196,546 research outputs found
The development of delusion revisited: A transdiagnostic framework
No full textThis study proposes a transdiagnostic framework for delusion development, analysing psychiatric (schizophrenia, bipolar disorder, major depressive disorder) and neurological disorders (stroke, and neurodegenerative diseases) in which delusions are predominant. Our aim is to identify a transdiagnostic core of neural and cognitive alterations associated with delusions across distinct clinical disorders. Reviewed empirical evidence suggests delusions are associated: on the neural level with changes in the ventromedial prefrontal cortex (vmPFC) networks, and on the neuropsychological level with dysfunction in the processes (generation of affective value, the construction of internal models of the world, and the reflection about Self and/or Other's mental states) that these network mediate. The concurrent aberration of all these processes could be critical for the clinical transition to a psychotic delusional state. In particular, delusions could become clinically manifest when (1) stimuli are attributed an aberrant affective salience, that (2) is explained by the patient within distorted explanatory internal models that (3) are poorly inhibited by cognitive control systems. This framework extends the two-factor account of delusion model and suggests that common neural mechanisms for the delusions in psychiatric and in neurological disorder
Clinical, morphological features and prognostic factors associated with interstitial lung disease in primary Sjӧgren's syndrome: A systematic review from the Italian Society of Rheumatology
No full textObjective: To evaluate the prevalence, clinical presentation, serological and morphological features of, and therapeutic options for Interstitial Lung Disease (ILD) in primary Sjögren's Syndrome (pSS). Methods: Pubmed was searched between February 1996 and December 2018 using a combination of MESH terms related to pSS and ILD. Selected works were subjected to blind evaluation by two authors and a senior author in case of disagreement. The work followed PRISMA guidelines and was registered on PROSPERO (CRD42018118669). Results: About 20% of pSS patients have ILD, with a 5-y survival of 84% and a need for supplemental oxygen in the 11–33% range. A significant proportion of ILD patients are seronegative without sicca syndrome. ILD seems to be associated with higher levels of Lactic Dehydrogenases and positivity for Anti-Ro52k. The prevalent pattern in High Resolution Computed Tomography is Nonspecific Interstitial Pneumonia (NSIP), but all other patterns can be present. No difference in mortality was found between patients with NSIP and Usual Interstitial Pneumonia patterns. Amyloidosis and primary lung lymphoma can be observed in about 10% of pSS patients. Conclusion: The recognition of pSS underlying an ILD can be challenging in seronegative patients with no or mild sicca symptoms. A complete diagnostic assessment, including minor salivary glands and, in some cases, lung biopsy, should be performed on all patients at risk. A better recognition of the clinical or serological markers of ILD progression in these patients is warranted to drive the physicians to an early diagnosis and an effective treatment
Quantitative chest tomography indexes are related to disease activity in systemic sclerosis: results from a cross-sectional study
No full textObjective The aim of this study is to verify if there are correlations between quantitative chest tomography (QCT) indexes and disease activity (DA) in a cohort of patients with systemic sclerosis (SSc). Methods SSc patients were assessed for DA and underwent high resolution chest tomography (CT). CT images were analysed with an operator-independent algorithm extracting the QCT indexes. DA assessment was conducted according to the EUSTAR index, where a score ≥2.5 indicates high DA (hDA). Correlations between clinical data and QCT indexes were investigated with the Spearman's test. The Mann-Whitney test assessed the distribution of the QCT indexes among the groups. Receiver operating characteristics (ROC) curve and linear regression analysis were conducted in order to identify the best cut-off value and contribution for each QCT index in assessing hDA in SSc patients. Results Sixty patients (52 females, mean age 53.2 years, mean disease duration 5.3 years) were enrolled. A significant difference was found in QCT indexes distribution between patients with hDA and those with low DA. A mild strength correlation between QCT indexes and DA was observed. Once performed ROC curves and linear regression, Skewness on parenchymal lung <1.85 gave a significant contribution to the model in identifying subjects with hDA (p<0.001), showing sensitivity 79.5%, specificity 68.7%, and accuracy 76.6%. Conclusion QCT indexes correlate with SSc DA. These data introduce new possibilities for QCT application in clinical practice, especially in patient's follow-up. Moreover, QCT could be implemented in a new SSc DA score based on operator- independent parameters
Hepatic PPARs: their role in liver physiology, fibrosis and treatment
No full textComplex molecular and cellular mechanisms are involved in the pathway of liver fibrosis. Activation and transformation of hepatic stellate cells (HSCs) are considered the two main reasons for the cause and development of liver fibrosis. The peroxisome proliferator-activated receptors (PPARs) belonging to the family of ligand-activated transcription factors play a key role in liver homeostasis, regulating adipogenesis and inhibiting fibrogenesis in HSCs. Normal transcriptional function of PPARs contributes to maintain HSCs in quiescent phase. A reduced expression of PPARs in HSCs greatly induces a progression of liver fibrosis and an increased production of collagen. Here, we discuss role and function of PPARs and we take into consideration molecular factors able to reduce PPARs activity in HSCs. Finally, although further validations are needed, we illustrate novel strategies available from in vitro and animal studies on how some PPARs-agonists have been proved effective as antifibrotic substances in liver disease
Revisiting default mode network function in major depression: Evidence for disrupted subsystem connectivity
No full textBackground. Major depressive disorder (MDD) is characterized by alterations in brain function that are identifiable also during the brain's 'resting state'. One functional network that is disrupted in this disorder is the default mode network (DMN), a set of large-scale connected brain regions that oscillate with low-frequency fluctuations and are more active during rest relative to a goal-directed task. Recent studies support the idea that the DMN is not a unitary system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in depression, however, is unclear.
