Access to chiral dihydrophenanthridines via a palladium(0)-catalyzed Suzuki coupling and C-H arylation cascade reaction using new chiral-bridged biphenyl bifunctional ligands.

A class of chiral-bridged biphenyl phosphine-carboxylate bifunctional ligands CB-Phos has been developed and successfully applied to Pd(0)-catalyzed single enantioselective C-H arylation and a one pot cascade reaction involving Suzuki cross-coupling and C-H arylation. The catalytic system provides a new and convenient way for the synthesis of versatile chiral dihydrophenanthridines with rich structures and broad functional group tolerance. Good to excellent yields with high enantioselectivities were generally achieved. The reaction mechanism of the cascade reaction was also preliminarily discussed.

Dehiscence and Fistula Formation Following Anterior Palatal Reconstruction With Vomer Flap.

BACKGROUND AND PURPOSE: Anterior palatal reconstruction using vomer flaps has been described during primary cleft lip repair. In this procedure, the mucoperiosteal tissue of the vomer is elevated to reconstruct the nasal mucosa overlying the cleft of the hard palate. Here the authors, evaluate the efficacy of a technique in which a superiorly based vomer flap is sutured to the lateral nasal mucosa. The authors assess vomer flap dehiscence rates and compare the likelihood of fistula development in this cohort to patients who underwent palatoplasty without vomer flap reconstruction. METHODS: A retrospective chart review was conducted of all palatoplasties performed by the senior author at an academic institution during a 7-year period. Medical records were reviewed for demographic variables, operative characteristics, and postoperative complications up to 1 year following surgery. Logistic regression analysis was conducted to assess the effects of vomer flap reconstruction on fistula formation, adjusting for age and sex. RESULTS: Fifty-eight (N=58) patients met the inclusion criteria. Of these, 38 patients (control group) underwent cleft palate reconstruction without previous vomer flap placement. The remaining 20 patients underwent cleft lip repair with vomer flap reconstruction before palatoplasty (vomer flap group). When bilateral cases were counted independently, 25 total vomer flap reconstructions were performed. Seventeen of these 25 vomer flap reconstructions (68%) were completely dehisced by the time of cleft palate repair. In the vomer flap group, 3 of the 20 patients (15%) developed fistulas in the anterior hard palate following the subsequent palatoplasty procedure. In the control group, only 1 of the 38 patients (2.6%) developed a fistula in the anterior hard palate. There was no significant association between cohorts and the development of anterior hard palate fistulas [odds ratio=10.88, 95% confidence interval (0.99-297.77) P=0.07], although analysis was limited by low statistical power due to the small sample size. CONCLUSIONS: In our patient population, anterior palatal reconstruction using a superiorly based vomer flap technique was associated with complete dehiscence in 68% of cases. Fistula formation in the anterior hard palate was also proportionately higher following initial vomer flap reconstruction (15% versus 2.6%). These results prompted the senior author to adjust his surgical technique to 1 in which the vomer flap overlaps the oral mucosa. While follow-up from these adjusted vomer flap reconstruction cases remains ongoing, early evidence suggests a reduced requirement for surgical revision following implementation of the modified technique.

Barriers of Three-Dimensional Printing in Craniofacial Plastic Surgery Practice: A Pilot Study and Literature Review.

OBJECTIVE: Three-dimensional printing (3Dp) and modeling have demonstrated increasing utility within plastic and reconstructive surgery (PRS). This study aims to understand the prevalence of how this technology is utilized in craniofacial surgery, as well as identify barriers that may limit its integration into practice. METHODS: A survey was developed to assess participant demographics, characteristics of 3Dp use, and barriers to utilizing three-dimensional technologies in practice. The survey was distributed to practicing craniofacial surgeons. A secondary literature review was conducted to identify solutions for barriers and potential areas for innovation. RESULTS: Fifteen complete responses (9.7% response rate) were analyzed. The majority (73%) reported using three-dimensional modeling and printing in their practice, primarily for surgical planning. The majority (64%) relied exclusively on outside facilities to print the models, selecting resources required to train self and staff (55%), followed by the cost of staff to run the printer (36%), as the most common barriers affecting 3Dp use in their practice. Of those that did not use 3Dp, the most common barrier was lack of exposure (75%). The literature review revealed cost-lowering techniques with materials, comparability of desktop commercial printers to industrial printers, and incorporation of open-source software. CONCLUSIONS: The main barrier to integrating 3Dp in craniofacial plastic and reconstructive surgery practice is the perceived cost associated with utilizing the technology. Ongoing literature highlights the cost-utility of in-house 3Dp technologies and practical cost-saving methods. The authors' results underscore the need for broad exposure for currently practicing attendings and trainees in 3Dp practices and other evolving technologies.

FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma.

Genomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to FGFR inhibition. However, the depth and duration of response is often limited. Here, we conduct integrative transcriptomics, metabolomics, and phosphoproteomics analysis of patient-derived models to define pathways downstream of oncogenic FGFR2 signaling that fuel ICC growth and to uncover compensatory mechanisms associated with pathway inhibition. We find that FGFR2-mediated activation of Nuclear factor-κB (NF-κB) maintains a highly glycolytic phenotype. Conversely, FGFR inhibition blocks glucose uptake and glycolysis while inciting adaptive changes, including switching fuel source utilization favoring fatty acid oxidation and increasing mitochondrial fusion and autophagy. Accordingly, FGFR inhibitor efficacy is potentiated by combined mitochondrial targeting, an effect enhanced in xenograft models by intermittent fasting. Thus, we show that oncogenic FGFR2 signaling drives NF-κB-dependent glycolysis in ICC and that metabolic reprogramming in response to FGFR inhibition confers new targetable vulnerabilities.

Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

Using Large Language Models to Generate Educational Materials on Childhood Glaucoma.

PURPOSE: To evaluate the quality, readability, and accuracy of large language model (LLM) generated patient education materials (PEMs) on childhood glaucoma, and their ability to improve existing online information's readability. DESIGN: Cross-sectional comparative study. METHODS: We evaluated responses of ChatGPT-3.5, ChatGPT-4, and Bard to three separate prompts requesting they write PEMs on "childhood glaucoma." Prompt A required PEMs be "easily understandable by the average American." Prompt B required PEMs be written "at a 6th-grade level using Simple Measure of Gobbledygook (SMOG) readability formula." We then compared responses' quality (DISCERN questionnaire, Patient Education Materials Assessment Tool (PEMAT)), readability (SMOG, Flesch-Kincaid Grading Level (FKGL)), and accuracy (Likert Misinformation scale). To assess the improvement of readability for existing online information, Prompt C requested LLM rewrite 20 resources from a Google search of keyword "childhood glaucoma" to the American Medical Association-recommended "6th-grade level." Rewrites were compared on key metrics such as readability, complex words (≥3 syllables), and sentence count. RESULTS: All 3 LLM generated PEMs that were of high quality, understandability, and accuracy (DISCERN≥4, ≥70% PEMAT understandability, Misinformation score=1). Prompt B responses were more readable than Prompt A responses for all 3 LLM (p≤0.001). ChatGPT-4 generated the most readable PEMs compared to ChatGPT-3.5 and Bard (p≤0.001). Although Prompt C responses showed consistent reduction of mean SMOG and FKGL scores, only ChatGPT-4 achieved the specified 6th-grade reading level (4.8 ± 0.8 and 3.7 ± 1.9, respectively). CONCLUSION: LLMs can serve as strong supplementary tools in generating high quality, accurate, and novel PEMs, and improving the readability of existing PEMs on childhood glaucoma.

Blind Spots in Therapy: Unveiling Drug-Induced Angle-Closure Glaucoma Through a National Analysis.

OBJECTIVE: To identify and quantify medications causing angle-closure glaucoma through the FDA Federal Adverse Event Reporting System (FAERS). DESIGN: National, retrospective database analysis. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: 11,737,133 total adverse event reports from the FDA Federal Adverse Event Reporting System (FAERS) database 2004-2022Q3, which included 1,629 reports of angle-closure glaucoma. METHODS: Drugs associated with reports of angle-closure glaucoma were identified in FAERS. To ascertain if these reports yielded statistically significant signals, we used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC) as a part of a disproportionality analysis. We considered a signal to be detected when all four disproportionality analysis metrics were positive. RESULTS: We identified a total of 1,629 adverse event reports linked to 611 suspected drugs over the course of 20 years (2004-2023Q3). Frequently reported drugs included topiramate (520 reports) and citalopram (69 reports), amongst many others. 18 medications yielded a positive signal, including lesser-known medications like olanzapine, phentermine, and ranibizumab. Tropicamide exhibited the most robust statistical significance (n=18; PRR: 164.263; ROR (95% CI): 167.95 (104.994-268.655); EBGM (EBGM05): 162.421 (109.5); IC (IC05): 7.344 (4.591)), while acetazolamide was the second strongest (n=51; PRR: 113.088; ROR 95% CI: 114.782 (86.665-152.021); EBGM (EBGM05): 109.506 (86.501); IC (IC05): 6.775 (5.115)). CONCLUSION: Drug-induced glaucoma included both well-known medications such as topiramate as well as lesser-known medications such as olanzapine, phentermine, and ranibizumab. Clinician awareness of these findings is important.

