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Background: Atypical teratoid rhabdoid tumor (ATRT) is an aggressive brain tumor that mainly affects young children. Our recent study reported a promising therapeutic strategy to trigger DNA damage, impede homologous recombination repair, and induce apoptosis in ATRT cells by targeting ribonucleotide reductase regulatory subunit M2 (RRM2). COH29, an inhibitor of RRM2, effectively reduced tumor growth and prolonged survival in vivo. Herein, we explored the underlying mechanisms controlling these functions to improve the clinical applicability of COH29 in ATRT., Methods: Molecular profiling of ATRT patients and COH29-treated cells was analyzed to identify the specific signaling pathways, followed by validation using a knockdown system, flow cytometry, q-PCR, and western blot., Results: Elevated E2F1 and its signaling pathway were correlated with poor prognosis. RRM2 inhibition induced DNA damage and activated ATM, which reduced Rb phosphorylation to promote Rb-E2F1 interaction and hindered E2F1 functions. E2F1 activity suppression led to decreased E2F1-dependent target expressions, causing cell cycle arrest in the G1 phase, decreased S phase cells, and blocked DNA damage repair., Conclusion: Our study highlights the role of ATM/Rb/E2F1 pathway in controlling cell cycle arrest and apoptosis in response to RRM2 inhibition-induced DNA damage. This provides insight into the therapeutic benefits of COH29 and suggests targeting this pathway as a potential treatment for ATRT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Patients with human immunodeficiency virus (HIV) are at increased risk for developing other gynecologic conditions, including herpes simplex virus (HSV) and vulvar intraepithelial neoplasia (VIN)/carcinoma. We describe the case of a woman with a history of microinvasive vulvar squamous cell carcinoma who presented with hypertrophic ulcerated vulvar and peri -anal masses concerning for malignancy. This case highlights the need to maintain a high index of suspicion for malignancy and herpes simplex virus, even with negative polymerase chain reaction (PCR) test, as well as the difficulty of treating this often-resistant lesion., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: To identify factors important to patients for their return to elective imaging during the coronavirus disease 2019 (COVID-19) pandemic., Methods: In all, 249 patients had elective MRIs postponed from March 23, 2020, to April 24, 2020, because of the COVID-19 pandemic. Of these patients, 99 completed a 22-question survey about living arrangement and health care follow-up, effect of imaging postponement, safety of imaging, and factors important for elective imaging. Mann-Whitney U, Fisher's exact, χ 2 tests, and logistic regression analyses were performed. Statistical significance was set to P ≤ .05 with Bonferroni correction applied., Results: Overall, 68% of patients felt imaging postponement had no impact or a small impact on health, 68% felt it was fairly or extremely safe to obtain imaging, and 53% thought there was no difference in safety between hospital-based and outpatient locations. Patients who already had imaging performed or rescheduled were more likely to feel it was safe to get an MRI (odds ratio [OR] 3.267, P = .028) and that the hospital setting was safe (OR 3.976, P = .004). Staff friendliness was the most important factor related to an imaging center visit (95% fairly or extremely important). Use of masks by staff was the top infection prevention measure (94% fairly or extremely important). Likelihood of rescheduling imaging decreased if a short waiting time was important (OR = 0.107, P = .030)., Conclusion: As patients begin to feel that it is safe to obtain imaging examinations during the COVID-19 pandemic, many factors important to their imaging experience can be considered by radiology practices when developing new strategies to conduct elective imaging., (Copyright © 2020 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether recently identified genetic loci for primary angle-closure glaucoma (PACG) are associated with disease severity., Design: Case-control study., Participants: Eight hundred four PACG patients and 943 control participants of Chinese ethnicity from Singapore., Methods: The 8 PACG-associated single nucleotide polymorphisms (SNPs; rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 on chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) identified from genome-wide association studies were tested for association with disease severity using logistic regression adjusted for age and gender. A P value of 0.006 was set as significant after Bonferroni correction for testing of 8 loci. We also calculated the weighted genetic risk score (GRS) weighted by the estimated individual SNP effect size on PACG calculated as logarithm of the odds ratio (OR). Disease severity was based on the visual field mean deviation (MD) and classified as early to moderate (MD, >-12 dB) and severe (MD, <-20 dB)., Main Outcome Measures: Association of PACG loci with severe disease., Results: Of the 804 PACG patients, genotyping data were available for 768 individuals and included 436 with mild-to-moderate PACG and 206 with severe PACG. The PACG patients