Alternating Hot-Cold Water Immersion Facilitates Motor Function Recovery in the Paretic Upper Limb Following Stroke: A Pilot Randomized Controlled Trial.

OBJECTIVE: This study aimed to assess the effectiveness of alternating hot-cold water immersion (AHCWI) in patients with acute stroke. DESIGN: A single-blind pilot randomized controlled trial SETTING: Department of rehabilitation medicine of a medical center PARTICIPANTS: Twenty-four early stroke survivors with moderate-to-severe arm paresis Interventions: In addition to conventional rehabilitation, eligible patients were randomly assigned to an AHCWI group (n = 12, for AHCWI) or a control group (n = 12, for upper limb (UL) cycling exercises) five times per week for 6 weeks. MAIN OUTCOME MEASURES: The Fugl-Meyer Assessment motor UL (FMA-UL) score, Motricity Index UL (MI-UL) score, modified Motor Assessment Scale, (including its UL sections, MMAS and MMAS-UL), Berg Balance Scale, Barthel Index (BI), and modified Ashworth Scale were assessed by the same uninvolved physical therapist at baseline and after 4 and 6 weeks of intervention. RESULTS: Compared with the control group, the AHCWI group performed better, with significant group effects (P < 0.05), and exhibited significant improvements in FMA-UL, MI-UL, and MMAS-UL scores at 4 and 6 weeks (P < 0.05). Although the remaining outcomes were not significantly different, they favored the AHCWI group. Notably, a significant difference was observed in the BI at 4 weeks (P = 0.032). Significant changes in the muscle tone or adverse effects were not observed in either group after the intervention. CONCLUSIONS: AHCWI with stroke rehabilitation is feasible and may facilitate motor function recovery of the paretic UL after a stroke.

Mechanistic Insights into Dibasic Iminosugars as pH-Selective Pharmacological Chaperones to Stabilize Human α-Galactosidase.

The use of pharmacological chaperones (PCs) to stabilize specific enzymes and impart a therapeutic benefit is an emerging strategy in drug discovery. However, designing molecules that can bind optimally to their targets at physiological pH remains a major challenge. Our previous study found that dibasic polyhydroxylated pyrrolidine 5 exhibited superior pH-selective inhibitory activity and chaperoning activity for human α-galactosidase A (α-Gal A) compared with its monobasic parent molecule, 4. To further investigate the role of different C-2 moieties on the pH-selectivity and protecting effects of these compounds, we designed and synthesized a library of monobasic and dibasic iminosugars, screened them for α-Gal A-stabilizing activity using thermal shift and heat-induced denaturation assays, and characterized the mechanistic basis for this stabilization using X-ray crystallography and binding assays. We noted that the dibasic iminosugars 5 and 20 protect α-Gal A from denaturation and inactivation at lower concentrations than monobasic or other N-substituted derivatives; a finding attributed to the nitrogen on the C-2 methylene of 5 and 20, which forms the bifurcated salt bridges (BSBs) with two carboxyl residues, E203 and D231. Additionally, the formation of BSBs at pH 7.0 and the electrostatic repulsion between the vicinal ammonium cations of dibasic iminosugars at pH 4.5 are responsible for their pH-selective binding to α-Gal A. Moreover, compounds 5 and 20 demonstrated promising results in improving enzyme replacement therapy and exhibited significant chaperoning effects in Fabry cells. These findings suggest amino-iminosugars 5 and 20 as useful models to demonstrate how an additional exocyclic amino group can improve their pH-selectivity and protecting effects, providing new insights for the design of pH-selective PCs.

A practical synthesis of nitrone-derived C5a-functionalized isofagomines as protein stabilizers to treat Gaucher disease.

Isofagomine (IFG) and its analogues possess promising glycosidase inhibitory activities. However, a flexible synthetic strategy toward both C5a-functionalized IFGs remains to be explored. Here we show a practical synthesis of C5a-S and R aminomethyl IFG-based derivatives via the diastereoselective addition of cyanide to cyclic nitrone 1. Nitrone 1 was conveniently prepared on a gram scale and in high yield from inexpensive (-)-diethyl D-tartrate via a straightforward method, with a stereoselective Michael addition of a nitroolefin and a Nef reaction as key steps. A 268-membered library (134 × 2) of the C5a-functionalized derivatives was submitted to enzyme- or cell-based bio-evaluations, which resulted in the identification of a promising ß-glucocerebrosidase (GCase) stabilizer demonstrating a 2.7-fold enhancement at 25 nM in p.Asn370Ser GCase activity and a 13-fold increase at 1 µM in recombinant human GCase activity in Gaucher cell lines.

