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This study investigates the effects of Phyllanthus amarus extract (PAE) on immune responses, growth, and resistance to Vibrio alginolyticus in white shrimp (Litopenaeus vannamei). In vitro PAE treatment did not alter the cell viability of haemocytes and significantly enhanced immune parameters such as phenoloxidase (PO) activity, phagocytic activity, and superoxide anion (O2−) production. We conducted two feeding trials to examine the effects of PAE on the growth, disease resistance, and innate immune parameters of white shrimp. In the first in vivo trial, shrimps (4.01 ± 0.03 g) were fed a diet containing 0 g (control), 10 g (PAE10), 20 g (PAE20), or 40 g (PAE40) of PAE per kilogram of feed for 56 days. After the feeding period, the PAE20 group showed a significantly higher weight gain and specific growth rate than shrimp fed the control diet. Furthermore, after challenge with V. alginolyticus, shrimp fed a diet containing PAE showed significantly higher survival than those fed the control diet. The second in vivo trial (28 days) was performed to identify the mechanisms of enhanced immunity in PAE-fed shrimp. Shrimp fed the PAE20 diet generally had the highest total haemocyte count, PO activity, phagocytic activity, and O2− production, followed by the PAE40 and PAE10 groups. Thus, our results suggest that administration of 20 g of PAE per kilogram of feed can enhance immunity, growth, and resistance to V. alginolyticus in white shrimp.

This study was to examine the immunomodulatory effects of oxytetracycline (OTC) on the white shrimp Litopenaeus vannamei (Boone, 1931). Immune parameters were not suppressed by OTC treatment in haemocytes in vitro. A total of 96 healthy shrimp were divided into four groups. Group 1 was the control group. Group 2 received 50 mg OTC/kg body weight/day. Group 3 received 1 g β-glucan/kg feed. Group 4 received 50 mg OTC/kg body weight/day and 1 g/kg β-glucan. OTC residues were more highly accumulated in the hepatopancreas than in muscle tissue during the rearing period, and the addition of β-glucan prolonged the retention time of OTC in the muscle tissue. Additionally, dietary administration of OTC in combination with β-glucan facilitated the excretion of OTC from the hepatopancreas. Shrimp that orally ingested OTC alone had an elevated total haemocyte count, phagocytosis, superoxide anion production and prophenoloxidase activity, and these immunostimulatory effects were further enhanced in shrimp receiving OTC in combination.

BACKGROUND The use of mobile health technologies has been necessary to deliver patient education to patients with diabetes during the COVID-19 pandemic. OBJECTIVE This open-label randomized controlled trial evaluated the effects of a diabetes educational platform—Taipei Medical University–LINE Oriented Video Education—delivered through a social media app. METHODS Patients with type 2 diabetes were recruited from a clinic through physician referral. The social media–based program included 51 videos: 10 about understanding diabetes, 10 about daily care, 6 about nutrition care, 21 about diabetes drugs, and 4 containing quizzes. The intervention group received two or three videos every week and care messages every 2 weeks through the social media platform for 3 months, in addition to usual care. The control group only received usual care. Outcomes were measured at clinical visits through self-reported face-to-face questionnaires at baseline and at 3 months after the intervention, including the Simplified Diabetes Knowledge Scale (true/false version), the Diabetes Care Profile–Attitudes Toward Diabetes Scales, the Summary of Diabetes Self-Care Activities, and glycated hemoglobin (HbA1c) levels. Health literacy was measured at baseline using the Newest Vital Sign tool. Differences in HbA1c levels and questionnaire scores before and after the intervention were compared between groups. The associations of knowledge, attitudes, and self-care activities with health literacy were assessed. RESULTS Patients with type 2 diabetes completed the 3-month study, with 91 out of 181 (50.3%) patients in the intervention group and 90 (49.7%) in the control group. The change in HbA1c did not significantly differ between groups (intervention group: mean 6.9%, SD 0.8% to mean 7.0%, SD 0.9%, P=.34; control group: mean 6.7%, SD 0.6% to mean 6.7%, SD 0.7%, P=.91). Both groups showed increased mean knowledge scores at 12 weeks, increasing from 68.3% (SD 16.4%) to 76.7% (SD 11.7%; PPP=.001; self-care activities: mean difference 0.3, SD 1.2, P=.03). A 100% utility rate was achieved for 8 out of 21 (38%) medication-related videos. Low health literacy was a significant risk factor for baseline knowledge scores in the intervention group, with an odds ratio of 2.80 (95% CI 1.28-6.12; P=.01); this became insignificant after 3 months. CONCLUSIONS The social media–based program was effective at enhancing the knowledge, attitudes, and self-care activities of patients with diabetes. This intervention was also helpful for patients with low health literacy in diabetes knowledge. The program represents a potentially useful tool for delivering diabetes education to patients through social media, especially during the COVID-19 pandemic. CLINICALTRIAL ClinicalTrials.gov NCT04876274; https://clinicaltrials.gov/ct2/show/results/NCT04876274

