Regulatory role of oxidative stress in retrorsine - Induced apoptosis and autophagy in primary rat hepatocytes.

Pyrrolizidine alkaloids (PAs) are a group of naturally occurring alkaloids widely present in plants. PAs are highly hepatotoxic and have been documented to cause many incidents of human and animal poisoning. Retrorsine (RTS) is a pyrrolizidine alkaloid (PA) derived from the Compositae Senecio, which has been shown to cause hepatotoxicity. Human liver poisoning occurs through the consumption of RTS-contaminated food, and animals can also be poisoned by ingesting RTS-containing toxic plants. The mechanism of RTS-induced liver toxicity is not fully understood. In this study, we demonstrated that RTS-induced oxidative stress plays a pivotal role in RTS-induced liver toxicity involving apoptosis and autophagy. The results showed that RTS treatment in the cultured Primary rat hepatocytes caused cytotoxicity and release of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a time- and dose-dependent manner. Our study showed that treatment of RTS induced ROS and MDA (malondialdehyde, a lipid peroxidation marker) in the hepatocytes, and reduced antioxidant capacity (GSH content, SOD activity), suggesting RTS treatment caused oxidative stress response in the hepatocytes. Furthermore, we found that RTS induced apoptosis and autophagy in the hepatocytes, and RTS-induced apoptosis and autophagy could be alleviated by ROS scavenger N-acetylcysteine (NAC) and the MAPK pathway inhibitors suggesting ROS/MAPK signaling pathway plays a role in RTS induced apoptosis and autophagy. Collectively, this study reveals the regulatory mechanism of oxidative stress in RTS-induced apoptosis and autophagy in the hepatocytes, providing important insights of molecular mechanisms of hepatotoxicity induced by RTS and related pyrrolizidine alkaloids in liver. This mechanism provides a basis for the prevention and treatment of PA poisoning in humans and animals.

Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation at 10 Hz in Fibromyalgia: A Systematic Review and Meta-analysis.

OBJECTIVE: The purpose of this review was to systematically assess the effectiveness of 10-Hz repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia. DATA SOURCES: We searched PubMed, Cochrane Library, Embase, Web of Science, and Ovid databases as of November 6, 2021. STUDY SELECTION: The inclusion criteria for this review were randomized controlled trials of 10-Hz rTMS for fibromyalgia, exploring the effects of 10-Hz rTMS on pain, depression, and quality of life in patients with fibromyalgia. DATA EXTRACTION: Data extraction was performed independently by 2 evaluators according to predefined criteria, and the quality of the included literature was assessed using the Cochrane Bias Risk Assessment Tool. The measurement outcomes include visual analog scale, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire, and so on. DATA SYNTHESIS: A total of 488 articles were screened, and the final 7 selected high-quality articles with 217 patients met our inclusion criteria. Analysis of the results showed that high-frequency transcranial magnetic stimulation at 10 Hz was significantly associated with reduced pain compared with sham stimulation in controls (standardized mean difference [SMD]=-0.72; 95% confidence interval [CI], -1.12 to -0.33; P<.001; I2=46%) and was able to improve quality of life (SMD=-0.70; 95% CI, -1.00 to -0.40; P<.001; I2=15%) but not improve depression (SMD=-0.23; 95% CI, -0.50 to 0.05; P=.11; I2=33%). In addition, a subgroup analysis of pain conducted based on stimulation at the primary motor cortex and dorsolateral prefrontal cortex showed no significant difference (SMD=-0.72; 95% CI, -1.12 to -0.33; P=.10; I2=62%). CONCLUSIONS: Overall, 10-Hz rTMS has a significant effect on analgesia and improved quality of life in patients with FMS but did not improve depression.

Antidepressant-like effects of geniposide in chronic unpredictable mild stress-induced mice by regulating the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 networks.

