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Objective: The POSEIDON criteria stratified patients with poor ovarian response into four subgroups with exclusive characteristics and assisted reproductive technology success rates. However, limited studies focused on miscarriage in the POSEIDON population. This study aimed to explore whether the miscarriage rate different among low prognosis patients according to POSEIDON criteria., Materials and Methods: This is a retrospective observational study. All clinical pregnancies achieved after in vitro fertilization or intracytoplasmic sperm injection treatment between January 1998 and April 2021 were analyzed. The primary outcome was miscarriage, defined as the pregnancy loss before 20 weeks of gestation age. Miscarriage rate was estimated per clinical pregnancy and gestational sac., Results: A total of 1222 clinical pregnancies from 1088 POSEIDON patients met the inclusion criteria. The miscarriage rates per clinical pregnancy in each POSEIDON subgroup were as follows: Group 1: 11.7 %, Group 2: 26.5 %, Group 3: 20.9 %, and Group 4: 37.5 %. The miscarriage rate per gestational sac showed a similar trend as the clinical miscarriage rate. Multivariate regression analysis showed that advanced maternal age is an independent factor for miscarriage (Group 2 vs. 1: OR 2.476; Group 4 vs. 3: OR 2.252). Patients with diminished ovarian reserve (DOR) have higher miscarriage risks but without significance (Group 3 vs. 1: OR 1.322; Group 4 vs. 2: OR 1.202)., Conclusion: Miscarriage rates differed among low prognosis patients according to the POSEIDON criteria. Age remains a determined risk for miscarriage. DOR might be a potential factor for miscarriage, but it didn't account for a significant impact in POSEIDON patients., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This study aimed to investigate the association between semen quality and air pollution in southern Taiwan., Materials and Methods: In this retrospective study, 4338 males aged 21-70 years were recruited between 2001 and 2018 from a reproductive medical center. Semen quality was assessed according to standardized methods outlined in the World Health Organization (WHO) Laboratory Manual 1999 and 2010, including total sperm count, progressive sperm motility (%), rapid progressive sperm motility (%), and sperm with normal morphology (%). All designated national air quality automatic continuous monitoring stations measured the levels of air pollution [particulate matter (PM 10 and PM 2.5 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), carbon monoxide (CO), ozone (O 3 )], and was documented by Environmental Protection Administration in Taiwan. We collected data on the levels of air pollution based on the participants' residential addresses., Results: In our study, we found that progressive and rapid progressive sperm motility significantly decreased annually (p < 0.05). In addition, increasing age influenced total sperm count, progressive sperm motility, rapid progressive sperm motility, and sperm with normal morphology (p < 0.05). Among different air pollution, we observed SO 2 was associated with lower rapid progressive sperm motility and lower sperm with normal morphology (β = -0.103, p = 0.043; β = 0.118, p = 0.001, respectively). However, NO 2 was associated with higher rapid progressive sperm motility and a high number of sperm with normal morphology (β = 0.129, p = 0.002; β = 0.127, p < 0.001, respectively)., Conclusions: The semen quality in southern Taiwan appears to have declined in recent years. The participant's age for semen analysis was most strongly associated with semen parameters, Moreover, a significant association between SO 2 and NO 2 levels and semen motility was observed, even after adjusting for multiple comparisons. Further study is required to analyze the dose-dependent effect of SO 2 and NO 2 on semen parameters., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Aims: Cellulose nanofibrils (CNF, or NFC), cellulose nanocrystals (CNC, or NCC), and Tempo (2,2,6,6-tetramethylpiperidine-1-oxyl radical) oxidized CNF (Tempo-CNF) were compared for the short-term effect on mice fed with a high-fat and high-sugar (Western diet, WD) to investigate their effect when combined with a sub-optimal diet., Scope: Thirty C57B/C female mice (10 weeks old; 5-6 mice/group) were given water, cellulose, or three types of nanocellulose once daily in a dose of 30 mg/kg body weight by oral gavage. After six weeks, weight changes, fecal output, glucose homeostasis, and gut permeability showed no significant among groups. Serum analysis including triglycerides, cholesterol and total bile acids and small intestinal morphology including villus length, villus width, crypt depth, goblet cell count and goblet cell density were no difference for all groups. Only CNC group had higher excretion of bile acids in the feces., Conclusions: These results suggest that current treated dose using three types of nanocellulose had no detrimental effects on blood lipid level and small intestinal morphology., Competing Interests: Declaration of competing interest The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Concomitate supraspinatus and subscapularis tear is not rare, and the suture bridge technique is one of the most effective methods for rotator cuff repair. However, some limitations exist in the use of such a technique for simultaneous supraspinatus and subscapularis repair. We introduce the technique of a merged lateral row for suture bridge rotator cuff repair, in which the lateral suture of the supraspinatus and subscapularis is placed in the greater tuberosity. We believe that this technique can reduce both the duration and cost of surgery and decrease soft-tissue damage. It can also allow the "comma tissue," to be simultaneously repaired., (© 2022 The Authors.)