The effect of hospice care on place of death among centenarians remained unexplored. Using data obtained from National Health Insurance Research Database (2002-2010), we compared the differences in place and cause of death between centenarians and noncentenarians. These data were stratified into centenarian (n = 2495) and noncentenarian (n = 820 563) death. Data in place and cause of death and hospice care interventions were retrieved. Poisson regression models were used to evaluate factors associated with the centenarians’ place of death. Time series models were used to predict the number of centenarian deaths until 2025. Most (63.8%) of the centenarians died at their own homes, followed by 30.5% who died in hospital. Hospice home care was involved in only 0.3% of the centenarian deaths but in 1.8% of the noncentenarian deaths. The leading causes of death among centenarians were respiratory diseases (16.6%), circulatory diseases (15.2%), and pneumonia (14.8%). Among the centenarians, those who died of circulatory disease, old age, and respiratory diseases were more likely to die at their own homes. We forecasted the number of annual centenarian deaths to reach 800 in 2025. Therefore, an increase in the provision of advanced care planning and earlier home hospice care intervention may enable centenarians to die at their own residence.

Viruses are obligate intracellular parasites relying on host cells to obtain biosynthetic precursors and energy to successfully infect the host. The metabolic profile of the host cell is known to be altered in response to viral infection to satisfy the resources demanded during viral replication. Previous data of ours showed that white spot syndrome virus (WSSV) elicited in a crustacean host (Procambarus clarkii) a rapid and long-lasting release of crustacean hyperglycemic hormone (CHH), a well-known carbohydrate-regulating and stress response-mediating endocrine hormone. Therefore, the WSSV-enhanced release of CHH could be responsible at least in part for the metabolic alterations in the WSSV-challenged host. To investigate the possible metabolic roles of CHH in the host-parasite interaction, we studied whether silencing CHH gene expression could inhibit WSSV propagation in tissues and reduce the mortality of the WSSV-infected animals. Data presented in this study showed that CHH gene silencing indeed resists the WSSV infection. Injection of CHH dsRNA at the dosage of 140 μg/g BW caused significant decreases of viral copy number in tissues of WSSV-infected host, particularly showing a pronounced effect in the endodermal tissues (including hepatopancreas and gastrolith disk). Furthermore, results from the cumulative mortality showed that the treatment of CHH dsRNA delayed death from WSSV. Injection of CHH dsRNA at the dosages of 70, 17, and 10 μg/ g BW significantly extended the mean survival time. Together, this study concludes that the silencing of the CHH gene does have an inhibitory effect on the replication of the white spot syndrome virus and can assist the host to mitigate the invasion of WSSV, through attenuating CHH-mediated stress responses.

BACKGROUND Nonadherence to medications, failure to prevent exposure to asthma triggers, lack of knowledge about using medications, and fixed mindsets contribute to poor asthma control in children. Digital learning could provide a new strategy for improving health-related outcomes in children with asthma. OBJECTIVE The aim of this study is to develop and design a digital educational program, titled Module of Inhaler and Asthma Triggers for Children (MIRACLE), for Indonesian children with asthma. The program comprises an interactive narrative and a serious game. It was proposed to increase the understanding of asthma self-management, instruct on proper inhaler techniques, improve asthma control, and promote a growth mindset for children with asthma. METHODS Two phases of research were conducted to develop the program. In the first phase, a literature search and two rounds of the Delphi technique were conducted to obtain agreement from an expert panel regarding elements of asthma self-management and the design of interactive narratives and a serious game. The expert panel item statements were evaluated using the content validity index (CVI). In the second phase, the SERES framework, Norma Engaging Multimedia Design, and Psychological Theory of Growth Mindset were applied to create a storyline, learn objectives, and game challenges. RESULTS In the first phase, 40 experts were invited to participate in Delphi round 1. Forty responses were collected to generate 38 item statements that consisted of part 1, elements of asthma self-management (25 items), and part 2, design of an interactive narrative and a serious game (13 items); 38 experts were involved in Delphi round 2. In total, 24 statements in part 1 and 13 items in part 2 had item-CVI values >0.80. The average CVI was 0.9, which was considered acceptable. Four narrative plots and five game sessions were developed during the second phase. Challenges with the scenario, scoring, and feedback on asthma difficulties were designed to promote a growth mindset for learners. CONCLUSIONS We developed a culture-specific, computer-based asthma program containing an interactive narrative and a serious game to deliver asthma self-management and promote a growth mindset among Indonesian children.