Evidence exists suggesting the anti-depressive activities of geniposide (GP), a major compound in Gardenia jasminoides Ellis. Accordingly, the present study attempts to explore the anti-depressive mechanism of GP in chronic unpredictable mild stress (CUMS)-induced depression-like behaviors of mice. CUMS-induced mice were given GP daily and subjected to behavioral tests to observe the effect of GP on the depression-like behaviors. It was noted that GP administration reduced depression-like behaviors in CUMS mice. Transcriptome sequencing was conducted in three control and three CUMS mice. Differentially expressed circRNAs, lncRNAs and mRNAs were then screened by bioinformatics analyses. Intersection analysis of the transcriptome sequencing results with the bioinformatics analysis results was followed to identify the candidate targets. We found that Gata2 alleviated depression-like behaviors via the metabolism- and synapse-related pathways. Gata2 was a target of miR-25-3p, which had binding sites to circ_0008405 and Oip5os1. circ_0008405 and Oip5os1 competitively bound to miR-25-3p to release the expression of Gata2. GP administration ameliorated depression-like behaviors in CUMS mice through regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks. Taken together, GP may exert a potential antidepressant-like effect on CUMS mice, which is ascribed to regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks.

Z16b, a natural compound from Ganoderma cochlear is a novel RyR2 stabilizer preventing catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited, lethal ventricular arrhythmia triggered by catecholamines. Mutations in genes that encode cardiac ryanodine receptor (RyR2) and proteins that regulate RyR2 activity cause enhanced diastolic Ca2+ release (leak) through the RyR2 channels, resulting in CPVT. Current therapies for CPVT are limited. We found that Z16b, a meroterpenoid isolated from Ganoderma cochlear, inhibited Ca2+ spark frequency (CaSF) in R2474S/ + cardiomyocytes in a dose-dependent manner, with an IC50 of 3.2 µM. Z16b also dose-dependently suppressed abnormal post-pacing Ca2+ release events. Intraperitoneal injection (i.p.) of epinephrine and caffeine stimulated sustained ventricular tachycardia in all R2474S/+ mice, while pretreatment with Z16b (0.5 mg/kg, i.p.) prevented ventricular arrhythmia in 9 of 10 mice, and Z16b administration immediately after the onset of VT abolished sVT in 9 of 12 mice. Of translational significance, Z16b significantly inhibited CaSF and abnormal Ca2+ release events in human CPVT iPS-CMs. Mechanistically, Z16b interacts with RyR2, enhancing the "zipping" state of the N-terminal and central domains of RyR2. A molecular docking simulation and point mutation and pulldown assays identified Z16b forms hydrogen bonds with Arg626, His1670, and Gln2126 in RyR2 as a triangle shape that anchors the NTD and CD interaction and thus stabilizes RyR2 in a tight "zipping" conformation. Our findings support that Z16b is a novel RyR2 stabilizer that can prevent CPVT. It may also serve as a lead compound with a new scaffold for the design of safer and more efficient drugs for treating CPVT.

Is pinworm infection still a public health concern among children in resource-rich regions? Trends in pinworm infection prevalence and associated factors among children in Hualien County, Taiwan: a retrospective cross-sectional study.

BACKGROUND: Enterobius vermicularis (pinworm) is a common intestinal parasitic infection in children. A gradual decrease in the prevalence of pinworm infection has been noted in resource-rich settings, such as Taiwan. However, the influence of sociodemographic factors on the temporal trend in pinworm infection rates in children under the current pinworm infection prevention policy in Taiwan is not well characterized. This study aimed to evaluate the trend of pinworm infection prevalence and the associated factors among children in Hualien County, Taiwan. METHODOLOGY: In this retrospective cross-sectional study, we included a total of 56,197 students (aged 6-10 years) in grades 1 and 4 in Hualien in 2009-2018. Children were screened for pinworm infection using adhesive cellophane perianal swabs in the routine student health examination. Logistic regression was conducted to evaluate the factors associated with pinworm infection. Associations between dependent and independent variables were measured by odds ratios. The Cochran-Armitage test was used to assess whether there were significant trends in different stratifications. Variables with P-values < 0.05 were considered statistically significant. RESULTS: A total of 56,197 school-age children from grades 1 and 4 during 2009-2018 were included. Young age and male sex were risk factors for pinworm infection (P < 0.001). A negative correlation between body mass index and enterobiasis was observed, and decreased pinworm infection was noted during the study reference period. Children living in suburban and rural areas had higher odds of having a pinworm infection than those living in urban areas (P < 0.001). A significant decrease in the overall prevalence rate of pinworm infection was observed among children in 2009-2018 (P < 0.001). However, there was no obvious change in the pinworm infection rate in rural areas during this period (P = 0.953), and it was higher than that in urban and suburban areas. CONCLUSIONS: The overall prevalence of pinworm infection gradually decreased from 2009 to 2018 among school-age children in Hualien. However, there was no declining trend in pinworm infection in rural areas. Young age, male sex, and rural residence were significantly associated with pinworm infection. Pinworm infection remains a major public health concern among children in rural areas of Hualien.

