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(R,S)-methadone ((R,S)-MTD) is a racemic µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers used for the treatment of opioid use disorder (OUD) and pain. (R)-MTD is used as an OUD treatment, has high MOR potency, and is believed to mediate (R,S)-MTD’s therapeutic efficacy. (S)-MTD is in clinical development as an antidepressant and is considered an N-methyl-D-aspartate receptor (NMDAR) antagonist. In opposition to this purported mechanism of action, we found that (S)-MTD does not occupy NMDARs in vivo in rats. Instead, (S)-MTD produced MOR occupancy and induced analgesia with similar efficacy as (R)-MTD. Unlike (R)-MTD, (S)-MTD was not self-administered and failed to increase locomotion or extracellular dopamine levels indicating low abuse liability. Moreover, (S)-MTD antagonized the effects of (R)-MTD in vivo and exhibited unique pharmacodynamic properties, distinct from those of (R)-MTD. Specifically, (S)-MTD acted as a MOR partial agonist with a specific loss of efficacy at the MOR-galanin 1 receptor (Gal1R) heteromer, a key mediator of the dopaminergic effects of opioids. In sum, we report novel and unique pharmacodynamic properties of (S)-MTD that are relevant to its potential mechanism of action and therapeutic use, as well as those of (R,S)-MTD.

Suicide prevention is one of the great issues of the current era. Institutions such as the World Health Organization, have continued to search for all possible alternatives for early detection and timely prevention. Suicide rates have grown more and more in the world, and Mexico, although it is not the country with the most suicides, is one of the countries with the highest growth in recent years. At present, the use of social networks has generated great changes in the way we communicate. Expressing yourself through a social network begins to be more common than expressing ourselves to human beings. Several studies, which will be presented later, show that it is possible to determine from the content of social networks: cases of depression, risk of suicide, and other mental problems. The use of technological tools, such as Natural Language Processing, has served as an effective ally for the early detection of risks, such as abuse, bullying or even detecting emotional problems. The present research seeks to carry out an in-depth analysis in the state of the art of the application of Natural Language Processing as an ally for the detection of suicide risk from the analysis of texts for Mexican Spanish in Social Networks.

Alexithymia is a condition that partially or completely deprives you of the ability to identify and describe emotions, and to show affective connotations in the actions of an individual. This problem has been taken to different research projects that seek to study its characteristics, forms of prevention, and implications, and that try to determine a measurement for the experience of an individual with this construct as well as the responses they provide to certain stimuli. Other studies that were reviewed aimed to find a connection between the responses of subjects diagnosed with alexithymia when facing a dynamic of emotional facial expressions to recognize and their assigned grade based on the Toronto Alexithymia Scale (TAS), a metric frequently used to evaluate the presence or absence of alexithymia in an individual. In this work, a review of the different articles that study this connection, as well as articles that describe the state of the art of the implementation of artificial intelligence algorithms applied to the treatment or prevention of secondary alexithymia is presented.

A series of imidazo[1,2-a]pyridine-chromones were synthesized by microwave-assisted Groebke–Blackburn–Bienayme reaction (GBBR) under eco-friendly conditions (20 mol% ammonium chloride catalyst in EtOH). Chromones and imidazo[1,2-a]pyridines are a privileged core of high interest in medicinal chemistry.

Cassava Bacterial Blight and Cassava Bacterial Necrosis are two bacterial diseases affecting cassava, respectively caused by Xanthomonas phaseoli pv. manihotis (Xpm) and Xanthomonas cassavae (Xc). Since both pathogens may be present on leaves and cause similar symptoms, we developed a new molecular diagnostic tool to detect and distinguish between Xpm and Xc. Based on genome sequences from the target species as well as from non-target species, in silico analysis was performed to select candidate primers through a novel strategy targeting specificity. Experimental validation enabled to establish a duplex-PCR diagnostic tool that will be useful for future surveillance programs and better disease control.

Transcription activator-like effectors (TALEs) are proteins found in the genus Xanthomonas of phytopathogenic bacteria. These proteins enter the nucleus of cells in the host plant and can induce the expression of susceptibility genes (S genes), triggering disease. TALEs bind the promoter region of S genes following a specific code, which allows the prediction of binding sites based on TALEs amino acid sequences. New candidate S genes can then be discovered by finding the intersection between genes induced in the presence of TALEs and genes containing predicted effector binding elements. By contrasting differential expression data and binding site predictions across different datasets, patterns of TALE diversification or convergence may be unveiled, but this requires the seamless integration of different genomic and transcriptomic data. With this in mind, we present daTALbase, a curated relational database that integrates TALE-related data including bacterial TALE sequences, plant promoter sequences, predicted TALE binding sites, transcriptomic data of host plants in response to TALE-harboring bacteria, and other associated data. The database can be explored to uncover new candidate S genes as well as to study variation in TALE repertories and their corresponding targets. The first version of the database here presented includes data for Oryza sp.–Xanthomonas pv. oryzae interactions. Future versions of the database will incorporate information for other pathosystems involving TALEs.