International audience; Early studies recognizing the importance of the decapod eyestalk in the endocrine regulation of crustacean physiology-molting, metabolism, reproduction, osmotic balance, etc.-helped found the field of crustacean endocrinology. Characterization of putative factors in the eyestalk using distinct functional bioassays ultimately led to the discovery of a group of structurally related and functionally diverse neuropeptides, crustacean hyperglycemic hormone (CHH), molt-inhibiting hormone (MIH), gonad-inhibiting hormone (GIH) or vitellogenesis-inhibiting hormone (VIH), and mandibular organ-inhibiting hormone (MOIH). These peptides, along with the first insect member (ion transport peptide, ITP), constitute the original arthropod members of the crustacean hyperglycemic hormone (CHH) superfamily. The presence of genes encoding the CHH-superfamily peptides across representative ecdysozoan taxa has been established. The objective of this review is to, aside from providing a general framework, highlight the progress made during the past decade or so. The progress includes the widespread identification of the CHH-superfamily peptides, in particular in non-crustaceans, which has reshaped the phylogenetic profile of the superfamily. Novel functions have been attributed to some of the newly identified members, providing exceptional opportunities for understanding the structure-function relationships of these peptides. Functional studies are challenging, especially for the peptides of crustacean and insect species, where they are widely expressed in various tissues and usually pleiotropic. Progress has been made in deciphering the roles of CHH, ITP, and their alternatively spliced counterparts (CHH-L, ITP-L) in the regulation of metabolism and ionic/osmotic hemostasis under (eco)physiological, developmental, or pathological contexts, and of MIH in the stimulation of ovarian maturation, which implicates it as a regulator for coordinating growth (molt) and reproduction. In addition, experimental elucidation of the steric structure and structure-function relationships have given better understanding of the structural basis of the functional diversification and overlapping among these peptides. Finally, an important finding was the first-ever identification of the receptors for this superfamily of peptides, specifically the receptors for ITPs of the silkworm, which will surely give great impetus to the functional study of these peptides for years to come. Studies regarding recent progress are presented and synthesized, and prospective developments remarked upon.

This study was aimed to evaluate the correlation between the polymorphisms of the UDP-glucuronosyltransferases1A7 (UGT1A7) gene and the risk of lung carcinogenesis in the Taiwanese population. A total of 230 lung cancer patients and 230 age-and gender-matched healthy individuals were enrolled in this case control study. UGT1A7*1 was defined as a high activity allele, while UGT1A7*2, UGT1A7*3 and UGTIA7*4 were categorized as low activity alleles. The relationship between EGFR mutations and UGT1A7 polymorphisms was investigated in this study. The frequency of UGT1A7*2 and UGT1A7*3 was significantly higher in the lung cancer group than in the control group (p = 0.03, odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.04-1.99 for UGT1A7*2; and p = 0.01, OR = 1.56, 95% CI = 1.11-2.18 for UGTIA7*3). The frequency of lower activity alleles was significantly higher in the lung cancer group than in the control group (p = 0.03, OR = 1.58, 95% CI = 1.04-2.40 for the high-activity allele/low-activity allele (H/L) group; and p ＜ 0.01, OR = 2.23, 95% CI = 1.29-3.84 for the low-activity allele/low-activity allele (L/L) group). This difference was only significant in the male subgroup, with odds ratio of 1.87 (95% CI = 1.05-3.36, p = 0.03) for the H/L group and 2.638 (95% CI = 1.28-5.42, p ＜ 0.01) for the L/L allele group. Yet, pathologic type and epidermal growth factor receptor (EGFR) mutations did not affect the distribution of UGT1A7 in the patient group. The results suggested that the polymorphisms of the metabolic gene, UGT1A7, may contribute to reduced enzyme activity and subsequently affect the detoxification of carcinogens. It is therefore concluded that UGT1A7 polymorphism is associated with lung carcinogenesis for the Taiwanese population.

This study investigates the effects of three medicinal herbal extracts, namely Bidens pilosa (BPE), Lonicera japonica (LJE), and Cyathula officinalis (COE), on nonspecific immune parameters of cobia (Rachycentron canadum) in vitro and in vivo. During in vitro tests, BPE treatment increased reactive oxygen species (ROS) production in a dose-dependent manner in primary head kidney leukocytes. Similarly, ROS production rates were enhanced by LJE (50 and 100 mg/ml) and COE (100 mg/ml). This suggests that these three herbal extracts possess immunostimulating properties. We then conducted two feeding trials to examine the effects of these three herbal extracts on growth and innate immune parameters of cobia, and sought an optimal dietary supplementation proportion required for activating the non-specific immune responses. In the first trial, we supplemented the diet with 1, 5, or 10% of the individual extracts. After a ten-week feeding trial, no negative impacts on weight gain, feed conversion rate, and survival rate were observed in fish offered experimental diets. Further, ROS production, phagocytic capacity of the head kidney leukocytes, and serum lysozyme activity were enhanced by differing degrees in fish fed the herbal extracts compared to fish in the control group. A similar albumin/globulin ratio was seen between each experimental group and the control group regardless of the type and dose of herbal extract used, indicating these medicinal herbal extracts are safe for cobia. We then performed a 30-day feeding trial with lower extract concentrations (1, 3, and 5% of the diet) to identify dose responses in cobia at various time points so that we could establish a cost-effective manner of administering the three extracts for cobia. All BPE fed fish had higher ROS production compared to the control group, while phagocytosis rate and index were simultaneously raised in only the BPE30 group (3% BPE). Immune parameters such as ROS production, phagocytic rate, and serum lysozyme activity were triggered when fish received 30 g LJE per kg of feed. However, ROS production only increased in the LJE10 group (1% LJE) on day 30 and was not enhanced in the LJE50 group (5% LJE). Additionally, although the phagocytic rate and phagocytic index were induced in the LJE50 group, serum lysozyme activity was not elevated in this group (LJE50) at any time point examined. ROS production was greatly improved in all COE fed groups, but only the COE30 group (3% COE) showed prolonged enhanced phagocytic rate over the 30-day feeding trial.

