Early-Term Neonates Demonstrate a Higher Likelihood of Requiring Phototherapy Compared to Those Born Full-Term.

Early-term neonates (with a gestational age (GA) of 37 and 0/7 weeks to 38 and 6/7 weeks) face higher morbidities, including respiratory and neurodevelopmental issues, than full-term (39 and 0/7 weeks to 40 and 6/7 weeks) infants. This study explores whether hyperbilirubinemia necessitating phototherapy also differs between these groups. A retrospective study was conducted on neonates born from January 2021-June 2022, excluding those with specific conditions. Evaluated factors included GA, birth weight, bilirubin levels, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and feeding type, with phototherapy given as per AAP guidelines. Of 1085 neonates, 356 met the criteria. When stratifying the neonates based on the need for phototherapy, a higher proportion of early-term neonates required phototherapy compared to full-term (p < 0.05). After factoring in various risks (GA; birth weight; gender; feeding type; G6PD deficiency; transcutaneous bilirubin levels at 24 h and 24-48 h postpartum; maternal diabetes; and the presence of caput succedaneum or cephalohematoma), early-term neonates were more likely to need phototherapy than full-term babies (OR: 2.15, 95% CI: 1.21 to 3.80). The optimal cut-off for transcutaneous bilirubin levels 24-48 h postpartum that were used to predict phototherapy need was 9.85 mg/dl. In conclusion, early-term neonates are at a greater risk for developing jaundice and requiring phototherapy than full-term neonates. Monitoring bilirubin 24-48 h postpartum enhances early prediction and intervention.

Comprehensive Analysis of Risk Factors for Bronchopulmonary Dysplasia in Preterm Infants in Taiwan: A Four-Year Study.

Bronchopulmonary dysplasia (BPD) is a major respiratory condition mainly affecting premature infants. Although its occurrence is global, risk factors may differ regionally. This study, involving 3111 infants with birth weight ≤ 1500 gm or gestational age (GA) < 30 weeks, aimed to identify risk factors for BPD and BPD/mortality in Taiwan using data from the Taiwan Neonatal Network. The BPD criteria were based on the National Institute of Child Health and Human Development standards. Average GA was 27.5 weeks, with 23.7% classified as small for GA (SGA). Multivariate analysis highlighted low GA, low birth weight, and other perinatal factors as significant risk indicators for BPD. For moderate-to-severe BPD, additional risk factors included male gender and SGA, endotracheal intubation (ETT) or cardiopulmonary cerebral resuscitation (CPCR) in initial resuscitation. In the moderate-to-severe BPD/death group, SGA and ETT or CPCR in initial resuscitation remained the only additional risk factors. The study pinpoints male gender, SGA and ETT or CPCR as key risk factors for moderate-to-severe BPD/death in low-birth-weight infants in Taiwan, offering a basis for focused interventions and further research.

Maternal Age, the Disparity across Regions and Their Correlation to Sudden Infant Death Syndrome in Taiwan: A Nationwide Cohort Study.

Sudden infant death syndrome (SIDS) has always been a regrettable issue for families. After sleeping in the supine position was proposed, the incidence of SIDS declined dramatically worldwide. However, SIDS still accounts for the top 10 causes of infant deaths in Taiwan. Recognizing the risk factors and attempting to minimize these cases are imperative. We obtained information on cases with SIDS from the National Health Insurance Research Database in Taiwan and interconnected it with the Taiwan Maternal and Child Health Database to acquire infant-maternal basal characteristics between 2004 and 2017. The SIDS subjects were matched 1:10 considering gestational age to normal infants. After case selection, a total of 953 SIDS cases were included. Compared with healthy infants, SIDS infants had younger parents, lower birth weight, and lower Apgar scores. After adjusting for potential confounders, infants with mothers aged <20 years had 2.81 times higher risk of SIDS. Moreover, infants in the non-eastern region had a significantly lower risk of SIDS than those in the eastern region. We concluded that infants of young mothers (especially maternal age <20 years) and infants in the eastern region of Taiwan had a higher risk of SIDS than their counterparts.

AUY922 induces retinal toxicity through attenuating TRPM1.

