Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

An Appraisal of the Preventive Effect of Statins on the Development of Graves' Ophthalmopathy: A Hospital-Based Cohort Study.

INTRODUCTION: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. METHODS: This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. RESULTS: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort. CONCLUSION: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups. TRAIL REGISTRATION: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019.

Alpha event-related decreases during encoding in adults with ADHD - An investigation of sustained attention and working memory processes.

BACKGROUND: Executive functioning deficits are central to established neuropsychological models of ADHD. Oscillatory activity, particularly the alpha rhythm (8-12 Hz) has been associated with cognitive impairments in ADHD. However, most studies to date examined such neural mechanisms underlying executive dysfunction in children and adolescents with ADHD, raising the question of whether and to what extent those ADHD-related working memory impairments are still present in adults. To this end, the current study aimed to investigate the role of alpha event-related decreases (ERD) during working memory processes in adults with and without ADHD. METHODS: We collected electroencephalographic (EEG) data from 85 adults with a lifetime diagnosis of ADHD and 105 controls (aged 32-64), while they performed a continuous performance (CPT) and a spatial delayed response working memory task (SDRT). Time-frequency and independent component analysis (ICA) was used to identify alpha (8-12 Hz) clusters to examine group and condition effects during the temporal profile of sustained attention and working memory processes (encoding, maintenance, retrieval), loads (low and high) and trial type (go and nogo). RESULTS: Individuals with ADHD exhibited higher reaction time-variability in SDRT, and slower response times in SDRT and CPT, despite no differences in task accuracy. Although working memory load was associated with stronger alpha ERD in both tasks and both groups (ADHD, controls), we found no consistent evidence for attenuated alpha ERD in adults with ADHD, failing to replicate effects reported in children. In contrast, when looking at the whole sample, the correlations of alpha power during encoding with inattention and hyperactivity-impulsivity symptoms were significant, replicating prior findings in children with ADHD, but suggesting an alternate source for these effects in adults. CONCLUSIONS: Our results corroborate the robustness of alpha as a marker of visual attention and suggest that occipital alpha ERD normalizes in adulthood, but with unique contributions of centro-occipital alpha ERD, suggesting a secondary source. This implies that deviations in processes other than previously reported visuospatial cortex engagement may account for the persistent symptoms and cognitive deficits in adults with a history of ADHD.

The Fifth Residue of the Coat Protein of Turnip Mosaic Virus Is Responsible for Long-Distance Movement in a Local-Lesion Host and Aphid Transmissibility in a Systemic Host.

HC-Pro and coat protein (CP) genes of a potyvirus facilitate cell-to-cell movement and are involved in the systemic movement of the viruses. The interaction between HC-Pro and CP is mandatory for aphid transmission. Two turnip mosaic virus (TuMV) isolates, RC4 and YC5, were collected from calla lily plants in Taiwan. The virus derived from the infectious clone pYC5 cannot move systemically in Chenopodium quinoa plants and loses aphid transmissibility in Nicotiana benthamiana plants, like the initially isolated virus. Sequence analysis revealed that two amino acids, P5 and A206, of YC5 CP uniquely differ from RC4 and other TuMV strains. Recombination assay and site-directed mutagenesis revealed that the fifth residue of leucine (L) at the N-terminal region of the CP (TuMV-RC4), rather than proline (P) (TuMV-YC5), is critical to permit the systemic spread in C. quinoa plants. Moreover, the single substitution mutant YC5-CPP5L became aphid transmissible, similar to RC4. Fluorescence microscopy revealed that YC5-GFP was restricted in the petioles of inoculated leaves, whereas YC5-CPP5L-GFP translocated through the petioles of inoculated leaves, the main stem, and the petioles of the upper uninoculated leaves of C. quinoa plants. In addition, YC5-GUS was blocked at the basal part of the petiole connecting to the main stem of the inoculated C. quinoa plants, whereas YC5-CPP5L-GFP translocated to the upper leaves. Thus, a single amino acid, the residue L5 at the N-terminal region right before the 6DAG8 motif, is critical for the systemic translocation ability of TuMV in a local lesion host and for aphid transmissibility in a systemic host.

Age, Dose, and Locomotion: Decoding Vulnerability to Ketamine in C57BL/6J and BALB/c Mice.