Assessing the Reliability of Facial Feminization Content on Social Media and Its Impact on the Dissemination of Misinformation.

BACKGROUND: The surge in social media usage has transformed the dissemination and consumption of healthcare information, notably impacting plastic surgery and cosmetic specialties. This study focuses on the influence of social media, particularly Instagram and TikTok, in shaping perceptions of individuals seeking facial feminization (FF) procedures. METHODS: Using the validated DISCERN scale, we assessed the reliability and accuracy of FF content on TikTok and Instagram. The study also analyzed the relationship between content reliability on engagement metrics (likes, comments, views) and the type of content shared (educational, testimonial, promotional). RESULTS: The analysis encompassed 225 TikTok videos and 75 Instagram posts. TikTok content showed 9.33% as "very poor," 66.2% as "poor," 22.6% as "fair," and only 1.33% as "excellent." Similarly, Instagram content demonstrated 14.67% as "very poor" and 69.33% as "poor," with no content rated as "good" or "excellent." Educational content received higher reliability scores on both platforms. TikTok engagement metrics showed lower reliability ratings correlating with more views, comments, and likes. CONCLUSION: The study underscores the critical role of social media in shaping patient perspectives on FF procedures. The prevalence of inaccurate information necessitates a focus on responsible engagement by healthcare professionals, aiming to provide accurate, educational content that aligns with patients' informational needs and ultimately enhances surgical outcomes.

Oxidation of Molybdenum-Based Single-Metallic/bimetallic Carbide MXenes in Aqueous Suspensions: Mechanistic Insights.

Molybdenum carbide MXenes have garnered considerable attention in electronics, energy storage, and catalysis. However, they are prone to oxidative degradation, but the associated mechanisms have not been systematically explored. Therefore, the oxidation mechanisms of Mo-based single-metallic/bimetallic carbide MXenes including Mo2CTx, Mo2TiC2Tx, and Mo2Ti2C3Tx in aqueous suspensions were investigated for the first time in this study. Similar to Ti3C2Tx MXene, Mo-based MXenes were found to undergo oxidative degradation in their aqueous dispersions, leading to the disruption of their crystal structure and subsequent loss of optical and electronic properties. Notably, the Mo2CTx MXene deviated from this typical oxidation behavior as it produced an amorphous product with Mo ions instead of highly crystalline Mo-oxides during oxidation. Similarly, the Mo2TiC2Tx and Mo2Ti2C3Tx MXenes did not yield crystalline Mo-oxides; instead, they produced highly crystalline anatase TiO2 and a Mo-ion-containing amorphous product simultaneously. Furthermore, high-temperature annealing of the oxidized Mo2CTx MXene powder at 800 °C transformed the amorphous Mo-containing product into highly crystalline MoO2 crystals. These findings highlight the unconventional oxidation behavior of Mo-based MXenes, which suggests that the formation of crystalline Mo-based oxides requires a higher activation energy during oxidation than that of TiO2. The unique oxidative pathway reported herein can help elucidate the oxidation mechanisms of Mo-based MXene dispersions and their products. The insights from this study can pave the way for fundamental studies in academia as well as broaden the applications of Mo-based MXenes in various industries.

Large-scale annotated dataset for cochlear hair cell detection and classification.

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

Continuous Wave Transscleral Cyclophotocoagulation and Endoscopic Cyclophotocoagulation in Childhood Glaucoma: A Meta-analysis.

PURPOSE: To report the outcomes of continuous wave-transscleral cyclophotocoagulation (TS-CPC) and endoscopic cyclophotocoagulation (ECP) in childhood glaucoma. METHODS: We performed a systematic search of relevant databases. We collected data on age, follow-up duration, type of glaucoma, previous surgical interventions, preoperative and postoperative intraocular pressure (IOP), preoperative and postoperative number of glaucoma medications, adverse events, number of sessions, and success rates at different time points. The main outcome measures are the amount of IOP and glaucoma medication reduction. RESULTS: We included 17 studies studying 526 patients (658 eyes); 11 evaluated the effectiveness of TS-CPC (268 patients, 337 eyes), 5 evaluated ECP (159 patients, 197 eyes), and one study compared both techniques (56 patients, 72 eyes for TS-CPC vs. 43 patients, 52 eyes for ECP). The median duration of follow-up was 28 months in the TS-CPC group and 34.4 months in the ECP group. The mean number of treatment sessions was 1.7 in the TS-CPC and 1.3 in the ECP. In the TS-CPC group, the mean IOP was significantly reduced from 31.2±8 to 20.8±8 mmHg at the last follow-up (P<0.001). The mean number of glaucoma medications was reduced from 2.3±1.3 to 2.2±1.3 (P=0.37). In the ECP group, there was also a significant reduction in the mean IOP from 32.9±8 mmHg with a mean of 1.7±0.7 glaucoma medications to 22.6±9.8 mmHg (P<0.0001) on 1.2±1.1 medications (P=0.009) at the last follow-up. CONCLUSION: Both TS-CPC and ECP were effective in reducing the IOP and glaucoma medications in childhood glaucoma. Multiple treatment sessions were required.