BACKGROUND: Ocular adverse events are common dose-limiting toxicities in cancer patients treated with HSP90 inhibitors, such as AUY922; however, the pathology and molecular mechanisms that mediate AUY922-induced retinal toxicity remain undescribed. METHODS: The impact of AUY922 on mouse retinas and cell lines was comprehensively investigated using isobaric tags for relative and absolute quantitation (iTRAQ)­based proteomic profiling and pathway enrichment analysis, immunohistochemistry and immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, MTT assay, colony formation assay, and western blot analysis. The effect of AUY922 on the Transient Receptor Potential cation channel subfamily M member 1 (TRPM1)-HSP90 chaperone complex was characterized by coimmunoprecipitation. TRPM1-regulated gene expression was analyzed by RNAseq analysis and gene set enrichment analysis (GSEA). The role of TRPM1 was assessed using both loss-of-function and gain-of-function approaches. RESULTS: Here, we show that the treatment with AUY922 induced retinal damage and cell apoptosis, dysregulated the photoreceptor and retinal pigment epithelium (RPE) layers, and reduced TRPM1 expression. Proteomic profiling and functional annotation of differentially expressed proteins reveals that those related to stress responses, protein folding processes, regulation of apoptosis, cell cycle and growth, reactive oxygen species (ROS) response, cell junction assembly and adhesion regulation, and proton transmembrane transport were significantly enriched in AUY922-treated cells. We found that AUY922 triggered caspase-3-dependent cell apoptosis, increased ROS production and inhibited cell growth. We determined that TRPM1 is a bona fide HSP90 client and characterized that AUY922 may reduce TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex. Additionally, GSEA revealed that TRPM1-regulated genes were associated with retinal morphogenesis in camera-type eyes and the JAK-STAT cascade. Finally, gain-of-function and loss-of-function analyses validated the finding that TRPM1 mediated the cell apoptosis, ROS production and growth inhibition induced by AUY922. CONCLUSIONS: Our study demonstrates the pathology of AUY922-induced retinal toxicity in vivo. TRPM1 is an HSP90 client, regulates photoreceptor morphology and function, and mediates AUY922-induced cytotoxicity.

Ocular characteristics in a variant microcephalic primordial dwarfism type II.

BACKGROUND: Microcephalic osteodysplastic primordial dwarfism, type II (MOPD II) is a rare disease that is assumed to be caused by a pericentrin (PCNT) gene mutation. Clinical manifestations have been reported in pediatrics and neurology; however, only a few ocular findings have been documented. CASE PRESENTATION: We present three unrelated cases of MOPD II with similar facial features and short stature. Unlike the cases described in the literature, all subjects had normal birth weight and height but their growth was retarded thereafter. In addition to delayed milestones, they have a broad forehead, maxillary protrusion, long peaked nose, high nasal bridge, low-set large ears, extreme reromicrogenia, and normal-sized teeth. These three patients had similar ocular manifestations with the short axial length associated with high hyperopia more than + 9 diopters (D) and macular scarring. The oldest subject was a 20 year-old male without neurological symptoms. One female subject had developed alopecia during the previous 2 years. The other female subject had moyamoya disease, but a genetic study revealed a normal PCNT gene. CONCLUSION: This is the first report of MOPD II focusing on ocular findings, suggesting that macular dystrophy and high hyperopia are the common ocular characteristics of MOPD II. Prompt referral to an ophthalmologist is essential. Although refractive amblyopia can be treated with optical correction, visual prognosis may be poor due to maculopathy.

Author Correction: Major ocular trauma in Taiwan: 2002-2004 versus 2012-2014.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Major ocular trauma in Taiwan: 2002-2004 versus 2012-2014.