Split-face comparison of the efficacy of picosecond 532 nm Nd:YAG laser and Q-switched 755 nm Alexandrite laser for treatment of freckles.

To date, there has been little study of comparison between picosecond 532 nm laser and 755 nm Q-switched Alexandrite lasers in the treatment of freckles. To evaluate the efficacy and safety of picosecond 532 nm laser (PS 532) and 755 nm Q-switched Alexandrite laser (QSAL) for treatment of freckles in a split-face manner. Eighteen patients with freckles were enrolled in the study. The right and left sides of their faces were randomly assigned to either a QSAL-treated group or PS 532-treated group. The degree of pain, satisfaction with the results, and adverse events associated with the laser treatment were evaluated using a questionnaire. All of the patients were followed up at 4 and 12 weeks after one treatment session. Among the 18 patients, PS 532 was found to be associated with less pain (3.56 ± 2.431) than QSAL (3.94 ± 1.893), but the difference was not statistically significant. The curative effect and satisfaction associated with 755 nm Q-switched Alexandrite laser was greater than that of picosecond 532 nm laser (P < .001). Both picosecond 532 nm laser and QSAL are effective in the treatment of freckles, and QSAL has a greater rate of satisfaction and curative effect.

[The Effectiveness of a Shared Reading Program Among Parents of Newborns].

BACKGROUND: Early parent-child shared reading has been demonstrated to promote the development of literacy, reading skills and learning achievement in young children. Parent-child shared reading intervention programs may strengthen the willingness and reading competence of parents. PURPOSE: To explore the attitudes and skills related to parent-child shared reading before and after an intervention program conducted in a nursery room and outpatient pediatric clinic. METHODS: A single-group pretest-posttest quasi-experimental design was conducted. Seventy-five parents of newborns in the baby rooms from two hospitals in Hualien County were conveniently sampled. Parents who had just given birth received health education before discharge from the hospital from nurses focusing on the knowledge and skills of shared reading. Three age-matched picture books with reading fact sheets and consultation support were offered free to parents of children in three, respective, age groups (newborn, 4-months old and 6-months old) during parent-child visits to the pediatric clinic for regular health examinations and vaccinations. A self-designed questionnaire was administered to analyze the parents' demographic variables, reading environment, parents' attitudes toward parent-child shared reading, and familiarity with regard to parent-child shared reading skills. RESULTS: Parent-child reading attitudes were positively correlated with skill familiarity (r = .39). The presence or absence of children's books at home, the parent-child relationship, and parental reading habits explained 32.0% of the variance in parent-child shared-reading attitudes (R2 = .32). The presence or absence of children's books at home and the presence or absence of a library card for the child explained 44.0% of the variation in familiarity with co-reading skills (R2 = .44). Parent-child shared reading attitude scores (t = -5.14, p < .001) and skill familiarity of parents (t = -7.52, p < .001) both increased significantly after the intervention program. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Parent-child shared reading educational intervention programs may be used to improve parental attitudes and skills related to parent-child shared reading.

Survey of the triple-mentoring program for students at a religious medical school.

BACKGROUND: Tzu Chi University in Taiwan offers a unique mentoring program. This program differs from others as it comprises triple mentorship, namely, faculty mentors, Tzu Cheng/Yi De (TC/YD; senior volunteers), and school counselors. This study aimed to survey the role functions of the mentors from the perspective of medical students. METHODS: The Role Functions of the Mentoring Program Scale (RFMPS) was developed on the basis of literature reviews and focus groups and it underwent exploratory factor analysis for internal consistency and reliability. RFMPS comprises four role functions, namely, mental, educational, career, and humanistic/moral guidance counseling. The survey was distributed to 171 medical students via an online network with two-month intervals and was analyzed using multivariate analysis of variance. RESULTS: The overall response rate was 64% (116/171). The mean scores of the four role functions in descending order belonged to faculty mentors, TC/YD, and school counselors. For humanistic/moral guidance, students had an equal preference for the faculty mentors and TC/YD over school counselors. As for educational, career, and mental guidance counseling, students preferred faculty mentors over TC/YD and school counselors. Faculty mentors provided students with the required guidance counseling for all the four role functions, especially educational guidance; TC/YD in particular offered prominent humanistic/moral guidance and career counseling; school counselors were less preferred but guided students in need. CONCLUSIONS: Medical students value different role functions provided by faculty mentors, TC/YD, and school counselors. A diversified focus could be provided by the faculty mentors, particularly in educational, career, mental, and humanistic/moral counseling; TC/YD specialized in humanistic/moral guidance; and the school counselors carried out their role function only when needed. Humanistic/moral guidance is equally preferred to other types of guidance, which can be equally valuable in future mentoring programs.