Ketamine has been abused as a psychedelic agent and causes diverse neurobehavioral changes. Adolescence is a critical developmental stage but vulnerable to substances and environmental stimuli. Growing evidence shows that ketamine affects glutamatergic neurotransmission, which is important for memory storage, addiction, and psychosis. To explore diverse biological responses, this study was designed to assess ketamine sensitivity in mice of different ages and strains. Male C57BL/6J and BALB/c mice were studied in adolescence and adulthood separately. An open field test assessed motor behavioral changes. After a 30-min baseline habituation, mice were injected with ketamine (0, 25, and 50 mg/kg), and their locomotion was measured for 60 min. Following ketamine injection, the travelled distance and speed significantly increased in C57BL/6J mice between both age groups (p < 0.01), but not in BALB/c mice. The pattern of hyperlocomotion showed that mice were delayed at the higher dose (50 mg/kg) compared to the lower dose (25 mg/kg) of ketamine treatment. Ketamine accentuated locomotor activation in adolescent C57BL/6J mice compared to adults, but not in the BALB/c strain. Here, we show that ketamine-induced locomotor behavior is modulated by dose and age. The discrepancy of neurobehaviors in the two strains of mice indicates that sensitivity to ketamine is biologically determined. This study suggests that individual vulnerability to ketamine's pharmacological responses varies biologically.

Sequential provocation of Ekbom's syndrome and acute mania following AstraZeneca COVID-19 vaccination.

ChAdOx1 nCoV-19 vaccine (so called AZ vaccine), is widely used to prevent the SARS-CoV-2 pandemic and shows powerful effectiveness to deter community transmission. There are common immunogenicity-related side effects such as fever, myalgia, lethargy, and headache; however, rare report on the neuropsychiatric problems (Ramasamy et al., 2021). In Taiwan, more than 15,200,000 doses of AZ vaccine were injected by the end of 2022. Here we presented a unique case with separated episode of Ekbom's syndrome, also called delusion of parasitosis, and mania following successive AZ vaccination in three-month interval.

An importance-performance analysis of teachers' perception of STEM engineering design education.

There is an increasing worldwide trend toward the development of science, technology, engineering, and mathematics (STEM) education using engineering design (ED) practice. Considering that teachers play pivotal roles in terms of student interest in STEM subjects and careers, it is important to explore teachers' perceptions of STEM-ED education. We analysed survey data from 184 technology teachers who participated in empowerment training (using a STEM-ED curriculum) in 2017, 2018, 2021, and 2022. We used an importance-performance analytical model to investigate the teachers' perceptions of STEM-ED itself, its impact on students, and the challenges experienced during implementation. The results showed that various improvements were required for STEM-ED promotion and for the preparation of STEM-ED lessons. Analysis of variance revealed that the age groups taught and the number of weekly teaching hours significantly affected the teachers' perceptions of STEM-ED. These findings will assist educational institutions worldwide in planning future education policies, designing teacher empowerment courses, and understanding teachers' needs in efforts to improve STEM-ED.

Hysteroscopic removal, with or without laparoscopic assistance, of first-trimester cesarean scar pregnancy.

