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Chimeric antigen receptor T cell (CAR-T) therapy in hematologic malignancies has made great progress, but there are still some problems. First, T cells from tumor patients show an exhaustion phenotype; thus, the persistence and function of the CAR-Ts are poor, and achieving a satisfactory curative effect is difficult. Second, some patients initially respond well but quickly develop antigen-negative tumor recurrence. Thirdly, CAR-T treatment is not effective in some patients and is accompanied by severe side effects, such as cytokine release syndrome (CRS) and neurotoxicity. The solution to these problems is to reduce the toxicity and enhance the efficacy of CAR-T therapy. In this paper, we describe various strategies for reducing the toxicity and enhancing the efficacy of CAR-T therapy in hematological malignancies. In the first section, strategies for modifying CAR-Ts using gene-editing technologies or combining them with other anti-tumor drugs to enhance the efficacy of CAR-T therapy are introduced. The second section describes some methods in which the design and construction of CAR-Ts differ from the conventional process. The aim of these methods is to enhance the anti-tumor activity of CAR-Ts and prevent tumor recurrence. The third section describes modifying the CAR structure or installing safety switches to radically reduce CAR-T toxicity or regulating inflammatory cytokines to control the symptoms of CAR-T-associated toxicity. Together, the knowledge summarized herein will aid in designing better-suited and safer CAR-T treatment strategies. [ABSTRACT FROM AUTHOR]

The photoisomerization‐induced cytotoxicity in photopharmacology provides a unique pathway for phototherapy because it is independent of endogenous oxygen. In this study, we developed a biosafe photoisomerizable zinc(II) complex (Zn1), which releases its trans ligand (trans‐L1) after being irradiated with blue light. This causes the complex to undergo photoisomerization and produce the toxic cis product (cis‐L1) and generate singlet oxygen (1O2). The resulting series of events caused impressive phototoxicity in hypoxic A431 skin cancer cells, as well as in a tumor model in vivo. Interestingly, Zn1 was able to inhibit tumor microtubule polymerization, while still showing good biocompatibility and biosafety in vivo. This photoisomerizable zinc(II) complex provides a novel strategy for addressing the oxygen‐dependent limitation of traditional photodynamic therapy. [ABSTRACT FROM AUTHOR]

The photoisomerization‐induced cytotoxicity in photopharmacology provides a unique pathway for phototherapy because it is independent of endogenous oxygen. In this study, we developed a biosafe photoisomerizable zinc(II) complex (Zn1), which releases its trans ligand (trans‐L1) after being irradiated with blue light. This causes the complex to undergo photoisomerization and produce the toxic cis product (cis‐L1) and generate singlet oxygen (1O2). The resulting series of events caused impressive phototoxicity in hypoxic A431 skin cancer cells, as well as in a tumor model in vivo. Interestingly, Zn1 was able to inhibit tumor microtubule polymerization, while still showing good biocompatibility and biosafety in vivo. This photoisomerizable zinc(II) complex provides a novel strategy for addressing the oxygen‐dependent limitation of traditional photodynamic therapy. [ABSTRACT FROM AUTHOR]

The creation of self‐healing polymers from commodity olefins is of great interest and importance but has remained a challenge to date. We report here for the first time the synthesis of self‐healing polymers by catalyst‐controlled polymerization of a simple commodity diene, isoprene. We found that polyisoprenes having an appropriate mixture (ca. 70/30) of 3,4‐ and cis‐1,4‐microstructures synthesized by using a half‐sandwich scandium catalyst could act as excellent self‐healing elastomers without any external intervention. The unprecedented self‐healability could be ascribed to nanoscale heterogeneities formed by microphase separation of the relatively hard 3,4‐segments from a flexible cis‐1,4‐segment matrix. The hydrogenated polyisoprenes (without C=C bonds) with the analogous microstructures also exhibited excellent mechanical and self‐healing properties, further demonstrating that even simple polyolefins can be made self‐healable if the microstructures are appropriately regulated. [ABSTRACT FROM AUTHOR]