IL-22 has opposing effects in different tissues, from pro-inflammatory (skin, joints) to protective (liver, intestine) but little is known about its effects on neuronal tissue. We examined this using the induced models of experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). During EAU, IL-22 was produced by CD4+ eye-infiltrating cells, most of which co-produced IL-17. IL-22-/- mice immunized for EAU or for EAE had exacerbated disease, as did wild type mice treated with anti-IL-22 systemically or intraocularly during the expression phase of EAU. Retinal glial Müller cells in uveitic eyes had upregulated IL-22rα1 expression. Furthermore, IL-22 upregulated IL-22rα1 on Müller cells in culture and enhanced their ability to suppress effector T cells. Finally, IL-22 injected concurrently with IL-1β into the eye inhibited IL-1-induced expression of multiple proinflammatory and proapoptotic genes in retinal tissue. Our results suggest that IL-22 can function locally within the CNS to ameliorate inflammatory damage and provide neuroprotection by affecting multiple molecular and cellular pathways.

This article describes a case of persistent sexual arousal syndrome (PSAS) seen by the Gynecology Consult Service of the National Institutes of Health. This syndrome was first described in 2001 and is characterized by excessive and unrelenting sexual arousal in the absence of desire. PSAS has only recently come to the attention of the health care community, and its prevalence in the population is not completely known. It is important to report cases of this syndrome in order to help clarify its prevalence, etiology, and prognosis and to determine possible methods of treatment.

Autoimmune uveitis (AU) has an incidence similar to multiple sclerosis, it develops spontaneously and is a major cause of blindness. We hypothesized that AU could be triggered by endogenous microbiota in view of anecdotal evidence linking AU to systemic infections. We tested this in R161H mice, a new model of AU developed in our lab. R161H mice express a transgenic T cell receptor (TCR) specific to retinal protein IRBP and develop spontaneous uveitis starting at 4 weeks of age. R161H mice treated with an antibiotic cocktail, or reared under germ free conditions, had a significant delay in disease onset and intensity compared to controls, as well as fewer IL-17-secreting T cells in the gut LP. Notably, conventionally housed R161H mice consistently displayed 2-5x more Th17 cells in their LP compared to WT littermates, even when crossed onto an IRBP-deficient background. Compared to polyclonal T cells, R161H TCR transgenic T cells were more readily activated by extracts of gut contents in vitro and adopted the Th17 phenotype in the gut with higher frequency in vivo. Experiments utilizing Nur77 reporter mice and pZap70, revealed clear evidence that IRBP-specific T cells receive an activation signal through their TCR in the gut. These data not only have implications for etiology of human uveitis, but also raise the possibility that activation of autoreactive TCRs by commensal microflora may be a more common trigger of autoimmune diseases than is currently appreciated

This pharmacoepidemiological study was undertaken to determine if the combination of electroconvulsive therapy (ECT) and the anticonvulsants valproate (VPA) or carbamazepine (CBZ) is safe and efficacious. The charts of seven patients receiving ECT and VPA or CBZ (ECT-anticonvulsant group) concurrently between May 8, 1989, and May 9, 1993, were reviewed to determine the indication for each treatment, the number and type of ECT treatments, the seizure duration, adverse events, and the efficacy of the combination. The ECT-anticonvulsant group was compared to patients not treated with anticonvulsants (ECT-alone group) to determine if there were any differences in the two groups. Three patients had a marked clinical improvement, two a moderate response, one a minimal response, and one no response. The ECT-AC group, compared to the control group, had a shorter duration of seizures when unilateral treatments were used. However, there were no differences in the other variables compared. One patient had moderate confusion, and the other mild confusion and hypomania. This small case series suggests that the combination of ECT and anticonvulsants is safe and may be considered in patients for whom prophylaxis with anticonvulsant drugs is planned. Further controlled studies are needed to confirm our findings.

Characteristic levels of 33 psychological and 2 endocrine variables (urinary and plasma 17-OHCS) were estimated in a ‘normal’ population consisting of 22 men and 24 women under everyday life circumstances. All pairs of variables were correlated across subjects. Previous reports of the lack of a significant correlation between urinary and plasma 17-OHCS were confirmed. Hence the 2 variables cannot be held to provide similar information in such subjects. The significant psychological correlates of urinary 17-OHCS were more numerous and more consistent across sexes that the correlates of plasma 17-OHCS. The best psychological predictors of urinary 17-OHCS were scores on the Taylor Anxiety Scale (positively related), the Leary Hostility Scale (positively related) and the Nowlis Social Affection Scale (negatively related). The previously reported inverse relationship between urinary 17-OHCS and ‘Effectiveness of Psychological Defenses’ was confirmed in women, not in men. No relationship was found between Effectiveness of Defenses and plasma 17-OHCS. The concept, Effectivenss of Defenses as used here referred to overall operation of character defenses rather than to defenses against a specific external challenge, as was true in other studies. Pending further refinements of concept and technique, only cautious generalizations should be made from defenses against an external challenge to defenses in general.