Search

Abstract Background Anxiety and depressive disorders, characterized by high incidence and functional impairments, are emotional disorders with shared etiological and maintenance mechanisms. Dialectical behavior therapy (DBT) is a promising approach for the transdiagnostic treatment of emotional disorders. Developing a brief DBT intervention can facilitate the adoption of evidence-based therapy. Methods This protocol is for a 3-year single-blinded, two-arm randomized controlled trial. Individuals with depressive or anxiety disorder will be randomly allocated to a modified DBT–informed transdiagnostic psychotherapy group or a treatment-as-usual group. The intervention group will receive DBT individual therapy for 15 weeks. Power analyses revealed that the cohort should include a minimum of 250 participants. Preintervention, postintervention, and follow-up (after 3 months) assessments will be conducted. Primary outcomes will be severities of depression and anxiety rated by blind assessors. Intent-to-treat and per-protocol analyses will be conducted using the hierarchical linear model. Effect sizes will be estimated using Cohen’s d. Result To the best of our knowledge, the proposed study will be the first randomized controlled trial to evaluate the efficacy of a modified DBT intervention in managing transdiagnostic emotional disorders in Chinese individuals. Conclusion This intervention is expected to improve clinical outcomes, daily functioning, and quality of life. The trial will enrich the empirical evidence for transdiagnostic interventions, facilitating the implementation of evidence-based therapy and reducing the high prevalence and challenges (e.g., disability) of emotional disorders in the Chinese population. Trial registration number NCT05989451

Abstract The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.

Abstract Background Frailty increases the risks of hospitalization, injury, fall, psychological disorders, and death in older adults. Accurate estimation of the prevalence of frailty is crucial for promoting health in these individuals. Therefore, this study was conducted to estimate the prevalence of frailty and prefrailty in older adults residing in Indonesia. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, six electronic databases were searched (without any language restriction) for relevant articles from inception to February 2023. Studies on the prevalence of frailty and prefrailty in older adults (age ≥ 60 years) residing in Indonesia were included in the analysis. A random-effects model was selected a priori because of the expected high degree of heterogeneity in the study, followed by sensitivity analysis, subgroup analysis, and meta-regression. The protocol of this review study was registered in the PROSPERO database (CRD42022381132). Results A total of 79 studies were identified, of which 20 were finally included in the analysis. The pooled prevalence of frailty and prefrailty in older adults in Indonesia was 26.8% and 55.5%, respectively. The pooled prevalence of frailty and prefrailty was 37.9% and 44.8% in nursing homes, 26.3% and 61.4% in hospitals, and 21.1% and 59.6% in community settings, respectively. Furthermore, the pooled prevalence of frailty and prefrailty was 21.6% and 64.3%, 18.7% and 62%, and 27.8% and 59.8% in studies using the Frailty Index-40, FRAIL, and Fried Frailty Phenotype questionnaires, respectively. However, the parameters did not vary significantly across measurement tools or study settings. Publication bias was not detected while the year of data collection influenced the heterogeneity between the studies. Conclusions To the best of our knowledge, this study is the first meta-analysis to report the prevalence of frailty and prefrailty in older adults residing in Indonesia. The gradual increase in the number of older adults with frailty or prefrailty in Indonesia is concerning. Therefore, the government, private sectors, health-care professionals, and the community must jointly design effective strategies and policies to address this problem.

Objective: To evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome. Materials and methods: We retrospectively studied 6245 pregnant women with singleton pregnancy who had undergone amniocentesis between 15 and 27 weeks’ gestation at Mackay Memorial Hospital between January 2014 and June 2020. Fifty-five cases had high AFAFP levels (>2.0 MoM). We investigated the abnormal fetal outcomes. Results: Among the fifty-five cases with high AFAFP levels (>2.0 MoM), thirty (54.5%) had fetal chromosomal abnormalities, major structural abnormalities, and/or adverse obstetric events. Eight cases (14.5%) had chromosomal abnormalities including trisomy 21 (3 cases), trisomy 18 (3 cases), mosaic trisomy 18 (1 cases), and mosaic ring 13 (1 case). Seventeen cases (30.9%) had major structural abnormalities including abdominal wall defect (6 cases) and central nervous system (5 cases), gastrointestinal tract (3 cases), cardiovascular (2 cases), and genitourinary tract (2 cases) abnormalities. Fifteen cases (27%) had adverse obstetric events, including preterm delivery (5 cases), intrauterine fetal demise (4 cases), small for gestational age (4 cases), preeclampsia (4 cases), gestational diabetes mellitus (2 cases), gestational hypertension (1 case), preterm prelabor rupture of membrane (1 case), prolonged labor (1 case), and preterm uterine contraction (1 case). Conclusion: A high AFAFP level (>2.0 MoM) in midtrimester can be associated with abnormal fetal outcome, including chromosomal abnormalities, major structural abnormalities, and adverse obstetric events. Women with a prenatal diagnosis of high AFAFP levels (>2.0 MoM) should be alerted of the possibility of abnormal fetal outcomes, and further detailed genetic studies and serial sonographic examinations are recommended.

Abstract Increased prevalence of sleep disorders has been found in patients with functional dyspepsia; however, direction of causality remains unclear. Our aim was to compare the risk of incident functional dyspepsia between patients with and without sleep disturbance from a large population-based sample. Utilizing a nation-wide health insurance administrative dataset, we assembled an 11-year historic cohort study to compare subsequent incidence of diagnosed functional dyspepsia between adult patients with any diagnosis of sleep disturbance and age- and gender-matched controls. Hazard ratios adjusted for other relevant comorbidities and medications were calculated using Cox regression models. 45,310 patients with sleep disorder and 90,620 controls were compared. Patients with sleep apnea had a 3.3-fold (95% confidence interval: 2.82 ~ 3.89) increased hazard of functional dyspepsia compared with controls. This increased risk persisted regardless of previously diagnosed depression coexisted. Sleep disturbance was associated with an increased risk of subsequent functional dyspepsia. Potential mechanisms are discussed.

