Increased concentrations of platelet- and endothelial-derived microparticles in patients with myocardial infarction and reduced renal function- a descriptive study

Abstract Background Patients with chronic kidney disease (CKD) have a high risk of recurring thrombotic events following acute myocardial infarction (AMI). Microparticles (MPs) are circulating small vesicles shed from various cells. Platelet microparticles (PMPs) reflect platelet activation and endothelial microparticles (EMPs) reflect endothelial activation or dysfunction. Both increase following AMI, and may mediate important biological effects. We hypothesized that AMI patients with CKD have further elevated PMPs and EMPs compared with non-CKD patients, despite concurrent antithrombotic treatment. Methods We performed a descriptive study of patients with AMI. Fasting blood samples were acquired from 47 patients on dual antiplatelet treatment. Patients were stratified by renal function: normal (H; n = 19) mean eGFR 88; moderate CKD (CKD3; n = 15) mean eGFR 47, and severe CKD (CKD4–5; n = 13) mean eGFR 20 mL/min/1.73 m2. MPs were measured by flow-cytometry and phenotyped according to size (< 1.0 μm) and expression of CD41 (GPIIb; PMPs) and CD62E (E-selectin; EMPs). In addition, expression of platelet activation markers P-selectin (CD62P) and CD40ligand (CD154) were also investigated. Results PMPs expressing CD40 ligand were higher in CKD4–5: 210 /μl (174–237); median and interquartile range; vs. group H; 101 /μl (71–134; p < 0.0001) and CKD 3: 142 /μl (125–187; p = 0.006). PMPs expressing P-selectin were higher in CKD4–5 compared with H, but not in CKD3. EMPs were higher in CKD4–5; 245 /μl (189–308) compared with H; 83 /μl (53–140; p < 0.0001) and CKD3; 197 /μl (120–245; p < 0.002). Conclusions In AMI patients, PMPs and EMPs from activated platelets and endothelial cell are further elevated in CKD patients. This indicate impaired endothelial function and higher platelet activation in CKD patients, despite concurrent antiplatelet treatment

Vesicular glutamate transporter 2 expression in the ventral tegmental area of outbred male rats following exposure to nicotine and alcohol

Background: Initiation of use/co-use of nicotine and alcohol, commonly occurring in an episodic manner during adolescence, can imprint vulnerability to the developing brain and lead to addiction. The ventral tegmental area (VTA) is a key heterogeneous region of the mesocorticolimbic circuit involved in the binge-drinking and intoxication step of the addiction circuit. Higher human post-mortem VTA expression of vesicular glutamate transporter 2 (VGLUT2), a marker of the glutamatergic phenotype also expressed in dopaminergic [Tyrosine Hydroxylase (Th)-positive] neurons, has been associated with chronic nicotine use and co-use with alcohol. Methods: The present study aimed to map and characterize the Vglut2- and Th-expressing neurons in the VTA of adolescent male rats exposed or not to prolonged (six-weeks) episodic (three consecutive days/week) nicotine and/or alcohol administration. Nicotine (0.35 mg/kg free base) was injected subcutaneously, whereas alcohol (2 g/kg 20%) was administrated via gavage. Vglut2 and Th mRNA was assessed in the anterior and posterior VTA by use of in situ hybridization. Results: The profile of neurons varied with substance-exposure among VTA subregions. Th-only expressing neurons were more abundant in the posterior VTA of the group exposed to nicotine-only, compared to controls. The same neurons were, on the contrary, less present in the anterior VTA of animals exposed to alcohol-only, who also displayed a higher number of Vglut2-expressing neurons in the lateral anterior VTA. Conclusions: VTA Vglut2- and Th-only neurons seem differentially involved in the effects of adolescent episodic nicotine and alcohol exposure in the anterior and posterior VTA

Quality indicators for woodwind reed material

For the generation of sound, some woodwind musical instruments, e.g. oboe, bassoon, clarinet and saxophone, are provided with mouthpieces made from reeds. These reeds are the culms of Arundo donax, a tall, cane-like perennial grass. A general problem is that the material is of varying quality, yet externally differences cannot be observed. Hence, large proportions of the prepared reeds are unusable. One hypothesis is that the changes in quality are correlated with differences in the chemical and anatomical structure of the tissue. Therefore, a comparison of superior and inferior mouthpieces, used by professional musicians, was undertaken to determinate potential indicators of quality. Nuclear microprobe analysis of reeds was carried out and complemented by scanning electron and light microscopy. The elemental levels of Si, P, S, Cl, K and Ca were compared between good and poor mouthpieces using appropriate statistical tests. No statistically significant differences could be identified. Microscopical observations showed that partial occlusion of vessels by tylose formation was associated with material deemed unusable