Effects of probiotics on cecal microbiome profile altered by duck Escherichia coli 17 infection in Cherry Valley ducks.

Avian colibacillosis is one of the most serious infectious bacterial diseases that endanger the modern poultry industry. Lactobacillus is believed to inhibit intestinal pathogens and maintain a healthy gut microbiota. This study aimed to investigate Lactobacillus supplementation in Cherry Valley ducks to prevent the intestinal flora dysbiosis caused by Duck Escherichia coli 17. One hundred and twenty healthy one day old Cherry Valley ducks were randomized to three study groups (Group I = the control group; Group II = duck Escherichia coli 17 challenge group and Group III = DE17 challenge group supplemented with lactic acid bacteria composite preparation). Cherry Valley ducks in Group II and Group III were gavage challenged with DE17 (1 × 105 CFU/mL) on day 14. Pyrosequencing of the V3/V4 variable regions of the genes encoding for 16S rRNA was used for sequence analysis. The results showed that the normal intestinal microecology was affected by DE17, including a relative increase in proteobacteria. At the same time, the Lactobacillales were increased and harmful bacteria were decreased in different intestinal segments of ducks in Group III, compared to those in Group II. Network analysis showed that dietary lactic acid bacteria addition improved the interaction pattern within the cecal microbiota of ducks and the result showed that in Ruminococcus_2 was independently present in the group III and Lachnospiraceae_NK4A136_group species correlation existed between group I and group III. This study proved that oral supplementation with Lactobacillus casei 1.2435, Lactobacillus rhamnosus 621 and Lactobacillus rhamnosus A4 can mitigate DE17 induced intestinal flora dysbiosis.

Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan.

RASopathies are developmental diseases caused by mutations in rat sarcoma-mitogen-activated protein kinase pathway genes. These disorders, such as Noonan syndrome (NS) and NS-related disorders (NSRD), including cardio-facio-cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congenital heart disease and hypertrophic cardiomyopathy (HCMP) can exhibit major associated characteristics. A retrospective study was conducted at the Mackay Memorial Hospital, National Taiwan University Hospital, Buddhist Tzu-Chi General Hospital, Chang-Gung Memorial Hospital, Taichung Veterans General Hospital, and Chung Shan Medical University Hospital from January 2007 to December 2018. We reviewed the clinical records of 76 patients with a confirmed molecular diagnosis of RASopathies, including NS, CS, CFC syndrome, and NSML. We evaluated the demographic data and medical records with clinical phenotypes of cardiac structural anomalies using cross-sectional and color Doppler echocardiography, electrocardiographic findings, and follow-up data. A total of 47 (61.8%) patients had cardiac abnormalities. The prevalence of cardiac lesions according to each syndrome was 62.7, 50.0, 60.0, and 66.7% in patients with NS, CFC syndrome, CS, and NSML, respectively. An atrial septal defect was usually combined with other cardiac abnormalities, such as pulmonary stenosis (PS), HCMP, ventricular septal defect, or patent ductus arteriosus. Patients with NS most commonly showed PS. In patients with NSRD and cardiac abnormalities, HCMP (29.4%) was the most commonly observed cardiac lesion. PTPN11 was also the most frequently detected mutation in patients with NS and NSRD. Cardiac abnormalities were the most common symptoms observed in patients with RASopathies at the time of their first hospital visit. Performing precise analyses of genotype-cardiac phenotype correlations in a larger cohort will help us accurately diagnose RASopathy as soon as possible.

The transcriptional regulator PhoP mediates the tolC molecular mechanism on APEC biofilm formation and pathogenicity.