Background: The presence of only morphologically poor embryos (MPEs) on day3 is common in autologous in vitro fertilization (IVF), particularly among p Tel: 886-7-7317123 Ext. 8916. Fax: 886-7-7322915.atients who have advanced maternal age or are poor responders. However, there are limited data regarding the disposition of embryos from patients who only produced MPEs on day3. The present study was designed to investigate the possible benefits of extended culturing MPEs. Try to detect whether the extended culture (day4 or day5 culture) can improve the live birth rate per cycle?, Methods: This retrospective, observational, single-center, cohort study examined 224 IVF/intracytoplasmic sperm injection (ICSI) cycles between January 2010 and June 2015, in which women only produced MPEs on day3. A total of 544 MPEs were analyzed. The defines a day3 embryo as an MPE if it fails to develop to eight cells, blastomeres of equal size, and less than 20% cytoplasmic fragments. Of the 224 cycles, 89 (39.7%) underwent fresh embryo transfer on day3, and 135 (60.3%) underwent extended culture. Of the 135 extended cultures, 54 cycles (40.0%) experienced day4, or day5 embryo transfer, 16 cycles (11.9%) had all embryos frozen, and 65 cycles (48.1%) had total embryo arrest., Results: Analysis of patient baseline demographic data, cycle characteristics, and cycle outcomes for day3 transfer group and extended culture group indicated that a higher body mass index in the day3 transfer group was the only significant difference (p = 0.006). Both fresh transfer groups had low live birth rates (LBRs) (4.5% vs. 7.4% p = 0.46). After extended culture, 65 cycles (48.1%) were cancelled because the embryos exhibited developmental arrest and 70 cycles (51.9%) grew to day4 or day5. Thirteen frozen embryo transfer (FET) cycles and 22 frozen blastocysts derived from MPEs were thawed. There were more high-quality embryos (p < 0.001), higher implantation rates (IRs) (p = 0.038), and higher LBRs (p = 0.042) for embryos that underwent FET cycles. MPES in extended culture transfer have favorable survival than MPES in day3 transfer., Conclusion: The extended culture of MPEs in fresh transfer cycles did not increase the LBR. However, younger females with the extended culture of MPEs followed by FET resulted in significantly higher LBRs and may be a feasible strategy to improve outcomes for patients with poor embryo quality. However, day3 embryo transfer may be a better choice if a fresh transfer is unrestricted and avoid the cycle cancellation. Extended culture may decrease to the transfer of developmental potential arrest embryos to patients., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the real-world effectiveness and costs of eribulin to those of capecitabine in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes., Methods: This study extracted data from the Health and Welfare Database in Taiwan to identify MBC patients, and then eribulin and capecitabine users were matched at a 1:1 ratio by age, residential region, Charlson Comorbidity Index score, and molecular subtype of BC cell. The overall survival (OS) and time-to-treatment discontinuation (TTD) curves were plotted using the Kaplan-Meier method. Healthcare utilization and costs between the two groups were compared., Results: A total of 24,550 MBC patients were identified, and 298 patients were enrolled in each group after matching. The median OS was 11.8 months for eribulin (95%CI: 11.5-13.5 months) and 15.2 months for capecitabine (95%CI: 15.3-17.9 months; HR = 1.7, p < 0.0001). The median TTD was 4.0 months for eribulin and 6.6 months for capecitabine (HR = 1.6; p < 0.0001). No significant difference was found between the two groups in