Epidemiology, Patient Characteristics, and Treatment Patterns of Myasthenia Gravis in Taiwan: A Population-Based Study.

INTRODUCTION: Myasthenia gravis (MG) is a chronic neuromuscular disease leading to significant disease burden. This study aimed to investigate the epidemiology of MG in Taiwan. METHODS: A retrospective study was conducted using the Taiwan National Health Insurance Research Database. Prevalent patients with MG diagnosis (either ocular or generalized MG) from 2013 to 2019 were identified, and 2813 patients with initial MG diagnosis from 2014 to 2019 were further defined as the incident cohort. Patient characteristics, treatment patterns, and the occurrence of MG-related events were analyzed. RESULTS: The number of prevalent patients with MG increased from 4476 in 2013 to 5752 in 2019, with the prevalence rate increasing from 19 to 24 per 100,000 population. The incidence rate also slightly increased from 1.9 to 2.3 per 100,000 population during the study period. Almost all incident patients (99%, n = 2791) received MG-related treatment during the follow-up period. Among 1876 patients who received monotherapy as their initial treatment in the outpatient setting, the mean time from the index date to initial treatment was 48.8 (standard deviation 164.3) days, and most patients received acetylcholinesterase inhibitors (88.5%, n = 1661) as their initial treatment. During the first year after the index date, 133 (4.7%) incident patients experienced their first myasthenic crisis, and 96.2% of these events occurred within 3 months. CONCLUSION: The prevalence of MG increased steadily in Taiwan, and the treatment of patients with MG was consistent with guidelines. Despite a high treatment rate, patients still experienced MG-related events, highlighting the limitation of current treatments and emphasizing the need for early intervention and novel treatment approaches.

Demands for medical imaging and workforce Size: A nationwide population-based Study, 2000-2020.

PURPOSE: The aim of this study was to investigate associations between workforce and workload among radiologists in Taiwan. MATERIALS AND METHODS: Data for the period 2000-2020 describing the demand for imaging services and radiologists have been obtained from databases and statistical reports of the Ministry of Health and Welfare. The future demand for radiologists was based on Taiwanese people aged 40 and over. RESULTS: The workforce of Taiwan's radiologists has increased by 6 % annually over the past 20 years (from 450 to 993), performing 2125, 3202 and 3620 monthly examinations (mainly conventional radiography and CT) in medical centers, regional hospitals and district hospitals. Between 2000 and 2020, the use of CT and MRI increased by more than 3.5 times. Demand for interventional radiology also increased by 1.77 times, 2.25 times, and 5 times, respectively. To maintain this volume of services in 2040, at least 1168 radiologists are needed, about 1.18 times more in 2020. CONCLUSION: Taiwan has 2.4 to 2.9 times fewer radiologists than the United States and 3 times fewer than Europe, while the annual workload is approximately 2 to 3.4 times greater than that of the United States and 1.4 to 2.5 times greater than that of the United Kingdom. This report may serve as a reference for policy makers who address the challenges of the growing workload among radiologists in countries of similar situations.

Comparing Three Profoundly Influential Prognostic Scores in Cirrhotic Patients with Acute-on-Chronic-Liver Failure Admitted to the ICU: Prediction of One-Month Mortality-A Retrospective Cohort Study.