We investigated the temporal changes in major eye injuries in Taiwan by reviewing the medical records of all patients with ocular trauma hospitalized at the National Cheng Kung University Hospital during 2002-2004 and 2012-2014. A total of 169 eyes (161 patients) during 2002-2004 and 121 eyes (120 patients) during 2012-2014 were enrolled (mean ± SD age: 41.9 ± 20.8 years in 2002-2004, and 51.8 ± 19.3 years in 2012-2014). Males accounted for ~75% of patients. The most frequent injury-causing object was metallic material (~24%), and blunt traumas were most frequently attributable to traffic accidents and falls. The most common locations of injuries for males and females were the workplace and home, respectively. Open-globe injuries occurred in ~70% of eyes, requiring primary repair, cataract extraction, and/or intraocular lens implantation. The frequencies of fall injury, lacrimal system laceration, lens injury, corneal/scleral foreign bodies, and use of intracameral antibiotics increased from 2002-2004 to 2012-2014, while those of closed-globe injury, vitreous haemorrhage, optic nerve injury, and medical treatment decreased. The final visual acuity remained poor (≤20/200) in >1/3 of injured eyes. Despite therapeutic advancements, major eye injuries still pose a high risk for poor visual outcome.

Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light.

Oxidative stress plays a key role in age-related macular degeneration and hereditary retinal degenerations. Light damage in rodents has been used extensively to model oxidative stress-induced photoreceptor degeneration, and photo-oxidative injury from blue light is particularly damaging to photoreceptors. The endogenous factors protecting photoreceptors from oxidative stress, including photo-oxidative stress, are continuing to be elucidated. In this study, we evaluated the effect of blue light exposure on photoreceptors and its relationship to Nrf2 using cultured murine photoreceptor (661W) cells. 661W cells were exposed to blue light at 2500 lux. Exposure to blue light for 6-24 h resulted in a significant increase in intracellular reactive oxygen species (ROS) and death of 661W cells in a time-dependent fashion. Blue light exposure resulted in activation of Nrf2, as indicated by an increase in nuclear translocation of Nrf2. This was associated with a significant induction of expression of Nrf2 as well as an array of Nrf2 target genes, including antioxidant genes, as indicated by quantitative reverse transcription PCR (qRT-PCR). In order to determine the functional role of Nrf2, siRNA-mediated knockdown studies were performed. Nrf2-knockdown in 661W cells resulted in significant exacerbation of blue light-induced reactive oxygen species levels as well as cell death. Taken together, these findings indicate that Nrf2 is an important endogenous protective factor against oxidative stress in photoreceptor cells. This suggests that drugs targeting Nrf2 could be considered as a neuroprotective strategy for photoreceptors in AMD and other retinal conditions.

A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure.

Retinal ischemia-reperfusion (I/R) is a pathophysiological process contributing to cellular damage in multiple ocular conditions, including glaucoma, diabetic retinopathy, and retinal vascular occlusions. Rodent models of I/R injury are providing significant insights into mechanisms and treatment strategies for human I/R injury, especially with regard to neurodegenerative damage in the retinal neurovascular unit. Presented here is a protocol for inducing retinal I/R injury in mice through elevation of intraocular pressure (IOP). In this protocol, the ocular anterior chamber is cannulated with a needle, through which flows the drip of an elevated saline reservoir. Using this drip to raise IOP above systolic arterial blood pressure, a practitioner temporarily halts inner retinal blood flow (ischemia). When circulation is reinstated (reperfusion) by removal of the cannula, severe cellular damage ensues, resulting ultimately in retinal neurodegeneration. Recent studies demonstrate inflammation, vascular permeability, and capillary degeneration as additional elements of this model. Compared to alternative retinal I/R methodologies, such as retinal arterial ligation, retinal I/R injury by elevated IOP offers advantages in its anatomical specificity, experimental tractability, and technical accessibility, presenting itself as a valuable tool for examining neuronal pathogenesis and therapy in the retinal neurovascular unit.

Refractive Changes in Amblyopic Children with High Anisometropia.