As a transcriptional regulator of the classical binary regulatory system, PhoP plays an important role in the life activities of avian pathogenic Escherichia coli (APEC). In previous experiments, we found that the absence of phoP affects APEC biofilm formation and pathogenicity. To further explore the molecular mechanism of phoP regulation of these phenomena, the differentially expressed gene tolC was screened based on phoP-derived transcriptional data, and the specific sequence identity of the PhoP binding sequence was predicted by bioinformatics and verified by electrophoretic mobility shift assay (EMSA). The results showed that PhoP can directly bind to the tolC promoter. On this basis, tolC deletion and complementary strains were constructed. Biofilm formation was quantified by crystal violet staining and rdar morphology change was observed in these strains. Loss of tolC reduced biofilm formation. We also examined pathological changes in organ paraffin sections by challenging chicks with the strains. After loss of tolC, the clinical signs of pericarditis and liver and spleen enlargement in chicks were alleviated, and pathogenicity to the host cells was decreased. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that tolC deletion downregulated secA/secB/secE/secY transcript levels, which are part of the type II secretion system secreting virulence effector element. These results indicate that tolC contributes to the phoP-mediated effect on APEC biofilm formation and pathogenicity.

A qualitative study of clinical narrative competence of medical personnel.

BACKGROUND: Medicine practiced with narrative competence is called narrative medicine, which has been proposed and used as a model of humane and effective medical practice. Despite the in-depth discussions of narrative medicine, the study of narrative competence in literature is limited; therefore, this study aims to explore the dimensions and connotations of the clinical narrative competence of medical personnel. METHODS: This qualitative study used in-depth interviews to collect participants' experience and perspectives regarding narrative competence, followed by thematic analysis of the transcripts. Through purposive sampling, this study successfully recruited 15 participants (nine males and six females in 2018-2019) who were engaged in narrative medicine or medical humanity education from different medical schools and hospitals across Taiwan. The authors performed manual thematic analysis to identify the themes and concepts of narrative competence through a six-step theme generation process. RESULTS: There were four major themes of narrative competence generalized and conceptualized: narrative horizon, narrative construction (including narrative listening, narrative understanding, narrative thinking, and narrative representation), medical relationship (including empathy, communication, affiliation, and inter-subjectivity), and narrative medical care (including responsive care, balanced act, and medical reflection). These four themes were further integrated into a conceptual framework and presented in a diagram. CONCLUSIONS: Cultivating narrative competence in medical education can complement traditional biomedical orientation. Regardless of their treatment orientation, narrative medicine-informed health practitioners may take advantage of their multi-dimensional narrative competence, as presented in this article, to enhance their awareness and preparation in different areas of competence in medical services. In addition, the results of this study can be used as a framework for the development of the behavioral indicators of narrative competence, which can be taken as the basis for medical education curriculum design.

Antagonistic trait of Lactobacillus reuteri S5 against Salmonella enteritidis and assessment of its potential probiotic characteristics.

Salmonella enteritidis is an important foodborne pathogen that has caused multiple outbreaks of infection associated with poultry and egg consumption. Thus, the prevention and inhibition of Salmonella enteritidis infection are of great concern. Lactic acid bacteria have anti-pathogenic activity; however, their underlying mechanisms and modes of action have not yet been clarified. In this study, the antibacterial mechanism of Lactobacillus reuteri S5 (L. reuteri S5) against Salmonella enteritidis ATCC13076 (S. enteritidis ATCC13076) was studied by different methods. We found that L. reuteri S5 was able to form a stable biofilm formation, colonizing the entire intestinal tract of chickens. In addition, bacterial cultures and the cell-free supernatant (CFS) of L. reuteri S5 inhibited SE ATCC13076 growth, and this growth inhibition was also observed in the co-culture assay. This effect may be predominantly caused by antimicrobial metabolites produced by L. reuteri S5. Furthermore, treatment with the CFS of L. reuteri S5 resulted in a significant reduction in the expression of Salmonella virulence, motility and adhesion genes and a significant reduction in the motility ability and inhibitory effect on biofilm formation. In addition, the damage to the membrane structure and intracellular structure induced by the CFS of L. reuteri S5 could be observed on Transmission electron microscopy images and dodecyl sulfate, sodium salt (SDS)-Polyacrylamide gel electrophoresis confirmed the disruptive action of the CFS of L. reuteri S5 on the cytoplasmic membrane. Our findings demonstrate that L. reuteri S5, an intestinal Lactobacillus species associated with chicken health, is able to form biofilm and stably colonize chicken intestines. It also possesses anti-SE activity, preventing SE growth, inhibits the expression of SE genes involved in adhesion and invasion, virulence and cell membrane integrity, inhibits SE biofilm formation and motility, damages or destroys bacterial structures, and inhibits intracellular protein synthesis. L. reuteri S5 therefore has potential applications as a probiotic agent.

