Cardiovascular biomarkers in patients with psoriasis

Psoriasis is a systemic inflammatory disease of the skin with associated comorbidity. Severe forms of psoriasis are associated with increased mortality, which might be due to cardiovascular (CV) comorbidity. In this study, we investigated in 79 patients with psoriasis compared to 80 healthy volunteers different biomarkers that play a role in vascular disease and inflammation, such as C‐reactive protein (CRP), human soluble CD40 ligand (sCD40L), oxidized low‐density lipoprotein (ox‐LDL), human matrix Gla protein (MGP) and fetuin‐A. Our results showed that CRP (P < 0.0001), sCD40L (P < 0.0001) and MGP (P < 0.0001) were increased in the patient cohort. Fetuin‐A showed decreased serum levels in patients with psoriasis (P < 0.0001), whereas ox‐LDL did not show any significant difference. In multivariate analyses controlling for sex, age and BMI, these findings were confirmed. Thus, CV biomarkers are altered in patients with psoriasis. If the decrease in fetuin‐A as well as the increase in sCD40L can be proven in further studies, these biomarkers may help to characterize a subgroup of patients who are at risk to develop CVD and/or monitor the effect of therapeutic antipsoriatic strategies on concomitant diseases. This knowledge may be useful in the management of high‐need patients with psoriasis.     

Analysis of human immunodeficiency virus-infected tissues by amplification and in situ hybridization reveals latent and permissive infections at single-cell resolution.

Latent and productive viral infections are at the extremes of the spectrum of virus-cell interactions that are thought to play a major role in the ability of such important human pathogens as human immunodeficiency virus (HIV) to elude host defenses and cause disease. The recent development of PCR-based methods to amplify target sequences in individual cells in routinely fixed tissues affords opportunities to directly examine the subtle and covert virus-cell relationships at the latent end of the spectrum that are inaccessible to analysis by conventional in situ hybridization techniques. We have now used PCR in situ with in situ hybridization to document latent and permissive HIV infection in routinely fixed and paraffin-embedded tissue. In one of the first specimens we examined, a tumor biopsy from an HIV-infected individual, we found many of the lymphocytes and lymphocytes infiltrating the tumor had HIV DNA that was detectable only by PCR in situ. The fraction of positive cells varied regionally, but there were foci where most of the cells contained HIV DNA. Most of these lymphocytes and macrophages are latently infected, as we could detect HIV RNA in fewer than one in a thousand of these cells. We also detected HIV RNA, surprisingly, in 6% of the tumor cells, where the number of copies of viral RNA per cell was equivalent to productively infected cell lines. The alternative states of HIV-gene expression and high local concentration of latently infected lymphocytes and monocytes revealed by these studies conceptually supports models of lentiviral pathogenesis that attribute persistence to the reservoir of latently infected cells and disease to the consequences of viral-gene expression in this population. The magnitude of infection of lymphocytes documented in this report is also consistent with the emerging view that HIV infection per se could contribute substantially to depletion of immune cells in AIDS.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

Profiling of synthesis‐related impurities of the synthetic cannabinoid Cumyl‐5F‐PINACA in seized samples of e‐liquids via multivariate analysis of UHPLC−MSn data

Vaping of synthetic cannabinoids via e‐cigarettes is growing in popularity. In the present study, we tentatively identified 12 by‐products found in a pure sample of the synthetic cannabinoid Cumyl‐5F‐PINACA (1‐(5‐fluoropentyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H‐indazole‐3‐carboxamide), a prevalent new psychoactive substance (NPS) in e‐liquids, via high‐resolution mass spectrometry fragmentation experiments (HRMS/MS). Furthermore, we developed a procedure to reproducibly extract this synthetic cannabinoid and related by‐products from an e‐liquid matrix via chloroform and water. The extracts were submitted to flash chromatography (F‐LC) to isolate the by‐products from the main component. The chromatographic impurity signature was subsequently assessed by ultra‐high‐performance liquid chromatography coupled to mass spectrometry (UHPLC–MS) and evaluated by automated integration. The complete sample preparation sequence (F‐LC + UHPLC–MS) was validated by comparing the semi‐quantitative signal integrals of the chromatographic impurity signatures of five self‐made e‐liquids with varying concentrations of Cumyl‐5F‐PINACA [0.1, 0.2, 0.5, 0.7 and 1.0% (w/w)], giving an average relative standard deviation of 6.2% for triplicate measurements of preparations of the same concentration and 10.5% between the measurements of the five preparations with different concentrations. Lastly, the chromatographic signatures of 14 e‐liquid samples containing Cumyl‐5F‐PINACA from police seizures and Internet test purchases were evaluated via hierarchical cluster analysis for potential links. For the e‐liquid samples originating from test purchases, it was found that the date of purchase, the identity of the online shop, and the brand name are the critical factors for clustering of samples.     

Cognitive vulnerability differentially predicts symptom dimensions of depression

Background

We examined the association of cognitive vulnerability to depression with changes in homogeneous measures of depressive symptoms.

Methods

Baseline and 1-year follow-up data were obtained from 2981 participants of the Netherlands study of depression and anxiety. Multivariate regression analyses were carried out on cognitive reactivity, locus of control and implicit and explicit self-depressive associations in combination with negative life events. The purpose of this analysis was to predict changes on the mood/cognition and anxiety/arousal subscales of the inventory of depressive symptomatology - self report.

Results

Cognitive reactivity, locus of control and explicit self-depressive associations were independently associated with changes in depressive symptoms after adjustment for covariates and baseline severity (all p<0.01). Negative life-events interacted with cognitive vulnerability to depression to predict depressive symptoms. Locus of control (b₁=0.16, SE=0.02, η²=0.01; b₂=0.10, SE=0.02, η²=0.004, F=8.69, p<0.01) and explicit self-depressive associations (b₁=0.10, SE=0.03, η²=0.02; b2=0.02, SE=0.04, F=7.50, p<0.01) were more strongly associated with the cognitive (b₁) than the somatic (b₂) symptom dimension of depression.

Limitations

The study sample is over-inclusive of depressed patients. Therefore it might be problematic generalizing the findings to the general population.

Conclusion

Cognitive etiological factors may play a role in a “cognitive” subtype of depression. The findings strengthen the notion that homogeneous measures of depressive symptoms enable a greater degree of discrimination between subtypes than a multidimensional conception of depression.