Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion.

Transporting epithelial cells build apical microvilli to increase membrane surface area and enhance absorptive capacity. The intestinal brush border provides an elaborate example with tightly packed microvilli that function in nutrient absorption and host defense. Although the brush border is essential for physiological homeostasis, its assembly is poorly understood. We found that brush border assembly is driven by the formation of Ca(2+)-dependent adhesion links between adjacent microvilli. Intermicrovillar links are composed of protocadherin-24 and mucin-like protocadherin, which target to microvillar tips and interact to form a trans-heterophilic complex. The cytoplasmic domains of microvillar protocadherins interact with the scaffolding protein, harmonin, and myosin-7b, which promote localization to microvillar tips. Finally, a mouse model of Usher syndrome lacking harmonin exhibits microvillar protocadherin mislocalization and severe defects in brush border morphology. These data reveal an adhesion-based mechanism for brush border assembly and illuminate the basis of intestinal pathology in patients with Usher syndrome. PAPERFLICK:

IMPLICATIONS OF COMPLETE POSTERIOR VITREOUS DETACHMENT IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION.

BACKGROUND/PURPOSE: To evaluate the status of the posterior vitreous hyaloid on presenting optical coherence tomography images of the macula and its relationship to clinical characteristics, treatment patterns, and outcomes in eyes with central retinal vein occlusion. METHODS: This is a retrospective longitudinal cohort study of consecutive patients with acute, treatment-naive central retinal vein occlusion diagnosed between 2009 and 2021 who had at least 12 months of follow-up. Clinical characteristics, treatment patterns, and outcomes were analyzed between eyes stratified based on the presence or absence of a complete posterior vitreous detachment (PVD) on optical coherence tomography at presentation. RESULTS: Of 102 acute, treatment-naive central retinal vein occlusions identified, 52 (51%) had complete PVD at presentation and 50 (49%) did not. Central subfield thickness was significantly lower in those with complete PVD (12 months: 284.9 ± 122.9 µ m vs. 426.8 ± 286.4 µ m, P < 0.001; last follow-up: 278 ± 127.9 vs. 372.8 ± 191.0 µ m, P = 0.022). One-year intravitreal injection burden was significantly less for those with a complete PVD than those without (5.1 ± 3.6 injections vs. 6.7 ± 3.3 injections, P = 0.013). CONCLUSION: Central retinal vein occlusion with complete PVD on presentation had significantly lower central subfield thickness and 1-year injection burden. Assessment of the vitreomacular interface in central retinal vein occlusion may serve as a prognostic imaging biomarker.

The effect of childbirth trauma on willingness to donate milk in women following perinatal loss: The mediating role of resilience.

Limited studies have been conducted on Chinese women's willingness to donate milk following perinatal loss. In this study, we explore the relationship among childbirth trauma, willingness to donate milk, and resilience in women following perinatal loss, and the mediating effect of resilience between childbirth trauma and willingness to donate milk. A cross-sectional study was carried out throughout 4 months. We used convenience sampling methods and recruited 241 women following a perinatal loss from eight tertiary hospitals in Sichuan Province, China. Participants completed four questionnaires during a face-to-face individual interview: the general information questionnaire, the Willingness to Donate Milk Scale (WMDS), the City Birth Trauma Scale, and the Brief Resilience Scale. SPSS 20.0 was used to analyze the collected data. In our study, childbirth trauma was negatively correlated with the total and each dimension score of WMDS (p < 0.001). Resilience was positively correlated with the total and each dimension score of WMDS (p < 0.001). Resilience partially mediated the relationship between childbirth-related symptoms and willingness to donate milk (ß = -0.38, 95% confidence interval [CI]: -0.50 to -0.26), which accounted for 69.03% of the total effect. Resilience partially mediated the relationship between general symptoms and willingness to donate milk (ß = -0.31, 95% CI: -0.40 to -0.21), which accounted for 66.89% of the total effect. Resilience partially mediated the relationship between childbirth trauma and willingness to donate milk in women following perinatal loss. Our findings suggest that resilience can play a significant role in mediating the relationship between childbirth trauma and willingness to donate milk in women following perinatal loss. These results could help healthcare professionals design interventions for physical and mental recovery after perinatal loss.