were significantly older (mean age, 64.3 ± 9.1 years vs. 56.4 ± 8.9 years; P < 0.001) and there were proportionately more women compared with control participants (58.4% vs. 49.0%; P < 0.001). Of the 8 loci investigated, we observed significant evidence of association with severe PACG at 1 SNP, namely rs3816415 in EPDR1 (OR, 2.03; 95% confidence interval [CI], 1.49-2.78; P = 1 × 10 -5 ). A higher-weighted GRS was associated significantly with severe PACG, with an OR of 3.11 (95% CI, 1.95-4.96) comparing the lowest quartile with the highest quartile., Conclusions: Our results show that EPDR1 is associated significantly with severe PACG, suggesting that it may predispose patients to more aggressive disease development. Individuals with PACG with a higher GRS were associated with a higher risk of severe PACG., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Compare required osteoplasty predicted by a 3D virtual dynamic hip model in femoroacetabular impingement patients to actual osteoplasty performed., Materials and Methods: Retrospective study on 20 consecutive FAI patients with a preoperative CT who underwent arthroscopy from October 2016 to September 2017. A 3D virtual dynamic hip model was created from the CT. The model displayed virtual osteoplasty depth required to restore physiologic range of motion on an osteoplasty map. Depths of virtual osteoplasty and actual osteoplasty at surgery were compared and correlated with alpha angle, lateral center edge angle, femoral version, and acetabular version., Results: Actual femoroplasty depth correlated with alpha angle (r = 0.85, p ≤ 0.001) and actual acetabuloplasty depth correlated with lateral center edge angle (r = 0.83, p < 0.001). Virtual osteoplasty depth did not correlate with alpha angle (p = 0.25), lateral center edge angle (p = 0.50), femoral version (p = 0.09), or acetabular version (p = 0.09). The 3D model predicted a mean virtual osteoplasty of 6.2 ± 0.3 mm compared to mean actual osteoplasty of 5.9 ± 1.1 mm. There was no significant difference between the two means (p = 0.26), though there was a significant difference in variance (p = 0.001). There was poor test reliability between virtual osteoplasty compared with actual osteoplasty (ICC = 0.30)., Conclusion: 3D model predicted virtual osteoplasty depths varied with actual osteoplasty and was independent of 2D measurements., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: People with schizophrenia have higher rates of smoking than the general population, and lower quit rates. Several randomised controlled trials have investigated the effectiveness of pharmacological interventions for smoking cessation over the past 20 years. We did a systematic review and pairwise and network meta-analysis of smoking abstinence to guide decision making in offering pharmacological interventions for smoking cessation for people with schizophrenia spectrum disorders., Methods: We systematically reviewed PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and China National Knowledge Infrastructure from inception to Sept 30, 2019, for randomised controlled trials of varenicline, bupropion, and nicotine replacement therapy for smoking cessation for people with schizophrenia spectrum disorders or psychotic disorders who were smokers at the time of study recruitment. Data were extracted from published studies on smoking abstinence outcomes and psychotic symptoms. We did pairwise and network meta-analyses for the primary outcome of smoking abstinence. Sensitivity analyses were done on study inclusion criteria, duration, quality, and location. This study is registered with the international prospective register of systematic reviews PROSPERO, CRD42018102343., Findings: A total of 15 111 records were identified by the database searches, and 163 full-text articles were assessed for eligibility. 145 articles were then excluded for several reasons including insufficient data, or abstracts published in later studies, and 18 studies were included in the meta-analysis. In the pairwise meta-analyses, four studies with 394 participants assessed varenicline (RR 3·75, 95% CI 1·96-7·19, p<0·0001; I 2 =0%), four studies with bupropion and 292 participants (RR 3·40, 95% CI 1·58-7·34, p=0·0002; I 2 =0%), and three studies with 561 participants assessed nicotine replacement therapy (RR 4·27, 95% CI 1·71-10·65, p=0·0002; I 2 =0%). All three treatments were deemed superior to placebo. In the network meta-analysis, varenicline was superior to bupropion (RR 2·02, 95% CI 1·04-3·93; p=0·038) but no significant difference was found between varenicline and nicotine replacement therapy, or bupropion and nicotine replacement therapy. No agents were associated with changes in psychiatric symptoms, but varenicline was associated with higher rates of nausea than was placebo., Interpretation: We found evidence to support use of pharmacological agents for smoking cessation for people with psychosis. Varenicline might be superior to bupropion; however, additional direct testing and combination trials of pharmacological agents for smoking cessation are required to inform clinical decision making for people with psychosis., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Venous aneurysms are benign vascular lesions usually located in the