The effect of social media communication on consumer perceptions of brands

Researchers and brand managers have limited understanding of the effects social media communication has on how consumers perceive brands. We investigated 504 Facebook users in order to observe the impact of firm-created and user-generated social media communication on brand equity, brand attitude and purchase intention by using a standardized online survey throughout Poland. To test the conceptual model, we analyzed 60 brands across three different industries: non-alcoholic beverages, clothing and mobile network operators. When analyzing the data, we applied the structural equation modeling technique to both investigate the interplay of firm-created and user-generated social media communication and examine industry-specific differences. The results of the empirical studies showed that user-generated social media communication had a positive influence on both brand equity and brand attitude, whereas firm-created social media communication affected only brand attitude. Both brand equity and brand attitude were shown to have a positive influence on purchase intention. In addition, we assessed measurement invariance using a multi-group structural modeling equation. The findings revealed that the proposed measurement model was invariant across the researched industries. However, structural path differences were detected across the models

Impact of a structured institutional lead management programme at a high volume centre for transvenous lead extractions in Switzerland

BACKGROUND: Transvenous lead extraction (TLE) is the recommended management strategy for a variety of cardiac implantable electronic device (CIED) infections, malfunctions and other conditions. Large registries have established the safety and efficacy of TLE per se but temporal outcome data after the introduction of an institutional lead management programme remain scarce. OBJECTIVE: To investigate the impact of a structured institutional lead management programme on TLE outcomes. METHODS: All patients who underwent TLE at our institution between January 2013 and December 2020 were included. We assessed procedural outcomes after TLE for two separate time periods: from January 2013 to December 2018 and January 2019 to December 2020 (after introduction of a structured institutional lead management programme). RESULTS: In 2013–2018, the median number of TLE procedures per year at our centre was 14 (range 10–19, total 84). In 2019/2020, the median number of interventions per year increased to 46 (range 41–51, total 92). Noninfectious indications for TLE became more frequent (p <0.001), and the proportion of TLEs due to infections decreased. Median lead dwell time was not different (4.3 years [2013–2018] vs 4.4 years [2019–2020], p = 0.43). Clinical success rates improved from 90% to 98% (p = 0.020) and complete procedural success increased from 85% to 95% (p = 0.027). There was a trend towards a lower number of TLE-associated complications (p = 0.07). CONCLUSION: A structured institutional lead management programme and increasing experience significantly improve TLE outcomes. TLE can be safely performed in high-volume centres, allowing for a more liberal extraction policy, including in the case of non-infectious TLE indications

Pulsed-field ablation for the treatment of left atrial reentry tachycardia.

BACKGROUND We describe our initial experience using a multipolar pulsed-field ablation catheter for the treatment of left atrial (LA) reentry tachycardia. METHODS We included all patients with LA reentry tachycardia treated with PFA at our institution between September 2021 and March 2022. The tachycardia mechanism was identified using 3D electro-anatomical mapping (3D-EAM). Subsequently, a roof line, anterior line, or mitral isthmus line was ablated as appropriate. Roof line ablation was always combined with LA posterior wall (LAPW) ablation. Positioning of the PFA catheter was guided by a 3D-EAM system and by fluoroscopy. Bidirectional block across lines was verified using standard criteria. Additional radiofrequency ablation (RFA) was used to achieve bidirectional block as necessary. RESULTS Among 22 patients (median age 70 (59-75) years; 9 females), we identified 27 LA reentry tachycardia: seven roof dependent macro-reentries, one posterior-wall micro-reentry, twelve peri-mitral macro-reentries, and seven anterior-wall micro-reentries. We ablated a total of 20 roof lines, 13 anterior lines, and 6 mitral isthmus lines. Additional RFA was necessary for two anterior lines (15%) and three mitral isthmus lines (50%). Bidirectional block was achieved across all roof lines, 92% of anterior lines, and 83% of mitral isthmus lines. We observed no acute procedural complications. CONCLUSION Ablation of a roof line and of the LAPW is feasible, effective, and safe using this multipolar PFA catheter. However, the catheter is less suited for ablation of the mitral isthmus and the anterior line. A focal pulsed-field ablation catheter may be more effective for ablation of these lines. This study shows the feasibility to ablate linear lesions with a multipolar pulsed-field ablation catheter. 27 left atrial reentry tachycardia were treated in 22 patients