IntroductionThe treatment effect of bright light therapy (BLT) on major depressive disorder (MDD) has been proven, but the underlying mechanism remains unclear. Neuroimaging biomarkers regarding disease alterations in MDD and treatment response are rarely focused on BLT. This study aimed to identify the modulatory mechanism of BLT in MDD using resting-state functional magnetic resonance imaging (rfMRI).Materials and methodsThis double-blind, randomized controlled clinical trial included a dim red light (dRL) control group and a BLT experimental group. All participants received light therapy for 30 min every morning for 4 weeks. The assessment of the Hamilton Depression Rating Scale-24 (HAMD-24) and brain MRI exam were performed at the baseline and the 4-week endpoint. The four networks in interest, including the default mode network (DMN), frontoparietal network (FPN), salience network (SN), and sensorimotor network (SMN), were analyzed. Between-group differences of the change in these four networks were evaluated.ResultsThere were 22 and 21 participants in the BLT and dRL groups, respectively. Age, sex, years of education, baseline severity, and improvement in depressive symptoms were not significantly different between the two groups. The baseline rfMRI data did not show any significant functional connectivity differences within the DMN, FPN, SN, and SMN between the two groups. Compared with the dRL group, the BTL group showed significantly increased functional connectivity after treatment within the DMN, FPN, SN, and SMN. Graph analysis of the BLT group demonstrated an enhancement of betweenness centrality and global efficiency.ConclusionBLT can enhance intra-network functional connectivity in the DMN, FPN, SN, and SMN for MDD patients. Furthermore, BLT improves the information processing of the whole brain.Clinical trial registrationThe ClinicalTrials.gov identifier was NCT03941301.

Objective: We reported a fetus that presenting with persistent left superior vena cava (PLSVC), polyhydramnios, and a small gastric bubble during prenatal examination and identified VACTERL association after birth. Case report: A 34-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age and the result was normal. Subsequently, an ultrasound revealed single umbilical artery (SUA) at 21 weeks of gestation. She received a detailed fetal anatomy survey that presented the same findings and PLSVC. A small visible gastric bubble was noted at that time, and the other organs were unremarkable. Polyhydramnios was identified at 30 weeks of gestation and amnioreduction was subsequently performed at 32 weeks of gestation. However, polyhydramnios was persisted despite amnioreduction and intrauterine growth restriction was also detected. A cesarean section was performed because of fetal distress at 36 + 2 weeks, and a 1832-g female baby was delivered. Pre-axial polydactyly at left thumb, SUA and esophageal atresia with distal tracheoesophageal fistula (TEF) were identified after birth. The neonate died at age of 4 days because of surgical complication following esophageal anastomosis. Conclusion: Prenatal diagnosis of PLSVC associated with polyhydramnios and a small gastric bubble may indicate esophageal atresia with TEF, and further examination for associated syndromes such as VACTERL association is warranted.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from 2q11.1-q12.1 associated with fetal bilateral radial dysplasia. Case report: A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of club hands on fetal ultrasound. The internal organs of the fetus were normal. Amniocentesis revealed a karyotype of 47,XY,+mar [13]/46,XY [11]. The parental karyotypes were normal. Simultaneous array comparative genomic hybridization (aCGH) analysis of the DNA extracted from uncultured amniocytes revealed the result of arr 2q11.1q12.1 (95,529,039–102,825,556) × 3.0 [GRCh37 (hg19)]. The pregnancy was terminated at 20 weeks of gestation, and a malformed fetus was delivered with isolated bilateral radial dysplasia. The cord blood had a karyotype of 47,XY,+mar[24]/46,XY[16]. Polymorphic DNA marker analysis of the DNAs extracted from umbilical cord and parental bloods excluded uniparental disomy for chromosome 2. Metaphase fluorescence in situ hybridization analysis confirmed an sSMC derived from chromosome 2q11.1-q12.1 in cultured amniocytes. Conclusion: High-level mosaicism for an sSMC derived from chromosome 2q11.1-q12.1 can be associated with fetal abnormalities.

Objective: The purpose of this study was to estimate and compare total gestational weight gain (GWG) and the trimester-specific mean rate of GWG based on pre-pregnancy body mass index (BMI) as recommended by the Institute of Medicine (IOM).Materials and methods: The medical records of 470 participants who had received antenatal care at medical teaching hospitals in northern Taiwan and who delivered after 37 weeks of pregnancy were analyzed. Results: The mean total GWG was 13.84 (SD = 4.33) kg, and nearly 60% of women had not complied with the current IOM recommendations for total GWG. The best-fit model for the mean GWG rate revealed that all groups had a GWG rate of zero in the 1st trimester and had an equivalent mean GWG rate in the 3rd trimester. Women tended to have excessive weekly GWG in the 2nd and 3rd trimesters, and women with a higher pre-pregnancy BMI were more likely to have excessive weekly GWG in the 2nd and 3rd trimesters. Moreover, the plurality of normal-weight (30.4%), overweight (75.8%) and obese (62.5%) women experienced excessive weekly weight gain during the 2nd and 3rd trimesters. Few women met the recommended 2009 IOM weekly weight-gain guidelines in the 2nd trimester, but more met them in the 3rd trimester. Conclusion: These findings indicate that most pregnant Taiwanese women currently exceed the total and weekly GWG recommendations of the IOM. More specifically, weekly GWG in excess of the IOM recommendations is common among normal-weight, overweight and obese women. Keywords: Body mass index, Hierarchical linear modeling, Pregnancy, Gestational weight gain, Body weight