OBJECTIVE: To demonstrate the implementation and potential benefits of hysteroscopic removal, with or without concomitant laparoscopic assistance, of first-trimester cesarean scar pregnancies (CSPs). DESIGN: Patients with prior cesarean deliveries may have scar formation at the muscular wall of the uterine isthmus, resulting in a cesarean scar defect (CSD), also known as an isthmocele or diverticulum. When implantation of a trophoblast occurs at the CSD, a CSP develops, and with progression onto higher gestational age, it carries risks for serious complications, such as placenta previa spectrum, life-threatening bleeding, uterine rupture, and cesarean hysterectomy. Therefore, early termination is often recommended. Given that the chorionic frondosum only penetrates the decidual basalis layer during the first trimester and does not invade the distal myometrial segment until early second trimester, operative hysteroscopy can be a reliable and efficient treatment modality for early intervention. This narrated video features the systematic approach and surgical management for patients with first-trimester CSPs. SETTING: Academic tertiary hospital. PATIENT(S): Three multiparous women between 34 and 38 years of age diagnosed with CSPs within the first trimester. INTERVENTION(S): Initial assessment with transvaginal ultrasonography and color Doppler flow identifies the site of implantation and measures the residual myometrial thickness (RMT), which are important parameters for classifying the CSPs into type I or type II. Type I CSPs often present at an earlier gestational age, have a thicker RMT, and grow toward the uterine cavity, while type II CSPs are frequently noted at a higher gestational age, have a thinner RMT, demonstrate obvious scar dehiscence, and often invade toward the bladder. The patients received either operative hysteroscopy alone or with concomitant laparoscopic assistance and repair of CSD dehiscence. For all hysteroscopic operations, misoprostol (200 µg) was given 4 hours before the procedure while oxytocin (20 U in 1000 mL isotonic solution, intravenous infusion) was infused immediately after removal of the placental tissue. For laparoscopic excision and repair of the dehiscent scar, local injection of 5 mL terlipressin acetate (1 mg) was added before the initiation of laparoscopic CSD excision. MAIN OUTCOME MEASURE(S): Appraisal of the parameters used for preoperative assessment, the efficacy of the surgical procedures, and the intention to minimize the associated risks and morbid sequalae were evaluated. RESULT(S): Most of the type I CSPs or type II CSPs with gestational age <8 weeks and RMT >3 mm can be successfully treated with operative hysteroscopy alone. In contrast to blind dilatation and curettage, operative hysteroscopy offers direct visualization to ensure complete removal of the chorionic villi, which can occasionally be buried deep within the concavity of the CSD. It is worth noting that gently sweeping the decidua basalis from the myometrium with the loop resectoscope is more than enough to separate the chorionic villi within and completely displace the placental tissues without causing massive hemorrhage. For type II CSPs in late first-trimesters showing distended CSDs and diminished RMT, laparoscopy can be established before the hysteroscopic procedure for better surveillance and to prevent inadvertent myometrial perforation. Then, hysteroscopic removal of CSP can further induce uterine contractions to help reduce blood loss during subsequent laparoscopic repair of CSD. CONCLUSION(S): Accurate diagnosis and timely management of CSPs during the first trimester are crucial for preventing significant morbidities associated with advanced gestational age. Operative hysteroscopy offers the benefit of direct visualization for competent detachment of the decidua basalis of the CSP from the steep concavity of the CSD. Furthermore, the employment of laparoscopy for type II CSPs helps avoid inadvertent complications related to the thin RMT and allows concomitant repair of the extensive dehiscence.

A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18-hACE2-transgenic mice, accompanied by a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.

Marker-Assisted Development and Evaluation of Monogenic Lines of Rice cv. Kaohsiung 145 Carrying Blast Resistance Genes.

Rice blast is a serious threat to global rice production. Large-scale and long-term cultivation of rice varieties with a single blast resistance gene usually leads to breakdown of resistance. To effectively control rice blast in Taiwan, marker-assisted backcrossing was conducted to develop monogenic lines carrying different blast resistance genes in the genetic background of an elite japonica rice cultivar, Kaohsiung 145 (KH145). Eleven International Rice Research Institute (IRRI)-bred blast-resistant lines (IRBLs) showing broad-spectrum resistance to local Pyricularia oryzae isolates were used as resistance donors. Sequencing analysis revealed that the recurrent parent, KH145, does not carry known resistance alleles at the target Pi2/9, Pik, Pita, and Ptr loci. For each IRBL × KH145 cross, we screened 21 to 370 (average of 108) plants per generation from the BC1F1 to BC3F1/BC4F1 generation. A total of 1,499 BC3F2/BC4F2 lines carrying homozygous resistance alleles were selected and self-crossed for four to six successive generations. The derived lines were also evaluated for background genotype using genotyping by sequencing, for blast resistance under artificial inoculation and natural infection conditions, and for agronomic performance in multiple field trials. In Chiayi and Taitung blast nurseries in 2018 to 2020, Pi2, Pi9, and Ptr conferred high resistance, Pi20 and Pik-h moderate resistance, and Pi1, Pi7, Pik-p, and Pik susceptibility to leaf blast; only Pi2, Pi9, and Ptr conferred effective resistance against panicle blast. The monogenic lines showed agronomic traits, yield, and grain quality similar to those of KH145, suggesting the potential of growing a mixture of lines to achieve durable resistance in the field.

Event-Related Potentials During Decision-Making in a Mixed-Strategy Game.