Congenital generalized lipodystrophy in Taiwan.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by scarce adipose tissue. This disease is distributed worldwide, but little is known about these patients in the Chinese population. Here, we delineate the phenotype and prognosis of CGL in our cohort. METHODS: Patients diagnosed with CGL from 8 medical centers were reviewed. The initial presentation, laboratory findings, and molecular testing were retrospectively analyzed. RESULTS: A total of 16 patients were analyzed, and the current median age was 3.5 years (range, 9 months-17.5 years). In all patients, molecular results confirmed BSCL2 mutation. c.782dupG (p.Ile262Hisfs*12) was the most common genotype identified. All patients had triangular faces and muscular hypertrophy. In addition, 75% presented with hepatomegaly, 19% had cardiomegaly, and 44% exhibited acanthosis nigricans. Developmental delay was noted in 5 out of 9 patients (56%) with a median developmental quotient (DQ)/intelligence quotient (IQ) of 61. Thirteen patients (81.3%) had high triglyceride levels. Eight patients received leptin analysis, and 7 of them (88%) had low leptin levels. One patient exclusively received a lipid-lowering drug, 4 patients were exclusively placed on a fat-restricted diet, 5 patients were administered combination therapy, and 5 patients received no treatment. Three patients (19%) who developed diabetes mellitus received both oral hypoglycemic agents and insulin. Three patients (19%) experienced loss of ambulation and died prematurely. CONCLUSION: Our findings highlight the uniqueness of the genotype and phenotype in our cohort. Further long-term surveillance for comorbidities is necessary for early detection and management of these patients.

Psychosocial issues discovered through reflective group dialogue between medical students.

BACKGROUND: The biopsychosocial model is a comprehensive approach emphasizing holistic medical care. However, medical curricula that incorporate narrative reflective writing and group dynamic discussion of psychosocial issues among patients and their family members in reflective dialogue groups are currently underutilized. The aim of this study was to determine psychosocial issues among patients and their family members through medical students' reflective dialogue groups. METHODS: This study was completed as part of a pediatric clerkship. Fifty medical students were rotated to the department of Pediatrics. They completed a narrative writing assignment concerning patients' psychosocial issues and participated in a reflective group discussion during the rotation. The recordings of the six reflective group sessions were transcribed for thematic analysis. A six-step theme generation process was conducted in the first reading stage of all transcripts by four researchers. Subsequently, initial codes were generated and potential themes sought before possible themes were reviewed and thematic maps generated. Names for each theme were defined and a scholarly report of the analysis was presented through a consensus-based approach. RESULTS: A total of 108 psychosocial issues were coded and categorized as the following six main themes: medical communication, the intricate medical ecological system, role and function of a family, development of medical professionalism, ethical dilemmas, and various patient perspectives from diverse cultural backgrounds. All these themes underlie the complexity of clinical encounters. CONCLUSIONS: Clinical care is an extremely complex interactive ecological network involving human behavior, family, and public health care systems. The discovery of psychosocial problems by medical students as narrators in this study illustrates that medical care should focus not only on illnesses but also patients' psychosocial narratives.

Correction to: Psychosocial issues discovered through reflective group dialogue between medical students.

Following publication of the original article [1], the authors reported that they had had mistakenly put the wrong IRB number in the last paragraph of the Methods section (as IRB NO.: IRB101-80 instead of IRB102-20 as given in the Ethics approval and consent to participate in Declarations). The corrected last paragraph on the Method section should read as follows.

[Introduction to Genetic/Rare Disease and the Application of Genetic Counseling].