Colorectal cancer is the leading cause of cancer-related deaths worldwide, and early detection has proven to be an effective method for reducing mortality. The machine learning method can be implemented to build a noninvasive stratifying tool that helps identify patients with potential colorectal precancerous lesions (polyps). This study aimed to develop a noninvasive risk-stratified tool for colorectal polyps in asymptomatic, healthy participants. A total of 20,129 consecutive asymptomatic patients who underwent a health checkup between January 2005 and August 2007 were recruited. Positive relationships between noninvasive risk factors, such as age, Helicobacter pylori infection, hypertension, gallbladder polyps/stone, and BMI and colorectal polyps were observed (p < 0.0001), regardless of sex, whereas significant findings were noted in men with tooth disease (p = 0.0053). A risk stratification tool was developed, for colorectal polyps, that considers annual checkup results from noninvasive examinations. For the noninvasive stratified tool, the area under the receiver operating characteristic curve (AUC) of obese females (males) aged 50 years old), the AUCs of the stratifying tools were >85%. Our results indicate that the risk stratification tool can be built by using random forest and serve as an efficient noninvasive tool to identify patients requiring colonoscopy.

Objective: We present prenatal diagnosis of a familial 5p14.3-p14.1 deletion in a fetus with congenital heart disease on prenatal ultrasound. Case report: A 33-year-old woman underwent amniocentesis at 18 weeks of gestation because of fetal ventricular septal defect (VSD) and echogenic bowel on prenatal ultrasound. Amniocentesis revealed a karyotype of 46,XX,del (5) (p14p14). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed a 5.589-Mb 5p14.3-p14.1 deletion or arr 5p14.3p14.1 (19, 497, 649–25,086,268) × 1.0 [GRCh37 (hg19)] encompassing CDH18, CDH12, PMCHL1, PRDM9 and CDH10. Cytogenetic and aCGH analyses of the parents showed that the phenotypically normal mother carried the 5p14.3-p14.1 deletion. The father did not have such a deletion. The parents elected to continue the pregnancy, and a 3426-g female baby was delivered at 38 weeks of gestation with no gross abnormalities. The infant postnatally manifested VSD, atrial septal defect and patent ductus areriosus, and underwent cardiac surgery to treat the congenital heart disease. When follow-up at age 1 year and 4 months, she had a body weight of 8.8 Kg (50th–75th centile), a body height of 75.6 cm (85th–95th centile) and normal psychomotor development. Conclusion: Fetuses with a 5p14.3-p14.1 deletion may present congenital heart disease on prenatal ultrasound, and aCGH is helpful for prenatal diagnosis under such a circumstance. Keywords: 5p14.3-p14.1 deletion, Cadherin, Congenital heart defect, Prenatal diagnosis

Objective: To present the calculated frequencies, male to female sex-ratio, and modes of ascertainments in different levels of chromosomal mosaicism (CM) detected at amniocentesis. Materials and methods: This's a 10-years retrospective study between January 2008 and December 2017 and there were 13,752 cases of amniocentesis performed in MacKay Memorial Hospital, Taipei, Taiwan. Eight hundred and thirty four cases of CM were collected in this study. We reviewed their types of chromosomal abnormalities of mosaicism, the modes of ascertainment (including: advanced maternal age, abnormal ultrasound findings, abnormal maternal serum screening result, and other reasons), maternal age, gestational age at amniocentesis, fetal gender, and perinatal findings. After amniocentesis, in situ culture was performed and the results of karyotype with CM were divided in to three levels. Results: In our sample of 13,752 amniocentesis, 834 cases with all levels of CM were collected in this study. Of them, there were 562 cases (4.09%) with level I mosaicism, 207 cases (1.51%) of level II mosaicism, and 65 cases (0.47%) of level III mosaicism (Table 1). In the group of advanced of maternal age (AMA), their calculated frequencies, 4.18% in level I, 1.46% in level II and 0.41% in level III, were very similar to those in total cases (p value = 0.206) without statistical significance. In the group of abnormal ultrasound findings, the calculated frequency was much higher in level III (0.87%), however, there was no statistical significance because of the small numbers of level III. In our cases of amniocentesis, the case numbers of male case (50.20%) is very similar to female (49.80%), and the male to female ratio was 1.01. But, we found more cases of male with CM (444 cases) than female (390 cases). The sex-ratio in different levels’ calculated frequencies of CM showed similar in level I, and male prevalence was found in level II and III with statistical significance (p value = 0.022). The male prevalence also revealed in both numerical and structural abnormalities in level II and level III, but no difference in the cases of level I. Conclusion: In conclusion, our observation showed a novel finding of higher male prevalence of CM in level II and III, and both in numerical and structural abnormalities. It's consistent with the theory of better survival in male embryo after partial self-correction of initial chromosomal aberrations, male-specific selection against chromosomal abnormalities.