The decisions we make are sometimes influenced by interactions with other agents. Previous studies have suggested that the prefrontal cortex plays an important role in decision-making and that the dopamine system underlies processes of motivation, motor preparation, and reinforcement learning. However, the physiological mechanisms underlying how the prefrontal cortex and the dopaminergic system are involved in decision-making remain largely unclear. The present study aimed to determine how decision strategies influence event-related potentials (ERPs). We also tested the effect of levodopa, a dopamine precursor, on decision-making and ERPs in a randomized double-blind placebo-controlled investigation. The subjects performed a matching-pennies task against an opposing virtual computer player by choosing between right and left targets while their ERPs were recorded. According to the rules of the matching-pennies task, the subject won the trial when they chose the same side as the opponent, and lost otherwise. We set three different task rules: (1) with the alternation (ALT) rule, the computer opponent made alternating choices of right and left in sequential trials; (2) with the random (RAND) rule, the opponent randomly chose between right and left; and (3) with the GAME rule, the opponent analyzed the subject's past choices to predict the subject's next choice, and then chose the opposite side. A sustained medial ERP became more negative toward the time of the subject's target choice. A biphasic potential appeared when the opponent's choice was revealed after the subject's response. The ERPs around the subject's choice were greater in RAND and GAME than in ALT, and the negative peak was enhanced by levodopa. In addition to these medial ERPs, we observed lateral frontal ERPs tuned to the choice direction. The signals emerged around the choice period selectively in RAND and GAME when levodopa was administered. These results suggest that decision processes are modulated by the dopamine system when a complex and strategic decision is required, which may reflect decision updating with dopaminergic prediction error signals.

Outcomes of olfaction in patients with empty nose syndrome after submucosal implantation.

BACKGROUND: Olfactory dysfunction, such as hyposmia, is a significant symptom of empty nose syndrome (ENS). The efficacy of surgical intervention in olfaction improvements for ENS has not been investigated extensively. OBJECTIVE: The aim of this study was to evaluate changes in olfaction after surgical treatment for ENS. METHODS: This prospective cohort study at a tertiary medical center enrolled patients with ENS indicated for surgical treatment between June 2015 and June 2019. The Sniffin' Sticks 12-items odor identification test (SS-12) and subjective olfaction rating were completed by patients before and after surgery to assess olfaction. RESULTS: A total of 40 patients completed the survey both before and after surgical treatment. Prior to surgery, 25% of the patients had olfactory dysfunction detected by SS-12, whereas 80% of the patients reported a reduction in olfactory function by subjective rating. The degree of olfactory dysfunction by both assessments significantly improved following surgery. The age was a significant predictor of postoperative improvement. CONCLUSION: Surgical treatment is helpful in improving olfaction in patients with ENS who commonly suffer from olfactory dysfunction. Younger patients may benefit more from surgical intervention in aspect of olfaction.

Endosperm cell size reduction caused by osmotic adjustment during nighttime warming in rice.

High night temperature (HNT) often reduces yield in field crops. In rice, HNT during the ripening stage diminishes endosperm cell size, resulting in a considerable reduction in final kernel weight; however, little is known about the underlying mechanisms at cell level. In this study, we performed picolitre pressure-probe-electrospray-ionization mass spectrometry to directly determine metabolites in growing inner endosperm cells of intact seeds produced under HNT conditions, combining with 13C feeding and water status measurements including in situ turgor assay. Microscopic observation in the inner zone suggested that approximately 24.2% of decrease in cell expansion rate occurred under HNT at early ripening stage, leading to a reduction in cell volume. It has been shown that HNT-treated plants were subjected to mild shoot water deficit at night and endosperm cell turgor was sustained by a decline in osmotic potential. Cell metabolomics also suggests that active solute accumulation was caused by a partial inhibition of wall and starch biosynthesis under HNT conditions. Because metabolites were detected in the single cells, it is concluded that a partial arrest of cell expansion observed in the inner endosperms was caused by osmotic adjustment at mild water deficit during HNT conditions.

Association between maternal age at delivery and allergic rhinitis in schoolchildren: A population-based study.

BACKGROUND: Some studies have shown associations of maternal age at delivery with asthma and food allergy in offspring. However, the relationship between maternal age at delivery and allergic rhinitis is largely unclear. This study aimed to investigate the association between maternal age at delivery and allergic rhinitis in a population sample of Asian children, and to explore potential effect modifiers. METHODS: A total of 1344 singleton-birth children (763 boys, 56.8%; mean age, 6.4 years) participating in the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort were evaluated by a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and interviewed by pediatricians. Allergic sensitization was determined by using Phadiatop Infant. Multiple logistic regression models with covariates adjustment were performed to investigate the association of maternal age at delivery with allergic rhinitis and allergic sensitization in offspring. RESULTS: Among 1344 study children, 793 (59%) had physician-diagnosed allergic rhinitis. Advanced maternal age at delivery (≥40 years) was significantly associated with increased odds of allergic rhinitis (adjusted odds ratio [AOR] = 4.58, 95% confidence interval [CI]: 1.90-11.03) and allergic sensitization (AOR = 2.86, 95% CI: 1.13-7.22) in offspring. A sex-stratified analysis revealed that the association of advanced maternal age with allergic rhinitis was statistically significant only in female offspring (AOR = 7.02, 95% CI: 1.89-26.14). Stratified analyses by birth order or environmental tobacco smoke exposure during pregnancy did not reveal any significant differences. CONCLUSION: Advanced maternal age at delivery was associated with increased risk of allergic rhinitis in Asian children, probably more pronounced among girls.