A Novel missense mutation of COL2A1 gene in a large family with stickler syndrome type I.

Stickler syndrome type I (STL1, MIM 108300) is characterized by ocular, auditory, skeletal and orofacial manifestations. Nonsyndromic ocular STL1 (MIM 609508) characterized by predominantly ocular features is a subgroup of STL1, and it is inherited in an autosomal dominant manner. In this study, a novel variant c.T100>C (p.Cys34Arg) in COL2A1 related to a large nonsyndromic ocular STL1 family was identified through Exome sequencing (ES). Bioinformatics analysis indicated that the variant site was highly conserved and the pathogenic mechanism of this variant may involve in affected structure of chordin-like cysteine-rich (CR) repeats of ColIIA. Minigene assay indicated that this variant did not change alternative splicing of exon2 of COL2A1. Moreover, the nonsyndromic ocular STL1 family with 16 affected members showed phenotype variability and certain male gender trend. None of the family members had hearing loss. Our findings would expand the knowledge of the COL2A1 mutation spectrum, and phenotype variability associated with nonsyndromic ocular STL1. Search for genetic modifiers and related molecular pathways leading to the phenotype variation warrants further studies.

Myasthenia Gravis Presenting as Lutz Posterior Internuclear Ophthalmoplegia.

Myasthenia gravis can mimic central neurological disorders and should be considered in the differential diagnosis of any form of pupil-sparing ophthalmoplegia. We report an unusual manifestation of myasthenia gravis presenting as bilateral internuclear ophthalmoplegia (INO) of abduction, sometimes referred to as Lutz posterior INO (or reverse INO).

Retrospective outcome analyses for headaches in a pain rehabilitation interdisciplinary program.

BACKGROUND: Incapacitating chronic migraine and other severe headaches can have significant impact on peoples' lives, including family and occupational functioning. Although a number of reports have investigated the prevalence and medical treatment of chronic headache, few have reported on the efficacy of treating these disorders within a comprehensive, intensive chronic pain rehabilitation program (CPRP), instead of a headache-specific program. CPRPs provide treatment of headache by focusing not only on physical pain, but also its association with impaired mood and function. METHODS: We examined the efficacy of CPRP in patients with chronic headache via a retrospective analysis of 123 patients (76.4% female), ages 21 to 85, who completed the CPRP at the Cleveland Clinic between January 2007 and December 2011, and were diagnosed using International Classification of Headache Disorders, 2nd edition and International Classification of Headache Disorders, 2nd edition revision, with migraine or headache as a major complaint. Outcome measures included: pain intensity scores present at the moment of questioning where 10 is the maximal (0-10/10), Depression Anxiety Stress Scale (DASS) scores, (measuring mood), and Pain Disability Index scores (measuring function). Repeated measures t-tests were used. RESULTS: Average pain score on admission was 6.4, and 3.4 upon discharge. Average function on admission was moderately impaired, and normalized on discharge. The average depression score was in the moderate range, and had normalized on discharge. The average anxiety score on admission was in the severe range and was in the mild range on discharge. CONCLUSIONS: Results indicate that individuals had statistically and clinically meaningful improvement in pain, mood, and function. Data suggest that an interdisciplinary CPRP approach for patients diagnosed with headache can be effective in helping to decrease pain, as well as normalize mood and function. Thus, CPRPs serve as an alternative treatment to multidisciplinary headache programs, interventional pain techniques, and primary care standard headache care.

Production of cost-competitive bioethanol and value-added co-products from distillers' grains: Techno-economic evaluation and environmental impact analysis.