Summary: Background: Demoralization is distinctive psychological distress that involves hopelessness, helplessness, loss of purpose and meaning, and existential distress. Cancer patients' demoralization has been well documented, but little is known regarding older cancer patients and the related factors. Therefore, this study evaluated demoralization syndrome in older cancer patients. Methods: Cancer patients over 61 years old (n = 113, female 59.3%, mean age 65.7 years, range 61–80) diagnosed with heterogeneous types of cancer were recruited. They completed questionnaires in a hospital's inpatient and outpatient units. Their demoralization was measured using the Demoralization Scale-Mandarin Version (DS-MV). The Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), Beck Scale for Suicide Ideation (BSS), and Posttraumatic Growth Inventory (PTGI) were used to measure other psychological statuses and the association with demoralization. Results: The mean DS-MV score was 28.1 (SD = 16.3). In this sample, 57.7% had moderate to high demoralization (18.6% had moderate demoralization, and 38.1% had high demoralization). Twenty-three percent reported a DT score of five and above, 5.5% reported a PHQ-9 score of 10 and above, and 23.9% reported a BSS score greater than zero. Demoralization was associated with suicide ideation, depression, distress, lower education, and the cancer site. Demoralization was not associated with posttraumatic growth, gender, work status, or religion. Conclusion: More than half of older cancer patients have moderate to high demoralization and it is associated with depression, suicide ideation, and distress. Screening and interventions that are better tailored to older cancer patients could improve the quality of care in cancer treatment. Keywords: aged, cancer, depression, hospice care/psychology, morale

Objective: We present two cases of late-onset bilateral fetal pleural effusions associated with fetal Down syndrome. Case reports: Case 1. A 33-year-old Vietnamese woman had undergone regular sonographic examinations since 23 weeks of gestation and no abnormality had been noted. However, bilateral moderate pleural effusions were found at 33 weeks of gestation, and massive pleural effusion, ascites and polyhydramnios developed at 34 weeks of gestation. Aspiration of the pleural effusion was subsequently performed. Clinical laboratory surveys of the aspiration fluid excluded toxoplasmosis and cytomegalovirus infection. Cytogenetic analysis of cultured lymphocytes derived from pleural effusion revealed a karyotype of 47,XX,+21. The parents elected to continue the pregnancy. Intrauterine fetal demise occurred at 37 weeks of gestation, and a macerated female baby was delivered. Postnatal cytogenetic analysis of the umbilical cord confirmed the prenatal diagnosis. Case 2. A 41-year-old Pakistani woman had undergone regular sonographic examinations and no abnormality had been noted. However, isolated bilateral mild pleural effusions were noted at 27 weeks of gestation. Amniocentesis revealed a karyotype of 47,XY,+21 and simultaneous array comparative genomic hybridization analysis of uncultured amniocytes confirmed the diagnosis of Down syndrome. The pregnancy was subsequently terminated. Conclusion: Fetuses with Down syndrome may present late-onset bilateral pleural effusions. Prenatal diagnosis of late-onset bilateral pleural effusions should raise the possibility of fetal Down syndrome and cytogenetic investigation is warranted.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 21q11.2-q21.1, and we review the literature of an sSMC(21) with a duplication of 21q11.2-q21.1. Case report: A 40-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+mar [18]/46,XX [4]. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. aCGH analysis of cultured amniocytes revealed a 2.855-Mb duplication of 21q11.2-q21.1 encompassing the genes of LIPI, ABCC13 and NRIP1. Metaphase fluorescence in situ hybridization analysis on cultured amniocytes revealed a result of 47,XX,+mar .ish der(13/21) (D13/21Z1+) [10]. Spectral karyotyping analysis determined the origin of chromosome 21 in the sSMC. A female fetus was delivered with no phenotypic features of Down syndrome and no structural abnormalities. We discuss the genotype–phenotype correlation of LIPI, ABCC13 and NRIP1, and review the literature of an sSMC(21) associated with dup(21)(q11.2q21.1). Conclusion: aCGH is useful for identification of the nature and genetic component of a prenatally detected sSMC.

Objective: We present prenatal diagnosis and molecular genetic characterization of a de novo interstitial deletion of 2q (2q31.1-q32.1) and discuss the genotype–phenotype correlation. Case report: A 34-year-old, primigravid woman was referred to the hospital at 20 weeks of gestation for genetic counseling because of a prenatally detected de novo interstitial deletion of chromosome 2q (2q31.1-q32.1). She underwent amniocentesis at 17 weeks of gestation because of advanced maternal age and an increased first-trimester nuchal translucency (NT) thickness of 3.6 mm. Amniocentesis revealed a karyotype of 46,XY. However, array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniotic fluid and amniocytes revealed a 13.29-Mb deletion at chromosome 2q31.3-q32.1. The parents did not have such a deletion. Prenatal ultrasound findings were unremarkable. After counseling of the genotype–phenotype correlation of such a chromosome aberration with congenital malformations, the parents elected to terminate the pregnancy. The fetus postnataly manifested hypertelorism and syndactyly of the second and third toes of bilateral feet. Cytogenetic analysis of the umbilical cord revealed a karyotype of 46,XY,del(2)(q31q32). aCGH analysis on the DNA extracted from the cord blood confirmed a 13.35-Mb deletion of 2q31.1-q32.1 encompassing HOXD13, ZNF385B, ITGA4, CERKL, PDE1A, FRZB and ZNF804A. Polymorphic DNA marker analysis revealed a paternal origin of the deletion. Conclusion: Fetuses with an interstitial deletion of 2q31.1-q32.1 may be associated with increased first-trimester NT. Haploinsufficiency of HOXD13 is associated with syndactyly. Genomic microarray is useful in detecting subtle chromosomal abnormalities in fetuses with increased NT and normal karyotype.

