Neural disruption to theory of mind predicts daily social functioning in individuals at familial high-risk for schizophrenia

Theory-of-mind (ToM) ability is foundational for successful social relationships, and dependent on a neurocognitive system, which includes temporoparietal junction and medial prefrontal cortex. Schizophrenia is associated with ToM impairments, and initial studies demonstrate similar, though more subtle deficits, in unaffected first-degree relatives, indicating that ToM deficits are a potential biomarker for the disorder. Importantly, the social consequences of ToM deficits could create an additional vulnerability factor for individuals at familial high risk (FHR). However, behavioral studies of ToM are inconsistent and virtually nothing is known about the neural basis of ToM in FHR or the relationship between ToM and social functioning. Here, FHR and non-FHR control participants underwent functional MRI scanning while reasoning about a story character’s thoughts, emotions or physical appearance. Afterwards, participants completed a 28-day online ‘daily-diary’ questionnaire in which they reported daily social interactions and degree of ToM reasoning. FHR participants demonstrated less neural activity in bilateral temporoparietal junction when reasoning about thoughts and emotions. Moreover, across all participants, the degree of neural activity during ToM reasoning predicted several aspects of daily social behavior. Results suggest that vulnerability for schizophrenia is associated with neurocognitive deficits in ToM and the degree of deficit is related to day-to-day social functioning.     

Renin–angiotensin system inhibition is not associated with increased sudden cardiac death,cardiovascular mortality or all-cause mortality in patients with aortic stenosis

Background

Renin–angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS.

Methods

All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses.

Results

769 (41%) patients received RASI. During a median follow-up of 4.3 ± 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95%CI: 0.50–2.83], p = 0.694), cardiovascular (HR: 1.05 [95%CI: 0.62–1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95%CI: 0.55–1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040).

Conclusions

RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression.     

Reduced variability in tacrolimus pharmacokinetics following intramuscular injection compared to oral administration in cynomolgus monkeys: Investigating optimal dosing regimens

Tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. However, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. Therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (IM) injection and to determine the optimal IM dosing regimens in primate models. Six male cynomolgus monkeys (Macaca fascicularis) were used in the study. Doses of 0.1 mg/kg and 5 mg were administered via IM injection and oral administration, respectively, once to determine single-dose pharmacokinetics and once daily for 5 days to determine multiple-dose pharmacokinetics. According to pharmacokinetic model estimates, the inter- and intra-individual variabilities in bioavailability following IM injection were remarkably reduced compared with those following oral administration. Monte Carlo simulations revealed that C_peak, C_trough and AUC would also have less variability following IM injection compared with oral administration. In this study, we found that the pharmacokinetic characteristics of tacrolimus were more constant following IM injection compared with oral administration. These results suggest that IM injection can be an alternative route of administration fin non-human primate model studies.     

MRA 联合DWI对急性脑卒中动脉狭窄的诊断价值

 目的 探讨核磁共振血管成像(MRA)联合磁共振弥散加权成像(DWI)序列对急性脑卒中动脉狭窄的诊断价值。方法 选取2015-03至2018-03入院的80例急性卒中患者为研究对象,对其MRA、DWI 以及高分辨核磁血管(HR-MRA)检查结果进行回顾性分析,以HR-MRA诊断结果为金标准,将MRA及MRA联合DWI的诊断结果进行比较。结果 MRA诊断为基底动脉狭窄的灵敏度、特异度、准确率分别为50.00%、96.87%和87.50%,MRA联合DWI检查,诊断为基底动脉狭窄的灵敏度、特异度、准确率分别为75.00%、96.87%、92.50%,后者灵敏度和准确率均高于前者。MRA诊断为大脑中动脉的灵敏度、特异度、准确率分别为63.15%、70.49%和68.75%,MRA联合DWI诊断为大脑中动脉的灵敏度、特异度、准确率分别为89.47%、86.88%、87.5%,联合诊断各项指标均高于MRA诊断。结论 相比单独MRA检查,MRA联合DWI能更准确判断动脉狭窄的部位。     

Revealing an unusual transparent phase of superhard iron tetraboride under high pressure

First principles–based electronic structure calculations of superhard iron tetraboride (FeB₄) under high pressure have been undertaken in this study. Starting with a “conventional” superconducting phase of this material under high pressure leads to an unexpected phase transition toward a semiconducting one. This transition occurred at 53.7 GPa, and this pressure acts as a demarcation between two distinct crystal symmetries, metallic orthorhombic and semiconducting tetragonal phases, with Pnnm and I4₁/acd space groups, respectively. In this work, the electron–phonon coupling-derived superconducting T_c has been determined up to 60 GPa and along with optical band gap variation with increasing pressure up to 300 GPa. The dynamic stability has been confirmed by phonon dispersion calculations throughout this study.The shorter interatomic distances of metal under external pressure consequently increase the valence and conduction band widths, which leads to the enhancement of free electron-like behavior. The development of creating immensely substantial pressure at laboratories enables us to observe the core electrons overlapping under enormous compression and dramatically influences the electronic properties of normally free electron metals such as Li and Na (1–3). The metal-to-insulating phase transformation has been contrived both experimentally and theoretically for both the normal metals while exerting pressure on them. This observation propelled us to investigate the electronic and structural phase transformation of the experimentally synthesized superhard material iron tetraboride (FeB₄) under high pressure (4–8). The intriguing factor of choosing FeB₄ is that the material was proposed as a “conventional” Fe-based superconductor, in contradiction to the discovery of an “unconventional” Fe-based superconductor because of its large electron–phonon coupling. Here we report the exotic phase transition of FeB₄ from metal to semiconductor at 53.7 GPa, even though we started with the metallic orthorhombic phase Pnnm of FeB₄, which shows the superconducting temperature T_c up to 60 GPa. The new phase after 53.7 GPa has I4₁/acd space group symmetry with a finite fundamental band gap, which increases along with pressure monotonically. All of the considered structures have been tested to have a thermodynamic stability from phonon dispersion calculations. The reason behind the phenomena could be the overlap of atomic cores at higher pressure ranges, which increases the hybridization of valence electrons and their repulsive interactions with core electrons. The immediate technological outcome of this scenario of metal-to-semiconducting phase transition could be to search for a transparent state of a material that is a metal under ambient conditions. This drastic change of electronic and structural properties can be observed in other materials as well, and hence this can open a field of studying them from a high-pressure perspective.