National registry of thoracoamniotic shunting using a double-basket catheter: A post-marketing surveillance registry of 295 patients with fetal hydrothorax.

OBJECTIVE: We report on the 1-year outcomes of fetuses who underwent thoracoamniotic shunting (TAS) with a double-basket catheter for fetal hydrothorax (FHT) using a national post-marketing surveillance registry. METHODS: This surveillance study was conducted for cases enrolled between 2011 and 2019. Preoperative, operative, and postoperative findings and outcomes had to be reported through the national surveillance website. RESULTS: Forty-three institutes enrolled 295 patients. In 60 patients, associated abnormalities were diagnosed after birth. Among the 235 patients with isolated hydrothorax, the survival rate at 1 year of age was 70.5%. Among these patients, 89% did not require oxygen or other respiratory support. The 1-year survival rate in complicated cases was 27%. Trisomy 21 was the most common associated problem (40%). Catheter associated problems, including dislocation (25%), obstruction (24%), and preterm rupture of the membranes (6%) were observed, but there were no severe maternal complications. TAS before 29.5 weeks of gestation (odds ratio [OR] 0.16) and skin edema and ascites (OR 0.06) were risk factors for death at one year, whereas appropriate shunt location for >28 days (OR 4.2) was a protective factor. CONCLUSION: We report a favorable survival rate in fetuses with isolated FHT treated with this double-basket catheter.

Peripapillary Atrophy Area as an Indicator of Glaucomatous Structural and Functional Progression.

Purpose: To determine whether peripapillary atrophy (PPA) area is an indicator of glaucomatous structural and functional damage and progression. Methods: In this retrospective longitudinal analysis from ongoing prospective study we qualified 71 eyes (50 subjects) with glaucoma. All subjects had a comprehensive ophthalmic examination, visual field (VF), and spectral-domain optical coherence tomography (OCT) testing in at least three visits. PPA was manually delineated on en face OCT optic nerve head scans, while observing the corresponding cross-sectional images, as the hyper-reflective area contiguous with the optic disc. Results: The mean follow-up duration was 4.4 ± 1.4 years with an average of 6.8 ± 2.2 visits. At baseline, PPA area was significantly associated only with VF's mean deviation (MD; P = 0.041), visual field index (VFI; P = 0.041), superior ganglion cell inner plexiform layer (GCIPL; P = 0.011), and disc area (P = 0.011). Longitudinally, PPA area was negatively and significantly associated with MD (P = 0.015), VFI (P = 0.035), GCIPL (P = 0.009), superior GCIPL (P = 0.034), and disc area (P = 0.007, positive association). Conclusions: Longitudinal change in PPA area is an indicator of glaucomatous structural and functional progression but PPA area at baseline cannot predict future progression. Translational Relevance: Longitudinal changes in peripapillary atrophy area measured by OCT can be an indicator of structural and functional glaucoma progression.

Impact of interpregnancy weight changes and perinatal outcomes: A retrospective study in Japan.

Previous studies have shown that interpregnancy weight fluctuations impact perinatal outcomes. In order to examine this in Japanese women, we analyzed the data of 2,861 women in their first and second pregnancies who delivered singletons between 2000 and 2022. We compared the second pregnancy perinatal outcomes of women whose interpregnancy body mass index (BMI) change was -1 to 1 unit with those of women whose BMI change was < -1 or ≥ 1 unit. An interpregnancy BMI change ≥ 1 unit was associated with an increased risk of developing gestational diabetes mellitus (adjusted odds ratio [aOR], 1.51; 95% confidence interval [CI], 1.18-1.95) and delivering a large for gestational age neonate (aOR, 1.67; 95% CI, 1.15-2.42) but a decreased risk of preterm birth (aOR, 0.66; 95% CI, 0.46-0.95). An interpregnancy BMI change < -1 unit was associated with a decreased risk of developing gestational diabetes mellitus (aOR, 0.51; 95% CI, 0.31-0.85). In a subgroup analysis of three groups divided according to prepregnancy BMI, interpregnancy BMI changes ≥ 1 unit in women with a BMI of < 18.5 kg/m2 before their first pregnancy were associated with a remarkable risk reduction of developing preterm birth (aOR, 0.30; 95% CI, 0.11-0.81). Interpregnancy BMI changes < -1 unit in women with a BMI of ≥ 25 kg/m2 before their first pregnancy were associated with a remarkable risk reduction of developing gestational diabetes mellitus (aOR, 0.33; 95% CI, 0.12-0.88). Weight gain during interpregnancy period was related to an increased risk of gestational diabetes mellitus and delivery of a large-for-gestational-age neonate, whereas weight loss was related to a decreased risk of developing gestational diabetes mellitus. These results indicate the importance of interpregnancy weight control as part of preconception care; therefore, women considering additional pregnancies should be educated on the importance of maintaining a healthy weight.