The creation of self‐healing polymers from commodity olefins is of great interest and importance but has remained a challenge to date. We report here for the first time the synthesis of self‐healing polymers by catalyst‐controlled polymerization of a simple commodity diene, isoprene. We found that polyisoprenes having an appropriate mixture (ca. 70/30) of 3,4‐ and cis‐1,4‐microstructures synthesized by using a half‐sandwich scandium catalyst could act as excellent self‐healing elastomers without any external intervention. The unprecedented self‐healability could be ascribed to nanoscale heterogeneities formed by microphase separation of the relatively hard 3,4‐segments from a flexible cis‐1,4‐segment matrix. The hydrogenated polyisoprenes (without C=C bonds) with the analogous microstructures also exhibited excellent mechanical and self‐healing properties, further demonstrating that even simple polyolefins can be made self‐healable if the microstructures are appropriately regulated. [ABSTRACT FROM AUTHOR]

The terpolymerization of a non‐polar olefin (such as ethylene) and two different polar functional olefins in a controlled fashion is of great interest and importance but has hardly been explored to date. We report for the first time the terpolymerization of ethylene (E) and two different methoxyaryl‐substituted propylenes (AR1P=hexylanisyl propylene; AR2P=methoxynaphthyl propylene or methoxypyrenyl propylene) by a half‐sandwich scandium catalyst. The terpolymerization took place in a sequence‐controlled fashion, affording unique multi‐block copolymers composed of two different ethylene‐alt‐methoxyarylpropylene sequences E‐alt‐AR1P (soft segments) and E‐alt‐AR2P (hard segments) and relatively short ethylene–ethylene (EE) blocks (crystalline segments). The terpolymers exhibited excellent elasticity and unprecedented self‐healing as a result of microphase separation of nanodomains of the crystalline EE segments and the hard amorphous E‐alt‐AR2P segments from a very flexible E‐alt‐AR1P matrix, demonstrating unique synergy of the three different components. [ABSTRACT FROM AUTHOR]

The terpolymerization of a non‐polar olefin (such as ethylene) and two different polar functional olefins in a controlled fashion is of great interest and importance but has hardly been explored to date. We report for the first time the terpolymerization of ethylene (E) and two different methoxyaryl‐substituted propylenes (AR1P=hexylanisyl propylene; AR2P=methoxynaphthyl propylene or methoxypyrenyl propylene) by a half‐sandwich scandium catalyst. The terpolymerization took place in a sequence‐controlled fashion, affording unique multi‐block copolymers composed of two different ethylene‐alt‐methoxyarylpropylene sequences E‐alt‐AR1P (soft segments) and E‐alt‐AR2P (hard segments) and relatively short ethylene–ethylene (EE) blocks (crystalline segments). The terpolymers exhibited excellent elasticity and unprecedented self‐healing as a result of microphase separation of nanodomains of the crystalline EE segments and the hard amorphous E‐alt‐AR2P segments from a very flexible E‐alt‐AR1P matrix, demonstrating unique synergy of the three different components. [ABSTRACT FROM AUTHOR]

The precise control of monomer sequence and stereochemistry in copolymerization is of much interest and importance for the synthesis of functional polymers, but studies toward this goal have met with only limited success to date. Now, the co‐syndiospecific alternating copolymerization of methoxyphenyl‐ and N,N‐dimethylaminophenyl‐functionalized propylenes with styrene by half‐sandwich rare‐earth catalysts is reported. This reaction efficiently afforded the corresponding functionalized propylene‐alt‐styrene copolymers with a perfect alternating sequence and excellent co‐syndiotacticity (rrrr >99 %), thus constituting the first example of co‐stereospecific alternating copolymerization of polar and non‐polar olefins. [ABSTRACT FROM AUTHOR]

The precise control of monomer sequence and stereochemistry in copolymerization is of much interest and importance for the synthesis of functional polymers, but studies toward this goal have met with only limited success to date. Now, the co‐syndiospecific alternating copolymerization of methoxyphenyl‐ and N,N‐dimethylaminophenyl‐functionalized propylenes with styrene by half‐sandwich rare‐earth catalysts is reported. This reaction efficiently afforded the corresponding functionalized propylene‐alt‐styrene copolymers with a perfect alternating sequence and excellent co‐syndiotacticity (rrrr >99 %), thus constituting the first example of co‐stereospecific alternating copolymerization of polar and non‐polar olefins. [ABSTRACT FROM AUTHOR]