Vesicular glutamate transporter 2 expression in the ventral tegmental area of outbred male rats following exposure to nicotine and alcohol

Background: Initiation of use/co-use of nicotine and alcohol, commonly occurring in an episodic manner during adolescence, can imprint vulnerability to the developing brain and lead to addiction. The ventral tegmental area (VTA) is a key heterogeneous region of the mesocorticolimbic circuit involved in the binge-drinking and intoxication step of the addiction circuit. Higher human post-mortem VTA expression of vesicular glutamate transporter 2 (VGLUT2), a marker of the glutamatergic phenotype also expressed in dopaminergic [Tyrosine Hydroxylase (Th)-positive] neurons, has been associated with chronic nicotine use and co-use with alcohol. Methods: The present study aimed to map and characterize the Vglut2- and Th-expressing neurons in the VTA of adolescent male rats exposed or not to prolonged (six-weeks) episodic (three consecutive days/week) nicotine and/or alcohol administration. Nicotine (0.35 mg/kg free base) was injected subcutaneously, whereas alcohol (2 g/kg 20%) was administrated via gavage. Vglut2 and Th mRNA was assessed in the anterior and posterior VTA by use of in situ hybridization. Results: The profile of neurons varied with substance-exposure among VTA subregions. Th-only expressing neurons were more abundant in the posterior VTA of the group exposed to nicotine-only, compared to controls. The same neurons were, on the contrary, less present in the anterior VTA of animals exposed to alcohol-only, who also displayed a higher number of Vglut2-expressing neurons in the lateral anterior VTA. Conclusions: VTA Vglut2- and Th-only neurons seem differentially involved in the effects of adolescent episodic nicotine and alcohol exposure in the anterior and posterior VTA

Digital inclusion and participation of people with intellectual disabilities during COVID‐19: A rapid review and international bricolage

This is an accepted manuscript of an article published by Wiley in Journal of Policy and Practice in Intellectual Disabilities on 14/01/2022, available online: https://doi.org/10.1111/jppi.12410 The accepted version of the publication may differ from the final published version.The COVID-19 pandemic has meant a rapid transfer of everyday activities to the online world. Information and communication technologies (ICTs) have become more embedded than ever in people's lives. This investigation addresses how this change has affected the lives of people with intellectual disabilities (ID). A two-step design was used. A rapid review was conducted on empirical studies published between January 2019 and June 2021. Search terms related to ID, ICT use and COVID-19. A qualitative international bricolage was also conducted corresponding to author nationalities. Data gathered from the review and bricolage were analysed separately using thematic analysis and relationally synthesised. Digital solutions to provide access to COVID-19 information and guidance seemed inadequate but were seldom empirically studied. Digital poverty, literacy and exclusion remain significant issues for people with ID internationally. People and their carers experienced reduced and removed service provision, loneliness and impoverished daily lives during the pandemic; amelioration of which was facilitated by digital solutions. One solution often used was videoconferencing. Prior experience of digital participation, adequate finances, connection, support and digital literacy mentoring for both people with ID and those providing services and support facilitated digital inclusion. Digital exclusion during COVID-19 was exacerbated by sociopolitical, structural, individual and support-related barriers. Although awareness of digital exclusion appears to have been raised, the extent to which this has led to action and change remains unclear. Despite digital exclusion and digital participation benefitting continuation of life, social and emotional well-being and autonomy, COVID-19 has not provided the impetus to eradicate digital poverty for people with ID. Governmental support, digital education, creativity and problem solving are required to enable people with ID the human right to be included in the digital world at this essential time and into the future.Published onlin

Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries

Background Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). Objectives To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C–protein C inhibitor (APC–PCI) complex. Methods Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case–control study. Autoantibodies (IgA/G/M) targeting cardiolipin and β2glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC–PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. Results Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-β2glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC–PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. Conclusions aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability—measured by increased levels of the APC–PCI complex—were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system