Valproic Acid-Induced Hyperammonemic Encephalopathy in a Patient with Bipolar Disorder: A Case Report.

Valproic acid (VPA) is widely used to control various seizure disorders and psychiatric disorders. Valproic acid-induced hyperammonemic encephalopathy (VHE) is a rare but dangerous complication of VPA-induced toxicity. For this case report, several risk factors were identified, including young age, polytherapy regimens, VPA overdose, poor liver function, and carnitine deficiency. The detailed mechanisms of VHE remained unclear. Hyperammonemia may be caused by hypocarnitinemia, leading to imbalanced VPA metabolism. VHE may initially cause gastrointestinal symptoms, followed by a decreased level of consciousness and seizure. Early diagnosis of VHE is important for physicians for the timely reversal of VHE by discontinuing administration of VPA and administering lactulose or levocarnitine. Here, we describe a patient with a bipolar disorder who presented with VHE after receiving a strict vegetarian diet in our hospital. We recommend that VHE be included in the differential diagnosis of patients with high serum VPA levels and strictly vegetarian diets, especially those presenting with acute gastrointestinal symptoms.

Genome-wide association mapping of gene loci affecting disease resistance in the rice-Fusarium fujikuroi pathosystem.

BACKGROUND: Rice bakanae disease has emerged as a new threat to rice production. In recent years, an increase in the occurrence and severity of bakanae disease has been reported in several areas in Asia. Although bakanae disease affects rice yield and quality, little is known about the genetics of bakanae resistance in rice. The lack of large-scale screens for bakanae resistance in rice germplasm has also limited the development and deployment of resistant varieties. RESULTS: A genome-wide association study (GWAS) was conducted to identify genes/loci conferring bakanae resistance in rice. A total of 231 diverse accessions from Rice Diversity Panel 1 (RDP1) were inoculated with a highly virulent Taiwanese Fusarium fujikuroi isolate and assessed for resistance using two parameters: (1) disease severity index based on visual rating and (2) colonization rate determined by reisolation of F. fujikuroi from the basal stems of infected rice seedlings. We identified 14 quantitative trait loci (QTLs) (10 for disease severity and 4 for colonization rate), including 1 mapped for both parameters. A total of 206 candidate genes were identified within the 14 QTLs, including genes encoding leucine-rich repeat (LRR)-containing and NB-ARC (nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4) proteins, hormone-related genes, transcription factor genes, ubiquitination-related genes, and oxidase/oxidoreductase genes. In addition, a candidate QTL (qBK1.7) that co-localized with the previously identified QTLs qBK1 and qFfR1, was verified by linkage analysis using a population of 132 recombinant inbred lines derived from IR64 x Nipponbare. GWAS delineated qBK1.7 to a region of 8239 bp containing three genes. Full-length sequencing across qBK1.7 in 20 rice accessions revealed that the coding regions of two LRR-containing genes Os01g0601625 and Os01g0601675 may be associated with bakanae resistance. CONCLUSIONS: This study facilitates the exploitation of bakanae resistance resources in RDP1. The information on the resistance performance of 231 rice accessions and 14 candidate QTLs will aid efforts to breed resistance to bakanae and uncover resistance mechanisms. Quantification of the level of F. fujikuroi colonization in addition to the conventional rating of visual symptoms offers new insights into the genetics of bakanae resistance.

Trends and prescription patterns of traditional Chinese medicine use among subjects with allergic diseases: A nationwide population-based study.