Existing data indicate that a Ca2+ signal stimulates ecdysteroid hormone production by crustacean molting glands (Y-organs). Ca2+ signaling is dependent on a tightly regulated Ca2+ gradient, with intracellular free Ca2+ maintained at a low basal level (typically sub-micromolar). This is achieved through the action of proteins intrinsic to the plasma membrane and the membranes of organelles. One such protein, the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), pumps Ca2+ from cytosol to the lumen of the endoplasmic reticulum. As a step toward understanding Ca2+-mediated regulation of ecdysteroidogenesis, we have begun investigating Ca2+ transport proteins in Y-organs. In studies reported here, we used a PCR-based strategy to clone from Y-organs of the blue crab (Callinectes sapidus) a cDNA encoding a putative SERCA protein. The cloned Cas-SERCA cDNA (3806 bp) includes a 3057-bp open reading frame that encodes a 1019-residue protein (Cas-SERCA). The conceptually translated protein has a predicted molecular mass of 111.42 × 103 and contains all signature domains of an authentic SERCA, including ten transmembrane domains and a phosphorylation site at aspartate 351. A homology model of Cas-SERCA closely resembles models of related SERCA proteins. Phylogenetic analysis shows Cas-SERCA clusters with SERCA proteins from other arthropods. An assessment of tissue distribution indicates the Cas-SERCA transcript is widely distributed across tissues. Studies using quantitative PCR showed Cas-SERCA transcript abundance increased significantly in Y-organs activated by eyestalk ablation, a pattern consistent with the hypothesis that Cas-SERCA functions to maintain Ca2+ homeostasis in Y-organs.

A cDNA (Liv-RPCH) encoding a putative red pigment-concentrating hormone was cloned from whiteleg shrimp (Litopenaeus vannamei) eyestalks. The deduced amino acid sequence of this cDNA was 93 residues long and consisted of a 21-residue signal peptide, a 9-residue red pigment-concentrating hormone (RPCH) mature peptide, a dibasic cleavage site, and a 61-residue RPCH precursor-related peptide (RPRP). The Liv-RPCH transcript was detected not only in neural tissues (eyestalks, brain, thoracic ganglia, and abdominal ganglia) but also in non-neural tissues (ovaries and heart). In vivo injection of synthetic RPCH (pELNFSPGW-NH2) caused significant increases in hemolymph vitellogenin (Vg) concentrations, ovarian Vg mRNA levels, and mean oocyte area, suggesting that RPCH has a positive role in promoting ovarian growth in L. vannamei. The effects of 5-HT on the expression of Liv-RPCH transcripts in selected tissues (eyestalks, brain, thoracic ganglia, and ovaries) were examined by using quantitative real-time PCR. Injection of 5-HT (20 μg g−1 body weight) resulted in elevated Liv-RPCH transcript levels in the ovaries 3 and 6 h after injection, but no significant effects were observed in the eyestalks, brain, or thoracic ganglia.

In the whiteleg shrimp Litopenaeus vannamei, the existence of six sinus gland peptides (SGPs) possessing vitellogenesis-inhibiting hormone (VIH) function has been previously demonstrated. Genomic and cDNA sequence information for two of these is already known. Here, we cloned cDNAs for the remaining three, i.e., those encoding Liv-SGP-A, -B, and -F. The deduced amino acid sequences were comprised of a signal peptide, a CHH precursor-related peptide, a mature peptide, and a C-terminal amidation signal. The genomic DNA for Liv-SGP-A, -B, -C, -F, and -G, was found to be organized as three exons and two introns. The insertion of the two introns were conserved in all VIH genes, with intron I being inserted six residues following the signal peptide, and intron II after the 40th residue of the mature peptide. We also quantified the relative simultaneous expression of Liv-SGP-A, -B, -C, -F, and -G in relation to molting and unilateral eyestalk ablation. The expression levels of each gene in the eyestalks of adults did not change significantly during molting or following unilateral eyestalk ablation. However, unilateral eyestalk ablation significantly decreased expression levels at 10 and 20 days for Liv-SGP-A and -C, and at 20 days for Liv-SGP-G in the eyestalks of subadults. This study has therefore clarified the genomic structure of the five major subtype I VIHs in L. vannamei, and elucidated their expression levels in the eyestalks in relation to molting and unilateral eyestalk ablation.