patients with >4 prior chemotherapy agents (OS: HR 1.1, 95%CI 0.8-1.5; TTD: HR 1.2, 95%CI 0.9-1.7). The total healthcare costs per patient during the treatment period were NT$580,523.8 for eribulin versus NT$497,223.8 for capecitabine (p < 0.0001), and total medication costs were NT$438,335.8 and NT$348,438.4 (p < 0.0001), respectively., Conclusion: Although eribulin showed an attenuated effect in the real-world setting in Taiwan, it may serve as an alternative for capecitabine in a heavy pretreated population. The total healthcare and medication costs were found to be higher with eribulin treatment., Competing Interests: Declaration of competing interest All author declare that they have no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To early detect coronavirus disease 2019 on an international cruise ship and prevent its spread, Taiwan's Central Epidemic Command Center implemented on-board quarantine measures on a cruise ship docked at the Port of Keelung, Taiwan, on February 8, 2020. Quarantine officers, medical professionals, and administrative staff from competent authorities conducted fever screening and investigated the present illness and travel history of 1738 passengers and 776 crew members on the ship. Throat swabs were collected from 128 (5.1%) passengers and crew members with fever or respiratory symptoms during the past 14 days or travel history to China, Hong Kong, or Macao within 30 days. All swabs tested negative for severe acute respiratory syndrome coronavirus 2 at the national reference laboratory. The whole process, from on-board preparation to the completion of testing, took 9 h. All passengers and crew were permitted to disembark and were required to take 14-day self-health management measures. No cases were reported by the end of the self-health management period., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Social deficit is a core symptom in autism spectrum disorder (ASD). Although deep brain stimulation (DBS) has been proposed as a potential treatment for ASD, an ideal target nucleus is yet to be identified. DBS at the central thalamic nucleus (CTN) is known to alter corticostriatal and limbic circuits, and subsequently increase the exploratory motor behaviors, cognitive performance, and skill learning in neuropsychiatric and neurodegenerative disorders., Objective: We first investigated the ability of CTN-DBS to selectively engage distinct brain circuits and compared the spatial distribution of evoked network activity and modulation. Second, we investigated whether CTN-DBS intervention improves social interaction in a valproic acid-exposed ASD rat offspring model., Methods: Brain regions activated through CTN-DBS by using a magnetic resonance (MR)-compatible neural probe, which is capable of inducing site-selective microstimulations during functional MRI (fMRI), were investigated. We then performed functional connectivity MRI, the three-chamber social interaction test, and Western blotting analyses to evaluate the therapeutic efficacy of CTN-DBS in an ASD rat offspring model., Results: The DBS-evoked fMRI results indicated that the activated brain regions were mainly located in cortical areas, limbic-related areas, and the dorsal striatum. We observed restoration of brain functional connectivity (FC) in corticostriatal and corticolimbic circuits after CTN-DBS, accompanied with increased social interaction and decreased social avoidance in the three-chamber social interaction test. The dopamine D2 receptor decreased significantly after CTN-DBS treatment, suggesting changes in synaptic plasticity and alterations in the brain circuits., Conclusions: Applying CTN-DBS to ASD rat offspring increased FC and altered the synaptic plasticity