Efficacy and safety of a novel pain management device, AT-04, for endometriosis-related pain: study protocol for a phase III randomized controlled trial.

BACKGROUND: Endometriosis-related pain encompassing dysmenorrhea, dyspareunia, and chronic pelvic pain, reduces the quality of life in premenopausal women. Although treatment options for endometriosis alleviate this pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. The Angel Touch device (AT-04) is a portable magnetic fields irradiation device that incorporates a combination of mixed alternative magnetic fields at 2 kHz and 83.3 MHz. A phase III trial confirmed the efficacy and safety of AT-02, a prototype of AT-04, for pain relief in patients with fibromyalgia. METHODS: This is a phase III, multicenter, prospective, randomized, sham device-controlled, double-blind, parallel study. The participants will be premenopausal women aged > 18 years who have endometriosis-related pain with at least moderate severity. Considering dropouts, 50 participants have been deemed appropriate. Eligible women will be centrally registered, and the data center will randomly allocate them in a 1:1 ratio to the intervention and control groups. Women in the intervention group will receive electromagnetic wave irradiation generated by AT-04 and those who in the control group will wear a sham device for 16 weeks, and both groups will wear AT-04 for another 4 weeks. The primary outcome measure is the change in the Numeric Rating Scale score at 16 weeks compared with the baseline. Secondary outcome measures are efficacy for pelvic pain including dysmenorrhea and non-menstrual pain, and chronic pelvic pain not related to menstruation, dysmenorrhea, and dyspareunia, and improvement of quality of life during the study period. Safety will be evaluated by device defects and the frequency of adverse events. The study protocol has been approved by the Clinical Study Review Board of Chiba University Hospital, Chiba, Japan, and will be conducted in accordance with the principles of the Declaration of Helsinki and the Japanese Clinical Trials Act and relevant notifications. DISCUSSION: This study aims to develop a novel method of managing endometriosis-related pain. The AT-04 is an ultralow-invasive device that can be used without inhibiting ovulation, suggesting potential benefits to women of reproductive-age. Trial registration number Japan Registry of Clinical Trials (jRCTs032230278).

Endometriosis is a chronic inflammatory disorder that negatively impacts reproductive health via endometriosis-related pain, infertility, and endometriosis-associated ovarian cancer. Although current therapeutic options for endometriosis are effective for the endometriosis-related pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. This is the first randomized controlled trial to investigate the efficacy and safety of a novel portable pain management device, AT-04, that incorporates a combination of mixed alternating magnetic fields, for endometriosis-related pain. This is a multicenter, prospective, sham device-controlled, double-blind, parallel study. Enrolled women will have undergone standard hormonal treatment for endometriosis at baseline, and this allows for assessing whether the device remains effective when used in conjunction with existing treatment methods. The study also will explore the impact of AT-04 on reducing the size of ovarian endometriotic cysts that reflect the activity of endometriosis. The study reflects the strong desire by physicians to liberate women from the unbearable pain associated with endometriosis. The sole efficacy of AT-04 in treating endometriosis-related pain is difficult to evaluate as there is a possibility that menstrual cycles may influence the assessment of pain and quality of life. However, the study findings regarding the effectiveness of AT-04 for the treatment of endometriosis-related pain may benefit women with endometriosis who have pain that is not effectively relieved by other treatments. Consequently, it may contribute to the improvement of reproductive health within society.