neck, lower extremity, and abdomen, but rarely in the upper extremity. There may be a mistake or delay in diagnosis because they are uncommon. We report a case of a healthy 54-year-old man who had a cephalic venous aneurysm in his wrist that grew slowly over 20 years. The diagnosis was made on MRI and confirmed with excisional surgery. Radiologists should consider venous aneurysms in the differential when evaluating soft tissue masses as they will often be the first to make the correct diagnosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate whether newly identified genetic loci for primary angle-closure glaucoma (PACG) are associated with early stage angle-closure disease defined as primary angle closure suspect (PACS)., Design: Case-control study., Participants: A total of 1397 PACS patients and 943 controls of Chinese ethnicity from Singapore and 604 PACS patients and 287 controls of Indian ethnicity., Methods: The 8 PACG single nucleotide polymorphisms (SNPs; rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 son chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) were genotyped by Taqman assays. The association between SNP genotypes and PACS status was measured using logistic regression. A P value of 0.006 was set to account for the testing of 8 genetic loci using a Bonferroni correction. A meta-analysis was conducted to calculate the overall P value and accompanying per-allele odds ratios for each SNP analyzed., Main Outcome Measures: Association of PACG loci with PACS status., Results: The PACS patients were significantly older in both cohorts (Chinese, P < 0.001; Indian, P = 0.002), and there were also more women (P < 0.001, both Chinese and Indian cohorts). In the Chinese cohort, significant evidence of association was noted at 3 SNPs: rs1015213 [A] in PCMTD1-ST18 (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.36-4.11; P = 0.002), rs3816415 [A] in EPDR1 (OR, 1.49; 95% CI, 1.19-1.85; P < 0.001), and rs3739821 [G] in DPM2-FAM102A (OR, 1.40; 95% CI, 1.18-1.65; P < 0.001). Only PCMTD1-ST-18 was replicated modestly in the Indian population (P = 0.056). Meta-analysis showed significant evidence of association for PCMTD1-ST-18 (OR, 1.55; 95% CI, 1.18-2.04; P = 0.002) and DPM2-FAM102A (OR, 1.27; 95% CI, 1.12-1.45; P = 0.0002)., Conclusions: In this study, 2 of 8 PACG-associated loci were associated significantly with PACS status, the earliest stage in the angle-closure glaucoma disease course. The association of these PACG loci with PACS status suggests that these loci may confer susceptibility to a narrow angle configuration., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Infants with an immobile arm may be easily overlooked in primary care settings. Differential diagnoses include injuries, infections, neuropathies, ischemia and rarely, neoplasms. We report the case of a one-year-old boy with weakness in his left arm after minor trauma with a diagnosis of brachial plexus palsy initially. After rehabilitation for 2months, his weakness progressed to unsteady gait and quadriparesis. MRI revealed a huge solid tumor in the left supraclavicular fossa, which also involved the left brachial plexus, upper thoracic cavity, and left paravertebral space with invasion into the spinal canal. Microscopically, the medium-large polygonal tumor cells had an eccentric eosinophilic cytoplasm and immunostaining showed a loss of nuclear INI1 expression. Array comparative genomic hybridization of the tumor tissue confirmed a segmental deletion at chromosome region 22q11.23 involving the SMARCB1 gene. The final diagnosis was cervical paravertebral malignant rhabdoid tumor with intraspinal epidural and intradural invasion, a rare case of extrarenal extracranial rhabdoid tumor (ERRT). The intraspinal part of the tumor was resected followed by interval-compressed chemotherapy with vincristine-doxorubicin-cyclophosphamide alternating with ifosfamide-etoposide (VDC/IE). The tumor showed very good partial response to four cycles of chemotherapy with gradual recovery of neurological symptoms. ERRT is a very rare and aggressive tumor that mainly occurs in infants and children and may manifest with vague neurological symptoms when it involves the spinal cord and/or peripheral nerves. A neoplasm such as ERRT originating from or involving the brachial plexus should be considered in the differential diagnosis of an immobile arm in infancy., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: The Oncotype DX Breast Cancer Assay is validated to assess risk of distant recurrence and likelihood of chemotherapy (CT) benefit in estrogen receptor-positive ESBC in various populations. In Hong Kong, > 80% of breast cancers are early stage breast cancer (ESBC) and > 60% of these women receive CT. This prospective study measured changes in CT type and recommendations, as well as physician impression of assay impact in a homogenous Chinese population., Methods: Consecutive patients with estrogen receptor-positive, T1-3 N0-1mi M0 ESBC were offered enrollment. After surgery, physicians discussed treatment options with patients, then ordered the assay, then reassessed treatment recommendation considering assay results. Changes in treatment recommendation, CT utilization, physician confidence, and physician rating of influence on