in the corticolimbic and the corticostriatal circuits. This suggests that CTN-DBS could be an effective treatment for improving the social behaviors of individuals with ASD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Maternal nutrition is an extremely important health issue. We evaluated the impact of maternal high fat diet (HFD) on pregnancy outcomes, elucidated how the rat placenta and fetus respond to diet manipulation based on fetal sex, and identified candidate genes and pathways., Methods: Rats were fed a normal or HFD diet for 10 weeks before conception and during gestation. The placenta was collected on gestational day 21 and sexed. Placental histology was analyzed and placental candidate genes and pathways were identified using whole-genome RNA next-generation sequencing., Results: Pup weights in both sexes from HFD dams were reduced. The weight of the placenta from the HFD group was also decreased in both sexes, but changes in placental layer distributions were only significant for female fetuses. Maternal HFD altered the placental transcriptome in a sex-specific manner. Activation of the placental renin-angiotensin system (RAS) by maternal HFD was associated with fetal growth restriction in both fetal sexes., Conclusions: The placenta reacts to maternal HFD by altering the placental layer distribution and gene expression in a sex-specific manner. The male placenta in late gestation is thought to exhibit greater plasticity relative to the female placenta; however, fetuses of both sexes exhibited similar growth restriction. Our data reveal an association between the placental RAS and HFD-induced fetal growth restriction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Clinical prognosis appears to be varied in females with poor ovarian response (POR), and poor responders defined by the Bologna criteria might not be sufficiently homogeneous. The aim of this study was to determine the major predictor of reproductive outcomes in extremely low oocyte retrieval cycles., Materials and Methods: A cohort of fresh in vitro fertilization/intracytoplasmic sperm injection cycles (n = 858) was analyzed from January 2001 to September 2014. Females from whom zero, one, two, or three oocytes were retrieved following ovarian stimulation were examined. Univariate analyses were performed to determine the association of pregnancy rate with potential confounding variables. Multiple logistic regression analysis was subsequently performed to identify factors that affected the occurrence of pregnancy., Results: The clinical pregnancy rate was higher in women aged < 40 years, long protocol, and high embryo score in univariate analysis. After adjusting for confounding factors in multivariate analysis, the maternal age [odds ratio (OR) = 0.91], primary or secondary infertility (OR = 1.99), number of matured oocytes retrieved (OR = 0.64), and score of embryos transferred (OR = 1.39) were significantly associated with the clinical pregnancy rate per cycle and per transfer. In the age subgroup analysis, POR females aged < 35 years significantly demonstrated the highest number of matured oocytes, embryo scores, and clinical pregnancy rates compared with POR females aged 35-40 years and ≥ 40 years., Conclusion: This study highlights the predictive value of maternal age and embryo quality on the probability of pregnancy in females with extremely low oocyte retrieval cycles. Young females with few eggs collected can still achieve acceptable pregnancy probability as long as they have good-quality embryos. Future randomized control trials for POR using the Bologna criteria should first stratify patients into different age groups., (Copyright © 2017. Published by Elsevier B.V.)