Analysis of environmental factors influencing endemic cholera risks in sub-Saharan Africa.

The recurring cholera outbreaks in sub-Saharan Africa are of growing concern, especially considering the potential acceleration in the global trend of larger and more lethal cholera outbreaks due to the impacts of climate change. However, there is a scarcity of evidence-based research addressing the environmental and infrastructure factors that sustain cholera recurrence in Africa. This study adopts a statistical approach to investigate over two decades of endemic cholera outbreaks and their relationship with five environmental factors: water provision, sanitation provision, raising temperatures, increased rainfall and GDP. The analysis covers thirteen of the forty-two countries in the mainland sub-Saharan region, collectively representing one-third of the region's territory and half of its population. This breadth enables the findings to be generalised at a regional level. Results from all analyses consistently associate water provision with cholera reduction. The stratified model links increased water provision with a reduction in cholera risk that ranged from 4.2 % to 84.1 % among eight countries (out of 13 countries) as well as a reduction of such risk that ranged from 9.8 % to 68.9 % when there is increased sanitation provision, which was observed in nine countries (out of 13). These results indicate that the population's limited access to water and sanitation, as well as the rise in temperatures, are critical infrastructure and environmental factors contributing to endemic cholera and the heightened risk of outbreaks across the sub-Saharan region. Therefore, these are key areas for targeted interventions and cross-border collaboration to enhance resilience to outbreaks and lead to the end of endemic cholera in the region. However, it is important to interpret the results of this study with caution; hence, further investigation is recommended to conduct a more detailed analysis of the impact of infrastructure and environmental factors on reducing cholera risk.

DNA-based assay for calorimetric determination of protein concentrations in pure or mixed solutions.

It was recently reported that values of the transition heat capacities, as measured by differential scanning calorimetry, for two globular proteins and a short DNA hairpin in NaCl buffer are essentially equivalent, at equal concentrations (mg/mL). To validate the broad applicability of this phenomenon, additional evidence for this equivalence is presented that reveals it does not depend on DNA sequence, buffer salt, or transition temperature (Tm). Based on the equivalence of transition heat capacities, a calorimetric method was devised to determine protein concentrations in pure and complex solutions. The scheme uses direct comparisons between the thermodynamic stability of a short DNA hairpin standard of known concentration, and thermodynamic stability of protein solutions of unknown concentrations. Sequences of two DNA hairpins were designed to confer a near 20°C difference in their Tm values. In all cases, evaluated protein concentrations determined from the DNA standard curves agreed with the UV-Vis concentration for monomeric proteins. For multimeric proteins evaluated concentrations were greater than determined by UV-Vis suggesting the calorimetric approach can also be an indicator of molecular stoichiometry.

Hyphema and vitreous hemorrhage after micropulse cyclophotocoagulation a case report.

INTRODUCTION: We present two cases of vitreous hemorrhage after micropulse cyclophotocoagulation one of which had concurrent hyphema. To the best of our knowledge, these are the first cases of vitreous hemorrhage due to micropulse CPC in the United States. CASE DESCRIPTION: The first case is an 82-year-old woman with bilateral severe primary open angle glaucoma. BCVA in the right eye was 20/25, and 10-2 Humphrey visual field showed severe peripheral defects. The patient underwent MPCPC of the right eye and at one week, a settled 2 mm hyphema and vitreous hemorrhage confirmed by B-scan were noted. At three months, the patient had a BCVA of 20/80 with an IOP of 12 and retina consultation deferred a PPV. The second case is of a patient with bilateral moderate stage POAG who underwent MPCPC in both eyes. His original VA was 20/200 bilaterally. At 2 weeks, RE VA was count fingers at one foot and LE was 20/150-1. At two months, a RE B scan revealed dense vitreous opacities. Retina consultation revealed vitreous hemorrhage but a PPV was deferred. CONCLUSION: Clinicians should be aware of the risks of bleeding and the potential need for additional surgical interventions after MPCPC.

Ophthalmologic Presentations of Incontinentia Pigmenti.

