Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning.

Gut microbiota rearrangement induced by cold temperature is crucial for browning in murine white adipose tissue. This study provides evidence that DUSP6, a host factor, plays a critical role in regulating cold-induced gut microbiota rearrangement. When exposed to cold, the downregulation of intestinal DUSP6 increased the capacity of gut microbiota to produce ursodeoxycholic acid (UDCA). The DUSP6-UDCA axis is essential for driving Lachnospiraceae expansion in the cold microbiota. In mice experiencing cold-room temperature (CR) transitions, prolonged DUSP6 inhibition via the DUSP6 inhibitor (E/Z)-BCI maintained increased cecal UDCA levels and cold-like microbiota networks. By analyzing DUSP6-regulated microbiota dynamics in cold-exposed mice, we identified Marvinbryantia as a genus whose abundance increased in response to cold exposure. When inoculated with human-origin Marvinbryantia formatexigens, germ-free recipient mice exhibited significantly enhanced browning phenotypes in white adipose tissue. Moreover, M. formatexigens secreted the methylated amino acid Nε-methyl-L-lysine, an enriched cecal metabolite in Dusp6 knockout mice that reduces adiposity and ameliorates nonalcoholic steatohepatitis in mice. Our work revealed that host-microbiota coadaptation to cold environments is essential for regulating the browning-promoting gut microbiome.

The composition of the maternal breastmilk microbiota influences the microbiota network structure during early infancy.

BACKGROUND/PURPOSE(S): Human breastmilk (BM) is important for microbiome maturation in infants across different body sites. Streptococcus and Staphylococcus are considered universally predominant genera in the BM microbiota. However, whether the differential abundance of Streptococcus and Staphylococcus in BM can differentially affect microbiome maturation in infants remains unclear. METHODS: We recruited exclusively breastfeeding mothers from among the donors of the human milk bank established at National Cheng-Kung University Hospital. The donor mothers provided 35 BM samples at three months (3 M; before introducing children to complementary feeding) and 23 BM samples at six months (6 M; after introducing children to complementary feeding) postpartum. At both time points, samples from different body sites, including nasal swabs, oral swabs and stool, were collected from the mothers and their infants. RESULTS: Maternal BMI was inversely associated with coagulase-negative Staphylococcus (CoNS) abundance in breastmilk. Staphylococcus caprae representation in BM CoNS showed a negative correlation with Streptococcus abundance. Network analysis revealed that infants fed Staphylococcus-dominated BM had better gut and nasal microbiota networks than infants fed Streptococcus-abundant BM during early infancy. CONCLUSION: Our work suggests that maternal metabolic status plays a crucial role in Staphylococcus/Streptococcus competition in BM, which in turn can impact the development of the infant microbiota. Our microbiota co-occurrence network analysis might serve as a helpful bioinformatic tool to monitor microbiota maturation during early infancy.

Dynamics of spatial and temporal population structure of Pyricularia oryzae in Taiwan.

BACKGROUND: To gain a better understanding of how Pyricularia oryzae population shifts is important for selecting suitable resistance genes for rice breeding programs. However, the relationships between P. oryzae pathogenic dynamics, geographic distribution, rice varieties, and timeline are not well studied. RESULTS: Resistance genes Piz-5, Pi9(t), Pi12(t), Pi20(t), Pita-2, and Pi11 showed stable resistance to the Taiwan rice blast fungus over 8 years of observations. Furthermore, 1749 rice blast isolates were collected from 2014 to 2021 and categorized into five pathotype clusters based on their correlation analysis between the geographic sources and virulence of Lijiangxintuanheigu monogenic lines. A detailed map of their distributions in Taiwan is presented. Isolates collected from the western region of Taiwan had greater pathotype diversity than those from the east region. Isolates collected from the subtropical region had greater diversity than those from the tropical region. Rice cultivars carrying Pik alleles were highly susceptible to pathotype L4. Cultivars with Piz-t were highly susceptible to pathotype L5, and those with Pish were highly susceptible to pathotype L1. The geographical distribution of each pathotype was distinct, and the population size of each pathotype fluctuated significantly each year. CONCLUSION: The regional mega cultivars significantly impact the evolution of Pyricularia oryzae in Taiwan within the span of 8 years. However, the annual fluctuation of pathotype populations likely correlate to the rising annual temperatures that selected pathotype clusters by their optimal growth temperature. The results will provide useful information for effective disease management, and enable the R-genes to prolong their function in the fields. © 2023 Society of Chemical Industry.

