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Parkinson's disease patients suffer from both motor and nonmotor impairments. There is currently no cure for Parkinson's disease, and the most commonly used treatment, levodopa, only functions as a temporary relief of motor symptoms. Inhibition of the expression of the L-tryptophan-catabolizing enzyme tryptophan 2,3-dioxygenase (TDO) has been shown to inhibit aging-related α-synuclein toxicity in Caenorhabditis elegans. To evaluate TDO inhibition as a potential therapeutic strategy for Parkinson's disease, a brain-penetrable, small molecule TDO inhibitor was developed, referred to as NTRC 3531-0. This compound potently inhibits human and mouse TDO in biochemical and cell-based assays and is selective over IDO1, an evolutionary unrelated enzyme that catalyzes the same reaction. In mice, NTRC 3531-0 increased plasma and brain L-tryptophan levels after oral administration, demonstrating inhibition of TDO activity in vivo. The effect on Parkinson's disease symptoms was evaluated in a rotenone-induced Parkinson's disease mouse model. A structurally dissimilar TDO inhibitor, LM10, was evaluated in parallel. Both inhibitors had beneficial effects on rotenone-induced motor and cognitive dysfunction as well as rotenone-induced dopaminergic cell loss and neuroinflammation in the substantia nigra. Moreover, both inhibitors improved intestinal transit and enhanced colon length, which indicates a reduction of the rotenone-induced intestinal dysfunction. Consistent with this, mice treated with TDO inhibitor showed decreased expression of rotenone-induced glial fibrillary acidic protein, which is a marker of enteric glial cells, and decreased α-synuclein accumulation in the enteric plexus. Our data support TDO inhibition as a potential therapeutic strategy to decrease motor, cognitive, and gastrointestinal symptoms in Parkinson's disease.Previous research highlighted the correlation between parent-infant's attachment quality and joint attention skills. However, the underlying mechanisms of this relationship are still unclear. The aim of this study was to assess whether it is by mediating the expectation component in Internal Working Models that the quality of attachment style can affect joint attention. At first, 12- to 20-month-old infants were classified into secure and insecure groups using the Strange Situation Procedure. On a following day, using a violation-of-expectation paradigm, infants were habituated to two joint attention videos. Finally, the mean looking time duration of secure and insecure infants were compared with each other between two "divergent attention" and "joint attention" videos. Infants looked longer for divergent attention videos suggesting they did have expectation regarding the appropriate response in triadic interactions. In line with our main hypothesis, secure infants, but not insecure ones, looked longer in the divergent attention situation when an attachment-related context was present, revealing the possible mediating role of "expectations" in the correlation between attachment and joint attention.A correct identification of seropositive individuals for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is of paramount relevance to assess the degree of protection of a human population to present and future outbreaks of the COVID-19 pandemic. We describe here a sensitive and quantitative flow cytometry method using the cytometer-friendly non-adherent Jurkat T-cell line that stably expresses the full-length native spike "S" protein of SARS-CoV-2 and a truncated form of the human EGFR that serves a normalizing role. S protein and huEGFRt coding sequences are separated by a T2A self-cleaving sequence, allowing to accurately quantify the presence of anti-S immunoglobulins by calculating a score based on the ratio of fluorescence intensities obtained by double-staining with the test sera and anti-EGFR. The method allows to detect immune individuals regardless of the result of other serological tests or even repeated PCR monitoring. As examples of its use, we show that as much as 28% of the personnel working at the CBMSO in Madrid is already immune. Additionally, we show that anti-S antibodies with protective neutralizing activity are long-lasting and can be detected in sera 8 months after infection.

Although evidence-based psychological treatments for chronic pain (CP) have been demonstrated to be effective for a variety of outcomes, modest effects observed in recent reviews indicate scope for improvement. Self-compassion promotes a proactive attitude towards self-care and actively seeking relief from suffering. Consequently, more compassionate people experience better physical, psychological and interpersonal well-being.

We conducted a single-blind, randomized, controlled trial to examine the effects of a Mindful Self-Compassion program (MSC) on relevant clinical outcomes in patients with CP. Patients were randomly assigned to one of the two intervention arms MSC or cognitive-behavioural therapy (CBT). The protocols of both intervention arms were standardized and consisted of a 150-min session once a week during 8weeks formatted to groups of no more than 20 participants. The primary outcome was self-compassion, measured with the Self-Compassion Scale (SCS). The secondary outcomes were other pain-relms, pain interference and pain acceptance more than what CBT does. These results provide empirical support to guide clinical work towards the promotion of self-compassion in psychotherapeutic interventions for people with CP.

This randomized controlled trial compares the novel intervention (MSC program) with the gold standard psychological intervention for CP (CBT). MSC improves the levels of self-compassion, a therapeutic target that is receiving attention since the last two decades, and it also improves anxiety symptoms, pain interference and pain acceptance more than what CBT does. These results provide empirical support to guide clinical work towards the promotion of self-compassion in psychotherapeutic interventions for people with CP.Substance use disorders (SUD) are chronic relapsing medical conditions characterised by compulsive substance seeking and use. They constitute a substantial disease burden globally. Labelling of persons with SUD has created barriers to treatment but there are effective management strategies. Reversan order The dental profession has embraced reforms designed to address the SUD epidemic by promoting continuing education for practitioners and initiating curriculum changes in dental schools. Screening, Brief Intervention and Referral to Treatment (SBIRT) is an evidence-based model for managing patients with SUD. The use of a formative 1-station Objective Structured Clinical Examination (OSCE) for learning and assessment in SBIRT, operationalised with the MD3 rating scale is presented in this study. In 3 years of implementation, the SBIRT OSCE successfully integrated into the curriculum of the College of Dental Medicine, Columbia University. Mean score of total adherent behaviours was 11.80 (SD =4.23) (range 2 - 24) and Cronbach's coefficient alpha for across-items reliability in adherent behaviours was 0.

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