCF endpoint (P <0.0001 for both); significant reduction in PANSS total score was observed at day 8 and persisted to the end of the study. Most common adverse events were muscle rigidity (11.8%), akathisia (11.1%), injection-site pain (7.6%), weight gain (7.6%), and insomnia (7.6%). CONCLUSION: Paliperidone palmitate was efficacious in Latin American patients studied with an acute exacerbation and recent diagnosis of schizophrenia, and no new safety signals were identified.

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Curcumin, the most important secondary metabolite isolated from Curcuma longa, is known for its numerous purported therapeutic properties and as a natural dye. Herein, based on curcumin's intrinsic fluorescence, a search for improved curcumin-based fluorophores was conducted. Within the set of semi-synthetic curcumin derivatives i.e. mono (1), di (2), tri (3), tetra (4) benzylated and dibenzyl-fluoroborate (5), the fluorescence properties of 2 and 5 in solution outstood with a two-fold quantum yield compared to curcumin. Furthermore, all benzylated derivatives showed a favorable minimal cytotoxic activity upon screening at 25 µM against human cancer and non-tumoral COS-7 cell lines, with a reduction of its cytotoxic effect related to the degree of substitution. Fluorophores 2 and 5 are versatile bioimaging tools, as revealed by Confocal Fluorescence Microscopy (CFM), and showed permeation of living cell membranes of astrocytes and astrocytomas. When 2 is excited with a 405- (blue) or 543-nm (green) laser, it is possible to exclusively and intensively visualize the nucleus. However, the fluorescence emission fades as the laser wavelength moves towards the red region. In comparison, 5 allows selective visualization of cytoplasm when a 560-nm laser is used, showing emission in the NIR region, while it is possible to exclusively observe the nucleus at the blue region with a 405-nm laser.

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