Postpartum acute adrenal insufficiency of early-onset Sheehan syndrome: A case series study in a single center.

AIM: To identify the symptoms and relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. METHODS: We retrospectively reviewed the charts of 125 women admitted to our intensive care unit because of postpartum hemorrhage between January 2011 and December 2021. Three women developed acute adrenal insufficiency. We investigated the total blood loss, shock status, consciousness level upon arrival, and intensive care provided to the women. We also analyzed the symptoms and laboratory data that led to the diagnosis of acute adrenal insufficiency. Continuous variables were presented by median (minimum-maximum). RESULTS: The medians and ranges of age, total blood loss, and shock index [heart rate/systolic blood pressure] on admission were 33.1 (17.2-45.3) years, 3351 (595-20 260) g, and 0.94 (0.55-2.94), respectively. Seven women were older than 40 years, 28 experienced >5000 g blood loss, 17 had shock index >1.5, 27 had impaired consciousness upon arrival, and 15 underwent hysterectomy. Women who developed acute adrenal insufficiency were <40 years old and had a bleeding volume of over 5000 g, impaired consciousness upon arrival, and had undergone hysterectomy. They had experienced lactation failure, presented with hyponatremia-related symptoms on postpartum days 8-9, experienced general malaise, headache, and impaired consciousness, and showed severe hyponatremia. CONCLUSIONS: Massive postpartum hemorrhage over 5000 g, impaired consciousness upon arrival, and hysterectomy as a hemostatic measure were relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. Hyponatremia-related symptoms occurring after lactation failure are indicative of the onset of acute adrenal insufficiency.

Metroplasty increases the take-home baby rate by reducing pregnancy loss without changing the chance of conception in women with septate uterus: a retrospective, single-center, observational study.

BACKGROUND: Although abdominal or hysteroscopic metroplasty for septate uterus is considered to reduce pregnancy loss and increase the take-home baby (THB) rate in women with a history of recurrent pregnancy loss, there exists an inherent risk of impaired fertility. This study aimed to clarify the reproductive outcomes of women with septate uterus who underwent abdominal and hysteroscopic metroplasty in a single center. METHODS: This retrospective observational study enrolled 27 women who underwent metroplasty between 2007 and 2019. The analysis included women with septate uterus [European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) type U2)] or septate-bicornuate uterus (ESHRE/ESGE type U3b) who underwent either abdominal or hysteroscopic metroplasty. Women who did not have an immediate desire to conceive were excluded from the analysis. As a rule, we recommended pregnancy without surgery for women who had not experienced repeated pregnancy loss. Abdominal metroplasty (ABM) was performed using the modified Tompkins' method and hysteroscopic metroplasty was performed using hysteroscopic transcervical resection of the septum [transcervical metroplasty (TCM)]. The conception ratio was calculated as the number of women who achieved ≥ 1 conception/total number of women, the pregnancy loss ratio was calculated as the number of women who experienced ≥ 1 pregnancy loss/the number of women who conceived, and the THB ratio was calculated as the number of women who achieved ≥ 1 THB/total number of women. RESULTS: Seventeen women underwent ABM and 10 women underwent TCM. Thirty-three conceptions and 26 babies were taken home after surgery. ABM did not change the ≥ 1 conception ratio (76% vs. 83% before and after surgery, respectively; RR = 1.08, p = 0.80). Meanwhile, ABM decreased the ≥ 1 pregnancy loss ratio (100% vs. 36%, RR = 0.36, p < 0.001) and increased the ≥ 1 THB ratio (12% vs. 71%, RR = 6.00, p < 0.01). Similarly, TCM did not change the ≥ 1 conception ratio, decreased the ≥ 1 pregnancy loss ratio, and increased the ≥ 1 THB ratio. CONCLUSIONS: Both abdominal and hysteroscopic metroplasty for septate uterus increased the THB rate by preventing pregnancy loss without affecting the chance of pregnancy. TRIAL REGISTRATION: Not applicable.

