Large-Scale Thalamocortical Triple Network Dysconnectivities in Patients With First-Episode Psychosis and Individuals at Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: Aberrant thalamocortical connectivity and large-scale network interactions among the default mode network (DMN), salience network (SN), and executive control network (ECN) (ie, triple networks) have been regarded as critical in schizophrenia pathophysiology. Despite the importance of network properties and the role of the thalamus as an integrative hub, large-scale thalamocortical triple network functional connectivities (FCs) in different stages of the psychotic disorder have not yet been reported. STUDY DESIGN: Thirty-nine first-episode psychosis (FEP) patients, 75 individuals at clinical high risk (CHR) for psychosis, 46 unaffected relatives (URs) of schizophrenia patients with high genetic loading, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Modular community detection was used to identify cortical and thalamic resting-state networks, and thalamocortical network interactions were compared across the groups. STUDY RESULTS: Thalamic triple networks included higher-order thalamic nuclei. Thalamic SN-cortical ECN FC was greater in the FEP group than in the CHR, UR, and HC groups. Thalamic DMN-cortical DMN and thalamic SN-cortical DMN FCs were greater in FEP and CHR participants. Thalamic ECN-cortical DMN and thalamic ECN-cortical SN FCs were greater in FEP patients and URs. CONCLUSIONS: These results highlight critical modulatory functions of thalamic triple networks and the shared and distinct patterns of thalamocortical triple network dysconnectivities across different stages of psychotic disorders. The current study findings suggest that large-scale thalamocortical triple network dysconnectivities may be used as an integrative biomarker for extending our understanding of the psychosis pathophysiology and for targeting network-based neuromodulation therapeutics.

Mapping thalamocortical functional connectivity with large-scale brain networks in patients with first-episode psychosis.

Abnormal thalamocortical networks involving specific thalamic nuclei have been implicated in schizophrenia pathophysiology. While comparable topography of anatomical and functional connectivity abnormalities has been reported in patients across illness stages, previous functional studies have been confined to anatomical pathways of thalamocortical networks. To address this issue, we incorporated large-scale brain network dynamics into examining thalamocortical functional connectivity. Forty patients with first-episode psychosis and forty healthy controls underwent T1-weighted and resting-state functional magnetic resonance imaging. Independent component analysis of voxelwise thalamic functional connectivity maps parcellated the cortex into thalamus-related networks, and thalamic subdivisions associated with these networks were delineated. Functional connectivity of (1) networks with the thalamus and (2) thalamic subdivision seeds were examined. In patients, functional connectivity of the salience network with the thalamus was decreased and localized to the ventrolateral (VL) and ventroposterior (VP) thalamus, while that of a network comprising the cerebellum, temporal and parietal regions was increased and localized to the mediodorsal (MD) thalamus. In patients, thalamic subdivision encompassing the VL and VP thalamus demonstrated hypoconnectivity and that encompassing the MD and pulvinar regions demonstrated hyperconnectivity. Our results extend the implications of disrupted thalamocortical networks involving specific thalamic nuclei to dysfunctional large-scale brain network dynamics in schizophrenia pathophysiology.

Comparison of surgically induced astigmatism between anterior and total cornea in 2.2 mm steep meridian incision cataract surgery.

BACKGROUND: This study aimed to compare surgically induced astigmatism (SIA) on the anterior and total cornea during cataract surgery through a 2.2 mm steep meridian incision. METHODS: The study included 69 left eyes of 69 patients who had undergone cataract surgery. The 69 eyes were classified into three subgroups according to the preoperative steep meridian. Following phacoemulsification, an intraocular lens was inserted into the bag. The keratometric measurements were taken 12 months postoperatively, on the anterior cornea (automated keratometer and anterior keratometry [K] from a rotating Scheimpflug camera) and total cornea (equivalent K reading [EKR] 3.0 mm, EKR 4.5 mm, total corneal refractive power (TCRP) 2.0 mm ring, TCRP 3.0 mm zone, TCRP 4.0 mm zone). The SIA was analyzed for each parameter. RESULTS: On the double-angle polar plot, the summated vector mean values of SIA determined by the automated keratometer and Scheimpflug anterior K were 0.28 diopter (axis: 177°) and 0.37 diopter (axis: 175°) in with-the-rule (WTR) astigmatism; 0.03 diopter (axis: 156°) and 0.18 diopter (axis: 177°) in oblique astigmatism; 0.15 diopter (axis: 96°) and 0.17 diopter (axis: 73°) in against-the-rule (ATR) astigmatism. The mean SIAs on the total cornea ranged from 0.31 to 0.42 diopter in WTR astigmatism; from 0.16 to 0.27 diopter in oblique astigmatism; from 0.04 to 0.11 diopter in ATR astigmatism. Mean magnitude SIA ranged from 0.41 to 0.46 diopter on anterior corneal surface and 0.50 to 0.62 diopter on total cornea. J0 and J45 of the posterior cornea showed no significant changes after cataract surgery, and the changes in J0 and J45 did not show any statistical differences between the anterior and total cornea (all p > 0.05). CONCLUSIONS: There were no differences in the summed vector mean values of SIA between the anterior cornea and the total cornea.

Highly Efficient Photothermal Therapy with Cell-Penetrating Peptide-Modified Bumpy Au Triangular Nanoprisms using Low Laser Power and Low Probe Dose.

Photothermal therapy (PTT) exploits nanomaterials with optimal heat conversion and cellular penetration using near-infrared (NIR) laser irradiation. However, current PTT agents suffer from inefficient heat conversion, poor intracellular delivery, and a high dose of probes along with excessive laser irradiation, causing limited therapeutic outcomes. Here, bumpy Au triangular nanoprisms (BATrisms) are developed for increasing the surface area, improving cell penetration, shifting the absorption peak to the NIR region, and enhancing the photothermal conversion efficiency (∼86%). Further, leucine (L)- and lysine (K)-rich cell-penetrating peptides (LK peptides) were employed to largely improve their cellular uptake efficiency. Importantly, a significant in vivo therapeutic efficacy with LK-BATrisms was demonstrated in a triple-negative breast cancer xenograft mice model. A very small dose of LK-BATrism (2.5 µg Au) was enough to exert antitumor efficacy under very low laser power (808 nm, 0.25 W/cm2), causing minimal tissue damages while very efficiently killing cancer cells.