Here, Baijiu distillers' grains (BDGs) were employed in biorefinery development to generate value-added co-products and bioethanol. Through ethyl acetate extraction at a 1:6 solid-liquid ratio for 10 h, significant results were achieved, including 100 % lactic acid and 92 % phenolics recovery. The remaining BDGs also achieved 99 % glucan recovery and 81 % glucan-to-glucose conversion. Simultaneous saccharification and fermentation of remaining BDGs at 30 % loading resulted in 78.5 g bioethanol/L with a yield of 94 %. The minimum selling price of bioethanol varies from $0.149-$0.836/kg, contingent on the co-product market prices. The biorefinery processing of one ton of BDGs caused a 60 % reduction in greenhouse gas emissions compared to that of the traditional production of 88 kg corn-lactic acid, 70 kg antioxidant phenolics, 234 kg soybean protein, and 225 kg corn-bioethanol, along with emissions from BDG landfilling. The biorefinery demonstrated a synergistic model of cost-effective bioethanol production and low-carbon emission BDGs treatment.

Variant and clinical landscape of Leber hereditary optic neuropathy based on 1516 families with mtDNA variants in a tertiary centre.

AIMS: To investigate the clinical characteristics of Leber hereditary optic neuropathy (LHON) with mtDNA primary mutations to better understand features associated with prognosis. METHODS: This study enrolled 1540 LHON patients from 1516 unrelated families genetically confirmed by Sanger or whole-mitochondrial sequencing between 1997 and 2022. The spectrum of variants was summarised and compared in different ethnic groups. Clinical data from outpatients were collected, including onset age, disease course, optic disc categories and the corresponding visual acuity. RESULTS: Of the 1516 LHON families, 13 pathogenic mtDNA variants were detected, in which the proportion of m.11778G>A, m.3460G>A and m.3635G>A was significantly different from non-East Asians (p<0.0001). About 95% (1075/1131) of patients were between 8 and 40 years old at onset, with a median onset age of 16. The eyes of m.14484T>C patients presented with better visual acuity and slower progression across patients with different onset ages and initial severity. Eyes (N=439) with available fundus images were divided into four categories (C1-C4). The progression grades were derived from the category and the corresponding time course, where a higher grade (C3-C4 within 1 year) was associated with greater visual impairment than a lower grade (C1-C2 over 1 year) (p=4.60E-05) . A prognostic matrix showed that later onset and a higher progression grade are associated with higher risk of blindness. CONCLUSION: Compared with non-East Asians, Chinese LHON patients had higher proportions of m.11778G>A and m.3635G>A and lower m.3460G>A mutations. A novel progression grade derived from optic disc category was proposed. The prognostic matrix indicated that lower grade and younger-onset age are the most favourable prognostic factors.

Oxygen influences spatial heterogeneity and microbial succession dynamics during Baijiu stacking process.

The spontaneous solid-state stacking process (SSSP) of Baijiu is an environmentally friendly and cost-effective process for enriching and assembling environmental microorganisms to guarantee the subsequent fermentation efficiency. In this study, how SSSP create spatial heterogeneity of stacking piles were found through spatiotemporal sampling. The degree of difficulty in oxygen exchange categorizes the stacking pile into depleted (≤4%), transitional (4 %-17 %), and enriched (≥17 %) oxygen-defined layers. This results in variation in succession rates (Vdepleted > Vtransitional > Venriched), which accelerates spatial heterogeneity during SSSP. As a dominant species (65 %-99 %) in depleted and transitional layers, Acetilactobacillus jinshanensis can rapidly reduce oxygen disturbance by upregulating poxL and catE, that sustains spatial heterogeneity. The findings demonstrated the value of oxygen control in shaping spatial heterogeneity during SSSP processes, which can create specific functional microbiome. Adding spatial heterogeneity management will help achieve more precise control of such solid-state fermentation systems.

Asymmetric Purtscher-Like Retinopathy Caused by a Hypertensive Emergency and Undiagnosed Type 2 Diabetes.