their treatment recommendations were measured., Results: A total of 146 evaluable patients received pre- and post-testing treatment recommendations. CT recommendations (including changes in intensity of CT) were changed for 34 of 146 patients (23.3%; 95% confidence interval, 16.7%-31.0%); change in intensity occurred in 7 of 146 (4.8%). There were 27 changes in treatment recommendations of adding or removing CT altogether (18.5% change; 95% confidence interval, 12.6%-25.8%). CT recommendations decreased from 52.1% to 37.7%, a net absolute reduction of 14.4% (P < .001; 27.6% net relative reduction). Pre-assay, 96% of physicians agreed/strongly agreed that they were confident in their treatment recommendation; post-assay, 90% of physicians agreed/strongly agreed with the same statement. Thirty percent of physicians agreed/strongly agreed that the test had influenced their recommendation, similar to the proportion of changed recommendations., Conclusions: The Oncotype DX Assay appears to influence physician ESBC adjuvant treatment recommendations in Hong Kong., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) across different severity levels and to assess hemifield differences within each severity level., Design: Cross-sectional study., Participants: Three hundred four patients diagnosed with PACG were recruited from glaucoma clinics at a Singapore hospital., Methods: Point-wise total deviation values were recorded from the static automated perimetry (Swedish interactive threshold algorithm standard program 24-2; Humphrey model 750 [Carl Zeiss Meditec, Dublin, CA]) printouts. Patients were excluded if they had unreliable VFs (fixation losses >33% and false-positive responses >15%), had undergone only 10-2 VF testing, had VF defects not typical of glaucoma, or had undergone cataract extraction. Mild, moderate, and severe VF loss were defined by a mean deviation of -6.00 dB or more, -6.01 to -12.00 dB, and -12.01 dB or less, respectively. Each hemifield was divided into regions according to glaucoma hemifield test sectors. The average mean deviation (MD) of each region was obtained using total deviation values., Main Outcome Measures: Between- and within-hemifield differences of the regions across the severity levels., Results: After excluding ineligible cases, 249 patients with PACG were included in the analysis. Mean age of the patients was 65.7±8.6 years, with a 1:1 gender ratio. The number of patients who had mild, moderate, and severe VFs was 72 (28.9%), 78 (31.3%), and 99 (39.8%), respectively. For between-hemifield comparisons, all regions in the superior hemifield had worse MDs compared with their counterparts in the inferior hemifield across the severity spectrum. Likewise, for within-hemifield comparisons, MDs of the regions gradually worsened with increasing distance from the fixation point., Conclusions: In this group of clinic-based PACG patients, the superior hemifield was found to be affected more severely than the inferior hemifield, and the differences between them increased with worsening disease severity. The damage was consistently more pronounced in the nasal area., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG)., Design: Randomized controlled trial., Participants: Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled., Methods: Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required., Main Outcome Measures: The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery., Results: Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group., Conclusions: After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We studied children younger than 6years old who developed catastrophic epilepsy and were registered in the FACE study group to clarify their clinical characteristics and prevalence of seizure as well as epilepsy types., Subjects: Subjects were prospectively recruited from children with epilepsy who satisfied the following criteria and underwent intensive examination between 2009 and 2012 in 14 collaborative centers: (1) younger than 6years old and (2) more than 10 seizures/month refractory to all available medical treatments including ACTH therapy, leading to significant psychosocial morbidity., Methods: We analyzed epilepsy onset age, predominant seizure type, etiology, neuropsychological findings, and syndromic classification according to the pre-determined registration format., Results: A total of 314 children were enrolled in this study. Epilepsy onset age in 239 cases (80%) was younger than 12months. The most frequent seizure type was epileptic spasms (ES), followed by generalized tonic seizures (GTS), which accounted for 42% and 20%, respectively. West syndrome (WS) was the most frequent epileptic syndrome and accounted for 37%, followed by unclassified epilepsy at 21%, neocortical epilepsy at 19%, Lennox-Gastaut syndrome at 12%, Dravet syndrome at 4%, Rasmussen syndrome at 2%, and others. The two most frequent causes of epilepsy were cortical dysplasia and chromosomal anomalies, as shown in 16% and 6%, respectively. However, the etiology of nearly one half of all patients remained unknown. Psychomotor development was already worse than a moderate degree in 62% of subjects at the first examination., Conclusion: The highest proportion of catastrophic epilepsy was WS and