BACKGROUND: Acute-on-chronic-liver failure (ACLF) demonstrates high short-term mortality rates and usually requires intensive care unit (ICU) admission. Accurate prognostication of these patients is pivotal for timely referral for liver transplantation. The superiority of CLIF-C ACLF, CLIF-C ACLF lactate, and NACSELD-ACLF scores in Asian patients with ACLF admitted to an ICU remains inconclusive. AIMS: To compare the predictive performance of CLIF-C ACLF, CLIF-C ACLF lactate, and NACSELD-ACLF scores for one-month mortality. METHODS: 276 consecutive cirrhotic patients with ACLF admitted to ICU were enrolled. The prognostic values for one-month mortality were assessed by AUROC analysis. RESULTS: The primary cause of cirrhosis in this cohort was alcohol abuse (56.5%). AUROC analysis (95% confidence intervals) demonstrated that CLIF-C ACLF lactate [0.802 (0.747-0.856)] outperformed both CLIF-C ACLF [0.791 (0.733-0.848)] and NACSELD-ACLF [0.673 (0.606-0.740)] in predicting one-month mortality. However, no statistically significant difference was observed between the predictive abilities of CLIF-C ACLF and CLIF-C ACLF lactate. CONCLUSIONS: In critically ill cirrhotic patients with ACLF admitted to the hepatology ICU, CLIF ACLF-lactate outperformed CLIF-C ACLF and NACSELD-ACLF in predicting one-month mortality. Nevertheless, no statistically significant difference was observed between CLIF-C ACLF and CLIF-C ACLF lactate. Larger-scale multi-center prospective studies are warranted to validate these results.

Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors.

A class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC50 range of 0.001-0.026 µM by pre-incubation with the virus to avoid the virus entry. The more potent antiviral activities than the proteases inhibitory activities led to discovery that the synthesized compounds also inhibited Spike's receptor binding domain (RBD):angiotensin converting enzyme 2 (ACE2) interaction as a main target, and their antiviral activities were enhanced by inhibiting TMPRSS2 and/or Furin. To further confirm the blocking effect of 2f (81) on virus entry, SARS-CoV-2 Spike pseudovirus was used in the entry assay and the results showed that the compound inhibited the pseudovirus entry in a ACE2-dependent pathway, via mainly inhibiting RBD:ACE2 interaction and TMPRSS2 activity in Calu-3 cells. Finally, in the in vivo animal model of SARS-CoV-2 infection, the oral administration of 25 mg/kg 2f (81) in hamsters resulted in reduced bodyweight loss and 5-fold lower viral RNA levels in nasal turbinate three days post-infection. Our findings demonstrated the potential of the lead compound for further preclinical investigation as a potential treatment for SARS-CoV-2.

Bacterial coinfections in hospitalized children with COVID-19 during the SARS-CoV-2 Omicron BA.2 variant pandemic in Taiwan.

Background: Bacterial coinfections have been widely recognized in adults with coronavirus disease 2019 (COVID-19). However, bacterial coinfections in hospitalized children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been sufficiently researched. This study aimed to determine the clinical presentations and risk factors for bacterial coinfections of pediatric inpatients during the SARS-CoV-2 Omicron BA.2 variant pandemic. Methods: This retrospective, observational study included patients younger than 18 years of age who were hospitalized for COVID-19 confirmed by polymerase chain reaction (PCR) or antigen rapid tests during the SARS-CoV-2 Omicron BA.2 variant pandemic. Data and outcomes of these patients with or without bacterial coinfections were compared. Results: During this study period, 161 children with confirmed COVID-19 were hospitalized. Twenty-four had bacterial coinfections. The most frequently reported concurrent diagnosis was bacterial enteritis, followed by lower respiratory tract infections. Children with bacterial coinfections had higher white blood cell (WBC) counts and PCR cycle threshold values. The bacterial coinfection group comprised a relatively greater proportion of patients who required high-flow nasal cannula oxygen and remdesivir. The length of stay in the hospital and that in the intensive care unit were longer for children with COVID-19 with bacterial coinfections. Mortality was not observed in either group. Abdominal pain, diarrhea, and comorbidity with neurologic illnesses were risk factors for bacterial coinfections with COVID-19. Conclusion: This study provides clinicians with reference points for the detection of COVID-19 in children and its possible association with bacterial infections. Children with COVID-19 and neurologic diseases who present with abdominal pain or diarrhea are at risk of bacterial coinfections. Prolonged fever duration and higher PCR test cycle threshold values, WBC levels, and high-sensitivity C-reactive protein (hsCRP) levels may indicate bacterial coinfections in children with COVID-19.