Purpose: To characterize treatments and outcomes in incontinentia pigmenti. Methods: Cases of incontinentia pigmenti were consecutively identified from a retina practice. Inclusion criteria were patients with incontinentia pigmenti with at least 6 months of follow-up. All patients had a full ophthalmic examination, including imaging with widefield fundus photography and widefield fluorescein angiography. Eyes with areas of avascular retina were treated with laser photocoagulation (except for 1 eye with mild changes). Results: Thirty-six eyes of 18 patients with incontinentia pigmenti were included. The median age at presentation was 11 months. On presentation, 7 eyes had a visual acuity (VA) of 20/40 or better and 3 eyes had VA of 20/50 to 20/100. The remaining 26 eyes could fix and follow or had at least light perception (LP) VA given the patients' young age. Of the 36 eyes, 20 (56%) had retinal involvement. The mean follow-up for treated patients was 6.9 years. Seventy-four percent of treated eyes required 1 laser session only. No eye that received laser treatment subsequently developed a retinal detachment. Of the 26 eyes with initial fix-and-follow or LP VA, 12 had Snellen or Allen VA testing at follow-up. Nine of these eyes had a follow-up VA of 20/40 or better. Of 10 eyes with a Snellen or Allen VA recorded at the initial visit, 9 had a final VA that was the same or improved. Conclusions: Laser photocoagulation was effective in treating patients with retinal manifestations of incontinentia pigmenti. Except for 1 eye, VA remained stable at the final follow-up.

A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss.

Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met.

Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Corneal Hysteresis as a Marker for Patients with Secondary Glaucoma.

PURPOSE: To investigate and compare the association of corneal hysteresis (CH) in patients with secondary glaucoma to control patients and patients with primary open-angle glaucoma (POAG). Additionally, to determine the consistency of CH measurements in patients with secondary glaucoma. METHODS: A total of 84 patients (121 eyes) were prospectively included in this study. Twenty-three patients (46 eyes) were healthy controls, 24 patients (40 eyes) were diagnosed with POAG, and 27 patients (35 eyes) were diagnosed with a form of secondary glaucoma. CH and intraocular pressure (IOP) were measured using the Ocular Response Analyzer. Three measurements per eye were performed and used for the analysis and to determine fluctuations in CH data. One-way ANOVA with post-hoc Bonferroni analysis and Chi-Squared testing was done to determine differences between groups. RESULTS: All patients were matched for age. Patients in both POAG and secondary glaucoma groups were matched for age and IOP. All groups had similar sex and racial compositions as well as similar proportions of diabetes, hypertension, and hyperlipidemia. CH was lower (p < .05) in patients with POAG (9.32 ± 1.64) and secondary glaucoma (7.89 ± 3.18) when compared to healthy controls (11.16 ± 1.60). Fluctuations in CH measurements were minimal in all groups. Further analysis of the secondary glaucoma group revealed no differences in CH between different types of secondary glaucoma (p > .05). CONCLUSION: Patients with secondary glaucoma have lower CH when compared to POAG or control groups. The ORA exhibits precision of CH measurements for control, POAG, and secondary glaucoma groups, making it a reliable tool in management of secondary forms of glaucoma.

Unlocking the Potential of Porous Bi2Te3-Based Thermoelectrics Using Precise Interface Engineering through Atomic Layer Deposition.

Porous thermoelectric materials offer exciting prospects for improving the thermoelectric performance by significantly reducing the thermal conductivity. Nevertheless, porous structures are affected by issues, including restricted enhancements in performance attributed to decreased electronic conductivity and degraded mechanical strength. This study introduces an innovative strategy for overcoming these challenges using porous Bi0.4Sb1.6Te3 (BST) by combining porous structuring and interface engineering via atomic layer deposition (ALD). Porous BST powder was produced by selectively dissolving KCl in a milled mixture of BST and KCl; the interfaces were engineered by coating ZnO films through ALD. This novel architecture remarkably reduced the thermal conductivity owing to the presence of several nanopores and ZnO/BST heterointerfaces, promoting efficient phonon scattering. Additionally, the ZnO coating mitigated the high resistivity associated with the porous structure, resulting in an improved power factor. Consequently, the ZnO-coated porous BST demonstrated a remarkable enhancement in thermoelectric efficiency, with a maximum zT of approximately 1.53 in the temperature range of 333-353 K, and a zT of 1.44 at 298 K. Furthermore, this approach plays a significant role in enhancing the mechanical strength, effectively mitigating a critical limitation of porous structures. These findings open new avenues for the development of advanced porous thermoelectric materials and highlight their potential for precise interface engineering through the ALD.