Five bis(quinolylmethyl)-(1 H-indolylmethyl)amine (BQIA) compounds, that is, {(quinol-8-yl-CH2)2NCH2(3-Br-1 H-indol-2-yl)} ( L1H) and {[(8-R3-quinol-2-yl)CH2]2NCH(R2)[3-R1-1 H-indol-2-yl]} ( L2-5H) ( L2H: R1=Br, R2=H, R3=H; L3H: R1=Br, R2=H, R3= iPr; L4H: R1=H, R2=CH3, R3= iPr; L5H: R1=H, R2= nBu, R3= iPr) were synthesized and used to prepare calcium complexes. The reactions of L1-5H with silylamido calcium precursors (Ca[N(SiMe2R)2]2(THF)2, R=Me or H) at room temperature gave heteroleptic products ( L1, 2)CaN(SiMe3)2 ( 1, 2), ( L3, 4)CaN(SiHMe2)2 ( 3 a, 4 a) and homoleptic complexes ( L3, 5)2Ca ( D3, D5). NMR and X-ray analyses proved that these calcium complexes were stabilized through Ca⋅⋅⋅C−Si, Ca⋅⋅⋅H−Si or Ca⋅⋅⋅H−C agostic interactions. Unexpectedly, calcium complexes (( L3-5)CaN(SiMe3)2) bearing more sterically encumbered ligands of the same type were extremely unstable and underwent C−N bond cleavage processes as a consequence of intramolecular C−H bond activation, leading to the exclusive formation of ( E)-1,2-bis(8-isopropylquinol-2-yl)ethane. [ABSTRACT FROM AUTHOR]

A series of magnesium silylamido complexes supported by tetradentate aminophenolate ligands, LMgN(SiMe 3 ) 2 (L = {(2-R 1 )Ar-CH 2 N[(CH 2 ) 2 R 2 ]CH 2 -(4-R 4 -6-R 3 )C 6 H 2 O − }, R 1 = NMe 2 , R 2 = N i Pr 2 , R 3 = R 4 = Cl ( 1 ), R 3 = R 4 = cumyl ( 2 ); R 1 = NMe 2 , R 2 = NEt 2 , R 3 = R 4 = cumyl ( 3 ), R 3 = CPh 3 , R 4 = Me ( 4 ); R 1 = NEt 2 , R 2 = NEt 2 , R 3 = CPh 3 , R 4 = Me ( 5 ); R 1 = NMe 2 , R 2 = ( S )-1-butylpyrrolidine-2-yl, R 3 = R 4 = cumyl ( 6 ), R 3 = CPh 3 , R 4 = Me ( 7 )), were synthesized and fully characterized, and their catalytic behaviors for the ring-opening polymerization (ROP) of rac -lactide ( rac -LA) were explored. The monomeric nature and versatile coordination modes of these complexes in the solid state were further confirmed by X-ray diffraction studies on complexes 1 , 3 and 7 . In complex 1 , the N , N -diisopropylamino group on the alkylamino side arm does not coordinate to the metal centre, whilst the remaining three donors of the aminophenolate ligand and the silylamido group bond with the magnesium centre. By contrast, in complexes 3 and 7 , the arylamino moiety does not coordinate to the metal centre, while the alkylamino side arm coordinates. It is worth noting that the introduction of the N , N -dimethyl amino group to the pendant benzyl group realises the diastereoselective synthesis of multichiral aminophenolate magnesium complexes, which has not been achieved by the corresponding tridentate aminophenolate ligand. It was found that most of these magnesium complexes serve as highly active initiators for the ROP of rac -LA. The coordination pattern of the aminophenolate ligand exerted a considerable influence on the activity and stereoselectivity of the corresponding complex toward the polymerization of rac -LA, leading to the production of moderate to high heterotactic biased PLAs. The enantiopure complex 7 showed the highest heteroselectivity among these magnesium complexes ( P r = 0.80 in toluene, P r = 0.82 in THF). [ABSTRACT FROM AUTHOR]