Objective: We present prenatal diagnosis of low-level mosaic trisomy 12. Case Report: A 40-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, which revealed a karyotype of 47,XX,+12[5]/46,XX[24] consistent with 17.2% (5/29) mosaicism for trisomy 12. Repeat amniocentesis performed at 21 weeks of gestation revealed a karyotype of 47,XX,+12[4]/46,XX[6] consistent with 40% (4/10) mosaicism for trisomy 12. Interphase fluorescence in situ hybridization (FISH) on 112 uncultured amniocytes detected 23 cells with trisomy 12 consistent with 20.5% (23/112) mosaicism for trisomy 12. Polymorphic DNA marker analysis excluded uniparental disomy 12. Array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed a result of arr 12p13.33q24.33 (230,451–133,773,499) × 2.2, 17p12 (14,191,925–15,442,037) × 1.0 consistent with 10–20% mosaic trisomy 12. The father carried the 17p12 microdeletion. The fetal ultrasound findings were unremarkable. A 3958-g female fetus was delivered at 37 weeks of gestation with no phenotypic abnormality. The cord blood had a karyotype of 46,XX. Postnatal interphase FISH on urinary cells revealed 7.14% (7/98) mosaicism for trisomy 12. Conclusion: Low-level mosaic trisomy 12 at amniocentesis can be associated with a favorable pregnancy outcome. Interphase FISH and aCGH on uncultured amniocytes are useful for confirmation of low-level mosaic trisomy 12 at amniocentesis.

Cystic hygroma is a type of lymphangioma, which is a vascular anomaly associated with lymphatic malformations and formed by fluid accumulation mainly located at the cervicofacial and axillary regions. Cystic hygroma is mostly located in the neck (75%), followed by axilla (20%), retroperitoneum and intra-abdominal organs (2%), limbs and bones (2%), and mediastinum (1%). It is often associated with chromosome aneuploidies, hydrops fetalis, and even intrauterine fetal demise. The prognostic factors of the fetal cystic hygroma or lymphangioma are chromosome abnormalities, hydrops fetalis, septations, or thickness of the cystic hygroma and are associated with other major malformations. Prenatal managements including ultrasound serial follow-up, magnetic resonance imaging, or even intrauterine injection of sclerosing agents are suggested. For fetus with the risk of airway obstruction at delivery, ex utero intrapartum treatment is also indicated. Detailed prenatal counseling is necessary for better neonatal outcome.

Objective: We present perinatal imaging findings and molecular genetic analysis of thanatophoric dysplasia type I (TD1) in a fetus. Case Report: A 28-year-old woman was referred for genetic counseling at 22 weeks of gestation because of abnormal prenatal ultrasound findings. Level II ultrasound examination revealed a narrow chest, shortened and curved long limbs, protrusion of the abdomen, and macrocephaly. A tentative diagnosis of TD1 was made. After genetic counseling, the pregnancy was terminated and a malformed fetus was delivered. Postnatal radiography findings were consistent with the diagnosis of TD1, with additional findings of short ribs, platyspondyly, and horizontal acetabular roofs. Molecular genetic analysis using umbilical cord tissue revealed a heterozygous mutation of c.2419T>G (p.Ter807Gly) (X807G) in the fibroblast growth factor receptor 3 gene (FGFR3). Conclusion: A second-trimester fetus with a heterozygous c.2419T>G mutation in FGFR3 may present characteristic ultrasound and X-ray findings of TD1.

The outbreak of Zika virus followed by an increase in cases of fetal microcephaly in Brazil in 2015 has raised the concern of the association of Zika virus infection with fetal microcephaly and other central nervous system (CNS) malformations. Most patients with Zika virus infection are asymptomatic. However, according to a previous report, the most common symptom in pregnant women with Zika virus infection and fetal microcephaly is rash. Reported prenatal ultrasound findings are microcephaly, lissencephaly, agenesis of corpus callosum, intracranial calcification, cerebellar atrophy, ventriculomegaly, brain hypoplasia, microophthalmia, abnormal amniotic fluid volume, abnormal cerebral blood flow, abnormal umbilical artery blood flow, hydrocephalus, intrauterine growth restriction, and arthrogryposis which are mostly CNS lesions. Pregnant women who have a traveling history in active infection areas should have serological testing for Zika virus infection. Targeted ultrasound examinations at 18–20 weeks of gestation and serial ultrasound follow-ups are also suggested. In the cases of fetal microcephaly, intracranial anatomy and extracranial abnormalities should be also carefully examined. Amniocentesis might be needed for suspected Zika virus infection, genetic abnormalities, or other congenital infection.

Objective: We present molecular cytogenetic characterization of a prenatally detected derivative chromosome 9 [der(9)] of unknown origin. Case Report: A 35-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, which revealed a der(9) chromosome of unknown origin. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 2.593 Mb deletion of 9p24.3-p24.2 encompassing DOCK8, KANK1, DMRT1, and VLDLR and a 16.65 Mb duplication of 14q32.11-q32.33 encompassing DLK1, RTL1, MEG3, RTL1as, and MEG8. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis using D9S937 (9p24.2) and D14S605 (14q32.2) showed a paternal origin of 9p24.2 deletion and a paternal origin of 14q32.2 duplication consistent with a paternal origin of the de novo aberrant chromosome of der(9)t(9p;14q). The fetal karyotype was 46,XX,der(9)t(9;14) (p24.2;q32.11). Metaphase fluorescence in situ hybridization (FISH) analysis using RP11-57K23 (14q32.33), RP11-31F19 (9p24.3), RP11-30O14 (9p21.1), and RP11-1105I14 (14q11.2) confirmed an unbalanced reciprocal translocation of der(9)t(9p;14q). We discuss 9p deletion syndrome and 14q duplication syndrome in this case. Conclusion: Molecular cytogenetic techniques such as aCGH, FISH, and QF-PCR are useful in the determination of the origin and nature of a prenatally detected de novo derivative chromosome of unknown origin.