Crustacean Y-organs secrete ecdysteroid molting hormones. Ecdysteroids are released in increased amount during premolt, circulate in hemolymph, and stimulate the events in target cells that lead to molting. During much of the molting cycle, ecdysteroid production is suppressed by molt-inhibiting hormone (MIH), a peptide neurohormone produced in the eyestalks. The suppressive effect of MIH is mediated by a cyclic nucleotide second messenger. A decrease in circulating MIH is associated with an increase in the hemolymphatic ecdysteroid titer during pre-molt. Nevertheless, it has long been hypothesized that a positive regulatory signal or stimulus is also involved in promoting ecdysteroidogenensis during premolt. Data reviewed here are consistent with the hypothesis that an intracellular Ca2+ signal provides that stimulus. Pharmacological agents that increase intracellular Ca2+ in Y-organs promote ecdysteroidogenesis, while agents that lower intracellular Ca2+ or disrupt Ca2+ signaling suppress ecdysteroidogenesis. Further, an increase in the hemolymphatic ecdysteroid titer after eyestalk ablation or during natural premolt is associated with an increase in intracellular free Ca2+ in Y-organ cells. Several lines of evidence suggest elevated intracellular calcium is linked to enhanced ecdysteroidogenesis through activation of Ca2+/calmodulin dependent cyclic nucleotide phosphodiesterase, thereby lowering intracellular cyclic nucleotide second messenger levels and promoting ecdysteroidogenesis. Results of transcriptomic studies show genes involved in Ca2+ signaling are well represented in Y-organs. Several recent studies have focused on Ca2+ transport proteins in Y-organs. Complementary DNAs encoding a plasma membrane Ca2+ ATPase (PMCA) and a sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) have been cloned from crab Y-organs. The relative abundance of PMCA and SERCA transcripts in Y-organs is elevated during premolt, a time when Ca2+ levels in Y-organs are likewise elevated. The results are consistent with the notion that these transport proteins act to maintain the Ca2+ gradient across the cell membrane and re-set the cell for future Ca2+ signals.

Background: Abuse-deterrent formulations (ADFs) represent one novel strategy for curbing the potential of opioid abuse. Objective: We aim to compare and contrast the characteristics and applications of current abusedeterrent opioid products in clinical practice. Methods: Literature searches were conducted in databases (Pubmed Medline, International Pharmaceutical Abstracts, Google Scholar) and official reports. Relevant data were screened and organized into: 1) epidemiology of opioid abuse, 2) mitigation strategies for reducing opioid abuse, 3) development of ADFs, and 4) clinical experience with these formulations. Results: Increasing trends of opioid abuse and misuse have been reported globally. There are 5 types of abuse-deterrent opioid products: physical chemical barrier, combined agonist/antagonist, sequestered aversive agent, prodrug, and novel delivery system. The advantages and disadvantages of the 5 options are discussed in this review. A total of 9 products with abuse-deterrent labels have been approved by the Food and Drug Administration (FDA). The rates of abuse, diversion, and overdose deaths of these new products are also discussed. A framework for collecting in-time data on the efficacy, benefit and risk ratio, and cost-effectiveness of these new products is suggested to facilitate their optimal use. Limitations: The present review did not utilize systematic review standards or meta-analytic techniques, given the large heterogeneity of data and outcomes reviewed. Conclusions: ADFs provide an option for inhibiting the abuse or misuse of oral opioid products by hindering extraction of the active ingredient, preventing alternative routes of administration, or causing aversion. Their relatively high costs, uncertain insurance policies, and limited data on pharmacoeconomics warrant collaborative monitoring and assessment by government agencies, pharmaceutical manufacturers, and data analysis services to define their therapeutic role in the future. Key words: Opioid abuse, abuse-deterrent formulations, ADF, post-marketing, FDA guidance, cost impact, abuse liking, physician attitude, generic abuse-deterrent formulation, clinical application

Background Nonadherence to medications, failure to prevent exposure to asthma triggers, lack of knowledge about using medications, and fixed mindsets contribute to poor asthma control in children. Digital learning could provide a new strategy for improving health-related outcomes in children with asthma. Objective The aim of this study is to develop and design a digital educational program, titled Module of Inhaler and Asthma Triggers for Children (MIRACLE), for Indonesian children with asthma. The program comprises an interactive narrative and a serious game. It was proposed to increase the understanding of asthma self-management, instruct on proper inhaler techniques, improve asthma control, and promote a growth mindset for children with asthma. Methods Two phases of research were conducted to develop the program. In the first phase, a literature search and two rounds of the Delphi technique were conducted to obtain agreement from an expert panel regarding elements of asthma self-management and the design of interactive narratives and a serious game. The expert panel item statements were evaluated using the content validity index (CVI). In the second phase, the SERES framework, Norma Engaging Multimedia Design, and Psychological Theory of Growth Mindset were applied to create a storyline, learn objectives, and game challenges. Results In the first phase, 40 experts were invited to participate in Delphi round 1. Forty responses were collected to generate 38 item statements that consisted of part 1, elements of asthma self-management (25 items), and part 2, design of an interactive narrative and a serious game (13 items); 38 experts were involved in Delphi round 2. In total, 24 statements in part 1 and 13 items in part 2 had item-CVI values >0.80. The average CVI was 0.9, which was considered acceptable. Four narrative plots and five game sessions were developed during the second phase. Challenges with the scenario, scoring, and feedback on asthma difficulties were designed to promote a growth mindset for learners. Conclusions We developed a culture-specific, computer-based asthma program containing an interactive narrative and a serious game to deliver asthma self-management and promote a growth mindset among Indonesian children.