Effects of Lacticaseibacillus paracasei Strain Shirota on Daytime Performance in Healthy Office Workers: A Double-Blind, Randomized, Crossover, Placebo-Controlled Trial.

Lacticaseibacillus paracasei strain Shirota (LcS) modulates psychological homeostasis via the gut-brain axis. To explore the possible efficacy of LcS for improving daytime performance, we conducted a double-blind, randomized, crossover, placebo-controlled study of 12 healthy office workers with sleep complaints. The participants received fermented milk containing viable LcS (daily intake of 1 × 1011 colony-forming units) and non-fermented placebo milk, each for a 4-week period. In the last week of each period, the participants underwent assessments of their subjective mood and measurements of physiological state indicators via an electroencephalogram (EEG) and heart rate variability in the morning and afternoon. The attention score in the afternoon as assessed by the visual analog scale was higher in the LcS intake period than in the placebo intake period (p = 0.041). Theta power on EEG measured at rest or during an auditory oddball task in the afternoon was significantly lower in the LcS period than in the placebo period (p = 0.025 and 0.009, respectively). The change rate of theta power was associated with the change in attention score. Treatment-associated changes were also observed in heart rate and the sympathetic nerve activity index. These results indicate that LcS has possible efficacy for improving daytime performance, supported by observations of the related physiological state indicators.

SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier.

BACKGROUND: As a consequence of SARS-CoV-2 infection various neurocognitive and neuropsychiatric symptoms can appear, which may persist for several months post infection. However, cell type-specific routes of brain infection and underlying mechanisms resulting in neuroglial dysfunction are not well understood. METHODS: Here, we investigated the susceptibility of cells constituting the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP) to SARS-CoV-2 infection using human induced pluripotent stem cell (hiPSC)-derived cellular models and a ChP papilloma-derived epithelial cell line as well as ChP tissue from COVID-19 patients, respectively. RESULTS: We noted a differential infectibility of hiPSC-derived brain microvascular endothelial cells (BMECs) depending on the differentiation method. Extended endothelial culture method (EECM)-BMECs characterized by a complete set of endothelial markers, good barrier properties and a mature immune phenotype were refractory to SARS-CoV-2 infection and did not exhibit an activated phenotype after prolonged SARS-CoV-2 inoculation. In contrast, defined medium method (DMM)-BMECs, characterized by a mixed endothelial and epithelial phenotype and excellent barrier properties were productively infected by SARS-CoV-2 in an ACE2-dependent manner. hiPSC-derived brain pericyte-like cells (BPLCs) lacking ACE2 expression were not susceptible to SARS-CoV-2 infection. Furthermore, the human choroid plexus papilloma-derived epithelial cell line HIBCPP, modeling the BCSFB was productively infected by SARS-CoV-2 preferentially from the basolateral side, facing the blood compartment. Assessment of ChP tissue from COVID-19 patients by RNA in situ hybridization revealed SARS-CoV-2 transcripts in ChP epithelial and ChP stromal cells. CONCLUSIONS: Our study shows that the BCSFB of the ChP rather than the BBB is susceptible to direct SARS-CoV-2 infection. Thus, neuropsychiatric symptoms because of COVID-19 may rather be associated with dysfunction of the BCSFB than the BBB. Future studies should consider a role of the ChP in underlying neuropsychiatric symptoms following SARS-CoV-2 infection.

Reproductive outcomes following abdominal repair for cesarean scar defect in women who desire subsequent pregnancies: A single-center retrospective study.