Harnessing polyhydroxylated pyrrolidines as a stabilizer of acid alpha-glucosidase (GAA) to enhance the efficacy of enzyme replacement therapy in Pompe disease.

To discover small molecules as acid alpha-glucosidase (GAA) stabilizers for potential benefits of the exogenous enzyme treatment toward Pompe disease cells, we started from the initial screening of the unique chemical space, consisting of sixteen stereoisomers of 2-aminomethyl polyhydroxylated pyrrolidines (ADMDPs) to find out two primary stabilizers 17 and 18. Further external or internal structural modifications of 17 and 18 were performed to increase structural diversity, followed by the protein thermal shift study to evaluate the GAA stabilizing ability. Fortunately, pyrrolidine 21, possessing an l-arabino-typed configuration pattern, was identified as a specific potent rh-GAA stabilizer, enabling the suppression of rh-GAA protein denaturation. In a cell-based Pompe model, co-administration of 21 with rh-GAA protein significantly improved enzymatic activity (up to 5-fold) compared to administration of enzyme alone. Potentially, pyrrolidine 21 enables the direct increase of ERT (enzyme replacement therapy) efficacy in cellulo and in vivo.

[Reducing the Incidence of Feeding Intolerance in Premature Infants in the Neonatal Intensive Care Unit].

BACKGROUND ≥ PROBLEMS: Nutrition is very important for premature infants. Our recent research showed that the accuracy of recognition related to tube feeding was 74.8%, and the completeness of tube feeding was 74.3%. After analyzing this situation, the reasons found to be significantly associated with the low rates of tube-feeding recognition accuracy and completion included: inconsistent treatment of gastric residual by nurses in the neonatal intensive care unit (NICU), lack of sufficient assessment tools in the NICU, out-of-date specialist care guidelines, and lack of a regular inspection system. PURPOSE: Our aim was to improve tube-feeding-related recognition accuracy and completion to reduce the incidence of feeding intolerance. RESOLUTIONS: The intervention included developing a guideline manual for feeding procedures and making a gastric residual color card as a clinical-care reference. Holding on-the-job training and monitoring the quality of nursing care can reduce the incidence of feeding intolerance in preterm. RESULTS: The accuracy of tube-feeding recognition increased from 74.8% to 93.7%. The completion of tube feeding increased from 74.3% to 95.5%. The incidence of feeding intolerance in premature infants decreased from 71.8% to 39.0%. CONCLUSIONS: The results and process of this project provides a reference for improving the clinical care model for preterm infants in the NICU and for improving the enteral nutrition of preterm infants. The implementation of this project may improve the quality of nursing care and enable preterm infants to receive safer and more-complete care.

Bacillus Calmette-Guérin (BCG) osteomyelitis among children: Experience in a single tertiary center in central Taiwan.

BACKGROUND: The insidious nature of BCG-osteomyelitis makes it challenging for clinicians to detect it early on. METHODS: This 12-year retrospective analysis was conducted at a single tertiary hospital in central Taiwan. Electronic medical records of pediatric patients treated for BCG-osteomyelitis were reviewed. Demographics, clinical features, and laboratory findings were compared with patients diagnosed with culture-proven pyogenic osteomyelitis. RESULTS: In total, eight patients fulfilled our inclusion criteria. Their median age was 16 months, and no obvious gender prevalence was found. Six of the eight patients had lesions involving the lower extremities. When compared with the pyogenic osteomyelitis group, age of disease onset was found to be significantly younger in the BCG osteomyelitis group (p=0.038). Absence of fever and pain in the BCG osteomyelitis group was found to be statistically significant when compared with the pyogenic group (p=0.002 and p=0.026 respectively). CRP and ESR were found to be significantly higher in the pyogenic osteomyelitis group (p=0.000 and p=0.004 respectively). CONCLUSION: BCG-related osteomyelitis must be considered when evaluating an afebrile child presenting with an unexplainable swelling or limp, and especially when the lesion is located on a lower limb. Laboratory studies may reveal normal WBC and CRP, with a normal to modest elevation of ESR. Imaging studies, including plain radiographs, magnetic resonance imaging (MRI), or computed tomography (CT) should be employed to rule out BCG-related osteomyelitis. Early diagnosis help minimize inappropriate antibiotics use, and may lead to a better outcome.