Purpose: To report a case of Purtscher-like retinopathy (PLR) in the setting of a hypertensive emergency and undiagnosed type 2 diabetes mellitus (DM). Methods: A case was analyzed. Results: A 29-year-old, obese, hypertensive man presented with a 10-day history of progressive vision loss in the left eye with no history of trauma. The visual acuity was 20/25 OD and hand motions OS. A fundus examination showed dilated, tortuous veins; dot-blot and flame hemorrhaging; numerous cotton-wool spots; and polygonal areas of retinal whitening consistent with Purtscher flecken in the right eye and a vitreous hemorrhage in the left eye. The blood pressure was 226/125 mm Hg, and the hemoglobin A1c was 11.6%. The patient's presentation was concerning for a hypertensive emergency and type 2 DM as the etiology for the ocular findings. Conclusions: The presence of one condition in association with PLR does not exclude the presence of another concurrent etiology.

Causal complexity of environmental pollution in China: a province-level fuzzy-set qualitative comparative analysis.

Environmental problems are endowed with the causal complexity of multiple factors. Traditional quantitative research on the influencing mechanism of environmental pollution has tended to focus on the marginal effects of specific influencing factors but generally neglected the multiple interaction effects between factors (especially three or more). Based on the panel data of 30 Chinese provinces between 2011 and 2020, this study employs fuzzy set qualitative comparative analysis (fsQCA) - which can provide a fine-grained insight into the causal complexity of environmental issues - to shed light on the influencing mechanism of environmental pollution. The results show that there are several different configurations of pollution drivers which lead to high pollution or low pollution in provinces, confirming the multiple causality, causal asymmetry, and equifinality of environmental pollution. Furthermore, the combination effect of advanced industrial structure, small population size, and technological advance is significant in achieving a state of green environment compared to environmental regulation factors. In addition, spatiotemporal analysis of the configurations indicates that strong path dependencies and spatial agglomeration exist in current local environmental governance patterns. Finally, according to our findings, targeted policy recommendations are provided.

Non-Pharmaceutical Interventions against COVID-19 Causing a Lower Trend in Age of LHON Onset.

Leber hereditary optic neuropathy (LHON) is a monogenic but multifactorial disease vulnerable to environmental triggers. Little is known about how LHON onset changed during the COVID-19 pandemic and how non-pharmaceutical interventions (NPHIs) against COVID-19 impact LHON onset. One hundred and forty-seven LHON patients with the m.11778G>A mutation complaining of vision loss were involved between January 2017 and July 2022. The onset time points, age of onset, and possible risk factors were evaluated. Analyses were conducted among 96 LHON patients in the Pre-COVID-19 group and 51 in the COVID-19 group. The median (IQR) age of onset decreased significantly from 16.65 (13.739, 23.02) in pre-COVID-19 to 14.17 (8.87, 20.29) during COVID-19. Compared with the Pre-COVID-19 group, the COVID-19 group exhibited bimodal distribution with an additional peak at six; the first quarter of 2020 also witnessed a relatively denser onset, with no subsequent second spike. NPHIs against COVID-19 significantly changed patients' lifestyles, including higher secondhand smoke exposure (p < 0.001), adherence to masks (p < 0.001), reduction in time spent outdoors for leisure (p = 0.001), and prolonged screen time (p = 0.007). Multivariate logistic regression revealed that secondhand smoke exposure and mask-wearing were independent risk factors of younger LHON onset. Lower age of onset of LHON appeared after the breakout of the COVID-19 pandemic, and novel risk factors were detected, including secondhand exposure and long mask-wearing. Carriers of LHON mtDNA mutations, especially teenagers or children, should be advised to avoid secondhand smoke exposure and there are possible adverse outcomes of longer mask-wearing.

FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population.