A series of magnesium silylamido complexes supported by chiral aminophenolate ligands were synthesized, and their catalytic behaviors toward the ring-opening polymerization of rac-lactide (LA) and rac-β-butyrolactone (BBL) were explored. The reactions of Mg[N(SiMe3)2]2 with chiral tridentate aminophenols L1–10H [L = (S)-{[(1-R4, 2-pyrrolidinyl)CH2N(R3)-]}CH2-(6-R1-4-R2)-C6H2O−] in a 1 : 1 molar ratio in toluene gave the chiral aminophenolate magnesium silylamido complexes L1–10MgN(SiMe3)2 as enantiopure compounds or as pairs of diastereomers. As determined by X-ray analysis, structures a and b of diastereomer mixtures adopt the configuration of SCSNRNRMg-a and SCSNSNSMg-b, respectively. It was found that most of these magnesium complexes served as highly active initiators for the ring-opening polymerization of rac-LA. Besides, the stereoselectivity of chiral magnesium complexes gradually changed from isoselective-biased (Pm = 0.67) to heteroselective-enriched (Pr = 0.81) via a stepwise adjustment of the substituents of the ligand framework. It was noted that, as the rare reported active magnesium initiator for the ROP of rac-BBL, complexes 3–9 can efficiently initiate the ring-opening polymerization of rac-BBL in a controlled manner, giving moderate syndiotactic (Ps up to 0.73) PHBs. [ABSTRACT FROM AUTHOR]

Thepreparation and characterization of several zinc and magnesium complexesbearing chiral aminophenolate ligands, [(S)- or (R)-L]ZnN(SiMe3)2(1, 2), [(S)- or (R)-L]ZnOtBu (3, 4) and [(S)- or (R)-L]MgN(SiMe3)2(5, 6) ((S)- or(R)-L = (S)- or (R)-2-{N-benzyl-N-[(1-nbutyl-2-pyrrolidinyl)methyl]}aminomethyl-4-methyl-6-tritylphenolate),have been reported. While the X-ray diffraction studies as well asthe NMR spectroscopic data revealed that zinc and magnesium silylamidocomplexes possess similar structures both in the solid state and insolution, their catalytic performance toward rac-LApolymerization exhibited significant difference. The replacement ofzinc center by magnesium realized an interesting stereoselectivityswitch from isoselective (Pm= 0.80) toheteroselective (Pr= 0.81). The reactionsof enantiopure zinc complexes 1and 2with(S)-methyl lactate or (R)-tert-butyl lactate resulted in the target lactate complexes 7–9as a mixture of two diastereomers,but in different ratios. Two typical zinc lactate isomers 8αand 9β/9β′ were isolated and furthercharacterized by the X-ray diffraction method to have pentacoordinatedgeometry where the coordination of lactate carbonyl group displayssome hemilabile nature. The molecular structures of 8αand 9β/9β′ indicated that the specificconfiguration of lactate moiety in combination with the aminophenolateligand of given chirality would favor the formation of one of thetwo diastereomers in each case. Based on the structures of zinc lactatemodel complexes and the active propagating species, as well as thepreferential enchainment of one specific lactide monomer in the polymerization,a cooperation of enantiomorphic-site control and chain-end controlmechanisms involving three types of active species was proposed forthe formation of stereoblock PLAs from rac-LA byzinc initiators. Results of apparent rate constants for rac-, d-, and l-LA polymerizations by magnesium initiatorsare consistent with a chain-end control mechanism. The 13C NMR spectra of magnesium lactate complexes proved that the bondingof carbonyl group to magnesium center is stronger than that in zincactive species. The coordination number of magnesium species can expandeasily to six in the presence of coordinative molecules, suggestingthat the heteroselective magnesium active species have a hexacoordinatedcore structure. The difference of coordination geometry between zincand magnesium active species should be responsible for the stereoselectivityswitch in the polymerization of rac-LA. [ABSTRACT FROM AUTHOR]