Phosphatidylinositol 3-Akt-kinase-dependent phosphorylation of p21(Waf1/Cip1) as a novel mechanism of neuroprotection by glucocorticoids

The role of glucocorticoids in the regulation of apoptosis remains incongruous. Here, we demonstrate that corticosterone protects neurons from apoptosis by a mechanism involving the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). In primary cortical neurons, corticosterone leads to a dose- and Akt-kinase-dependent upregulation with enhanced phosphorylation and cytoplasmic appearance of p21(Waf1/Cip1) at Thr 145. Exposure of neurons to the neurotoxin ethylcholine aziridinium (AF64A) results in activation of caspase-3 and a dramatic loss of p21(Waf1/Cip1) preceding apoptosis in neurons. These effects of AF64A are reversed by pretreatment with corticosterone. Corticosterone-mediated upregulation of p21(Waf1/Cip1) and neuroprotection are completely abolished by glucocorticoid and mineralocorticoid receptor antagonists as well as inhibitors of PI3- and Akt-kinase. Both germline and somatically induced p21(Waf1/Cip1) deficiency abrogate the neuroprotection by corticosterone, whereas overexpression of p21(Waf1/Cip1) suffices to protect neurons from apoptosis. We identify p21(Waf1/Cip1) as a novel antiapoptotic factor for postmitotic neurons and implicate p21(Waf1/Cip1) as the molecular target of neuroprotection by high-dose glucocorticoids

Impact of actin filament stabilization on adult hippocampal and olfactory bulb neurogenesis

Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca(2+)-activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn(-/-)) mice as a model system for actin filament stabilization. In Gsn(-/-) mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca(2+)](i) increases and exocytotic neurotransmitter release were enhanced in Gsn(-/-) synaptosomes. Importantly, treatment of Gsn(-/-) synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca(2+) influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn(-/-) brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn(-/-) mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca(2+) influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn(-/-) hippocampus is associated with a special vascular niche for neurogenesis

Validation of a clinical model for predicting left versus right ventricular outflow tract origin of idiopathic ventricular arrhythmias.

BACKGROUND Prediction of the chamber of origin in patients with outflow tract ventricular arrhythmias (OTVA) remains challenging. A clinical risk score based on age, sex and presence of hypertension was associated with a left ventricular outflow tract (LVOT) origin. We aimed to validate this clinical score to predict an LVOT origin in patients with OTVA. METHODS In a two-center observational cohort study, unselected patients undergoing catheter ablation (CA) for OTVA were enrolled. All procedures were performed using an electroanatomical mapping system. Successful ablation was defined as a ≥80% reduction of the initial overall PVC burden after 3 months of follow-up. Patients with unsuccessful ablation were excluded from this analysis. RESULTS We included 187 consecutive patients with successful CA of idiopathic OTVA. Mean age was 52 ± 15 years, 102 patients (55%) were female, and 74 (40%) suffered from hypertension. A LVOT origin was found in 64 patients (34%). A score incorporating age, sex and presence of hypertension reached 73% sensitivity and 67% specificity for a low (0-1) and high (2-3) score, to predict an LVOT origin. The combination of one ECG algorithm (V2 S/V3 R-index) with the clinical score resulted in a sensitivity and specificity of 81% and 70% for PVCs with R/S transition at V3 . CONCLUSION The published clinical score yielded a lower sensitivity and specificity in our cohort. However, for PVCs with R/S transition at V3, the combination with an existing ECG algorithm can improve the predictability of LVOT origin