its related syndromes featuring ES and GTS, followed by neocortical epilepsy, whose psychomotor development was significantly retarded at examinations., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: To report the 8-year outcomes of Asian subjects who underwent trabeculectomy augmented by intraoperative 5-fluorouracil (5-FU) or placebo., Design: Retrospective review of a randomized controlled trial., Participants: Subjects with primary open-angle or angle-closure glaucoma., Methods: Study subjects were prospectively followed up for 3 years. After the last subject recruited had completed 8 years of follow-up, the charts of all subjects were reviewed to capture data from the year 3 visit onward. Kaplan-Meier survival function with Cox regression was performed to identify risk factors associated with trabeculectomy failure at 8 years., Main Outcome Measures: The primary outcome was trabeculectomy failure defined as intraocular pressure (IOP) >21 or <6 mmHg on 2 consecutive occasions after the first 6 weeks after surgery, repeat glaucoma surgery, or loss of light perception. Further end points were defined at IOP levels >17 and >14 mmHg. Secondary outcomes included IOP at 8 years and number of glaucoma medications. Complete success was defined using IOP end points ≤ 21, ≤ 17, or ≤ 14 mmHg at 8 years without medications., Results: Of the 243 enrolled subjects, 170 (70.0%) completed 8 years follow-up, 86 in the 5-FU and 84 in the placebo group. There was no significant difference in failure rates at 8 years for the failure definitions of IOP >21 mmHg (11.6% of the 5-FU group vs. 16.7% of the placebo group; P = 1.00), IOP >17 mmHg (23.3% of the 5-FU group vs. 31% of the placebo group; P = 0.78), and IOP >14 mmHg (46.5% of the 5-FU group vs. 58.3% of the placebo group; P = 0.37). Mean IOP at 8 years was 13.7 mmHg in the 5-FU versus 14.4 mmHg in the placebo group (P = 0.24). Mean number of medications was 0.65 drops in the 5-FU versus 0.93 drops in the placebo group (P = 0.06). Complete success with IOP ≤ 21 mmHg at 8 years was achieved in 48 subjects (55.8%) in the 5-FU and 33 subjects (39.3%) in the placebo group (P = 0.09). Absence of bleb microcysts at 1 year, preoperative IOP, and number of bleb needlings performed within the first year were significantly associated with failure., Conclusions: There was no significant difference in IOP between the 5-FU and the placebo group at 8 years., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Primordial germ cells (PGCs), specified early in development, proliferate and migrate to the developing gonad before sexual differentiation occurs in the embryo and eventually give rise to spermatogonia or oogonia. In this study, we discovered that nanos3 3'UTR, a common method used to label PGCs, not only directed PGC-specific expression of DsRed but also prolonged this expression up to 26 days post fertilization (dpf) when DsRed-nanos3 3'UTR hybrid mRNAs were introduced into 1- to 2-cell-stage embryos. As such, we employed this knowledge to express zebrafish leukemia inhibitory factor (Lif), basic fibroblast growth factor (Fgf2) and bone morphogenetic protein 4 (Bmp4) in the PGCs and evaluate their effects on PGC development in vivo for over a period of 3 weeks. The results show that expression of Fgf2 significantly increased PGC number at 14- and 21-dpf while Bmp4 resulted in severe ventralization and death of the embryos by 3 days. Expression of Lif resulted in a significant disruption of PGC migration. Mopholino knockdown experiments indicated that Lif illicited its effect on PGC migration through Lif receptor a (Lifra) but not Lifrb. The general approach described in this study could be used to achieve prolonged PGC-specific expression of other proteins to investigate their roles in germ cell and gonad development. The results also indicate that zebrafish PGCs have a mechanism to stabilize and prolong the expression of mRNA that carries nanos3 3'UTR. Understanding this mechanism may make it possible to achieve prolonged RNA expression in other cell types., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine the efficacy of a subconjunctival injection of hyaluronic acid (HA) with 5-fluorouracil (5FU) formulation as an adjunct in reviving bleb function by needling., Design: Prospective, randomized, controlled trial., Participants: Fifty patients with previous trabeculectomy and scheduled by the managing physician for a needling intervention., Methods: One eye of each patient was randomized to receive needling with HA-5FU mixture or needling with subconjunctival injection of 5FU solution alone., Main Outcome Measures: The primary outcome was the percentage of subjects with an intraocular pressure (IOP) <15 mmHg without any medications at 3 months. Secondary outcomes included the need for additional needling procedures and changes in bleb morphology., Results: Forty-nine subjects (25 in the HA-5FU group and 24 in the 5FU group) completed 3 months of follow-up. At baseline, there was no significant difference between the groups in terms of demographic features, subtype of glaucoma, vertical cup-to-disc ratio, or visual field indices. The mean number of glaucoma medications at baseline was higher in the 5FU group (0.8±1.1 [mean ± standard deviation] vs. 0.2±0.6, P = 