Mono(ketiminate) aluminum dimethyl complexes 1a – 5a and bis(ketiminate) aluminum methyl complex 2b were synthesized via the reactions of AlMe 3 with various N -aryl substituted ketimine compounds in a 1:1 or 1:2 molar ratio, respectively. The reaction of Al(O i Pr) 3 with the ketimine compound L 2 H resulted in a bis(ketiminate) aluminum isopropoxide complex 2c . All the complexes were characterized by 1 H and 13 C{ 1 H} NMR spectroscopy, either EA or HRMS analysis. X-ray diffraction measurement of complexes 2a and 3a confirmed that in the solid state both 2a and 3a exist as a tetrahedron structure with the aluminum atom center surrounded by the oxygen and nitrogen donors of the bis-chelating ketiminate ligand as well as two methyl groups. Besides, a triligated aluminum complex 3 (Al(L 3 ) 3 ) with a six-coordinated metal core and a dinuclear aluminum isopropoxide complex 6d [(L 6 ) 2 Al(μ-O i Pr) 2 Al(O i Pr) 2 ] with C 2 -symmetry were isolated and characterized by X-ray diffraction studies. All aluminum methyl complexes behaved as active initiators in the ring-opening polymerization (ROP) of rac- lactide ( rac -LA), affording isotactic-enriched polylactides (PLAs) with high molecular weights and broad molecular weight distributions at 70 °C. The steric and electronic characters of the ancillary ligands show significant effects both on the activity and the stereoselectivity. The introduction of an electron-withdrawing group on the para -position of N -aryl ring of the ligand resulted in an increase of the catalytic activity. However, the electronic character of ancillary ligands showed a neglectable effect on the ROP of ε -CL initiated by these aluminum complexes. For both monomers, bis(ketiminate) aluminum complex 2b was found to be more active than the corresponding mono(ketiminate) complex 2a of the same ligand. Aluminum isopropoxide complex 2c exerted better control for the polymerizations of both monomers, providing polymers with narrower molecular weight distributions and smaller molecular weights which are comparable to the theoretical values [ABSTRACT FROM AUTHOR]

An enantiopure zinc complex supported by an aminophenolate ligand with multiple stereogenic centers has been diastereoselectively synthesized via the variation of the ortho-substituent of a phenoxy moiety and the N-alkyl group of a chiral pyrrolidinyl ring in the ligand framework, which displays high isoselectivity in the polymerization of rac-lactide. [ABSTRACT FROM AUTHOR]

Reversible protonic ceramic electrochemical cells (R‐PCECs) have received increasing focus for their good capability of converting and storing energy. However, the widely used cobalt‐based air electrodes are less thermomechanically compatible with the electrolyte and lack stability, which largely limits the development of R‐PCECs. Herein, a cobalt‐free perovskite with a nominal composition of PrBa0.8Ca0.2Fe1.8Ce0.2O6δ (PBCFC) is reported, which is in–situ engineered to a (Ba, Ce) deficient‐PBCFC phase, a BaCeO3, and a CeO2 phase under typical operating conditions, delivering a low area–specific resistance of 0.10 Ωcm2 at 700 oC. The generated BaCeO3 and CeO2 particles increase the conduction/transfer of protons and oxygen ions, thus providing extra active sites for the oxygen reactions. When utilized as an air electrode on a single cell, it achieves encouraging performance at 700 °C: a peak power density of 1.78 Wcm−2 and a current density of 5.00 Acm−2 at 1.3 V in the dual mode of the fuel cell (FC) and electrolysis (EL) mode with reasonable Faradaic efficiencies. In addition, the cells exhibit favorable operational durability of 65 h (FC mode), 95 h (EL mode), and promising cycling stability of 200 h. [ABSTRACT FROM AUTHOR]