Variants in FDXR reportedly cause autosomal recessive auditory neuropathy and optic atrophy, expanding to retinal dystrophy. This study aimed to further clarify associated phenotypes. FDXR variants were selected from our in-house whole-exome sequencing dataset of 6397 families with different eye conditions. The clinical data of the identified patients were summarized. Biallelic pathogenic or likely pathogenic FDXR variants were identified in 11 unrelated patients, including 14 missense variants of which 10 were novel. Fundus observation showed complete optic disc pallor, silver wiring or severe attenuation of retinal vessels, and varying degrees of generalized retinal degeneration. Before the detection of FDXR variants, four patients were clinically diagnosed as congenital amaurosis due to the presence of nystagmus a few months after birth, while seven were diagnosed as early-onset severe retinal dystrophy due to the presence of nyctalopia and/or poor vision in early childhood. Biallelic FDXR variants are a frequent cause of congenital or early-onset severe retinal dystrophy, especially for patients with severe optic atrophy and retinal dystrophy in early childhood.

A novel UVA-associated circUBE2I mediates ferroptosis in HaCaT cells.

Alternative splicing of precursor messenger RNA (pre-mRNA), including linear splicing and back splicing, produces multiple isoforms that lead to diverse cell fates in response to stimuli including ultraviolet radiation (UVR). Although UVR-induced linear gene splicing has been extensively studied in skin cells, the UVR-induced gene back-splicing events that lead to the production of circular RNAs (circRNAs) have not been thoroughly investigated. The present study used circRNA transcriptome sequencing to screen the differentially expressed circRNAs in human keratinocytes (HaCaT) after UVA irradiation. A total of 312 differentially expressed circRNAs were found in HaCaT cells post-UVR. Among the UVA-induced differentially expressed circRNAs, circUBE2I-a novel circRNA formed by exons 2-6 of the UBE2I gene-was the most significantly upregulated circRNA. RT-qPCR assay further confirmed the increase of circUBE2I level in HaCaT cells after UVA irradiation or H2 O2 treatment. RNase R digestion experiment revealed the stability of circUBE2I. Overexpression of circUBE2I in keratinocytes induced ferroptosis after UVA or H2 O2 , preventable by the ferroptosis inhibitor ferrostatin-1. Our study provides new insights into the role of circular RNAs in UVA-induced skin cell damage and suggests that circUBE2I could be a therapeutic target in UVR-aroused ferroptosis in skin cells.

Evaluation of Two-Dimensional (2D) versus Three-Dimensional (3D) Video Tutorials in Cataract Surgery for New Trainees.

Purpose Microscopic ophthalmic surgery requires an understanding of three-dimensional (3D) spaces within the eye. Recently, there has been an increase in 3D video training tools in health care. Studies have evaluated the efficacy of 3D tutorials in general surgery, but little has been published within ophthalmology. We present a randomized study evaluating differences in surgically naïve trainees after watching either a 2D or 3D phacoemulsification tutorial. Design This was a double-blind, randomized study. A group of third and fourth year medical students at our institution were randomized with stratified randomization based on prior surgical courses to control for differences in baseline surgical skill. The two study arms were watching 2D or 3D instructional videos on phacoemulsification (Richard Mackool). Methods Participants received a preliminary survey and participated in an hour-long microscopic surgery session. During the session, participants performed tasks evaluating baseline microscopic spatial awareness and surgical skill. The students were then instructed to watch either a 2D or 3D video on phacoemulsification based on their randomized study arm. During the postintervention session, participants performed the biplanar incision and capsulorhexis steps of cataract surgery discussed in the video on model eyes. Students were evaluated on speed and overall capsulorhexis quality. Results Thirty-one students qualified for the study and completed the microscopic surgery session. Students in both groups had similar baseline speed and quality of preintervention microscopic tasks ( p > 0.05 for all tasks). Postintervention, students randomized to the 3D video performed significantly faster than the 2D group for biplanar incision (11.1 ± 5.5 s vs. 20.7 ± 10.5 s, p = 0.001). There were no statistically significant differences found between the groups in capsulorhexis timing ( p = 0.12) or quality score ( p = 0.60). Conclusions 3D video surgical training tutorials may improve speed of certain steps of cataract surgery for surgically naïve ophthalmology trainees. Given the limited sample size of this study, further investigation of their effectiveness is warranted.