0.04). An IOP <15 mmHg without medications was reached in 48.0% of subjects in the HA-5FU group and in 33.3% of subjects in the 5FU group (P = 0.2). At 3 months, both groups demonstrated a significant decrease in IOP from baseline (HA-5FU: decrease of 5.9 mmHg [95% confidence interval, 3.4-8.4]; 5FU: decrease of 6.0 mmHg [95% confidence interval, 3.2-8.2]; P<0.001 for both). Intergroup comparisons for IOP change from baseline was not significant (P = 0.9). However, repeat needling was required more frequently in the 5FU group compared with the HA-5FU group (50.0% vs. 12.0%; P = 0.004). There were no significant differences in the number of reported adverse events, bleb vascularity, or morphology between the 2 groups., Conclusions: Subconjunctival injection of HA-5FU to revive bleb function after bleb needling is as effective as 5FU solution. Fewer repeat needlings were required after treatment with HA-5FU, suggesting that the use of a combined formulation of HA-5FU may improve the overall outcomes of bleb needlings., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the tear cytokine profile from medicated glaucoma patients scheduled for trabeculectomy and to establish whether a specifically elevated cytokine level is related to early postoperative scarring., Design: Prospective case-control study., Participants: Sixty-one patients treated with topical antiglaucoma medications and 29 normal subjects with no prior topical treatment were recruited for the study., Methods: Schirmer strips were used to collect tear samples. A multiplex bead assay was used to quantify the presence of proinflammatory cytokines in the tears. The patients were followed up for 6 months after surgery to determine whether any postoperative intervention to maintain filtering bleb function was required., Main Outcome Measures: The level of cytokines in tear specimens from medicated glaucoma patients was the main outcome measure for the study. The need for postoperative bleb needling within 6 months was a secondary outcome measure., Results: Of the 17 cytokines assayed, only monocyte chemoattractant protein 1 (MCP-1) was elevated significantly in the medicated eyes compared with the unmedicated eyes (P < 0.0004). At 6 months after surgery, 18 (30%) of the 61 eyes required postoperative intervention. A much higher MCP-1 level was detected in these eyes compared with the remaining 43 that did not require intervention (P < 0.0001). The duration of use of topical medication correlated with increasing levels of MCP-1, although the types of glaucoma medication and the number of bottles of medications did not have any significant relationship with the level of MCP-1., Conclusions: In tears from topically medicated glaucoma eyes in an Asian population, MCP-1 was found to be the predominant cytokine elevated. Eyes with a propensity to scar in the early postoperative period have a significantly raised level of MCP-1., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate diurnal intraocular pressure (IOP) fluctuation in eyes with angle closure in comparison with normal subjects and to look for associated risk factors for IOP fluctuation., Design: Prospective, cross-sectional study., Participants: Ninety-eight eyes of 98 Asian subjects with angle closure (consisting of 32 primary angle-closure suspects [PACS], 34 subjects with primary angle closure [PAC], and 32 subjects with primary angle-closure glaucoma [PACG]) and 21 eyes of 21 normal control subjects., Methods: All angle-closure subjects were enrolled after laser peripheral iridotomy but before commencement of any medical or surgical treatment. Ophthalmic examination, including dynamic gonioscopy and automated perimetry, were performed, and diurnal IOP measurements were obtained using noncontact air-puff tonometry at hourly intervals between 8:00 am and 5:00 pm. Mean diurnal IOP, peak diurnal IOP, trough IOP, and IOP fluctuation (peak IOP-trough IOP) were compared between groups. Multiple linear regression analysis was performed to study the association of IOP fluctuation with clinical variables such as age, extent of peripheral anterior synechiae (PAS), central corneal thickness, vertical cup-to-disc ratio, and pattern standard deviation (PSD) on automated perimetry., Main Outcome Measures: Mean diurnal IOP, peak IOP, and IOP fluctuation., Results: Most subjects were Chinese (89.1%) and female (61.3%). Intraocular pressure fluctuation was significantly higher in PACG (5.4+/-2.4 mmHg) and PAC (4.5+/-2.3 mmHg) subjects compared with PACS subjects (3.7+/-1.2 mmHg) and normal controls (3.8+/-1.1 mmHg; P = 0.005), with highest IOP found in the early morning. The combined PACG and PAC group had more than twice the risk (odds ratio, 2.38; 95% confidence interval, 1.1-5.1; P = 0.025) of having IOP fluctuation of more than 3 mmHg compared with the combined PACS and normal group. Extent of PAS (Pearson's correlation coefficient, r = 0.37; P = 0.0001) and visual field PSD (r = 0.34; P = 0.0002) were found to be associated with greater IOP fluctuation., Conclusions: The PACG and PAC eyes showed diurnal IOP fluctuation of 4 to 5 mmHg, and this fluctuation was higher than in PACS subjects and normal controls. The degree of PAS and visual field loss were associated with IOP fluctuation in PAC and PACG eyes.