OBJECTIVE: To clarify the reproductive outcomes of women who underwent abdominal repair surgery for cesarean scar defect (CSD). STUDY DESIGN: This is a retrospective observational study performed in a tertiary center. We retrospectively reviewed 20 women who underwent abdominal repair between 2007 and 2021. The indication for the repair was a minimal residual myometrial thickness (RMT) of ≦3.0 mm. We investigated surgical complications, changes in minimal RMT before and three-months after the repair, and reproductive outcomes. RESULTS: The median age at the time of repair was 36 years (27-40), with a median body mass index of 21.0 (17.7-28.7) and a median of 1 prior cesarean section (1-5). Twelve women reported secondary infertility, while eight women were concerned about the potential risk of uterine rupture in future pregnancies due to thin RMT. Additionally, one woman had a co-existing vesicouterine fistula, two had abscess and hematoma formation at the precedent cesarean section, and three showed remarkable dehiscence of the defect. The median minimal RMT significantly increased to 5.05 mm (range; 2.5-14.2 mm) after the repair. Seven women had a total of eight live births, with a median duration from the repair to a live-birth pregnancy of 11.5 months (range; 4-20 months). No surgical complications occurred during the repair, and there were no instances of uterine rupture in subsequent pregnancies. However, one woman who became pregnant with twins following double blastocyst transfer required a cesarean section at 25 weeks of pregnancy due to bulging towards the bladder side of the repaired CSD. CONCLUSION: Abdominal repair for CSD is feasible in women with thin RMT who experience secondary infertility. Twin pregnancies can promote thinning of the CSD repair site, potentially increasing the risk of uterine rupture.

Death of children with Down syndrome by gestational age and cause.

BACKGROUND: We often encounter preterm infants with Down syndrome (DS) who die in the neonatal intensive care unit (NICU). In this study, we examined survival until NICU discharge and assessed the developmental prognosis of preterm infants with DS. METHODS: We retrospectively reviewed 416 infants with DS hospitalized during the past 27 years at our NICU. RESULTS: Death occurred in 8/20 (40%) infants at <32 weeks' gestation, 11/23 (48%) at 32-33 weeks, 9/99 (9%) at 34-36 weeks, and 9/274 (3%) at >36 weeks. In total, 84% of infants who died and 25% of those who survived had a non-reassuring fetal status (p < 0.001). Sex, small-for-gestational-age status, and postnatal transport were not associated with death. The main causes of death were bronchopulmonary dysplasia in 4/8 (50%) infants at <32 weeks' gestation, transient abnormal myelopoiesis in 11/20 (55%) and lymphatic dysplasia in 6/20 (30%) at 32-36 weeks, and varied causes at >36 weeks. Among survivors born at <34 weeks' gestation, 6/19 (32%) aged >2 years had moderate or severe cerebral palsy. CONCLUSIONS: These data on the high mortality and morbidity of preterm infants with DS may be useful for patient treatment and parent counseling in NICUs treating critically ill infants. IMPACT: Most infants with Down syndrome born at <34 weeks' gestation are born by cesarean section because of the non-reassuring fetal status. The mortality rate before discharge for infants with Down syndrome born at <34 weeks' gestation was 40%, and 30% of survivors developed moderate or severe cerebral palsy. The risk of death due to bronchopulmonary dysplasia and pulmonary hypertension was high in very preterm infants with Down syndrome despite the absence of chorioamnionitis. Infants with Down syndrome were born 1-2 weeks earlier than unaffected controls.

RISING STARS: Role of MED12 mutation in the pathogenesis of uterine fibroids.

Abstract: Uterine fibroids (UFs) are benign tumors arising from the uterus, characterized by accumulation of abundant extracellular matrix (ECM) and sex steroid-dependent growth. Women with symptomatic UFs have reduced quality of life and decreased labor productivity. Among the driver gene mutations identified in UFs, mutations in MED12, a component of the cyclin-dependent kinase (CDK) Mediator module, are the most common and observed in 50-80% of UFs. They are gain-of-function mutations and are more frequently observed in Black women and commonly observed even in small UFs. MED12 mutation-positive UFs (MED12-UFs) often develop multiple rather than solitary and have distinct gene expression profiles, DNA methylomes, transcriptomes, and proteomes. Gene expressions related to ECM organization and collagen-rich ECM components are upregulated, and impaired Mediator kinase activity and dysregulation of Wnt/ß-catenin signaling are identified in MED12-UFs. Clinically, the UF shrinking effect of gonadotropin-releasing hormone agonists and ulipristal acetate is dependent on the MED12 mutation status. Understanding of characteristics of MED12-UFs and functions of MED12 mutations for UF tumorigenesis may elucidate the pathophysiology of UFs, leading to the development of new therapeutic options in women with symptomatic UFs.