We incubated fragments of Litopenaeus vannamei ovary to investigate second messengers involved in the regulation of vitellogenin ( vg ) mRNA levels . The use of 100 nM recombinant vitellogenesis-inhibiting hormone (VIH) (corresponding to recombinant L. vannamei sinus gland peptide-G: rLiv-SGP-G) significantly reduced vg mRNA expression in sub-adults after 8 h incubation to less than 20% of the control. The concentration of intracellular cyclic guanosine monophosphate (cGMP) increased 3.2-fold relative to the control after 2 h incubation with rLiv-SGP-G. However, it reached levels 18-fold relative to the control after 0.5 h incubation with rLiv-SGP-G where 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor) was also added. Moreover, vg mRNA expression was significantly reduced to less than 50% of the control after 24 h incubation with 1 μM A23187 (a calcium ionophore). Thus, rLiv-SGP-G and calcium ionophore reduced vg mRNA expression in in vitro -cultured ovary, and cGMP may be involved in the signaling pathway of VIH. Overall, the above results suggest that vg mRNA expression might be inhibited in vitro by increasing intracellular cGMP and Ca 2+ in L. vannamei ovary.

Background The study compared the predictive outcomes of artificial neural network, support vector machine and random forest on the occurrence of anti-tuberculosis drug-induced hepatotoxicity. Methods The clinical and genomic data of patients treated with anti-tuberculosis drugs at Taipei Medical University-Wanfang Hospital were used as training sets, and those at Taipei Medical University-Shuang Ho Hospital served as test sets. Features were selected through a univariate risk factor analysis and literature evaluation. The accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve were calculated to compare the traditional, genomic, and combined models of the three techniques. Results Nine models were created with 7 clinical factors and 4 genotypes. Artificial neural network with clinical and genomic factors exhibited the best performance, with an accuracy of 88.67%, a sensitivity of 80%, and a specificity of 90.4% for the test set. The area under the receiver operating characteristic curve of this best model reached 0.894 for training set and 0.898 for test set, which was significantly better than 0.801 for training set and 0.728 for test set by support vector machine and 0.724 for training set and 0.718 for test set by random forest. Conclusions Artificial neural network with clinical and genomic data can become a clinical useful tool in predicting anti-tuberculosis drug-induced hepatotoxicity. The machine learning technique can be an innovation to predict and prevent adverse drug reaction.

Online_supplement_Appendix for Where and How Centenarians Die? The Role of Hospice Care by Yang-Ching Chen, Hsiao-Yun Hu, Hsien-Yu Fan, Wei-Shih Kao, Hsiang-Yin Chen and Sheng-Jean Huang in American Journal of Hospice and Palliative Medicine®

STUDY DESIGN A retrospective cohort study by using the Taiwanese National Health Insurance Research Database (NHIRD). OBJECTIVE The purpose of this study is to conduct a large-scale cohort study to investigate the relationship between scoliosis and depression. SUMMARY OF BACKGROUND DATA The association between scoliosis and depression has rarely been studied in Asian populations. METHODS The study cohort consisted of patients with diagnosis of scoliosis between 2003 and 2005 (N = 1409). A comparison cohort was constructed from five age- and gender-matched control subjects selected via random sampling (N = 7045). Data on adjusted hazard ratios (AHRs) of depression, 5-year freedom from depression rates, and risk factors for depression for the two cohorts were compared. All subjects were tracked for 5 years from the date of cohort entry to identify the development of depression. Cox proportional hazard regressions were performed to evaluate the 5-year freedom from depression rates. This study is supported by the University research grant without any study-specific conflicts. RESULTS During the 5-year follow-up period, 116 and 307 depression patients belonged to the scoliosis cohort and the comparison cohort, respectively. The AHRs of depression in patients with scoliosis was higher [AHR 1.95; 95% confidence interval (95% CI) 1.58-2.42; P

A new oral antidiabetic drug class, sodium-glucose co-transporter-2 inhibitors (SGLT-2 inhibitors), has been covered by national health insurance in Taiwan since May 2016. This study estimated the impacts of insurance coverage for SGLT-2 inhibitors on the replacement effects of antidiabetic drug use and the overall budget for antidiabetic drugs in Taiwan. Antidiabetic drugs were divided into nine categories based on the American Diabetes Association guidelines. We retrieved claims data from 2015 to 2017 for all patients diagnosed with diabetes mellitus from the National Health Insurance Research Database. An interrupted time series design and segmented regression were used to estimate the budget impact of insurance coverage for SGLT-2 inhibitors. Three scenarios were designed for the prescribing pattern for SGLT-2 inhibitors: (1) monotherapy, (2) metformin-based (m-based) drug prescriptions, and (3) metformin and sulfonylurea-based (m-s-based) drug prescriptions. From May 2016 to April 2017, the prescription rate for m-based SGLT-2 inhibitors increased from 0.43 to 3.50%, and the expenditure rate increased from 0.82 to 6.58%. We found that the prescription rates of m-based and m-s-based dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) decreased by 6.23 and 11.51% following the initiation of insurance coverage for SGLT-2 inhibitors, respectively. Furthermore, there was a 5.95% increase in the overall budget impact of antidiabetic drugs 1 year following the initiation of insurance coverage for SGLT-2 inhibitors. Both the prescription rates and expenditure rates for SGLT-2 inhibitors have increased since they have been covered by national health insurance in Taiwan, which significantly reduced usage of DPP-4 inhibitors but caused the positive growth of overall antidiabetic drug expenditures.