PURPOSE: To demonstrate the refractive changes of amblyopic children attributed to high anisometropia in the myopia endemic in Taiwan. METHODS: Amblyopic children younger than 10 years with myopic or hyperopic anisometropia 3 diopters (D) or more who had follow-up for more than 2 years and had final visual acuity of 20/30 or better in the amblyopic eye were included. RESULTS: The average age on the first visit was similar for the 13 myopic children (5.5 years) and 17 hyperopic children (5.3 years). Initially, the mean anisometropia was significantly different (myopic, 7.25 D vs. hyperopic, 3.89 D), but the visual acuity of the amblyopic eye (logarithm of the minimum angle of resolution) was similar between both groups at baseline (0.50 vs. 0.57). Myopization of the sound eye surpassed that of the amblyopic eye in the myopic group, which resulted in a yearly reduction of anisometropia of 0.51 D. However, hyperopia decreased synchronously in both eyes of the hyperopic children. The final degree of anisometropia was not significantly different between the two groups (4.07 D vs. 3.62 D). CONCLUSIONS: Growing up in a country with a high prevalence of myopia, children with myopic and hyperopic anisometropia in this study inevitably had myopization in both eyes. Myopic anisometropia decreases significantly over time, but hyperopic anisometropia remains constant.

Neuregulin/erythroblastic leukemia viral oncogene homolog 3 autocrine loop contributes to invasion and early recurrence of human hepatoma.

UNLABELLED: Intrahepatic metastasis is the primary cause of the high recurrence and poor prognosis of human hepatocellular carcinoma (HCC). However, neither its molecular mechanisms nor markers for its prediction before hepatectomy have been identified. We recently revealed up-regulation of erythroblastic leukemia viral oncogene homolog 3 (ERBB3) in human HCC. Here we examined the clinical and biological significance of ERBB3 in HCC. Up-regulation of ERBB3 in HCC was strongly associated with male gender (P < 0.001), chronic hepatitis B (P = 0.002), microscopic vascular invasion (P = 0.034), early recurrence (P = 0.003), and worse prognosis (P = 0.004). Phosphorylated ERBB3 and its ligands [neuregulins (NRGs)] were detected in both HCC tissues and cells. Phosphorylation of ERBB3 could be induced by conditioned media of HCC cells and abolished by the pretreatment of conditioned media with anti-NRG antibodies or by the silencing of the endogenous NRG expression of the donor HCC cells. Human epidermal growth factor receptor 2 was required for ERBB3 phosphorylation. The downstream phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene homolog pathways were primarily elicited by NRG1/ERBB3 signaling, whereas the mitogen-activated protein kinase/extracellular signal-regulated kinase pathways were elicited by both epidermal growth factor/epidermal growth factor receptor and NRG1/ERBB3 signaling. The activation and silencing of ERBB3-dependent signaling had potent effects on both the migration and invasion of HCC cells, but neither had significant effects on the proliferation of HCC cells, tumor formation, or tumor growth in vitro and in vivo. CONCLUSION: The constitutive activation of ERBB3-dependent signaling via the NRG1/ERBB3 autocrine loop plays a crucial role in the regulation of cell motility and invasion, which contribute to intrahepatic metastasis and early recurrence of HCC. ERBB3 is a marker for the prediction of intrahepatic metastasis and early recurrence. ERBB3-dependent signaling is a candidate target for the treatment of microscopic vascular invasion and for the prevention of HCC recurrence.

Paederus-induced keratitis.

PURPOSE: To report the clinical picture and management of 4 cases of presumed paederus-induced keratitis. METHODS: The clinical characteristics of the anterior segment and periocular area were presented. The outcomes and healing course of the corneal lesions were recorded. RESULTS: Each patient sustained an accidental eye injury from a beetle while riding a motorcycle. Three cases were complicated by periocular dermatitis. All patients had diffuse punctate epithelial erosions or large epithelial defects on the unilateral cornea. Prolonged corneal epithelialization was noted after lubrication with artificial tears and wearing a contact lens. Reepithelialization was promoted after topical supplementation with 20% autologous serum. All 4 patients had good visual outcomes. Two patients healed with a faint corneal scar. CONCLUSIONS: Paederus-induced keratitis could result in extensive involvement of the corneal surface. Keratitis with a large epithelial defect mimicking the corrosive lesion of a chemical burn requires aggressive therapy, such as autologous serum combined with a bandage contact lens. Avoiding contact with the crushed body of the beetle while rubbing the eye is mandatory to prevent this type of keratitis.