BACKGROUND: The alarmingly rising prevalence of allergic diseases has led to substantial healthcare and economic burdens worldwide. The integrated use of traditional Chinese medicines (TCM) and Western medicines has been common in treating subjects with allergic diseases in clinical practice in Taiwan. However, limited studies have been conducted to evaluate long-term trends and prescription patterns of TCM use among subjects with allergic diseases. Thus, we conducted a nationwide population-based study to characterize TCM use among subjects with allergic diseases. METHODS: A total of 241,858 subjects with diagnosed atopic dermatitis, asthma or allergic rhinitis in the period of 2003-2012 were identified from the National Health Insurance Research Database (NHIRD) in Taiwan and included in this study. We assessed trends and prescribed patterns related to TCM (both single herbs and herbal formulas) among the study subjects over the 10-year study period. RESULTS: The overall proportions of TCM use were 30.5%, 29.0% and 45.7% in subjects with atopic dermatitis, asthma and allergic rhinitis, respectively. We found increasing trends of TCM use among subjects having atopic dermatitis and asthma, with annual increase of 0.91% and 0.38%, respectively, over the 10-year study period while the proportion remained steadily high (from 46.6% in 2003 to 46.3% in 2012) among subjects having allergic rhinitis. Moreover, the number of hospitalization due to allergic diseases in TCM users was significantly smaller than that in non TCM users for all three allergic diseases. CONCLUSION: A notable proportion (30%-50%) of subjects with allergic diseases in Taiwan has used TCM, with the highest proportion of TCM use found in subjects with allergic rhinitis, whereas increasing trends of TCM use are found among subjects with atopic dermatitis and asthma, respectively. Our results suggest that TCM use may help reduce the severe episodes of allergic diseases necessitating hospitalizations.

Assessment of Cognitive and Motor Skills in Parkinson's Disease by a Robotic Object Hitting Game.

Parkinson's disease (PD) patients experience various symptoms including extrapyramidal motor disturbances and cognitive impairments, which cause difficulties in daily life. However, PD patients have rarely been studied under realistic task situations that require high-level interaction of cognitive and motor skills. The aim of this study was to investigate the contribution of cognitive and motor factors to the performance of PD patients under high cognitive and kinematic loads. Twenty-six PD patients and 14 control subjects participated in the study. The PD patients performed a task involving hitting targets and avoiding distractors in levodopa On and Off states. A robotic manipulandum device recorded the numbers of target and distractor hits and hand kinematics, including movement area and speed. Performance on standard cognitive batteries and the Movement Disorder Society - Unified Parkinson's Disease Rating Scale motor scores were examined. The results indicated that the PD patients hit significantly fewer targets and more distractors than did the controls (p < 0.05). In PD patients, the average hand speed was slower and the area of hand movement was smaller than those of the control subjects (p < 0.001). Levodopa significantly increased the average hand speed and movement area (p < 0.01), but levodopa had an insignificant effect on the number of correct targets hit and erroneous distractor hits. The scores of cognitive batteries predicted the performance with regard to both targets hit and distractor avoidance. Our results were indicative of a dynamic interaction between cognitive and kinematic skills while the PD patients performed a virtual reality game. Single-dose levodopa enhanced kinematic capacity, and the global intelligence level predicted game performance.

Genome-wide association study of rice genes and loci conferring resistance to Magnaporthe oryzae isolates from Taiwan.

BACKGROUND: Rice blast, caused by Magnaporthe oryzae, is an important rice disease occurring in all rice-growing areas. To manage blast disease effectively and in an environmentally friendly way, it is important to continually discover diverse resistant resources for breeding. In this study, genome-wide association study (GWAS) was used to map genes/loci resistant to rice blast in the open-access rice diversity panel 1 (RDP1), previously genotyped with a 44K single-nucleotide polymorphism array. Two geographically and genetically different M. oryzae isolates from Taiwan, D41-2 and 12YL-DL3-2, were used to challenge RDP1. Infected leaves were visually rated for lesion type (LT) and evaluated for proportion of diseased leaf area (%DLA) by image analysis software. RESULTS: A total of 32 quantitative trait loci (QTLs) were identified, including 6 from LT, 30 from DLA, and 4 from both LT and DLA. In all, 22 regions co-localized with previously reported resistance (R) genes and/or QTLs, including two cloned R genes, Pita and Ptr; 19 mapped R loci, and 20 QTLs. We identified 100 candidate genes encoding leucine-rich repeat-containing proteins, transcription factors, ubiquitination-related proteins, and peroxidases, among others, in the QTL intervals. Putative resistance and susceptibility haplotypes of the 32 QTL regions for each tested rice accessions were also determined. CONCLUSIONS: By using Taiwanese M. oryzae isolates and image-based phenotyping for detailed GWAS, this study offers insights into the genetics underlying the natural variation of blast resistance in RDP1. The results can help facilitate the selection of desirable donors for gene/QTL validation and blast resistance breeding.