Existing data indicate that a Ca

Objective Clinical information on tigecycline use in serious nosocomial infections is limited, and the efficacy is uncertain. The aim of this retrospective study was to assess the utilization pattern and the effectiveness of tigecycline in a tertiary medical center in Taiwan. Methods A retrospective study of the clinical and microbiological outcome of all patients treated with tigecycline for at least 72 hours over a 2-year period was conducted in a 730-bed teaching hospital. Results Data from 133 patients with 149 cases of nosocomial infection were analyzed in this assessment. The mean APACHE II score at the initiation of tigecycline therapy was 22.5 ± 8.8, and the mean duration of treatment was 11.4 ± 5.6 days. Pneumonia was the most frequently diagnosed clinical indication for tigecycline use (113 cases, 76%). An overall positive clinical outcome was observed in 75 cases (50%). Multidrug-resistant Acinetobacter baumannii (MDRAB) is the most common organism for tigecycline therapy (n = 59), with a positive clinical outcome of 38% in tigecycline monotherapy, 66% in dualtherapy, and 17% in triple-therapy (p = 0.031). The most commonly used combining agents with tigecycline to treat MDRAB infections were intravenous colistin, inhaled colistin, and cepoferazone/sulbactam, with positive clinical outcome rates of 53%, 100%, and 80%, respectively. Admission to intensive care unit was identified as a predictive factor for negative clinical outcome. Conclusion Our pneumonia-dominated study population demonstrated a lower clinical improvement rate of tigecycline compared to previous published data. Tigecycline monotherapy is not recommended for MDRAB infection, but colistin or cephoperazone/ sulbactam combined with tigecycline seemed to yield a good clinical outcome for MDRAB infection.

The PharmaCloud system, a cloud-based medication system, was launched by the Taiwan National Health Insurance Administration (NHIA) in 2013 to integrate patients' medication lists among different medical institutions. The aim of the preliminary study was to evaluate satisfaction with this system among physicians and pharmacists at the early stage of system implementation.A questionnaire was developed through a review of the literature and discussion in 6 focus groups to understand the level of satisfaction, attitudes, and intentions of physicians and pharmacists using the PharmaCloud system. It was then administered nationally in Taiwan in July to September 2015. Descriptive statistics and multiple regression were performed to identify variables influencing satisfaction and intention to use the system.In total, 895 pharmacist and 105 physician questionnaires were valid for analysis. The results showed that satisfaction with system quality warranted improvement. Positive attitudes toward medication reconciliation among physicians and pharmacists, which were significant predictors of the intention to use the system (β= 0.223, p 0.001). Most physicians and pharmacists agreed that obtaining signed patient consent was needed but preferred that it be conducted by the NHIA rather than by individual medical institutions (4.02 ± 1.19 vs. 3.49 ± 1.40, p 0.01).The preliminary study results indicated a moderate satisfaction toward the PharmaCloud system. Hospital pharmacists had a high satisfaction rate, but neither are physicians and community pharmacists. Continuously improvement on system quality has been performing based on the results of this preliminary survey. Policies and standardization processes, including privacy protection, are still warranted further actions to make the Taiwan PharmaCloud system a convenient platform for medication reconciliation.

Background. Cisplatin and carboplatin cause nephrotoxicity by forming platinum-DNA adducts and lead to cell death.Methods. One-hundred and sixteen Taiwanese lung cancer patients who received cisplatin or carboplatin more than twice were recruited, and their genotypes were determined. The risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease (RIFLE) criteria were used to evaluate the occurrence of nephrotoxicity. A logistic regression, multiple regression with a classification and regression tree (CART), and the Framingham study risk score were used to analyze interactions between genetic and nongenetic factors in producing platinum-induced nephrotoxicity.Results.ERCC1118C andTP5372Arg polymorphisms were associated with increased risks of platinum-induced nephrotoxicity. Other risk factors found included the platinum type, baseline serum creatinine (Scr), coadministration of vinorelbine, and the number of chemotherapy cycles. The overall prediction rate of the CART was 82.7%, with a sensitivity of 0.630 and specificity of 0.896. The Framingham study risk prediction model contained 7 factors. Its prediction rate was 84.5%, with a sensitivity of 0.643 and specificity of 0.909.Conclusions. Genetic polymorphisms ofERCC1andTP53are risk factors for nephrotoxicity. The CART analysis may provide a clinically applicable model to predict the risk of cisplatin- and carboplatin-induced nephrotoxicity.