Detection of respiratory pathogens by application of multiplex PCR panel during early period of COVID-19 pandemic in a tertiary hospital in Central Taiwan.

BACKGROUND: Respiratory tract infections (RTIs) represent a major cause of clinical visits worldwide. Viral epidemiology of RTIs in adults has been less studied compared to children. FilmArray respiratory panel (FA-RP), a multiplex, real time polymerase chain reaction method can simultaneously detect the nucleic acids of multiple pathogens. The purpose of this study is to analyze the epidemiology and clinical presentations of an RTI cohort. METHODS: This retrospective cohort study was conducted at China Medical University Hospital (CMUH) and China Medical University Children's Hospital (CMUCH), from January 2020 to June 2020. The FA-RP results were collected and analyzed according to upper versus lower RTIs. RESULTS: Among 253 respiratory samples tested, 135 (53.4%) were from adults and 118 (46.6%) from children. A total positive rate of 33.9% (86/253) was found, with 21.48% (29/135) in adults and 48.31% (57/118) in children. Human rhinovirus/Enterovirus (HRV/EV) was detected in most of the age groups and was more common in URIs. HRV/EV was found as a frequent co-detection virus. Among children, HRV/EV was the most detected pathogen of URIs, while the most predominant pathogen in LRIs was Mycoplasma pneumoniae. CONCLUSIONS: FA-RP has the potential to improve the detection rate of respiratory pathogens. The positive rate of FA-RP was higher in children compared to adults, which likely corresponds to the higher incidence of viral RTIs in children. Different pathogens may lead to different types of respiratory infections.

Development of EST-Molecular Markers from RNA Sequencing for Genetic Management and Identification of Growth Traits in Potato Grouper (Epinephelus tukula).

The accuracy and efficiency of marker-assisted selection (MAS) has been proven for economically critical aquaculture species. The potato grouper (Epinephelus tukula), a novel cultured grouper species in Taiwan, shows large potential in aquaculture because of its fast growth rate among other groupers. Because of the lack of genetic information for the potato grouper, the first transcriptome and expressed sequence tag (EST)-derived simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers were developed. Initially, the transcriptome was obtained from seven cDNA libraries by using the Illumina platform. De novo transcriptome of the potato grouper yielded 51.34 Gb and 111,490 unigenes. The EST-derived SSR and SNP markers were applied in genetic management, in parentage analysis, and to discover the functional markers of economic traits. The F1 juveniles were identified as siblings from one pair of parents (80 broodstocks). Fast- and slow-growth individuals were analyzed using functional molecular markers and through their association with growth performance. The results revealed that two SNPs were correlated with growth traits. The transcriptome database obtained in this study and its derived SSR and SNP markers may be applied not only for MAS but also to maintain functional gene diversity in the novel cultured grouper.

Clinical characteristics and outcomes of culture-negative versus culture-positive osteomyelitis in children treated at a tertiary hospital in central Taiwan.

BACKGROUND: The causative pathogen of pediatric osteomyelitis is often unidentified despite culturing attempts. This study evaluated and compared the clinical characteristics, therapeutic approach, and outcomes of osteomyelitis caused by unknown pathogens and identified microorganisms. METHOD: This 17-year retrospective study was conducted at a tertiary hospital in central Taiwan. Medical records of children aged less than 18 years with a diagnosis of osteomyelitis between 2003 and 2019 were reviewed. RESULT: In total, 70 patients (median age = 6.4 years; male = 65.7%) fulfilled the inclusion criteria, of whom 33 (47.1%) were culture negative. Staphylococcus aureus was the main pathogen (67.6% of identified bacteria). The proportion of methicillin-resistant S. aureus (MRSA) was 44% and 54.5% of the MRSA isolates exhibited clindamycin resistance. Compared to children with culture-positive osteomyelitis, those with culture-negative osteomyelitis had a lower rate of concomitant septic arthritis (40.5% vs. 15.2%, p = 0.019) and leukocytosis on presentation (45.9% vs. 21.2%, p = 0.030); they also required fewer surgical interventions (56.8% vs. 24.2%, p = 0.006) and received a shorter course of total antibiotic therapy (49.0 vs. 43.0 days, p = 0.045). In the culture-negative group, the MRSA coverage rate was 18.8% during initial empirical therapy and increased to 59.4% during further adjusted therapy. The overall complication rate was 18.6% and was lower in the culture-negative group (32.4% vs. 3.0%, p = 0.002). CONCLUSION: In areas where community-associated MRSA and clindamycin resistance strains are a concern, empirical glycopeptide-based therapy is suggested in pediatric osteomyelitis, particularly in those with culture-negative infections.