Glaucoma is the leading cause of irreversible blindness worldwide. Early detection is of utmost importance as there is abundant evidence that early treatment prevents disease progression, preserves vision, and improves patients' long-term quality of life. The structure and function thresholds that alert to the diagnosis of glaucoma can be obtained entirely via digital means, and as such, screening is well suited to benefit from artificial intelligence and specifically machine learning. This paper reviews the concepts and current literature on the use of machine learning for detection of the glaucomatous disc and visual field. [ABSTRACT FROM AUTHOR]

Highlights • Transition-metal-catalyzed C H bond activation has attracted substantial interest in recent years as an efficient, step-economic, and environmentally benign pathway for the synthesis of functional polymers. • The polymerization reaction may proceed through C H/C X cross-coupling, oxidative C H/C H coupling, and C H addition to unsaturated C C bonds. • C H activation may also serve as a chain transfer reaction for olefin polymerization and polymer post-functionalization. This review summarizes recent advances in this area. Abstract Transition-metal-catalyzed C H bond activation has attracted substantial interest in recent years as an efficient, step-economic, and environmentally benign pathway for the synthesis of functional polymers. The polymerization reaction may proceed through C H/C X cross-coupling, oxidative C H/C H coupling, and C H addition to unsaturated C C bonds. C H activation may also serve as a chain transfer reaction for olefin polymerization and polymer post-functionalization. This review summarizes recent advances in this area. [ABSTRACT FROM AUTHOR]

[Display omitted] • Binary mixtures of [EDMIM][BF 4 ] with methanol, acetonitrile and acetone were studied. • Densities, viscosities and volumetric properties have been obtained and discussed. • The Pitzer model and the Erying dynamic equation were used to fit the properties. • The interaction mechanism was analyzed at the molecular level by the COSMO-RS model. Densities and viscosities of binary mixtures of 1-ethyl-2,3-dimethylimidazolium tetrafluoroborate [EDMIM][BF 4 ] with methanol, acetonitrile and acetone at 293.15 to 333.15 K were studied in this work. Volumetric properties including the apparent molar volume, the excess molar volume, the partial molar volume and the excess partial molar volume were calculated from the density data. The empirical linear formula was used to correlate the densities of the binary systems, and the apparent molar volumes and the viscosity were fitted with the Pitzer model and the Erying dynamic equation, respectively. Finally, the COSMO-RS model was adopted to analyze the interaction mechanism at the molecular level. [ABSTRACT FROM AUTHOR]

To determine the clinical relevance of prelaminar wedge defects (PLWDs) detected by swept-source optical coherence tomography (SS-OCT) in primary open-angle glaucoma (POAG). In this retrospective case–control study, PLWDs were defined as triangular-shaped defects at the surface of the optic nerve prelaminar tissue, not adjacent to blood vessels, present on cross-sectional SS-OCT scans. Two observers masked to diagnosis independently reviewed scans to detect PLWDs and lamina cribrosa defects. History of disc hemorrhage, occurring within 2 years prior to imaging, was obtained from chart review. One eye per subject was randomly selected. Two-sided t-tests, analysis of variance with Bonferroni correction, and multivariable logistic regression analysis were performed to explore demographic and clinical features associated with PLWDs. 40 POAG and 23 control eyes were included. PLWDS were found in 27.5% of POAG (n = 11) and 4.3% of controls (n = 1, p =.04). Eyes with repeat SS-OCT imaging (7 POAG and 0 controls) had persistent PLWDs. More POAG eyes with PLWDs had a history of disc hemorrhage (45.5%) than POAG eyes without PLWDs (3.4%, p =.004). On multivariable analysis, compared to POAG without PLWDs, POAG with PLWDs had increased odds of observed disc hemorrhage (OR = 21.6, 95% CI, 2.2–589.0, p =.02) after adjusting for age, gender, visual field mean deviation and maximum intraocular pressure (IOP). POAG with PLWDs had more lamina cribrosa defects (45.5%) than POAG without PLWDs (3.4%, p =.01) but did not differ significantly from controls (8.7%, p =.07). Compared to all patients without PLWDs, patients with PLWDs had increased odds of having lamina cribrosa defects (OR = 44.8; 95% CI, 6.3–703.6, p <.001) after adjusting for age, gender, and maximum IOP. PLWDs were more frequently found in POAG than control eyes and were associated with a history of disc hemorrhage and lamina cribrosa defects. PLWDs may be a useful imaging biomarker of glaucomatous damage. [ABSTRACT FROM AUTHOR]