Linear scleroderma is a form of localized scleroderma characterized by sclerotic lesions distributed in a linear, band-like pattern. The "en coup de sabre" subtype of linear scleroderma is more often associated with systemic morbidity, including ocular, oral, and neurological abnormalities. Here, we report one patient with typical linear scleroderma "en coup de sabre" (LSCS). Initially, he presented with refractory partial seizures before the characteristic skins lesion on his head developed. This was a rare case with obvious brain parenchyma involvement. We did not prescribe medication but performed serial brain magnetic resonance imaging follow-up for the intraparenchymal lesion. The atrophic changes of the skin, face and brain remained the same, and his seizures had not worsened at the most recent follow-up. Parry-Romberg syndrome, a very similar condition, should be differentiated from LSCS.

Purpose: To report 3-year results of a randomized, controlled trial comparing the use of a single application of 5-fluorouracil (5-FU) with placebo in trabeculectomy surgery., Design: Prospective, randomized, double-blinded treatment trial., Participants: Two hundred forty-three Asian patients with primary open-angle or primary angle-closure glaucoma undergoing primary trabeculectomy., Methods: One eye of each patient was randomized to receive either intraoperative 5-FU or normal saline (placebo) during trabeculectomy., Main Outcome Measures: Primary outcome measure was the level of intraocular pressure (IOP). Secondary outcomes were progression of visual field loss, rates of adverse events, and interventions after surgery., Results: Of the 288 eligible patients, 243 were enrolled and 228 completed 3 years follow-up; 120 patients received 5-FU and 123 received placebo. Trial failure, according to predefined IOP criteria, was lower in the 5-FU group compared with the placebo group, although the difference was only significant with a failure criterion of IOP >17 mmHg (P = 0.0154). There was no significant difference in progression of optic disc and/or visual field loss over 36 months between 5-FU and placebo (relative risk [RR], 0.67; 95% confidence interval [CI], 0.34-1.31; P = 0.239). Uveitis occurred more often in the 5-FU-treated group (14/115 [12%] vs 5/120 [4%]; P = 0.032)., Conclusions: This is the first masked, prospective, randomized trial reporting the effect of adjunctive 5-FU in trabeculectomy surgery in an East Asian population. The trial shows that an increased success rate can be achieved for several years after a single intraoperative treatment with 5-FU. We conclude that 5-FU is relatively safe and can be routinely used in low-risk East Asian patients., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

We report the case of a girl with hemimegalencephaly (HME) and Lennox-Gastaut syndrome (LGS) treated by callosotomy at 1 year of age. Over 10 years, her seizure frequency and severity decreased markedly. Hemispherectomy is the main surgical option for HME although HME appears to correlate with a less favorable seizure outcome. However, the clinical presentation of LGS and possible generalized cortical dysplasia, which is indicative of a secondarily generalized epilepsy, might predict a favorable surgical outcome of corpus callosotomy in patients of HME, as in our case.

In this study, we attempted to determine if different locations of a tumor influence the hypothalamopituitary axis function and outcomes with childhood craniopharyngiomas. The preoperative, postoperative, and long-term follow-up endocrinological disturbances of 66 children with a craniopharyngioma were retrospectively studied. The patients were divided into two subgroups according to the location of the tumor (intrasellar and third ventricle floor). The mean age at onset was 8.02 (range, 1.42-17.58)years. These patients were followed-up for a median duration of 7.2 (range, 2-22)years. Vision problems as the first symptom were more common in Group One (with intrasellar tumors) compared to Group Two (55.6% vs 15.4%; p=0.001; Fisher's exact test). Increased intracranial pressure was the most common initial symptom in patients in Group Two (51.3%) and the second most common symptom in Group One (37%). The majority of patients in both Group One and Group Two required some forms of pituitary hormone supplements (96% vs 84%). At the last follow-up, more patients with intrasellar craniopharyngiomas needed cortisone supplements (79.2% in Group One vs 45.9% in Group Two; p=0.016; Fisher's exact test); however, children with third ventricle floor tumors had more prevalent weight gain (4.2% in Group One vs 27.0% in Group Two; p=0.038; Fisher's exact test). There were different initial presentations and endocrinological outcomes between children with intrasellar and third ventricle floor craniopharyngiomas. The intrasellar tumors had greater pituitary hormone disturbance. However, at the long-term follow-up, children with third ventricle floor tumors had a greater prevalence of being overweight and obese, which was associated with hypothalamic dysfunction.