Method. Here, we investigated the functional connectivity of distinct DMN subsystems and their interplay in depression using resting-state functional magnetic resonance imaging.
Results. We show that patients with MDD exhibit increased within-network connectivity in posterior, ventral and core DMN subsystems along with reduced interplay from the anterior to the ventral DMN subsystems.
Conclusions. These data suggest that MDD is characterized by alterations of subsystems within the DMN as well as of their interactions. Our findings highlight a critical role of DMN circuitry in the pathophysiology of MDD, thus suggesting these subsystems as potential therapeutic target
Proinsulin-expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions
No full textDiabetic neuropathy is the most common complication of diabetes and is frequently associated with foot ischemia and infection, but its pathogenesis is controversial. We hypothesized that proinsulin expression in peripheral blood mononuclear cells is a process relevant to this condition and could represent a link among hyperglycemia, nerve susceptibility, and diabetic foot lesions. We assessed proinsulin expression by using flow cytometry in dendritic cells from control participants and patients with type 2 diabetic with or without peripheral neuropathy or accompanied by diabetic foot. Among 32 non-neuropathic and 120 neuropathic patients with type 2 diabetic, we performed leg electromyography and found average sensory sural nerve conduction velocities of 48 ± 4 and 30 ± 4 m/s, respectively ( P < 0.03). Of those with neuropathy, 42 were without lesions, 39 had foot lesions, and 39 had neuroischemic foot lesions (allux oximetry <30 mmHg). In this well-defined diabetic population, but not in nondiabetic participants, a progressively increasing level of peripheral blood dendritic cell proinsulin expression was detected, which directly correlated with circulating TNF-α levels ( P < 0.002) and multiple conduction velocities of leg nerves ( P < 0.05). These results are consistent with the hypothesis that, in type 2 diabetes, proinsulin-expressing blood cells, possibly via their involvement in innate immunity, may play a role in diabetic peripheral neuropathy and foot lesions.-Sambataro, M., Sambado, L., Trevisiol, E., Cacciatore, M., Furlan, A., Stefani, P. M., Seganfreddo, E., Durante, E., Conte, S., Della Bella, S., Paccagnella, A., dei Tos, A. P. Proinsulin-expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions
Melatonin and melatonin-agonists for metabolic syndrome components in patients treated with antipsychotics: A systematic review and meta-analysis
No full textObjective: Metabolic side effects are a limiting factor in the use of antipsychotics, which remain the cornerstone of long-term management of patients with severe mental illness. There is contrasting evidence on a possible role of melatonin and melatonin-agonists in attenuating antipsychotic-induced metabolic abnormalities. Design: We conducted a systematic review (PubMed, PsycInfo, Cochrane databases, up to August 2020) and a random-effect meta-analysis of double-blind, randomized placebo-controlled trials (RCTs) involving melatonin and melatonin-agonists in the treatment of antipsychotic-induced metabolic changes. The primary outcome was the standardized mean difference (SMD) of composite metabolic outcomes built with metabolic syndrome components. Secondary outcomes were individual metabolic syndrome components, and other anthropometric, glucose metabolism, lipid profile, and psychopathology measures. Results: Out of the initial 41 studies, six documented five separate RCTs randomizing 248 patients (126 to melatonin/ramelteon, 122 to placebo) affected by schizophrenia-spectrum disorders and bipolar disorder. Melatonin/ramelteon outperformed placebo on the primary outcome (SMD −0.28, 95% CI = −0.39 ÷ −0.168), as well as on all individual components of metabolic syndrome (systolic blood pressure MD −3.266, 95% CI = −6.020 ÷ −0.511; fasting glucose MD −3.766, 95% CI = −5.938 ÷ −1.593; triglycerides MD −9.800, 95% CI = −19.431 ÷ −0.169; HDL MD 2.995, 95% CI = 0.567 ÷ 5.423), except waist circumference. Conclusions: Melatonin/ramelteon augmentation may be beneficial for non-anthropometric metabolic syndrome components in patients treated with antipsychotics