A 20-Year Study of Capsular Polysaccharide Seroepidemiology, Susceptibility Profiles, and Virulence Determinants of Klebsiella pneumoniae from Bacteremia Patients in Taiwan.

In this study, we selected bacteremic Klebsiella pneumoniae isolates from the Taiwan Surveillance of Antimicrobial Resistance program. A total of 521 isolates were collected over a period of 2 decades, including 121 from 1998, 197 from 2008, and 203 from 2018. Seroepidemiology showed that the top five capsular polysaccharide types were serotypes K1, K2, K20, K54, and K62, constituting 48.5% of the total isolates, and the respective ratios at each time point have remained similar over the past 2 decades. The antibacterial susceptibility tests showed that K1, K2, K20, and K54 were susceptible to most antibiotics, while K62 was relatively resistant compared to other typeable and nontypeable strains. In addition, six virulence-associated genes, clbA, entB, iroN, rmpA, iutA, and iucA, were predominant in K1 and K2 isolates of K. pneumoniae. In conclusion, serotypes K1, K2, K20, K54, and K62 of K. pneumoniae are the most prevalent serotypes and carry more virulence determinants in bacteremia patients, which may indicate their invasiveness. If further serotype-specific vaccine development is performed, these five serotypes should be included. Since the antibiotic susceptibility profiles were stable over a long duration, empirical treatment may be predicted according to serotype if rapid diagnosis from direct clinical specimens is available, such as PCR or antigen serotyping for serotype K1 and K2. IMPORTANCE This is the first nationwide study to examine the seroepidemiology of Klebsiella pneumoniae using blood culture isolates collected over a period of 20 years. The study found that the prevalence of serotypes remained consistent over the 20-year period, with high-prevalence serotypes associated with invasive types. Nontypeable isolates had fewer virulence determinants than other serotypes. With the exception of serotype K62, the other high-prevalence serotypes were highly susceptible to antibiotics. If rapid diagnosis using direct clinical specimens, such as PCR or antigen serotyping, is available, empirical treatment can be predicted based on serotype, particularly for K1 and K2. The results of this seroepidemiology study could also help the development of future capsule polysaccharide vaccines.

The Alteration of Akkermansiaceae/Lachnospiraceae Ratio Is a Microbial Feature of Antibiotic-Induced Microbiota Remodeling.

Antibiotic treatment has been shown to cause gut microbiota dysbiosis. However, lacking critical features defining gut microbiota dysbiosis makes it challenging to prevent. By co-occurrence network analysis, we found that despite short antibiotic courses eliminating certain microbial taxa, the Akkermansia genus played the role of a high-centrality hub to maintain microbiota homeostasis. When the antibiotic courses continued, the elimination of Akkermansia induced a significant microbiota remodeling of the gut microbiota networks. Based on this finding, we found that under long-term antibiotic stress, the gut microbiota was rearranged into a stable network with a significantly lower Akkermansiaceae/Lachnospiraceae (A/L) ratio and no microbial hub. By functional prediction analysis, we confirmed that the gut microbiota with a low A/L ratio also had enhanced mobile elements and biofilm-formation functions that may be associated with antibiotic resistance. This study identified A/L ratio as an indicator of antibiotic-induced dysbiosis. This work reveals that besides the abundance of specific probiotics, the hierarchical structure also critically impacts the microbiome function. Co-occurrence analysis may help better monitor the microbiome dynamics than only comparing the differentially abundant bacteria between samples.

Use artificial neural network to recommend the lumbar spinal endoscopic surgical corridor.