Purpose: This retrospective study was designed to clarify the role of West syndrome in post-callosotomy seizure outcome in patients with Lennox-Gastaut syndrome., Methods: From September 1989 to May 1999, 74 patients diagnosed with Lennox-Gastaut syndrome received anterior corpus callosotomy at Taipei Veterans General Hospital, Taiwan. All patients were followed for more than 4 years after surgery. Among them, 21 (28.4%) patients had a history of West syndrome (Group A) whereas 53 (71.6%) patients did not have a history of West syndrome (Group B). Postoperative seizure outcome was compared for these two patient groups., Results: A total of 16 (76.2%) patients in Group A (positive history) and 29 (54.7%) patients in group B (negative history) achieved significant improvement in seizures after surgery (e.g., seizure reduction of more than 50%). There was no statistical significance (p=0.088) in the difference in outcome between the two groups., Conclusions: A history of West syndrome does not appear to influence post-callosotomy seizure outcome in patients with Lennox-Gastaut syndrome.

Objective: To analyze findings and acute changes in electrocorticograms (ECoGs) obtained during corpus callosotomy in order to identify any relationships with the postoperative outcome of seizure activity., Methods: We retrospectively analyzed ECoGs obtained during anterior callosotomy (4-6 cm) in 48 patients with Lennox-Gastaut syndrome (32 boys and 16 girls, age 1-20 years, mean age 7.6 years) who underwent surgery between July 1993 and November 1996 to correlate recording findings with postoperative seizure activity. At the time of analysis, all patients had been followed postoperatively for more than 4 years., Results: Of 48 patients, 31 (64.6%) had significant improvement in seizure control after surgery. In pre-excisional ECoGs, 38 (79.2%) of 48 patients had bisynchronous epileptiform discharges. Patients (23 of 33 patients, 69.7%) with significant blockage of bisynchronous discharges recorded during callosotomy achieved the best postoperative seizure outcomes, but the difference did not reach statistical significance (P>0.05)., Conclusions: Based on our experience, changes in ECoG during callosotomy do not predict postoperative seizure outcome. Insignificant blockage of bisynchronous epileptiform discharges in ECoGs during callosotomy does not predict a worse prognosis than that associated with significant intraoperative blockage.

Background: Stereotactic breast biopsy of non-palpable lesions using the vacuum-assisted core needle biopsy (CNB) device and the large core excision biopsy system is a reliable biopsy method when compared with open biopsy. Its use in Western countries is well accepted. This study aimed to assess the feasibility and results of using these systems to perform stereotactic biopsy in Asian women., Methods: A total of 114 patients with non-palpable mammographic lesions underwent stereotactic breast biopsy using the vacuum-assisted CNB device and the large core excision biopsy system between November 1999 and December 2002. The indications for biopsy were mammographic abnormalities considered indeterminate or suspicious that were not palpable or visible on ultrasound. The methods adopted for biopsy in Asian women were reviewed and the results including the final pathology, complications, scarring and acceptance by patients were recorded., Results: Stereotactic breast biopsy was performed using the vacuum-assisted CNB device in 107 patients and the large core excision biopsy system in seven patients. Of those who underwent biopsy using the vacuum-assisted CNB device, 15 (14%) had moderate to severe bleeding during the procedure and seven (6.5%) had severe bruising afterwards. Carcinoma was detected in 31 of the 114 patients (27.2%)., Conclusion: Although Asian women in general have smaller and denser breasts than their Western counterparts, stereotactic breast biopsy using the vacuum-assisted CNB device and the large core excision biopsy system was feasible with modification of the individual steps during the procedure. Our results are comparable with those published previously and the procedure was well accepted by patients.

We have investigated the interaction between a new antineoplastic drug, 4-tert-butyl-[3-(2-chloroethyl)ureido] benzene (tBCEU), and distearoylphosphatidylcholine bilayers using differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and high-pressure infrared spectroscopy. The results obtained with the three different techniques indicate that the drug incorporates in the lipid bilayer. More specifically, the incorporation of the tBCEU results in a decrease in the phase transition temperature of the lipid and in an increase in the amount of gauche conformers in the liquid-crystalline phase. In the gel phase, high-pressure FT-IR results indicate that the incorporation of tBCEU decreases the acyl chain packing. In addition, the results suggest the presence of hydrogen bonding between the lipid carbonyl group and a hydrogen bond donor in the tBCEU molecule. A possible candidate for this donor is the NH group adjacent to the phenyl ring. A model is proposed for the incorporation of tBCEU in lipid bilayers, with the hydrophobic portion of the drug intercalated between the lipid bilayers and the hydrophilic region located close to the interfacial region of the bilayer.