Glucocorticoids, predominantly dexamethasone (DEX), are widely used to reduce the risk of prematurity-related chronic lung disease. However, prenatal DEX treatment links to adverse effects in later life, including hypertension. Given that sex differences exist in the blood pressure (BP) control, and that renal transcriptome is sex-specific, thus we intended to elucidate whether prenatal DEX-induced programmed hypertension is in a sex-specific manner and identify candidate genes and pathways using the whole-genome RNA next-generation sequencing (NGS) approach. Offspring were assigned to 4 groups (n=7-8/group): male control (MC), female control (FC), male DEX (MD), and female DEX (FD). Dexamethasone (0.1mg/kg body weight) or vehicle was intraperitoneally administered to pregnant SD rats from gestational day 16-22, to construct a DEX model. Rats were killed at 16weeks of age. Prenatal DEX induced sex-specific increase in BPs in male but not female adult offspring. Prenatal DEX elicited renal programming in a sex-specific fashion as demonstrated by 8 and 18 DEGs in male and female offspring, respectively. Among them, two genes, Hbb and Hba-a2, were shared. The resistance of female offspring to prenatal DEX-induced programmed hypertension is related to a lower Agt expression. Prenatal DEX induced programmed hypertension in adult male but not female offspring, which was related to renal programming affecting sex-biased genes and the RAS. Early identification of sex-specific underlying mechanisms could provide novel deprogramming strategy to reach maximal optimization in both sexes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Nitric oxide (NO) and hydrogen sulfide (H2S) pathways are involved in the development of hypertension, a condition that can originate from early life. We examined whether asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor)/NO and H2S generating pathway contributed to programmed hypertension in offspring exposed to prenatal dexamethasone (DEX) and postnatal high-fat (HF) and whether N-acetylcysteine (NAC) therapy prevented this process. We examined 16-week-old male rat offspring from five groups: control, DEX (0.1 mg/kg i.p. from gestational day 16-22), HF (58% high-fat diet from weaning to 4 months of age), DEX+HF, and NAC (1% in drinking water during lactation). Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which was prevented by maternal NAC therapy. We attributed the protective effects of NAC on two-hit induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma l-arginine-to-ADMA ratio, upregulation of gene expression of H2S-generating enzymes, restoration of renal 3-mercaptopyruvate sulphurtransferase (3MST) protein levels and activity, induction of plasma glutathione level, and reduction of oxidative stress. Manipulation of the ADMA-NO and H2S-generating pathways by maternal NAC therapy may be a potential approach to prevent programmed hypertension induced by two-hit insults., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Ectopic pregnancy is an obstetrical disease that is potentially associated with maternal death in the first trimester. It is one of the well-known complications following in vitro fertilization (IVF) with embryo transfer (ET). The incidence of ectopic pregnancy is estimated to be 2.1-8.6% of clinical pregnancy after IVF-ET, which is higher than natural conceptions (incidence rate 2%). This study aimed to re-evaluate the ectopic pregnancy rate in patients undergoing IVF-ET and to investigate the effects of embryo stage and frozen-thawed blastocyst transfer and ET during full bladder distention on ectopic pregnancy rate., Materials and Methods: This retrospective study reviewed women who achieved a clinical pregnancy after IVF-ET at the Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital between 1999 and 2013. We compared ectopic pregnancy rate following Day 3 ET with Day 5 ET, and after fresh ET with thawed ET. Besides, multivariate analysis was used to clarify the factors affecting ectopic pregnancy after IVF-ET., Results: Of the total 1213 clinical pregnancies after fresh ET, 18 (1.5%) were verified as ectopic, which is similar to the rate following natural conception. The ectopic pregnancy rates were similar for Day 3 (1.2%) and Day 5 (1.7%) ETs. The incidence of ectopic pregnancy in thawed ET cycles (0.6%) was not significantly reduced than fresh ET cycles (1.5%). Tubal ET (TET) and ET under full bladder distention had a significant effect on ectopic pregnancy., Conclusion: Thawed ET was not associated with a lower incidence of ectopic pregnancy than fresh ET, and embryo stage did not affect the rate of ectopic pregnancy. In addition, TET and ET under conditions of full bladder distention may increase the ectopic pregnancy rate., (Copyright © 2015. Published by Elsevier B.V.)