Objectives: The transforaminal and interlaminar approaches are the two main surgical corridors of full endoscopic lumbar surgery. However, there are no quantifying methods for assessing the best surgical approach for each patient. This study aimed to establish an artificial intelligence (AI) model using an artificial neural network (ANN). Materials and Methods: Patients who underwent full endoscopic lumbar spinal surgery were enrolled in this research. Fourteen pre-operative factors were fed into the ANN. A three-layer deep neural network was constructed. Patient data were divided into the training, validation, and testing datasets. Results: There were 899 patients enrolled. The accuracy of the training, validation, and test datasets were 87.3%, 85.5%, and 85.0%, respectively. The positive predictive values for the transforaminal and interlaminar approaches were 85.1% and 89.1%, respectively. The area under the curve of the receiver operating characteristic was 0.91. The SHapley Additive exPlanations algorithm was utilized to explain the relative importance of each factor. The surgical lumbar level was the most important factor, followed by herniated disc localization and migrating disc zone level. Conclusion: ANN can effectively learn from the choice of an experienced spinal endoscopic surgeon and can accurately predict the appropriate surgical approach.

Possible Association of Hysterectomy Accompanied with Opportunistic Salpingectomy with Early Menopause: A Retrospective Cohort Study.

Opportunistic salpingectomies (OSs) are concurrently performed with hysterectomies to prevent epithelial ovarian cancer. This study aimed to investigate the correlation between OS and early menopause in females who have undergone hysterectomies. This was a retrospective cohort study involving 79 females who had undergone a hysterectomy, with or without an OS, between January 2007 and December 2015. Their ages at surgery, at menopause, and the lengths of time from surgery to menopause were compared. An OS had been performed in 54 and not performed in 25 of the enrolled patients, comprising the OS and non-OS groups. Body mass index was significantly higher in the OS group (OS: 25.27 ± 4.17 vs. non-OS: 22.97 ± 3.27, p = 0.01). Additionally, menopausal sleep problems were more prevalent in the OS group than in the non-OS group (41% vs. 12%, p = 0.01). Notably, the time from surgery to menopause was significantly shorter in the OS group than in the non-OS group (OS: 1.84 ± 1.85 vs. non-OS: 2.93 ± 2.43, p = 0.031). After adjusting the covariates, the OS group was associated with a significantly shorter period between surgery and menopause (p = 0.029). In conclusion, these results showed that a hysterectomy plus an OS might cause earlier menopause than a hysterectomy only. An OS should be preoperatively discussed with patients regarding the possibility of early menopause. The findings of this study require further large-scale investigations to reinforce the results.

A Precision Health Service for Chronic Diseases: Development and Cohort Study Using Wearable Device, Machine Learning, and Deep Learning.

This paper presents an integrated and scalable precision health service for health promotion and chronic disease prevention. Continuous real-time monitoring of lifestyle and environmental factors is implemented by integrating wearable devices, open environmental data, indoor air quality sensing devices, a location-based smartphone app, and an AI-assisted telecare platform. The AI-assisted telecare platform provided comprehensive insight into patients' clinical, lifestyle, and environmental data, and generated reliable predictions of future acute exacerbation events. All data from 1,667 patients were collected prospectively during a 24-month follow-up period, resulting in the detection of 386 abnormal episodes. Machine learning algorithms and deep learning algorithms were used to train modular chronic disease models. The modular chronic disease prediction models that have passed external validation include obesity, panic disorder, and chronic obstructive pulmonary disease, with an average accuracy of 88.46%, a sensitivity of 75.6%, a specificity of 93.0%, and an F1 score of 79.8%. Compared with previous studies, we establish an effective way to collect lifestyle, life trajectory, and symptom records, as well as environmental factors, and improve the performance of the prediction model by adding objective comprehensive data and feature selection. Our results also demonstrate that lifestyle and environmental factors are highly correlated with patient health and have the potential to predict future abnormal events better than using only questionnaire data. Furthermore, we have constructed a cost-effective model that needs only a few features to support the prediction task, which is helpful for deploying real-world modular prediction models.

Serosal Injury to a Distended Stomach during Open Entry for Laparoendoscopic Single-Site Surgery.

Complications related to open entry for laparoscopic procedures are relatively rare, and the incidence of closed entry-related complications is 0.4 per 1000 cases. We report a case of serosal injury to a distended stomach that was caused during open entry. A 37-year-old woman presented with a 1-year history of dysmenorrhea. Transvaginal ultrasonography revealed a uterine myoma and cesarean section (C/S) wound defect. Laparoscopic single-site myomectomy and repair of the C/S wound defect were planned. Open abdominal entry was achieved at the umbilicus, and the patient's stomach was distended and injured by the electric knife (30 watts). After identifying the injury, we inserted a nasogastric tube to deflate the stomach and repaired the gastric serosal injury. The laparoscopic myomectomy and C/S defect repair were subsequently performed without complications. The patient has remained free from complications during the 1-year follow-up. Gastric serosal injury during open entry is a rare complication. Insertion of a nasopharyngeal tube and routine percussion of the abdomen before entering the abdominal cavity are the most important steps to prevent this complication.

The necessity of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy: a retrospective cohort study.

BACKGROUND: This study aimed to evaluate the necessity of abdominal drainage after laparoscopic appendectomy in patients with complicated appendicitis. METHODS: Patients with acute appendicitis undergoing laparoscopic appendectomy at two hospitals between January 2014 and December 2018 were retrospectively included. Complicated appendicitis was defined as the American Association for the Surgery of Trauma (AAST) grade ≥ II. The patients were classified according to the AAST grade and the indwelling of abdominal drainage. The postoperative surgical outcomes and recovery were compared among patient groups to evaluate the impact of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy. RESULTS: A total of 1241 patients was retrospectively included. Among them, there were 820 patients with simple appendicitis (AAST grade I) and 421 patients with complicated appendicitis (AAST grade ≥ II). For complicated appendicitis, the drainage group (N = 192) tended to harbor more overall complications, intra-abdominal abscess formation, time to resume a soft diet, and the postoperative length of hospitalization (P = 0.0000 for all). Multivariate logistic regression confirmed that abdominal drainage increased the risk of overall complications [Odds ratio (OR) 2.439; 95% confidence interval (CI) 1.597-3.726; P ≤ 0.0001] and failed to decrease the risk of intra-abdominal abscess formation (OR 1.655; 95% CI 0.487-5.616; P = 0.4193). Multivariate linear regression analysis also showed that the drainage group harbored longer postoperative length of hospitalization (Coefficients: 20.697; 95% CI 15.251-26.143; P < 0.0001) and time to resume a soft diet (Coefficients: 45.899; 95% CI 34.502-57.297; P < 0.0001). CONCLUSIONS: Abdominal drainage did not prevent overall complications in patients with complicated appendicitis; paradoxically, it delayed the convalescence. Our results discourage the routine use of abdominal drainage and suggest that abdominal drainage should be performed sparingly.

Panic Attack Prediction Using Wearable Devices and Machine Learning: Development and Cohort Study.

BACKGROUND: A panic attack (PA) is an intense form of anxiety accompanied by multiple somatic presentations, leading to frequent emergency department visits and impairing the quality of life. A prediction model for PAs could help clinicians and patients monitor, control, and carry out early intervention for recurrent PAs, enabling more personalized treatment for panic disorder (PD). OBJECTIVE: This study aims to provide a 7-day PA prediction model and determine the relationship between a future PA and various features, including physiological factors, anxiety and depressive factors, and the air quality index (AQI). METHODS: We enrolled 59 participants with PD (Diagnostic and Statistical Manual of Mental Disorders, 5th edition, and the Mini International Neuropsychiatric Interview). Participants used smartwatches (Garmin Vívosmart 4) and mobile apps to collect their sleep, heart rate (HR), activity level, anxiety, and depression scores (Beck Depression Inventory [BDI], Beck Anxiety Inventory [BAI], State-Trait Anxiety Inventory state anxiety [STAI-S], State-Trait Anxiety Inventory trait anxiety [STAI-T], and Panic Disorder Severity Scale Self-Report) in their real life for a duration of 1 year. We also included AQIs from open data. To analyze these data, our team used 6 machine learning methods: random forests, decision trees, linear discriminant analysis, adaptive boosting, extreme gradient boosting, and regularized greedy forests. RESULTS: For 7-day PA predictions, the random forest produced the best prediction rate. Overall, the accuracy of the test set was 67.4%-81.3% for different machine learning algorithms. The most critical variables in the model were questionnaire and physiological features, such as the BAI, BDI, STAI, MINI, average HR, resting HR, and deep sleep duration. CONCLUSIONS: It is possible to predict PAs using a combination of data from questionnaires and physiological and environmental data.