Objective: To present prenatal diagnosis and molecular cytogenetic characterization of a de novo 5q35 microdeletion associated with Sotos syndrome. Methods: This was the first pregnancy of a 29-year-old woman. The pregnancy was uneventful until 27 weeks of gestation when left ventriculomegaly was first noted. At 31 weeks of gestation, polyhydramnios, macrocephaly, and ventriculomegaly were prominent on ultrasound, and left pyelectasis and bilateral ventriculomegaly were diagnosed on magnetic resonance imaging. The woman underwent amniocentesis and cordocentesis at 32 weeks of gestation. Conventional cytogenetic analysis was performed using cultured amniocytes and cord blood lymphocytes. Array comparative genomic hybridization (aCGH) was performed on uncultured amniocytes and parental blood. Metaphase fluorescence in situ hybridization (FISH) was performed on cultured lymphocytes. Results: Conventional cytogenetics revealed a karyotype of 46,XX. aCGH on uncultured amniocytes revealed a de novo 1.07-Mb microdeletion at 5q35.2–q35.3 encompassing NSD1. Metaphase FISH analysis on the cord blood lymphocytes confirmed the deletion at 5q35.2. The postnatal phenotype was consistent with Sotos syndrome. Conclusion: Fetuses with Sotos syndrome may present macrocephaly, polyhydramnios, ventriculomegaly, and pyelectasis in the third trimester. aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome.

Objective: The aim of this study is to present the incidence, prenatal and postnatal findings, and modes of ascertainment in chromosomal deletions detected at amniocentesis. Materials and methods: We reviewed all the cases with chromosomal deletions, which were detected by amniocentesis in Mackay Memorial Hospital, Taipei, Taiwan, between January 1987 and December 2012. Data on the locations and types of deletion, reasons for performing amniocentesis, maternal age, gestational age at amniocentesis, fetal karyotypes, inheritance of deletions, and relative prenatal findings were collected. Results: Amniocentesis was performed in 33,305 cases within this period of time. Among these, 31 cases of chromosomal deletions were considered for the study. The mean gestational age at amniocentesis was 21.0 weeks (range from 15 weeks to 32 weeks) and the mean maternal age at amniocentesis was 32.1 years (range from 26 years to 37 years). Nineteen cases (61.3%) manifested fetal structural abnormalities on ultrasound, nine (29.0%) presented no ultrasound abnormalities, and three had an unknown status. The main modes of ascertainment included abnormal ultrasound findings in 10 cases (32.2%), advanced maternal age in 11 cases (35.5%), abnormal maternal serum screening results in six cases (19.6%), and other reasons in four cases (13.0%). Of the 27 cases with known inheritance, the deletion was inherited in two (6.6%) and de novo in 25 (92.6%). Males accounted for 11 (35.5%) and females for 20 (64.5%) cases. Chromosomal deletions are more often to occur in chromosomal 5(4 cases, 12.9%), chromosomal 18 (4 cases, 12.9%), chromosomal 4 (3 cases, 9.7%), chromosomal 7 (3 cases, 9.7%), chromosomal 10 (3 cases, 9.7%), chromosomal 11 (3 cases, 9.7%), and chromosomal 1 (2 cases, 6.5%). There were four cases of chromosomal mosaicism: two involved chromosome 5, one involved chromosome 10, and one involved chromosome 18. Twenty-three cases (74.2%) had terminal deletions and the other eight cases (26.7%) had interstitial-type deletions. Conclusion: In summary, we have presented the results of prenatal diagnosis for chromosomal deletions using amniocentesis. Chromosomal deletions are more likely to occur in females and more often in chromosomal 5p and 18q. Prenatal diagnosis at amniocentesis is frequently associated with advanced maternal age, abnormal ultrasound findings, and abnormal maternal serum screening. The frequency of ascertainment in chromosome deletion seems to be directly correlated with advanced maternal age and abnormal ultrasound findings. In cases with terminal deletions, prenatal ultrasound plays a more important role for prenatal diagnosis.

Cardiovascular diseases have continued to remain a leading cause of mortality and morbidity worldwide. Poor proliferation capability of adult cardiomyocytes disables the heart from regenerating new myocardium after a myocardial ischaemia event and therefore weakens the heart in the long term, which may result in heart failure and death. Delivery of cardioprotective therapeutics soon after the event can help to protect the heart from further cell death and improve cardiac function, but delivery methods and potential side effects of these therapeutics may be an issue. Advances in nanotechnology, particularly nanoparticles for drug delivery, have enabled researchers to obtain better drug targeting capability, thus increasing the therapeutic outcome. Detailed study of nanoparticles in vivo is useful as it can provide insight for future treatments. Nanogel can help to create a more favourable environment, not only for a sustained delivery of therapeutics, but also for a better navigation of the therapeutics to the targeted sites. Finally, if the damage to the myocardium is too severe for drug treatment, nanopatch can help to improve cardiac function and healing by becoming a platform for pluripotent stem cell-derived cardiomyocytes to grow for the purpose of cell-based regenerative therapy.

Induced pluripotent stem cells (iPSCs) are powerful tools for basic and translational research, as well as regenerative medicine. In routine human in vitro fertilization (IVF) practices, cumulus cells (CCs) are discarded, representing a potential source of biological materials for regenerative medicine. In this study, we derived patient-specific iPSCs using CCs from human infertility clinics for the first time. The human cumulus cell derived iPSCs (hc-iPSCs) were characterized for growth, karyotype, expression of pluripotency genes, and were subjected to embryoid bodies (EBs) and teratoma assays to evaluate their differentiation capacity. Hc-iPSCs display typical iPSC characteristics, and are capable of differentiating into all germ layers in vitro and in vivo. We further show that putative primordial germ cell like cells (PGCLCs) can be derived using hc-iPSCs. Our data demonstrate the feasibility of deriving patient-specific pluripotent stem cells using CCs.