Differences in Atrial Remodeling in Hypertrophic Cardiomyopathy Compared to Hypertensive Heart Disease and Athletes’ Hearts.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), hypertensive heart disease (HHD) and athletes' heart share an increased prevalence of atrial fibrillation. Atrial cardiomyopathy in these patients may have different characteristics and help to distinguish these conditions. METHODS: In this single-center study, we prospectively collected and analyzed electrocardiographic (12-lead ECG, signal-averaged ECG (SAECG), 24 h Holter ECG) and echocardiographic data in patients with HCM and HHD and in endurance athletes. Patients with atrial fibrillation were excluded. RESULTS: We compared data of 27 patients with HCM (70% males, mean age 50 +/- 14 years), 324 patients with HHD (52% males, mean age 75 +/- 5.5 years), and 215 endurance athletes (72% males, mean age 42 +/- 7.5 years). HCM patients had significantly longer filtered P-wave duration (153 +/- 26 ms) and PR interval (191 +/- 48 ms) compared to HHD patients (144 +/- 16 ms, p = 0.012 and 178 +/- 31, p = 0.034, respectively) and athletes (134 +/- 14 ms, p = 0.001 and 165 +/- 26 ms, both p &lt; 0.001, respectively). HCM patients had a mean of 4.9 +/- 16 premature atrial complexes per hour. Premature atrial complexes per hour were significantly more frequent in HHD patients (27 +/- 86, p &lt; 0.001), but not in athletes (2.7 +/- 23, p = 0.639). Left atrial volume index (LAVI) was 43 +/- 14 mL/m(2) in HCM patients and significantly larger than age- and sex-corrected LAVI in HHD patients 30 +/- 10 mL/m(2); p &lt; 0.001) and athletes (31 +/- 9.5 mL/m(2); p &lt; 0.001). A borderline interventricular septum thickness >/=13 mm and </=15 mm was found in 114 (35%) HHD patients, 12 (6%) athletes and 3 (11%) HCM patients. CONCLUSIONS: Structural and electrical atrial remodeling is more advanced in HCM patients compared to HHD patients and athletes

Preferential Re-Replication of Drosophila Heterochromatin in the Absence of Geminin

To ensure genomic integrity, the genome must be duplicated exactly once per cell cycle. Disruption of replication licensing mechanisms may lead to re-replication and genomic instability. Cdt1, also known as Double-parked (Dup) in Drosophila, is a key regulator of the assembly of the pre-replicative complex (pre-RC) and its activity is strictly limited to G1 by multiple mechanisms including Cul4-Ddb1 mediated proteolysis and inhibition by geminin. We assayed the genomic consequences of disregulating the replication licensing mechanisms by RNAi depletion of geminin. We found that not all origins of replication were sensitive to geminin depletion and that heterochromatic sequences were preferentially re-replicated in the absence of licensing mechanisms. The preferential re-activation of heterochromatic origins of replication was unexpected because these are typically the last sequences to be duplicated in a normal cell cycle. We found that the re-replication of heterochromatin was regulated not at the level of pre-RC activation, but rather by the formation of the pre-RC. Unlike the global assembly of the pre-RC that occurs throughout the genome in G1, in the absence of geminin, limited pre-RC assembly was restricted to the heterochromatin by elevated cyclin A-CDK activity. These results suggest that there are chromatin and cell cycle specific controls that regulate the re-assembly of the pre-RC outside of G1

Supportive and symptomatic management of amyotrophic lateral sclerosis

The main aims in the care of individuals with amyotrophic lateral sclerosis (ALS) are to minimize morbidity and maximize quality of life. Although no cure exists for ALS, supportive and symptomatic care provided by a specialist multidisciplinary team can improve survival. The basis for supportive management is shifting from expert consensus guidelines towards an evidence-based approach, which encourages the use of effective treatments and could reduce the risk of harm caused by ineffective or unsafe interventions. For example, respiratory support using noninvasive ventilation has been demonstrated to improve survival and quality of life, whereas evidence supporting other respiratory interventions is insufficient. Increasing evidence implicates a causal role for metabolic dysfunction in ALS, suggesting that optimizing nutrition could improve quality of life and survival. The high incidence of cognitive dysfunction and its impact on prognosis is increasingly recognized, although evidence for effective treatments is lacking. A variety of strategies are used to manage the other physical and psychological symptoms, the majority of which have yet to be thoroughly evaluated. The need for specialist palliative care throughout the disease is increasingly recognized. This Review describes the current approaches to symptomatic and supportive care in ALS and outlines the current guidance and evidence for these strategies

Genetics of schizophrenia in the South African Xhosa

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide