Increased response conflict in recreational cocaine polydrug users

Recent studies suggest that recreational use of cocaine is associated with significant impairments in the same cognitive control functions that are affected by chronic use. Here we tested whether recreational cocaine use can impact the emergence and resolution of response conflict in conflict-inducing tasks. Recreational cocaine polydrug users (n = 17) and cocaine-free controls (n = 17), matched for sex, age, intelligence, and alcohol consumption, performed a Simon task—which is known to induce response conflict. Recreational users showed a larger Simon effect, indicating that they had more difficulty resolving stimulus-induced response conflict. This finding is consistent with the recent literature showing that even small doses of cocaine are sufficient to compromise key cognitive control functions.     

Navigating the new landscape of second‐line treatment in advanced hepatocellular carcinoma

Sorafenib and lenvatinib are approved for first‐line treatment of patients with advanced hepatocellular carcinoma (HCC), and the efficacy of atezolizumab plus bevacizumab has been demonstrated versus sorafenib. Over time, first‐line treatment frequently fails, and regorafenib, cabozantinib, ramucirumab (for patients with alpha fetoprotein ≥400 ng/mL), nivolumab, pembrolizumab and ipilimumab plus nivolumab are approved for use after sorafenib (but not lenvatinib) treatment in advanced HCC. Given the considerable complexity in the therapeutic landscape, the objective of this review was to summarize the clinical evidence for second‐line agents and provide practical guidance for selecting the best sequential treatment approach. The timing and sequencing of treatment switches are key to optimizing patient outcomes in advanced HCC, and decisions should be informed by reasons for discontinuation of previous therapy and disease progression. It is important not to switch too soon, because sequential treatment benefit may then be lost, nor should switching be delayed too long. Effectiveness, safety and tolerability, patient quality of life, route of administration, dosing regimen, drug class, molecular target and individual patients’ characteristics, including comorbidities, inform the selection of second‐line systemic treatment, independently of the aetiology of HCC, tumour stage and the response to previous treatment. Biomarkers predictive of treatment effectiveness are of great value, but currently biomarker‐driven patient selection is possible only in the case of ramucirumab. The approval of new combination therapies for advanced HCC in the first‐line setting will further increase the complexity of decision‐making. However, the important factors will remain the individual patient’s characteristics and preferences.     

The genetic impact (C957T-DRD2) on inhibitory control is magnified by aging

Healthy aging beyond the age of 65 is characterized by a general decrease in cognitive control over actions: old adults have more difficulty than young adults in stopping overt responses. Responsible for this cognitive decrement is the continuous decline of striatal and extrastriatal dopamine (DA). The resource-modulation hypothesis assumes that genetic variability is more likely to result in performance differences when brain resources move away from close-to-optimal levels, as in aging. To test this hypothesis we investigated, first, whether individual differences in the C957T polymorphism at DRD2 gene (rs6277) contribute to individual differences in the proficiency to inhibit behavioral responses in a stop-signal task. Second, we assessed whether this genetic effect is magnified in older adults, due to the considerable decline in dopamine function. Our findings show that individuals carrying genotype associated with higher density of extrastriatal D2 receptors (C957T CC) were more efficient in inhibiting unwanted action tendencies, but not in term of response execution. This effect was stronger in older than in younger adults. Our findings support the idea that aging-related decline in dopamine availability alters the balance between genotypes and cognitive functions.     

Structural imaging of conjunctival filtering blebs in XEN gel implantation and trabeculectomy: a confocal and anterior segment optical coherence tomography study

Graefe's Archive for Clinical and Experimental Ophthalmology - To describe and compare the conjunctival filtering bleb features after XEN gel implantation and trabeculectomy using anterior...