The energetically demanding process of translation is linked to multiple signaling events through mTOR-mediated regulation of eukaryotic initiation factor (eIF)4F complex assembly. Disrupting mTOR constraints on eIF4F activity can be oncogenic and alter chemotherapy response, making eIF4F an attractive antineoplastic target. Here, we combine a newly developed inducible RNAi platform and pharmacological targeting of eIF4F activity to define a critical role for endogenous eIF4F in Myc-dependent tumor initiation. We find elevated Myc levels are associated with deregulated eIF4F activity in the prelymphomatous stage of the Eμ-Myc lymphoma model. Inhibition of eIF4F is synthetic lethal with elevated Myc in premalignant pre-B/B cells resulting in reduced numbers of cycling pre-B/B cells and delayed tumor onset. At the organismal level, eIF4F suppression affected a subset of normal regenerating cells, but this was well tolerated and rapidly and completely reversible. Therefore, eIF4F is a key Myc client that represents a tumor-specific vulnerability.

Misoprostol, a synthetic prostaglandin E1 analog, is initially used to prevent peptic ulcer. The initial US Food and Drug Administration-approved indication in the product labeling is the treatment and prevention of intestinal ulcer disease resulting from nonsteroidal anti-inflammatory drugs use. In recent two decades, misoprostol has approved to be an effective agent for termination of pregnancy in various gestation, cervical ripening, labor induction in term pregnancy, and possible management of postpartum hemorrhage. For the termination of second-trimester pregnancy using the combination of mifepristone and misoprostol seems to have the highest efficacy and the shortest time interval of abortion. When mifepristone is not available, misoprostol alone is a good alternative. Misoprostol, 400 μg given vaginally every 3–6 hours, is probably the optimal regimen for second-trimester abortion. More than 800 μg of misoprostol is likely to have more side effects, especially diarrhea. Although misoprostol can be used in women with scarred uterus for termination of second-trimester pregnancy, it is recommended that women with a scarred uterus should receive lower doses and do not double the dose if there is no initial response. It is also important for us to recognize the associated teratogenic effects of misoprostol and thorough consultation before prescribing this medication to patients regarding these risks, especially when failure of abortion occurs, is needed.

Objective: To present perinatal findings, modes of ascertainments, and modes of segregation in unbalanced reciprocal translocations detected at amniocentesis. Materials and Methods: Between January 1987 and July 2010, 40 cases with unbalanced reciprocal translocations were diagnosed by amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. The 40 cases originated from 29 families; 21 families with one case, 7 families with two cases, and 1 family with five cases. Results: Of 40 cases, 33 (82.5%) presented fetal ultrasound abnormalities and 7 (17.5%) presented no ultrasound abnormalities. Of 40 cases, 36 (90%) had a segregation mode of adjacent-1 2:2 segregation, 3 (7.5%) had a segregation mode of 3:1 segregation with tertiary trisomy, and 1 (2.5%) had a segregation mode of 3:1 segregation with tertiary monosomy. Of 29 families, 7 (24.1%) had de novo translocations and 22 (75.9%) had inherited translocations. In seven de novo cases, the main modes of ascertainments included abnormal ultrasound findings (n = 5) and advanced maternal age (n = 2). In 22 inherited families, the main modes of first ascertainment included abnormal ultrasound findings (n = 8), a previous aneuploid child (n = 8), advanced maternal age (n = 4), parental carrier status (n = 1), and abnormal maternal serum screening results (n = 1). Among 22 inherited families, 9 (40.9%) had a known parental carrier status, but 13 (59.1%) were unaware of parental carrier status at amniocentesis. Conclusion: Unbalanced reciprocal translocations detected at amniocentesis are frequently associated with abnormal ultrasound findings. Prenatal diagnosis of an unbalanced translocation may incidentally detect a balanced translocation in the family. Prenatal diagnosis of fetal structural abnormalities should alert structural chromosome rearrangements and prompt cytogenetic analysis of the fetus and parents if necessary.

Objective: To present perinatal findings, modes of ascertainment and parental decision in balanced reciprocal translocations detected at amniocentesis. Materials and Methods: Between January 1987 and August 2010, 82 cases with a simple reciprocal translocation, two cases with two separate simple reciprocal translocations and three cases with a complex chromosome rearrangement (CCR) were diagnosed by amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. The 87 cases originated from 76 families; 65 families with one case and 11 families with two cases. Results: In the 76 families, the main modes of ascertainment included advanced maternal age (n=38), a previous child with an unbalanced reciprocal translocation (n=11), recurrent miscarriage (n = 9), abnormal maternal serum screening results (n = 9), elective causes (n = 5), a previous child with congenital anomalies (n =2) and abnormal ultrasound findings (n = 2). In these families, there were 17 (22.4%) de novo cases including 14 simple translocations and three CCRs. Of 14 de novo cases with a simple translocation, one (7.1%) manifested a congenital malformation, which was related to an X-autosome translocation, and four (28.6%) were terminated. Of three de novo CCRs, two manifested congenital anomalies and one was terminated. In 87 cases, additional aneuploidy was noted in two cases including one inherited simple translocation with Turner syndrome, and one de novo CCR with concomitant deletions and duplication. Conclusion: Balanced reciprocal translocations detected at amniocentesis may be associated with fetal anomalies in cases of concomitant aneuploidy, de novo X-autosome translocation or de novo CCR. Genetic counseling of a de novo simple reciprocal translocation at amniocentesis remains difficult because approximately one-fourth of the parents opt for termination of the pregnancy, and detailed ultrasonography and array comparative genomic hybridization are helpful for parental counseling under such circumstances.