Background: Allergic rhinitis (AR) is the most common chronic allergic disease in school-age children. An increased prevalence of attention deficit hyperactivity disorder (ADHD) in AR patients has been reported; however, inattention and hyperactivity in AR children have not been investigated using objective and scientific measurements., Methods: We used AR symptom score, ADHD symptom scale, and computerized continuous performance test (CPT) to study the attention and impulsivity in AR children, age-matched controls, and ADHD children (aged 6-15 years). Univariate and multivariate linear regression analyses were applied to identify risk factors for impulsivity and inattention in AR children., Results: Twenty-nine controls, 10 ADHD, and 105 AR children were enrolled. There were no differences in age and sex among the three groups. The scores of Hyperactivity/Impulsivity subscales of ADHD symptoms from both parents and teachers were significantly higher in the AR children. The CPT in AR children revealed higher commission errors, shorter reaction times, and more perseveration. Risk factors for inattention and impulsivity in AR children included younger age, male sex, higher AR symptom scores, persistent AR, moderate/severe AR, multiple atopic diseases, family history of atopy, and possible comorbidity with ADHD., Conclusion: Care for AR children should not only involve treating their allergy, but also monitoring the possible comorbidities of impulsivity and inattention. In children with impulsivity, AR should be considered in addition to ADHD., (Copyright © 2013. Published by Elsevier B.V.)

Objective: To determine whether advanced male age influences the outcome of intracytoplasmic sperm injection (ICSI) following the cryopreservation of spermatozoa obtained through testicular sperm extraction (TESE)., Materials and Methods: Data were collected from infertile couples suffering from azoospermia who underwent TESE and ICSI from January 1998 to August 2010. There were 212 ICSI cycles using extracted testicular sperm after cryopreservation in this retrospective clinical analysis. The participating men all underwent testicular biopsy and subsequent tissue cryopreservation in a single academic tertiary care medical center. Those cryopreserved sperm were used during consecutive intracytoplasmic sperm injection treatment cycles. Female partners underwent individualized controlled ovarian hyperstimulation programs., Results: A total of 184 ICSI cycles were divided into the following two evaluation designs: (1) total cycles irrespective maternal age; (2) ICSI cycles with maternal age <34 years. Male partners were stratified into age categories at 5-year intervals (31-35 years, 36-40 years, and 41-51 years) in these two designs. In the first design, most outcomes of assisted reproductive techniques were similar during the three groups, but the maternal age is much lower in the first group, and the mean number of retried oocytes and estradiol level on the day of human chorionic gonadotropin injection was significantly higher in the first group. In the second design, the outcome of intracytoplasmic sperm injection and clinical factors including the estradiol level on the day of human chorionic gonadotropin injection, the number of retrieved oocytes, the rate of cleaved oocytes, the number of transferred embryos, the numbers of transferred good embryos, the clinical pregnancy rate per transfer cycle and the implantation rate were similar among the three groups of women aged <34 years after adjusting for female age., Conclusions: There is insufficient evidence to demonstrate an unfavorable effect of advanced paternal age on the fertility outcome for TESE-ICSI. The thawed testicular spermatozoa from males aged ≤ 40 years did not have an adverse impact on ICSI outcomes., (Copyright © 2013. Published by Elsevier B.V.)

Study Objective: To evaluate the effects of salpingectomy on the ovarian response to gonadotropins and in vitro fertilization-embryo transfer (IVF-ET) cycle outcomes in women with tubal factor infertility., Design: A retrospective study (Canadian Task Force Classification II-3) SETTING: An in vitro fertilization laboratory in a university hospital in Taiwan., Patients: We analyzed the outcomes of 288 consecutive fresh IVF-ET cycles in 251 consecutive women with tubal factor infertility from January 2001 to December 2011. Two hundred eighty-eight cycles were divided into 2 groups comprising 103 cycles with laparoscopic salpingectomy and 185 cycles with prior bilateral tubal sterilization, laparoscopic tuboplasty, or proximal tubal occlusion as the control group., Interventions: Controlled ovarian hyperstimulation and IVF-ET., Measurements and Main Results: The main outcome was measured by comparing the duration of stimulation, number of gonadotropin ampoules per cycle, number of follicles, number of oocytes retrieved, fertilization rate, implantation rate, clinical pregnancy rate, and live birth rate. We observed no significant difference in any ovarian response parameter between the salpingectomy and nonsalpingectomy groups. Implantation rates, clinical pregnancy rates, and live birth rates were similar. The mean numbers of follicles and oocytes retrieved ipsilateral to the operated side in the salpingectomy group were similar to the numbers of follicles and oocytes retrieved from the nonoperated ovary., Conclusions: Laparoscopic salpingectomy did not have a negative effect on the ovarian response in women with tubal factor infertility., (Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.)