Corrigendum: The phosphoproteome of choroid plexus epithelial cells following infection with Neisseria meningitidis.

[This corrects the article DOI: 10.3389/fcimb.2023.1113528.].

Can Glaucoma Suspect Data Help to Improve the Performance of Glaucoma Diagnosis?

Purpose: The presence of imbalanced datasets in medical applications can negatively affect deep learning methods. This study aims to investigate how the performance of convolutional neural networks (CNNs) for glaucoma diagnosis can be improved by addressing imbalanced learning issues through utilizing glaucoma suspect samples, which are often excluded from studies because they are a mixture of healthy and preperimetric glaucomatous eyes, in a semi-supervised learning approach. Methods: A baseline 3D CNN was developed and trained on a real-world glaucoma dataset, which is naturally imbalanced (like many other real-world medical datasets). Then, three methods, including reweighting samples, data resampling to form balanced batches, and semi-supervised learning on glaucoma suspect data were applied to practically assess their impacts on the performances of the trained methods. Results: The proposed method achieved a mean accuracy of 95.24%, an F1 score of 97.42%, and an area under the curve of receiver operating characteristic (AUC ROC) of 95.64%, whereas the corresponding results for the traditional supervised training using weighted cross-entropy loss were 92.88%, 96.12%, and 92.72%, respectively. The obtained results show statistically significant improvements in all metrics. Conclusions: Exploiting glaucoma suspect eyes in a semi-supervised learning method coupled with resampling can improve glaucoma diagnosis performance by mitigating imbalanced learning issues. Translational Relevance: Clinical imbalanced datasets may negatively affect medical applications of deep learning. Utilizing data with uncertain diagnosis, such as glaucoma suspects, through a combination of semi-supervised learning and class-imbalanced learning strategies can partially address the problems of having limited data and learning on imbalanced datasets.

Efficacy of redox nanoparticles for improving survival of transplanted cells in a mouse model of ischemic stroke.

The success of cell transplantation therapy for ischemic stroke is hindered by the low cell survival rate in poststroke brain, due in part to high free radical production and ensuing oxidative stress. We have developed redox nanoparticles to eliminate reactive oxygen species. In this study, we tested the protective efficacy of these redox nanoparticles in cell culture and a mouse model of ischemic stroke. Induced human dental pulp stem cells were subjected to oxygen-glucose deprivation and reoxygenation to recapitulate ischemia and reperfusion in the penumbra surrounding a cerebral infarct. Cell viability using WST-8 assay, apoptosis using TUNEL, free radicals using MitoSOX, and inflammatory cytokines using ELISA kit were measured in the presence and absence of redox nanoparticles after oxygen-glucose deprivation and reoxygenation. The scavenging activity of redox nanoparticles against reactive oxygen species was detected by electron spin resonance. Moreover, induced cells were transplanted intracerebrally into to the distal middle cerebral artery occlusion model with and without redox nanoparticles, and the survival rate measured. Cell viability was enhanced, while apoptosis, free radical generation, and inflammatory cytokine expression levels were reduced in cultures with redox nanoparticles. Further, reduced redox nanoparticles were detected in the cytoplasm, indicating free radical scavenging. Addition of redox nanoparticles also improved the survival rate of transplanted cells after 6 weeks in vivo. These redox nanoparticles may increase the applicability and success of induced stem cell therapy for ischemic stroke patents by promoting long-term survival.