Objective: To study the maternal and fetal outcomes in women with systemic lupus erythematosus (SLE). Materials and Methods: Over a period of 10 years, 24 pregnancies in 17 females with SLE in a single center were enrolled. Fetal and maternal outcomes were studied retrospectively. Results: The mean patient age was 27.7 years. Twenty-one of the 24 pregnancies occurred in the period of disease remission at the time of conception. Proteinuria presented in 12 pregnancies; however, no patient developed acute renal failure or deterioration of renal function. There were three cases of preeclampsia in this study. Two patients had their disease flare up and delivered stillborns. One woman with secondary antiphospholipid syndrome (APS) had a fetal loss. There was no maternal mortality. The mean gestation age was 34.3 weeks (range, 17-41 weeks), and the mean birth weight was 2,179 g. The mean APGAR scores were 8 and 9 at 1 and 5 minutes, respectively. One baby with congenital atrioventricular block was born to a mother with positive anti-SSA antibody. There were five cases (20.8%) of intrauterine growth retardation and 10 preterm deliveries (41.6%) in this study. Conclusion: Pregnancy is relatively safe in women with SLE in remission but should be considered as a high-risk pregnancy. APS is associated with poor pregnancy outcome. The patient needs to cooperate with obstetricians and physicians for optimal disease control and detailed monitoring throughout the gestation.

Objective: To investigate the impact of second-trimester maternal serum screening on prenatal diagnosis of Down syndrome and the use of amniocentesis in the Taiwanese population. Materials and Methods: From 1990 to 2000, 166,419 amniocenteses were analyzed cytogenetically in the Taiwanese population. Among these, 58.85% were for advanced maternal age, 4.5% for abnormal ultrasound findings, 26.17% for abnormal maternal serum screening results, 1.82% for a previous child with congenital anomaly, 1.02% for a family history of chromosome aberrations, and 7.63% for other purposes. Chromosome aberrations were detected in 4,217 cases (2.53%), of which 1,277 (30.28%) were Down syndrome. Of the Down syndrome cases, 65.86% were detected by amniocentesis for advanced maternal age, 5.95% for abnormal ultrasound findings, 21.14% for abnormal maternal serum screening results, 1.25% for a previous child with congenital anomaly, 1.18% for a family history of chromosome aberrations, and 4.62% for other purposes. Results: There was a prominent increase in the number of women undergoing amniocentesis in the Taiwanese population between 1990 and 2000. There was an 8.9-fold increase in the number undergoing amniocentesis for advanced maternal age, a 6.3-fold increase in that for abnormal ultrasound findings, a 46.2-fold increase in that for abnormal maternal serum screening results, a 2.9-fold increase in that for a previous child with congenital anomaly, a 5.6-fold increase in that for a family history of chromosome aberrations, and a 4.4- fold increase in that for other purposes. There was also a 35.7-fold increase in the number of prenatally detected Down syndrome cases, from seven in 1990 to 250 in 2000. The highest rates of Down syndrome were found in cases with abnormal ultrasound findings (1/99 tests). Down syndrome was 0.72-fold as common in amniocenteses performed because of positive serum screening results (1/161 tests) compared with the rate seen in the advanced maternal age group (1/116 tests). The detection rates increased from 1/449 tests in 1990, through 1/198 tests, 1/203 tests, 1/158 tests, 1/215 tests, 1/229 tests, 1/169 tests, 1/143 tests, 1/90 tests, 1/92 tests, to 1/123 tests in 2000. Conclusion: Both the number of women undergoing amniocentesis and the number of detected cases of Down syndrome increased during these years. Amniocentesis in this population no longer led to a significant improvement in the detection rate of Down syndrome. In view of the effective use of amniocentesis as a diagnostic procedure for Down syndrome, efforts should be made to use more efficient prenatal screening programs and to reduce the number of unnecessary amniocenteses.

Objective: We present a case of spontaneous uterine rupture caused by near-cornual pregnancy with placenta accreta and emphasize the possibility of uterine rupture at all stages of pregnancy. Case Report: A 32-year-old woman, gravida 3, para 2, was referred at 16 weeks of gestation under the condition of death on arrival. Uterine rupture with massive internal bleeding was diagnosed. Emergency hysterectomy was performed. There was a sagittal perforating arc near the right cornu from the anterior to the posterior surface over the dome of the uterus. The final histopathologic examination indicated a near-cornual pregnancy with placenta accreta. Complications of massive hemorrhage occurred, and the patient expired due to multiple organ failure. Conclusions: Spontaneous rupture of an unscarred uterus can occur at any stage of pregnancy. The placental implantation near the cornu with accreta may have been the cause of the uterine rupture in this patient. Noting the site of implantation should be an important component during antenatal sonography. Furthermore, uterine rupture should be included in the differential diagnosis of pregnant women with abdominal pain.

Objective: Vaginal stones are rare and primary vaginal stones are extremely rare. A primary vaginal stone originating from urinary stasis in the vagina may be due to anatomic abnormalities, vaginal outlet obstruction, infection, or vesicovaginal fistulae, while secondary vaginal stones result from crystallization of urinary constituents around a foreign body in the vagina. Case Report: This 43-year-old female had cerebral palsy due to tuberculosis meningitis when she was 3 years old. She had been bedridden with urinary and fecal incontinence since then. She was admitted to our medical ward due to acute abdominal distension with poor appetite and weight loss. On arrival, leukocytosis with dehydration was noted and medical treatment was given initially. Imaging studies showed stool impaction with abdominal ileus and a huge calcified density measuring 10 cm in diameter in the pelvis. Exploratory laparotomy showed that the mass was in the vagina. A laminated and pear-shaped mass was removed through an incision in the anterior vaginal cuff. Pathologic examination showed lithiasis composed of calcification mixed with fibrinous exudates and fragments of reactive squamous epithelium. The postoperative course was smooth with uneventful convalescence and she was discharged and doing well at the time of writing. Conclusion: Although vaginal stones are very rare, they may be formed in recumbent women due to urinary stasis, and the calculi may cause obstruction of the bowel or urinary tract.