Lipoprotein abnormalities in NIDDM with impaired extrahepatic insulin sensitivity hypertension and microalbuminuria
No full textWe investigated whether specific lipoprotein abnormalities are present in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension and/or microalbuminuria. Fifteen normotensive normoalbuminuric (H-M-), 32 hypertensive normoalbuminuric (H+M-), and 22 hypertensive microalbuminuric (H+M+) NIDDM patients and 20 sex-, age-, and weight-matched nondiabetic control subjects were studied. Lipoprotein size was measured by nondenaturing polyacrylamide gradient gel electrophoresis; insulin sensitivity was assessed by using a euglycemic hyperinsulinemic clamp and [6,6(2)H]glucose tracer infusion for simultaneous measurement of hepatic glucose output and whole-body glucose utilization. Total plasma and very-low-density lipoprotein cholesterol were higher in H+M+ than in control subjects (5.84+/-0.98 versus 4.97+/-0.98 and 0.57+/-0.54 Versus 0.26+/-0.21 mmol/L, mean+/-SD, P<.05). Plasma triglycerides were higher in H+M+ than in either control or H-M- subjects (2.17+/-1.32 versus 1.18+/-0.67 and 1.30+/-0.59 mmol/L, respectively; P<.05). The mean low-density lipoprotein diameter was 27.2+/-0.8 in control, 26.7+/-0.8 in H-M-, 26.5+/-0.8 nm in H+M- (P<.05 versus control subjects), and 26.0+/-0.8 nm in H+M+ subjects (P<.05 Versus control subjects). The mean cholesterol level of the large high-density lipoprotein particles was lower in H+M- and H+M+ (0.37+/-0.14 and 0.36+/-0.16 mmol/L) than in control and H-M- (0.54+/-0.41 and 0.54+/-0.27 mmol/L, P<.05) subjects. Whereas hepatic glucose output was less inhibited in all diabetic patients than in control subjects, whole-body glucose disposal was lower in H+M+ (97+/-13 mg/m(2) per minute, mean+/-SEM, P<.05) and H+M- (69+/-12 mg/m(2) per minute, P<.05) but not in H-M- (277/-38 mg/m(2) per minute) NIDDM patients than in control subjects (263+/-45 mg/m(2) per minute). Hypertension (without or with microalbuminuria) appears to be associated with small low-density lipoprotein particles and low high-density lipoprotein cholesterol(2), while microalbuminuria (with hypertension) is associated with elevated triglycerides in NIDDM patients. Moreover, in NIDDM patients the presence of hypertension with or without microaIbuminuria is associated with impaired extrahepatic insulin sensitivity. The atherogenic lipoprotein pattern might partially explain why NIDDM patients with microalbuminuria and hypertension are prone to cardiovascular disease
Lipoprotein abnormalities in non-insulin-dependent diabetic patients with impaired extrahepatic insulin sensitivity, hypertension, and microalbuminuria
No full textWe investigated whether specific lipoprotein abnormalities are present in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension and/or microalbuminuria. Fifteen normotensive normoalbuminuric (H-M-), 32 hypertensive normoalbuminuric (H+M-), and 22 hypertensive microalbuminuric (H+M+) NIDDM patients and 20 sex-, age-, and weight-matched nondiabetic control subjects were studied. Lipoprotein size was measured by nondenaturing polyacrylamide gradient gel electrophoresis; insulin sensitivity was assessed by using a euglycemic hyperinsulinemic clamp and [6,6(2)H]glucose tracer infusion for simultaneous measurement of hepatic glucose output and whole-body glucose utilization. Total plasma and very-low-density lipoprotein cholesterol were higher in H+M+ than in control subjects (5.84 +/- 0.98 versus 4.97 +/- 0.98 and 0.57 +/- 0.54 versus 0.26 +/- 0.21 mmol/L, mean +/- SD, P < .05). Plasma triglycerides were higher in H+M+ than in either control or H-M- subjects (2.17 +/- 1.32 versus 1.18 +/- 0.67 and 1.30 +/- 0.59 mmol/L, respectively; P < .05). The mean low-density lipoprotein diameter was 27.2 +/- 0.8 in control, 26.7 +/- 0.8 in H-M-, 26.5 +/- 0.8 nm in H+M- (P < .05 versus control subjects), and 26.0 +/- 0.8 nm in H+M+ subjects (P < .05 versus control subjects). The mean cholesterol level of the large high-density lipoprotein particles was lower in H+M- and H+M+ (0.37 +/- 0.14 and 0.36 +/- 0.16 mmol/L) than in control and H-M- (0.54 +/- 0.41 and 0.54 +/- 0.27 mmol/L, P < .05) subjects.(ABSTRACT TRUNCATED AT 250 WORDS)</jats:p
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