Children are more susceptible to medication errors because of differences in pharmacokinetics and pharmacodynamics compared to adults. Weight changes are common with growth in children and computer systems frequently are not updated with current information, which result in inaccurate weight-based dosing and thus harm children. This study evaluated the impact of a Computerized Physician Order Entry system with standardized pediatric dosing decision support (PDDS) function on reducing pediatric dosing errors. Outpatient prescriptions were analyzed from January to March during 2010 and 2011. The total number of pediatric prescriptions was 72,431 and 80,532 prior to and after system implementation, respectively. Out of 72,431 prescriptions, 1617 (2.23%) dosing errors were retrospectively detected by the system, whereas 15 dosing errors (0.02%) were detected by pharmacists prior to system implementation. Incorporating the system into practice resulted in a total of 210 successfully blocked dosing near misses, including 14 potentially fatal and 11 serious near misses. The final dosing error rate was significantly reduced from 2.23% to 0.66% (p

Objectives Obtaining an accurate medication history upon admission to the hospital can be challenging and time-consuming. This study evaluated the efficacy of a medication reconciliation program, conducted by pharmacists, with the assistance of medication usage data from the Taiwan National Health Insurance (NHI). Characteristics of patients at high risk for drug discrepancies were also determined. Methods Patients admitted between May 2008 and September 2009 were recruited. The type and class of medication discrepancies reported by pharmacists, the medication discrepancy rate, physician acceptance rate, and time taken for the intervention were studied. The degree of harm that could have resulted from the discrepancies was independently evaluated by four pharmacists. The association between selected variables and the occurrence of drug discrepancies was analyzed. Results Among 3013 patients interviewed, the pharmacists identified 243 patients (8%) with at least one medication discrepancy between the patient's medication history and admission orders. There were 576 discrepancies identified. About 19% of the errors prevented could have potentially caused moderate to severe harm. The average time for one intervention was 18 ± 9.8 min. The number of preadmission medications, age, frequency of outpatient visits within 3 months prior to this hospital admission, and the number of specialist outpatient clinics the patient had visited within 3 months before the admission were determined to be risk factors for drug discrepancies. Conclusions This medication reconciliation program, conducted by pharmacists, was made more efficient by medication usage data from the Taiwan NHI. Pharmacists can reconcile medications more effectively by selecting patients at high risk for unintentional drug discrepancies.

Existing data indicate that a stage-specific increase in intracellular free Ca 2 + stimulates ecdysteroid production by crustacean molting glands (Y-organs). The concentration of Ca 2 + in cytosol is controlled mainly by proteins intrinsic to the plasma membrane and to the membranes of organelles. Several families of proteins are involved, including Ca 2 + channels, Ca 2 + pumps (ATPases), and Ca 2 + exchangers. The family of Ca 2 + pumps includes plasma membrane calcium ATPases (PMCAs). As a step toward understanding the involvement of calcium signaling in regulation of ecdysteroidogenesis, we used a PCR-based cloning strategy (RT-PCR followed by 3′- and 5′-RACE) to clone from Y-organs of the blue crab ( Callinectes sapidus ) a cDNA encoding a putative PMCA. The 4292 base pair (bp) cDNA includes a 3510 bp open reading frame encoding a 1170-residue protein (Cas-PMCA). The conceptually translated protein has a relative molecular mass of 128.8 × 10 3 and contains all signature domains of an authentic PMCA, including ten transmembrane domains and a calmodulin binding site. The predicted membrane topography of Cas-PMCA is as expected for an authentic PMCA protein. A phylogenetic analysis of nonredundant amino acid sequences of PMCA proteins from different species showed Cas-PMCA clusters with other arthropod PMCA proteins. An assessment of tissue distribution showed the Cas-PMCA transcript to be broadly distributed in both neural and non-neural tissues. Studies using quantitative real-time PCR revealed stage-specific changes in Cas-PMCA abundance during the molting cycle, with peak expression occurring during premolt stage D2, a pattern consistent with the hypothesis that Cas-PMCA functions to maintain cellular Ca 2 + homeostasis in Y-organs.

The safety and efficacy of warfarin therapeutic range in Asians remain to be ascertained. Physicians in Taiwan consider Asians are more likely to have bleeding complications rather than thromboembolic events from warfarin. The aim of this study was to determine if the proper INR range for patients in Taiwan is different.A retrospective study was conducted with 161 patients on warfarin therapy for more than 24 consecutive months during March 1, 2006 to Sepember 30, 2008. Total follow-up time was 3,504 patient-months. The incidence rates of thromboembolic and bleeding events for INR categories were calculated.The overall incidence rates of INR ranges of1.5, 1.5 - 1.9, 2.0 - 2.4, 2.5 - 2.9, 3.0 - 3.4, and ≥ 3.5 were 8.1, 5.6, 2.0, 7.6, 33.3, and 121.2 per 1,000 patientmonths, respectively. The overall incidence rate at INR of3 is higher than that at INR of2 or 2 - 3 (p0.001), with the lowest incidence rate at INR between 2.0 and 2.4. When INR was maintained at a level2, patients taking warfarin for secondary prevention had a significantly higher event rate compared to the primary prevention group (p0.05). Age greater than 73 years was a risk factor for thromboembolic events before and after covariate adjustment.An INR range of 2 - 2.4 appeared to be associated with lower complications and better clinical outcomes in Taiwanese patients treated with warfarin. Lowering the intensity of anticoagulant therapy further does not decrease the number of events.