Neuropeptide S-initiated sequential cascade mediated by OX1, NK1, mGlu5 and CB1 receptors: a pivotal role in stress-induced analgesia.

BACKGROUND: Stress-induced analgesia (SIA) is an evolutionarily conserved phenomenon during stress. Neuropeptide S (NPS), orexins, substance P, glutamate and endocannabinoids are known to be involved in stress and/or SIA, however their causal links remain unclear. Here, we reveal an unprecedented sequential cascade involving these mediators in the lateral hypothalamus (LH) and ventrolateral periaqueductal gray (vlPAG) using a restraint stress-induced SIA model. METHODS: Male C57BL/6 mice of 8-12 week-old were subjected to intra-cerebroventricular (i.c.v.) and/or intra-vlPAG (i.pag.) microinjection of NPS, orexin-A or substance P alone or in combination with selective antagonists of NPS receptors (NPSRs), OX1 receptors (OX1Rs), NK1 receptors (NK1Rs), mGlu5 receptors (mGlu5Rs) and CB1 receptors (CB1Rs), respectively. Antinociceptive effects of these mediators were evaluated via the hot-plate test. SIA in mice was induced by a 30-min restraint stress. NPS levels in the LH and substance P levels in vlPAG homogenates were compared in restrained and unrestrained mice. RESULTS: NPS (i.c.v., but not i.pag.) induced antinociception. This effect was prevented by i.c.v. blockade of NPSRs. Substance P (i.pag.) and orexin-A (i.pag.) also induced antinociception. Substance P (i.pag.)-induced antinociception was prevented by i.pag. Blockade of NK1Rs, mGlu5Rs or CB1Rs. Orexin-A (i.pag.)-induced antinociception has been shown previously to be prevented by i.pag. blockade of OX1Rs or CB1Rs, and here was prevented by NK1R or mGlu5R antagonist (i.pag.). NPS (i.c.v.)-induced antinociception was prevented by i.pag. blockade of OX1Rs, NK1Rs, mGlu5Rs or CB1Rs. SIA has been previously shown to be prevented by i.pag. blockade of OX1Rs or CB1Rs. Here, we found that SIA was also prevented by i.c.v. blockade of NPSRs or i.pag. blockade of NK1Rs or mGlu5Rs. Restrained mice had higher levels of NPS in the LH and substance P in the vlPAG than unrestrained mice. CONCLUSIONS: These results suggest that, during stress, NPS is released and activates LH orexin neurons via NPSRs, releasing orexins in the vlPAG. Orexins then activate OX1Rs on substance P-containing neurons in the vlPAG to release substance P that subsequently. Activates NK1Rs on glutamatergic neurons to release glutamate. Glutamate then activates perisynaptic mGlu5Rs to initiate the endocannabinoid retrograde inhibition of GABAergic transmission in the vlPAG, leading to analgesia.

Correction to: Bariatric Surgery Did Not Increase the Risk of Gallstone Disease in Obese Patients: a Comprehensive Cohort Study.

In the section "Method" the first sentence should read as follows: This retrospective study was fully evaluated and approved by the Institutional Review Board of Buddhist Dalin Tzu Chi Hospital (approval B10603004) and was conducted in accordance with the principles of the Helsinki Declaration.

Bariatric Surgery Did Not Increase the Risk of Gallstone Disease in Obese Patients: a Comprehensive Cohort Study.