Quantitative Geometric Modeling of Blood Cells from X-ray Histotomograms of Whole Zebrafish Larvae.

Tissue phenotyping is foundational to understanding and assessing the cellular aspects of disease in organismal context and an important adjunct to molecular studies in the dissection of gene function, chemical effects, and disease. As a first step toward computational tissue phenotyping, we explore the potential of cellular phenotyping from 3-Dimensional (3D), 0.74 µm isotropic voxel resolution, whole zebrafish larval images derived from X-ray histotomography, a form of micro-CT customized for histopathology. As proof of principle towards computational tissue phenotyping of cells, we created a semi-automated mechanism for the segmentation of blood cells in the vascular spaces of zebrafish larvae, followed by modeling and extraction of quantitative geometric parameters. Manually segmented cells were used to train a random forest classifier for blood cells, enabling the use of a generalized cellular segmentation algorithm for the accurate segmentation of blood cells. These models were used to create an automated data segmentation and analysis pipeline to guide the steps in a 3D workflow including blood cell region prediction, cell boundary extraction, and statistical characterization of 3D geometric and cytological features. We were able to distinguish blood cells at two stages in development (4- and 5-days-post-fertilization) and wild-type vs. polA2 huli hutu ( hht ) mutants. The application of geometric modeling across cell types to and across organisms and sample types may comprise a valuable foundation for computational phenotyping that is more open, informative, rapid, objective, and reproducible.

Recession-Resection of the Vertical Rectus Muscles for Chin-up Vertical Abnormal Head Position Associated With Infantile Nystagmus Syndrome.

PURPOSE: To review the correction of chin-up abnormal head position (AHP) due to infantile nystagmus syndrome via surgery on the vertical rectus muscles, typically a combined recession-resection of these muscles. METHODS: This was a review of 6 patients who underwent surgical correction of chin-up vertical AHP in the context of infantile nystagmus syndrome at an academic institution. The correction of AHP, visual acuity, ductions, and ocular alignment were noted both preoperatively and postoperatively. The need for repeat surgery, induced strabismus, or correction of AHP were also noted. RESULTS: Six patients underwent surgery for chin-up AHP. A combined recession-resection of the vertical rectus muscles (bilateral inferior rectus muscle recession of 5 to 8 mm; bilateral superior rectus muscle resection of 7 to 8 mm) was performed in 4 of 6 patients, and isolated bilateral recession of the inferior rectus muscles was performed in the remaining 2 patients. Four of 6 patients (67%) achieved complete correction of their AHP at the last follow-up visit, with a mild residual chin-up AHP persisting in the other 2 patients. One patient developed large angle exotropia, one had restrictive hypertropia and horizontal plane null position, and another developed an incomitant horizontal strabismus with exotropia in right gaze. Reoperation was performed in the former 2 patients, with successful correction of the strabismus in each. CONCLUSIONS: Surgery on the vertical rectus muscles can reduce or eliminate a chin-up head position in patients with infantile nystagmus syndrome. Care should be taken to avoid producing a restriction of depression in abduction if the amount of resection is too large. [J Pediatr Ophthalmol Strabismus. 2022;59(6):410-415.].

Machine learning for predicting the treatment effect of orthokeratology in children.