Genetic disease or hereditary disease is a group of disorders that is caused by mutations in an individual's genome. The mutated genome or gene may be transmitted through the germ line during reproduction, causing certain recurrence risk in offspring and other family members. The heritability of these disorders is thus an important issue to deal with clinically. In Taiwan, a rare disease is defined as a disease that is prevalent in fewer than 1 in 10,000 individuals. As up to 80% of rare disease cases in Taiwan are genetic disease disorders, genetic disease may not rare. The pathophysiology of genetic/ rare disease is very complicated. Individual disorders may have their own unique mechanisms (such as Fragile X syndrome), with most of these mechanisms still unclear or unknown. The symptoms and signs of genetic/rare disease thus present the greatest variabilities and cause difficulties in making diagnoses. Most related patients may present multiple congenital anomalies, metabolic disorders, growth and developmental delays, defects in cognition, neuromuscular abnormalities, and defects in vision, hearing or other organ functions. Symptomatic and supportive treatment still comprise a major component of treatment of genetic/rare disease (with the exception of special formulae for several inborn errors of metabolic disease and enzyme replacement therapy in some lysosomal storage disease). Poor self-care ability is common and the burden on caregivers is huge. Most rare disease patients are treated using a comprehensive rehabilitation program that begins during very early childhood, receive individual educational programs, and are continuously monitored with regard to their growth, developmental, and nutritional status. Inter-professional patient care, genetic counseling, and the creation of family support networks play an important role in family management. Public awareness and the creation of appropriate social systems and resources allocation are mandatory for proper care. The incidence of each genetic/rare disease is rare, but collectively they are important public health issue and a challenge to medical care.

3-O-methyldopa levels in newborns: Result of newborn screening for aromatic l-amino-acid decarboxylase deficiency.

BACKGROUND: The diagnosis of aromatic l-amino-acid decarboxylase (AADC) deficiency is often delayed because a cerebrospinal fluid analysis is required to detect a neurotransmitter deficiency. We here demonstrated that an elevated concentration of l-dopa metabolite 3-O-methyldopa (3-OMD) in dried blood spots could be integrated into newborn screening program to precisely predict AADC deficiency. METHODS: After obtaining parental consent, an additional spot was punched from newborn filter paper, eluted, cleaned, and analyzed by tandem mass spectrometry. Newborns with a 3-OMD concentration exceeding 500ng/mL were referred for confirmatory testing. RESULTS: From September 2013 to December 2015, 127,987 newborns were screened for AADC deficiency. The mean 3-OMD concentration in these newborns was 88.08ng/mL (SD=27.74ng/mL). Four newborns exhibited an elevated 3-OMD concentration (range, 939-3241ng/mL). All four newborns were confirmed to carry two pathologic DDC mutations, indicating an incidence of AADC deficiency of 1:32,000. During the follow-up period, three patients developed typical symptoms of AADC deficiency. Among 16 newborns with mildly elevated 3-OMD levels, six were heterozygous for the DDC IVS6+4A>T mutation. CONCLUSION: Newborn screening of AADC deficiency was achieved with a 100% positive-predictive rate. An association for gestational age could be further elucidated.

High-grade serous carcinoma of the fallopian tube in a young woman with chromosomal 4q abnormality: A case report.

BACKGROUND: Few studies have reported an association between an increased risk of acquiring cancers and survival in patients with 4q deletion syndrome. This study presents a rare association between chromosome 4q abnormalities and fallopian tube high-grade serous carcinoma (HGSC) in a young woman. CASE SUMMARY: A 35-year-old woman presented with acute dull abdominal pain and a known chromosomal abnormality involving 4q13.3 duplication and 4q23q24 deletion. Upon arrival at the emergency room, her abdomen appeared ovoid and distended with palpable shifting dullness. Ascites were identified through abdominal ultrasound, and computed tomography revealed an omentum cake and an enlarged bilateral adnexa. Blood tests showed elevated CA-125 levels. Paracentesis was conducted, and immunohistochemistry indicated that the cancer cells favored an ovarian origin, making us suspect ovarian cancer. The patient underwent debulking surgery, which led to a diagnosis of stage IIIC HGSC of the fallopian tube. Subsequently, the patient received adjuvant chemotherapy with carboplatin and paclitaxel, resulting in stable current condition. CONCLUSION: This study demonstrates a rare correlation between a chromosome 4q abnormality and HGSC. UBE2D3 may affect crucial cancer-related pathways, including P53, BRCA, cyclin D, and tyrosine kinase receptors, thereby possibly contributing to cancer development. In addition, ADH1 and DDIT4 may be potential influencers of both carcinogenic and therapeutic responses.