To assist certain patient populations who are unable to tolerate intraoral films and/or sensors during endodontic therapy, an alternative technique (extraoral film placement) has been innovated by Newman and Friedman (2003). In this study, we devise and test a film/sensor-beam alignment aiming device for taking a periapical radiograph using this extraoral radiographic technique. An instrument is assembled from the following components: (1) two locator rings for bite-wing radiography, (2) two metal supporting indicator rods for bite-wing radiography, (3) a bite block for horizontal bite-wing radiography, and (4) a rubber tube of about 2 cm in length. Using our newly-devised aiming device to take periapical radiographs using the extraoral technique, appropriate images of the left upper and right lower molar areas for a series of 12 adult volunteers were successfully obtained. Angulation of the x-ray cone, with reference to the horizontal plane, was -20 degrees to -30 degrees and -10 degrees to -15 degrees for the upper and lower teeth, respectively. This study therefore shows that appropriate images can be easily obtained using this aiming device.

Inorganic arsenic has strong human carcinogenic potential, but the availability of an animal model to study toxicity is extremely limited. Here, we used the transgenic zebrafish line Tg(k18(2.9):RFP) as an animal model to study arsenite toxicity. This line was chosen because the red fluorescent protein (RFP) is expressed in stratified epithelia (including skin), due to the RFP reporter driven by the promoter of the zebrafish keratin 18 gene. We titrated doses of inorganic arsenite for zebrafish embryos and found that arsenite exposure at 50 microM for 120 h was suitable for mimicking a long-term, chronic effect. When embryos derived from Tg(k18(2.9):RFP) adults were treated with this arsenite dose and time of exposure, abnormal phenotypes were not noticeable under the light microscope. However, arsenic keratosis was visible in the epithelial cells under the fluorescent microscope. Morphological defects became more severe with increased dose and exposure duration, suggesting that the severity of skin lesions was dose- and time-dependent. Histochemical examination of keratosis after 4',6'-diamidino-2-phenylindole hydrochloride (DAPI) staining showed that the epithelial cells overproliferated after treatment with arsenite. Therefore, this Tg(k18(2.9):RFP) zebrafish line is an excellent model for studying toxicity induced by inorganic arsenite and may have potential for studying other environmental pollutants.

Zebrafish cytokeratin 18 (K18) is one of the type I keratin genes expressed the earliest after amputation of the zebrafish fin, but its spatiotemporal expression during early development is unclear. Whole-mount in situ hybridization revealed that k18 was a maternally inherited gene and that its expression is restricted to the single layer of enveloping cells on the surface of embryos during the gastrula stage. At later stages, K18 expression was detected in the epithelial cells, pronephric duct, digestive tract, dorsal aorta, and fins. By using microinjection, we generated the transgenic line Tg(k18(2.9):RFP), which carries an upstream 2.9-kb segment of k18 gene fused with a red fluorescent protein (RFP) reporter. The spatiotemporal distributions of red fluorescent signal of Tg(k18(2.9):RFP) line correlated well with endogenous k18 transcripts detected by whole-mount in situ hybridization, indicating that this line is capable of recapitulating endogenous k18 expression patterns. We noticed that the red fluorescence appeared strongly in the dorsal, pectoral, pelvic, anal, and caudal fins when transgenic fish became adults. Interestingly, we also found that when F1 female from the Tg(k18(2.9):RFP) line were mated with wild-type males, 100% (326/326) of F2 offspring expressed red fluorescence at the one-cell stage. In contrast, when F1 male from the Tg(k18(2.9):RFP) line were mated with wild-type females, only 49.8% (138/277) of F2 embryos exhibited red fluorescence. On the basis of these findings, we suggest that the transcript of zebrafish K18 is inherited as a maternal effect. We believe that Tg(k18(2.9):RFP) fish should be an excellent experimental animal for studying the zygotic regulatory mechanism of k18.

