Background Apathy is common in Parkinson's disease (PD) but its underlying white matter (WM) architecture is not well understood.  https://www.selleckchem.com/products/ipi-549.html  Moreover, how apathy affects cognitive functions in PD remains unclear. We investigated apathy-related WM network alterations and the impact of apathy on cognition in the context of PD. Methods Apathetic PD patients (aPD), non-apathetic PD patients (naPD), and matched healthy controls (HCs) underwent brain scans and clinical assessment. Graph-theoretical and network-based analyses were used for group comparisons of WM features derived from diffusion spectrum imaging (DSI). Path analysis was used to determine the direct and indirect effects of apathy and other correlates on different cognitive functions. Results The aPD group was impaired on neural integration measured by global efficiency (p = 0.009) and characteristic path length (p = 0.04), executive function (p less then 0.001), episodic memory (p less then 0.001) and visuospatial ability (p = 0.02), and had reduced connectivity between the bilateral parietal lobes and between the putamen and temporal regions (p less then 0.05). In PD, executive function was directly impacted by apathy and motor severity and indirectly influenced by depression; episodic memory was directly and indirectly impacted by apathy and depression, respectively; conversely, visuospatial ability was not related to any of these factors. Neural integration, though being marginally correlated with apathy, was not associated with cognition. Conclusions Our results suggest compromised neural integration and reduced structural connectivity in aPD. Apathy, depression, and motor severity showed distinct impacts on different cognitive functions with apathy being the most influential determinant of cognition in PD.Kurt Schneider introduced in the definition of the first-rank symptoms (FRS) the criterion that, where unequivocally present, the FRS are always psychological primaries and irreducible. This criterion, grounded on 'phenomenology' (description of subjective experiences), cannot be applied, according to Schneider, to delusions, either two-stage FRS delusional perception, or second-rank delusional notions. The Schneider's key criterion was neglected since the initial adoption of the 'Schneider's FRS' in the subsequent international literature (e.g. PSE, RDC, DSM, and ICD). The 'Schneider's FRS' (e.g. thought insertion, thought withdrawal, passivity, and influence) were persistently equivocated as 'delusions', in spite of the Schneider's FRS exclusion criterion. The internationally equivocated 'Schneider's FRS' (only homonymous of the original 'Schneider's FRS'), were eliminated in the DSM-5 and de-emphasized in ICD-11. However, the diagnostic value of the original 'Schneider's FRS', assessed on the basis of the strict compliance with the Schneider's criterion for their definition, was never determined. The 'damnatio memoriae' of the original Schneider's FRS may be premature. The definition and assessment of the 'experienced' symptoms of schizophrenia, only directly observed and reported by the patients, represent a specific, crucial, irreplaceable domain of psychopathology, to be carefully distinguished from the domain of the 'behavioral' symptoms observed by the clinician. Contemporary psychopathology research is aware of the absolute need for psychiatry to enhance precision and exactness in the definition of the experienced symptoms of schizophrenia, through the formulation of unequivocal inclusion and exclusion criteria (descriptive micro-psychopathology), in order to determine their value in research and care.Background Nitric oxide synthase (NOS) activity, an enzyme potentially involved in the major depressive episodes (MDE), could be indirectly measured by the L-Citrulline/L-Arginine ratio (L-Cit/L-Arg). The aim of this study was (1) to compare the NOS activity of patients with a MDE to that of healthy controls (HC); (2) to assess its change after antidepressant treatment. Methods A total of 460 patients with a current MDE in a context of major depressive disorder (MDD) were compared to 895 HC for NOS activity (L-Cit/L-Arg plasma ratio). L-Arg and L-Cit plasma levels were measured using a MS-based liquid chromatography method. Depressed patients were assessed at baseline, and after 3 and 6 months of antidepressant treatment for depression severity and clinical response. Results Depressed patients had a lower NOS activity than HC at baseline [0.31 ± 0.09 v. 0.38 ± 0.12; 95% confidence interval (CI) -0.084 to -0.062, p less then 0.0001]. Lower NOS activity at baseline predicted a higher response rate [odds ratio (OR) = 29.20; 95% CI 1.58-536.37; p = 0.023]. NOS activity in depressed patients increased significantly up to 0.34 ± 0.08 after antidepressant treatment (Est = 0.0034; 95% CI 0.0002-0.0067; p = 0.03). Conclusions Depressed patients have a decreased NOS activity that improves after antidepressant treatment and predicts drug response. NOS activity may be a promising biomarker for MDE in a context of MDD.Objective Patulous Eustachian tube appears to be caused by a concave defect in the anterolateral wall of the tubal valve of the Eustachian tube. This study aimed to compare the clinical features of patulous Eustachian tube patients with or without a defect in the anterolateral wall of the tubal valve. Methods Sixty-six patients with a patulous Eustachian tube completed a questionnaire, which was evaluated alongside endoscopic findings of the tympanic membrane, nasal cavity and Eustachian tube orifice. Results Females were more frequently diagnosed with a patulous Eustachian tube, but the valve defect was more common in males (p = 0.007). The ratio of patulous Eustachian tube patients with or without defects in the anterolateral wall of the tubal valve was 1.61. Weight loss in the previous six months and being refractory to conservative management were significantly associated with the defect (p = 0.035 and 0.037, respectively). Symptom severity was significantly higher in patients with the defect. Conclusion Patulous Eustachian tube patients without a defect in the anterolateral wall of the tubal valve can be non-surgically treated more often than those with the defect. Identification of the defect could assist in making treatment decisions for patulous Eustachian tube patients.