Purpose: To compare structural features in prelaminar and laminar tissues of the optic nerve head (ONH) in chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG), and control subjects. Materials and Methods: ONH imaging was performed using swept-source optical coherence tomography (SS-OCT) for measurements of minimum rim width at Bruch’s membrane opening (BMO-MRW), horizontal, and vertical lamina cribrosa depth (LCD). Prelaminar defects, categorized as hole and wedge, and lamina cribrosa (LC) defects were identified. Enhanced depth imaging spectral domain OCT (EDI-OCT) customized to perform high-resolution volume scans was used in conjunction to further characterize prelaminar holes. One eye per subject was analyzed. Results: Eighty subjects (20 CACG, 40 POAG, and 20 controls) were included in the study. CACG and POAG groups had similar mean deviation on Humphrey visual field testing (−6.9 ± 5.1 vs. −6.3 ± 6.0 dB,p> 0.05) and IOP on the day of imaging (14.0 ± 3.1 vs. 13.8 ± 2.7 mmHg,p> 0.05). Thinnest and global BMO-MRW in CACG (120.3 ± 44.8, 225.5 ± 53.9 μm) and POAG (109.7 ± 56.3, 213.8 ± 59.7 μm) groups were lower than controls (200.1 ± 40.8, 308.3 ± 70.8 μm;p< 0.001 for both). Prelaminar holes were most frequent in CACG (65.0%) than POAG (25.0%,p=0.008) or control groups (20.0%,p=0.01). After adjusting for demographic and ophthalmic covariates, CACG was associated with increased odds of having prelaminar holes compared to POAG (odds ratio, 9.79; 95% CI, 2.12–45.19;p=0.003). Hole volume was similar between CACG and POAG (p> 0.05), but the CACG group had more holes per scan than POAG (maximum 2.5 ± 1.9 vs. 1.2 ± 0.4,p=0.02). Prelaminar wedge defects were less common in the CACG than the POAG group (5.0% vs. 37.5%,p=0.02). The CACG group did not differ from controls in laminar characteristics, such as LCD and LC defects. Conclusions: SS-OCT evaluation of the ONH revealed more frequent prelaminar holes in CACG compared to POAG and control patients. [ABSTRACT FROM PUBLISHER]

Recent work suggests that hair cells are not the most vulnerable elements in the inner ear; rather, it is the synapses between hair cells and cochlear nerve terminals that degenerate first in the aging or noise-exposed ear. This primary neural degeneration does not affect hearing thresholds, but likely contributes to problems understanding speech in difficult listening environments, and may be important in the generation of tinnitus and/or hyperacusis. To look for signs of cochlear synaptopathy in humans, we recruited college students and divided them into low-risk and high-risk groups based on self-report of noise exposure and use of hearing protection. Cochlear function was assessed by otoacoustic emissions and click-evoked electrocochleography; hearing was assessed by behavioral audiometry and word recognition with or without noise or time compression and reverberation. Both groups had normal thresholds at standard audiometric frequencies, however, the high-risk group showed significant threshold elevation at high frequencies (10–16 kHz), consistent with early stages of noise damage. Electrocochleography showed a significant difference in the ratio between the waveform peaks generated by hair cells (Summating Potential; SP) vs. cochlear neurons (Action Potential; AP), i.e. the SP/AP ratio, consistent with selective neural loss. The high-risk group also showed significantly poorer performance on word recognition in noise or with time compression and reverberation, and reported heightened reactions to sound consistent with hyperacusis. These results suggest that the SP/AP ratio may be useful in the diagnosis of “hidden hearing loss” and that, as suggested by animal models, the noise-induced loss of cochlear nerve synapses leads to deficits in hearing abilities in difficult listening situations, despite the presence of normal thresholds at standard audiometric frequencies. [ABSTRACT FROM AUTHOR]