Major depressive disorder and attenuated negative symptoms in a child and adolescent sample with psychosis risk syndrome: the CAPRIS study

Some 70–80% of subjects with psychotic risk syndrome (PRS) have lifetime comorbidity, with depressive disorders being the most common. A high proportion of patients with PRS present nonspecific symptoms which can be confounding factors for diagnosis. Depressive and negative symptoms may be difficult to distinguish and it is important to differentiate them. The aim of this study is to assess the presence of depressive disorder in a child and adolescent sample of PRS and to examine the presence of negative symptoms and detect possible confounding characteristics between them and depressive symptoms. This is a naturalistic multi-site study with subjects who met PRS criteria. A sample of 89 PRS adolescent patients was included. Major depressive disorder (MDD) is the most prevalent comorbid disorder (34.83%). The sample was divided into patients who met criteria for MDD (PRS-MDD, n = 31) and those who did not have this disorder (PRS-ND, n = 44). We obtained significant differences in the attenuated negative symptoms (ANS) between PRS-MDD and PRS-ND (68.18 vs. 90.32%, respectively, p = 0.021). Subjects with MDD presented a higher score in ANS and Hamilton Depression Rating Scale (HDRS). Moreover, we obtained a correlation between negative symptomatology and HDRS score with a higher score on HDRS in subjects with higher negative symptom scores (r = 0.533, p < 0.001). More research is needed to fine tune differentiation between depressive and negative symptoms and learn more about the possible impact of MDD on PRS children and adolescents.

     

Clinical features,exercise hemodynamics,and determinants of left ventricular elevated filling pressure in heart‐transplanted patients

This study aimed to assess clinical, functional, and hemodynamic characteristics of heart‐transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi‐supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV‐FP: PCWP ≥15 mmHg at rest or ≥25 mmHg at peak exercise. Thirty‐one patients (54%) had normal LV‐FP and 26 patients (46%) had elevated LV‐FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left‐ and right‐sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV‐FP than in patients with normal LV‐FP. No between‐group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV‐FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV‐FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764).     

Starring roles for astroglia in barrier pathologies of gut and brain

The gastrointestinal tract is a highly innervated organ and enteric neuropathy is emerging as a central feature of a wide range of gut diseases. Although most considerations of the enteric nervous system have focused on neuronal dysfunction, a large population of astrocyte-like glia populates gut muscle layers and the intestinal mucosa, and mounting new evidence points toward enteric glia as active participants in gut pathology. Similarly, in the central nervous system increasing evidence suggests that dysfunctions of astrocytes play central roles in disease mechanisms. On the basis of the premise that gut-brain disease paradigms may exist, we explore the possibility that enteric glia constitute a previously unrecognized disease target in pathologies associated with intestinal barrier dysfunction, notably inflammatory bowel disease, necrotizing enterocolitis, irritable bowel syndrome, diabetes, autoimmune disease and neurotrophic virus infection of the gut.     

Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture,Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

We investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight-bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T-score > −1.0) to osteoporotic (T-score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR-484, miR-328-3p, miR-27a-5p, miR-28-3p, and miR-409-3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM-receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross-validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty-eight iliac ncRNAs were associated with risk of fracture (FDR < 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis-eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel-BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

A functional neuroimaging study of motivation and executive function

Executive functions, such as working memory, must intersect with functions that determine value for the organism. Functional imaging work in humans and single-unit recordings in non-human primates provide evidence that PFC might integrate motivational context with working memory. With functional magnetic resonance imaging (fMRI), we addressed the question of motivation and working memory, using a trial-related design in an object-working memory task. The design permitted the analysis of BOLD signal at separate stages, corresponding to encoding, maintenance, and retrieval. Subjects were motivated by a financial incentive during the task, such that they could gain a high or a low reward. The two different levels of reward also entailed greater or lesser risk of losing money for incorrect responses. In the high, relative to the low, reward condition, subjects shifted response bias, and showed a trend to greater sensitivity. We found main effects in fMRI BOLD signal for reward, which overlapped with BOLD effects for maintenance of information, in the right superior frontal sulcus and bilateral intraparietal sulcus. We also found an interaction between reward and retrieval from working memory in the right dorsolateral prefrontal cortex. Main effects of load and reward occurred in adjacent regions of the ventrolateral PFC during retrieval. The data demonstrate that when subjects perform a simple working memory task, financial incentives motivate performance and interact with some of the same neural networks that process various stages of working memory. Areas of overlap and interaction may integrate information about value, or they may represent a general effect of motivation increasing neural effort.     

Malignant appendiceal carcinoid with intussusception of the base manifesting as a cecal tumor: Report of a case

Summary A case of an appendiceal carcinoid tumor with regional lymph-node metastases is presented. The size of the tumor was remarkable, as the appendix was infiltrated throughout its length. The proximal part of the appendix was intussuscepted into the cecum. Preoperatively, the lesion was diagnosed as a polypoid tumor of the cecum. A primary right hemicolectomy was carried out. Read at the Annual meeting of the Norwegian Surgical Association, Oslo, October 21 to 23, 1976.     

Increased mortality in COPD among construction workers exposed to inorganic dust.

The aim of this study was to find out if occupational exposure to dust, fumes or gases, especially among never-smokers, increased the mortality from chronic obstructive pulmonary disease (COPD). A cohort of 317,629 Swedish male construction workers was followed from 1971 to 1999. Exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), gases and irritants (epoxy resins, isocyanates and organic solvents), fumes (asphalt fumes, diesel exhaust and metal fumes), and wood dust was based on a job-exposure matrix. An internal control group with "unexposed" construction workers was used, and the analyses were adjusted for age and smoking. When all subjects were analysed, there was an increased mortality from COPD among those with any airborne exposure (relative risk 1.12 (95% confidence interval (CI) 1.03-1.22)). In a Poisson regression model, including smoking, age and the major exposure groups, exposure to inorganic dust was associated with an increased risk (hazard ratio (HR) 1.10 (95% CI 1.06-1.14)), especially among never-smokers (HR 2.30 (95% CI 1.07-4.96)). The fraction of COPD among the exposed attributable to any airborne exposure was estimated as 10.7% overall and 52.6% among never-smokers. In conclusion, occupational exposure among construction workers increases mortality due to chronic obstructive pulmonary disease, even among never-smokers.