Purpose: Myopia treatment using orthokeratology (ortho-k) slows myopia progression. However, it is not equally effective in all patients. We aimed to predict the treatment effect of ortho-k using a machine-learning-assisted (ML) prediction model. Methods: Of the 119 patients who started ortho-k treatment between January 1, 2019, and January 1, 2022, 91 met the inclusion criteria and were included in the model. Ocular parameters and clinical characteristics were collected. A logistic regression model with least absolute shrinkage and selection operator regression was used to select factors associated with the treatment effect. Results: Age, baseline axial length, pupil diameter, lens wearing time, time spent outdoors, time spent on near work, white-to-white distance, anterior corneal flat keratometry, and posterior corneal astigmatism were selected in the model (aera under curve: 0.949). The decision curve analysis showed beneficial effects. The C-statistic of the predictive model was 0.821 (95% CI: 0.815, 0.827). Conclusion: Ocular parameters and clinical characteristics were used to predict the treatment effect of ortho-k. This ML-assisted model may assist ophthalmologists in making clinical decisions for patients, improving myopia control, and predicting the clinical effect of ortho-k treatment via a retrospective non-intervention trial.

Intra-arterial Chemotherapy as Primary Treatment for Cavitary Retinoblastoma: Excellent Response in Eight Tumors.

PURPOSE: The "cavitary" form of retinoblastoma has historically demonstrated minimal treatment response with intravenous chemoreduction, showing less robust regression and less reduction in tumor size. Intra-arterial chemotherapy (IAC) has been reported to more effectively treat retinoblastoma, allowing many previously unsalvageable eyes to now be saved. The purpose was to report treatment response of cavitary retinoblastoma tumors to IAC. DESIGN: Retrospective case series. PARTICIPANTS: Patients presenting with cavitary retinoblastoma who were treated with IAC. METHODS: Retrospective case series of all patients presenting with cavitary retinoblastoma between August 2014 and January 2019 who were treated with primary IAC. MAIN OUTCOME MEASURES: Tumor regression, recurrence, resolution of vitreous and subretinal seeds, number of treatments required, globe salvage, metastasis, and death. RESULTS: Eight cavitary retinoblastoma tumors in 6 eyes of 4 patients were treated with IAC. One hundred percent of the cavitary tumors regressed (8/8 tumors, in 6/6 eyes), and 100% of vitreous and subretinal seeds regressed, with 100% globe salvage. None of the tumors recurred, no patients developed metastases, and no patients died. Eyes were treated with a median of 4.5 cycles of IAC (range, 1-7), with fewer IAC treatments used in the later patients (1-3 treatments per eye for the most recent 3 eyes, compared with 6-7 treatments per eye for the earliest 3 eyes). Mean reduction in thickness was 73.4% (range, 59.7%-84.6%). Mean reduction in basal diameter was 45.5% (range, 24.8%-56.0%). CONCLUSIONS: Treatment with IAC results in regression of cavitary retinoblastoma, often with greater reduction in tumor size than has been reported previously with intravenous chemotherapy (IVC). Using up-front triple therapy (e.g., melphalan 0.4 mg/kg, carboplatin 50 mg, and topotecan 2 mg) and noting certain subtle signs of early regression can help to minimize unnecessary additional cycles of treatment.

Monascus pilosus YX-1125: An efficient digester for directly treating ultra-high-strength liquor wastewater and producing short-chain fatty acids under multiple-stress conditions.

Ultra-high-strength liquor wastewater (UHS-LWW) is rich in organic matter, and the required treatment is expensive. Here, an extremophilic strain Monascus pilosus YX-1125 was isolated for the direct conversion of UHS-LWW to short-chain fatty acids (SCFAs). Strain YX-1125 is an efficient SCFA producer with carbohydrate metabolic flexibility under multiple-stress conditions. Moreover, strain YX-1125 could tolerate up to 75 g/L, 100 g/L, and 50 g/L of ethanol, organic acids, and salt, respectively, without inhibition. In repeated-cycle fermentations, 17.8 g/L of butyric acid and 2.0 g/L of propionic acid were produced from UHS-LWW at the fifth cycle, which are the highest concentrations of wastewater-derived SCFAs reported to date. After SCFA recovery, a 98.9% COD reduction was achieved, which is estimated to reduce treatment costs by 91.7%. Results indicate that M. pilosus YX-1125 is a promising strain for the direct treatment of UHS-LWW, and for converting it into valuable biochemicals without any pre-treatment.