We isolated a 2.3 kb DNA segment from the upstream region of the zebrafish cytokeratin II (zfCKII) gene. Transgenic embryos, produced by using a series of 5' deletions linked to the red fluorescent protein (RFP) reporter, showed that the -141/+85 segment of zfCKII directed RFP expression in epidermal cells, whereas the -111/+85 segment did not. When -141/-111 was deleted from -355/+85 and microinjected into one-celled embryos, no fluorescence was observed at later stages, indicating that the -141/-111 segment is required for green fluorescent protein expression in epidermal cells. Furthermore, when a putative KLF-binding site at -119/-117 was mutated, RFP expression rates and intensities were reduced dramatically, although still observed, suggesting that -119/-117 within -141/-111 is a key cis-element for controlling epidermis-specific expression of the zfCKII gene. Finally, we generated a zebrafish transgenic line, Tg(zfCKII(2.3):RFP), which carries an upstream 2.3 kb regulatory region of the zfCKII gene fused with RFP. The expression pattern in the epidermal cells of Tg(zfCKII(2.3):RFP) fish recapitulated that of the endogenous gene. F2 embryos derived from Tg(zfCKII(2.3):RFP) males crossed with wild-type females revealed that the earliest onset of RFP expression was at the sphere stage, indicating that this transgenic approach can be used for studying zygotic expression of maternally inherited genes.

Although it is fairly common in the Western countries, Paget's disease of bone is very rare in Chinese individuals. Through an extensive literature search, only 8 Chinese Paget's disease cases were found in the English language literature and all were reported in local medical journals of Asia that may not be accessible to international readers. To enhance the awareness of the rarity of Paget's disease in Chinese individuals to pathologists worldwide, we present a case of Paget's disease in a 54-year-old Chinese male. We also compare the clinical features of Paget's disease reported in Chinese patients to Paget's disease reported in the Western countries. No familial cases and no malignant transformation are found in the reported cases of Paget's disease in Chinese patients. In addition, more often skull involvement, higher frequency of monostotic cases, and symptomatic cases are observed in this limited number of Paget's disease cases reported in Chinese individuals.

A composite lymphoma is defined as the simultaneous occurrence of two histologically different types of lymphomas situated in one anatomical location. Reports of composite B- and T-cell lymphomas, especially in the head and neck region, are rare. We describe a 76-year-old Taiwanese aboriginal female patient clinically presenting with a midfacial necrotizing lesion (MNL). Microscopic examination of the incisional biopsy specimen revealed extensive surface necrosis with infiltrates of inflammatory cells. Beneath the necrotic surface, there appeared to be two distinct populations of pleomorphic lymphoid cells exhibiting the characteristic features of the angiocentric distribution of the tumor cells and evidence of angiodestruction. Immunohistochemical staining revealed that these atypical lymphoid cells were positive for LCA, CD45, CD5, CD20, CD3 epsilon, CD8, bcl-2 and bcl-6 and negative for CD56, CD4, CD68, keratin, S-100, kappa and lambda. Furthermore, these atypical lymphoid cells also expressed EBV-encoded nuclear RNAs (EBERs) following in situ hybridization. Therefore, this was a case of composite lymphoma: angiocentric T-cell lymphoma (ATCL) (CD8+ cytotoxic/suppressor T-cell) and diffuse large B-cell lymphoma (DLBL) associated with the Epstein-Barr virus (EBV) and presenting clinically as MNL.