The choroid plexus acts as an immune cell reservoir and brain entry site in experimental autoimmune encephalomyelitis.

The choroid plexus (ChP) has been suggested as an alternative central nervous system (CNS) entry site for CCR6+ Th17 cells during the initiation of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). To advance our understanding of the importance of the ChP in orchestrating CNS immune cell entry during neuroinflammation, we here directly compared the accumulation of CD45+ immune cell subsets in the ChP, the brain and spinal cord at different stages of EAE by flow cytometry. We found that the ChP harbors high numbers of CD45int resident innate but also of CD45hi adaptive immune cell subsets including CCR6+ Th17 cells. With the exception to tissue-resident myeloid cells and B cells, numbers of CD45+ immune cells and specifically of CD4+ T cells increased in the ChP prior to EAE onset and remained elevated while declining in brain and spinal cord during chronic disease. Increased numbers of ChP immune cells preceded their increase in the cerebrospinal fluid (CSF). Th17 but also other CD4+ effector T-cell subsets could migrate from the basolateral to the apical side of the blood-cerebrospinal fluid barrier (BCSFB) in vitro, however, diapedesis of effector Th cells including that of Th17 cells did not require interaction of CCR6 with BCSFB derived CCL20. Our data underscore the important role of the ChP as CNS immune cell entry site in the context of autoimmune neuroinflammation.

Macular Retinoschisis from Optic Disc without a Visible Optic Pit or Advanced Glaucomatous Cupping (No Optic Pit Retinoschisis [NOPIR]).

PURPOSE: To review eyes with peripapillary and macular retinoschisis without a visible optic pit or advanced glaucomatous optic atrophy, or No Optic Pit Retinoschisis (NOPIR). DESIGN: Retrospective multicenter case series. SUBJECTS: The study included 11 eyes of 11 patients. METHODS: Retrospective study of eyes with macular retinoschisis without a visible optic pit, advanced optic nerve head cupping, or macular leakage on fluorescein angiography. MAIN OUTCOME MEASURES: Visual acuity (VA), retinoschisis resolution, months to resolution, and recurrence of retinoschisis RESULTS: The mean age was 68.1 ± 17.6 years, mean intraocular pressure was 17.4 ± 3.8 mmHg, and the mean spherical equivalent refractive error was -3.1 ± 2.9 diopters. No subject had pathologic myopia. Seven subjects were treated for glaucoma, and 9 subjects had nerve fiber layer defects on OCT. All eyes had retinoschisis in the outer nuclear layer (ONL) in the nasal macula and extending to the edge of the optic disc, and 8 subjects had fovea-involving retinoschisis. Three nonfoveal and 4 fovea-involved eyes were observed, and 4 fovea-involved eyes with vision loss underwent surgery. Surgery involved preoperative juxtapapillary laser followed by vitrectomy and membrane and internal limiting membrane peeling with intraocular gas and face-down position. The mean baseline VA was significantly worse in the surgery group than that in the observation group (P = 0.020). Retinoschisis resolved and vision improved in all surgical cases. The mean resolution time for the surgery group was 2.75 ± 0.96 months, which was shorter than that for the observation group (28.0 ± 21.2 months; P = 0.014). No eye developed recurrence of the retinoschisis after surgery. CONCLUSIONS: Peripapillary and macular retinoschisis can develop in eyes without a visible optic pit or advanced glaucomatous cupping. Eyes without foveal involvement and those with foveal involvement but only mild decrease in vision can be observed for spontaneous resolution. If there is persistent foveal involvement with vision loss, surgery can improve vision by resolving the macular retinoschisis. Surgery for fovea-involved macular retinoschisis without a visible optic pit resulted in faster anatomic resolution and better vision recovery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Segmentation-Free OCT-Volume-Based Deep Learning Model Improves Pointwise Visual Field Sensitivity Estimation.