PURPOSE: The aim of this study was to evaluate the influence of bariatric surgery on gallstone disease in obese patients. MATERIALS AND METHODS: This large cohort retrospective study was conducted based on the Taiwan National Health Insurance Research Database. All patients 18-55 years of age with a diagnosis code for obesity (ICD-9-CM codes 278.00-278.02 or 278.1) between 2003 and 2010 were included. Patients with a history of gallstone disease and hepatic malignancies were excluded. The patients were divided into non-surgical and bariatric surgery groups. Obesity surgery was defined by ICD-9-OP codes. We also enrolled healthy civilians as the general population. The primary end point was defined as re-hospitalization with a diagnosis of gallstone disease after the index hospitalization. All patients were followed until the end of 2013, a biliary complication occurred, or death. RESULTS: Two thousand three hundred seventeen patients in the bariatric surgery group, 2331 patients in the non-surgical group, and 8162 patients in the general population were included. Compared to the non-surgery group (2.79%), bariatric surgery (2.89%) did not elevate the risk of subsequent biliary events (HR = 1.075, p = 0.679). Compared to the general population (1.15%), bariatric surgery group had a significantly higher risk (HR = 4.996, p < 0.001). In the bariatric surgery group, female gender (HR = 1.774, p = 0.032) and a restrictive procedure (HR = 1.624, p = 0.048) were risk factors for gallstone disease. CONCLUSION: The risk for gallstone disease did not increase after bariatric surgery, although the risk was still higher than the general population. The benefit of concomitant cholecystectomy during bariatric surgery should be carefully evaluated.

Topographic effect on the phenology of Ficus pedunculosa var. mearnsii (Mearns fig) in its northern boundary distribution, Taiwan.

Mearns fig grows at the edge of coastal vegetation on uplifted coral reefs, its population and mutualistic-pollinators are susceptible to the influence of extreme weather. To determine the phenology of Mearns fig and the effects of various weather events under small-scale topographic differences, phenology was conducted for 3 years and 7 months. Results showed that Mearns figs had multiple leaf and fig productions year-round. Topographic effects caused population in Frog Rock Trail and Jialeshuei, which are less than 10 km away from each other, to exhibit different phenological patterns after experiencing severe weather events. Northeast monsoons led the Jialeshuei population to show low amounts of leaves and figs in winter and the phenological production was also susceptible to disturbances by typhoons in summer. Fig reproduction in such environment was disadvantageous to maintain pollinators. Besides, topographic complex in microhabitat of Frog Rock Trail protected some individuals from these same events thus safeguard population's survival. The phenology of Mearns fig would respond to the weather events sensitively, which serve as references for estimating the mutualism system, and as indicators of climate change.

Risk factors for contralateral inguinal hernia repair after unilateral inguinal hernia repair in male adult patients: analysis from a nationwide population based cohort study.

BACKGROUND: To identify the rate of and risk factors for contralateral inguinal hernia (CIH) after unilateral inguinal hernia repair in adult male patients. METHODS: This retrospective cohort study identified from the Taiwan National Health Insurance Research Database (NHIRD). Information on all adult patients who underwent primary unilateral inguinal hernia repair without any other operation was collected using ICD-9 diagnostic and procedure codes. The exclusion criteria were laparoscopic hernia repair, non-primary repair, complicated hernia, other combined procedures, female and undetermined gender. RESULTS: A total of 170,492 adult male patients were included, with a median follow-up of 87 months. The overall CIH rate was 10.5%, with a median time of 48 months to a subsequent hernia operation. The 1-year, 2-year, 3-year and 5-year-recurrent rate was 2.6, 3, 4.3, and 6.7% respectively. Further, 3.7% patients who underwent CIH repair had a complicated inguinal hernia. Multivariate analysis demonstrated that age > 45 y, direct hernia, cirrhosis (HR = 1.564), severe liver disease (HR = 1.663), prostate disease (HR = 1.178), congestive heart failure (HR = 1.138), and history of malignancy (HR = 1.116) had a significantly higher risk of CIH repair. CONCLUSIONS: Among adult male patients undergoing long-term follow-up, we identified several significant risk factors for CIH repair. If these risk factors are presented, the surgeon should inform the following risk of CIH repair to patients so that it can be repaired as soon as possible.