Purpose: The structural changes measured by optical coherence tomography (OCT) are related to functional changes in visual fields (VFs). This study aims to accurately assess the structure-function relationship and overcome the challenges brought by the minimal measurable level (floor effect) of segmentation-dependent OCT measurements commonly used in prior studies. Methods: We developed a deep learning model to estimate the functional performance directly from three-dimensional (3D) OCT volumes and compared it to the model trained with segmentation-dependent two-dimensional (2D) OCT thickness maps. Moreover, we proposed a gradient loss to utilize the spatial information of VFs. Results: Our 3D model was significantly better than the 2D model both globally and pointwise regarding both mean absolute error (MAE = 3.11 + 3.54 vs. 3.47 ± 3.75 dB, P < 0.001) and Pearson's correlation coefficient (0.80 vs. 0.75, P < 0.001). On a subset of test data with floor effects, the 3D model showed less influence from floor effects than the 2D model (MAE = 5.24 ± 3.99 vs. 6.34 ± 4.58 dB, P < 0.001, and correlation 0.83 vs. 0.74, P < 0.001). The gradient loss improved the estimation error for low-sensitivity values. Furthermore, our 3D model outperformed all prior studies. Conclusions: By providing a better quantitative model to encapsulate the structure-function relationship more accurately, our method may help deriving VF test surrogates. Translational Relevance: DL-based VF surrogates not only benefit patients by reducing the testing time of VFs but also allow clinicians to make clinical judgments without the inherent limitations of VFs.

The phosphoproteome of choroid plexus epithelial cells following infection with Neisseria meningitidis.

The Gram-negative bacterium Neisseria meningitidis, which causes meningitis in humans, has been demonstrated to manipulate or alter host signalling pathways during infection of the central nervous system (CNS). However, these complex signalling networks are not completely understood. We investigate the phosphoproteome of an in vitro model of the blood-cerebrospinal fluid barrier (BCSFB) based on human epithelial choroid plexus (CP) papilloma (HIBCPP) cells during infection with the N. meningitidis serogroup B strain MC58 in presence and absence of the bacterial capsule. Interestingly, our data demonstrates a stronger impact on the phosphoproteome of the cells by the capsule-deficient mutant of MC58. Using enrichment analyses, potential pathways, molecular processes, biological processes, cellular components and kinases were determined to be regulated as a consequence of N. meningitidis infection of the BCSFB. Our data highlight a variety of protein regulations that are altered during infection of CP epithelial cells with N. meningitidis, with the regulation of several pathways and molecular events only being detected after infection with the capsule-deficient mutant. Mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD038560.

Acute vulvar ulcer as a possible adverse event of gene-based COVID-19 vaccines: A review of 14 cases.

AIM: To evaluate whether an acute vulvar ulcer that developed after the COVID-19 vaccine administration is an adverse effect of the vaccine. METHODS: This is a descriptive study of two cases that we observed in addition to cases that have been reported in the literature. We searched for case reports in the PubMed. The consistency of clinical manifestations among cases and the association between ulceration and vaccination were assessed. RESULTS: Fourteen female patients were identified, including 12 patients from 8 literatures published in 2021 and 2022 and 2 patients from our cases. Of the 14 patients, 11 had received the BNT162b2 vaccine, 2 had received the ChAdOx1 nCoV-19 vaccine, and one had received the mRNA-1273 vaccine. The patient's ages were 16.9 ± 5.0 (mean ± SD) years. Postvaccination, the disease progressed in the following sequence (time interval from vaccination): fever and other systemic inflammatory reactions (0.9 ± 0.4 days), development of vulvar ulcers (2.4 ± 1.2 days), and resolution of the ulcer (16.9 ± 7.4 days). The ulcers eventually healed in all cases, except one where the prognosis was not noted. For two-dose vaccine recipients, more patients developed the ulcer after the full vaccination (the second or third doses) compared with after the first dose: n = 10 and n = 2, respectively. CONCLUSION: The acute vulvar ulcer was closely associated with COVID-19 vaccination in terms of temporality and vaccine doses, supporting the notion that a vulvar ulcer is an adverse event of the COVID-19 vaccines.