Atherosclerosis amelioration by allicin in raw garlic through gut microbiota and trimethylamine-N-oxide modulation.

Cardiovascular disease (CVD) is strongly associated with the gut microbiota and its metabolites, including trimethylamine-N-oxide (TMAO), formed from metaorganismal metabolism of ʟ-carnitine. Raw garlic juice, with allicin as its primary compound, exhibits considerable effects on the gut microbiota. This study validated the benefits of raw garlic juice against CVD risk via modulation of the gut microbiota and its metabolites. Allicin supplementation significantly decreased serum TMAO in ʟ-carnitine-fed C57BL/6 J mice, reduced aortic lesions, and altered the fecal microbiota in carnitine-induced, atherosclerosis-prone, apolipoprotein E-deficient (ApoE-/-) mice. In human subjects exhibiting high-TMAO production, raw garlic juice intake for a week reduced TMAO formation, improved gut microbial diversity, and increased the relative abundances of beneficial bacteria. In in vitro and ex vivo studies, raw garlic juice and allicin inhibited γ-butyrobetaine (γBB) and trimethylamine production by the gut microbiota. Thus, raw garlic juice and allicin can potentially prevent cardiovascular disease by decreasing TMAO production via gut microbiota modulation.

SMS reminders to improve outpatient attendance for public dental services: A retrospective study.

Patients who miss scheduled appointments reduce clinical productivity and delay access to care for other patients. Reminders have improved attendance for healthcare appointments previously, but it is not known if short message service (SMS) implementation reduces incidence of patients unable to attend (UTA) or who fail to attend (FTA) appointments in the public dental service. This paper studied the effectiveness of SMS reminders in increasing appointment attendance at outpatient public dental services in Queensland. Data were sourced from the adult service and the children and adolescent oral health service (CAOHS) at West Moreton Hospital and Health Service, a public dental service in Queensland. A total of 63,238 appointments pre-implementation of SMS reminders and 55,028 appointments post-implementation over a period of 2 years were analysed for rates of attendance, UTA and FTA. Characteristics of UTA and FTA appointments were analysed to identify factors that hindered improvement after implementation of reminders. For the CAOHS, the attendance rate decreased 4% (95% CI: 2%, 6%) following SMS implementation. The UTA rate also increased by 20% (95% CI: 15%, 25%). Following SMS implementation in the adult service, the attendance rate increased from 73.5 (95% CI: 72.6, 74.4) to 77.7 (95% CI: 76.6-78.8) per 100 appointments. The FTA rate post-implementation was 1.08 (95% CI: 1.00, 1.16) times that from pre-intervention, and the UTA rate decreased from 21.7 (95% CI: 21.2, 22.2) to 17.1 (95% CI: 16.6, 17.7) per 100 appointments. The SMS reminders had a mixed effect on the attendance, UTA and FTA rates for the CAOHS and adult services. Reminders reduced the rates of UTA for the CAOHS service and increased the rate of attendance for the adult service. There was an increase in the FTA rate for both services.

Pelvic inflammatory disease and causative pathogens in older women in a medical center in eastern Taiwan: A retrospective cross-sectional study.

OBJECTIVES: Most research into the management of pelvic inflammatory disease (PID) is in younger women and focuses on sexually transmitted pathogens such as N. gonorrhoeae or C. trachomatis. Non-sexually transmitted bacterial pathogens and PID in older women are rarely examined. The objective of this study is to explore cervical culture pathogens in women of different age groups in a medical center in eastern Taiwan. METHODS: We enrolled patients whose medical records were diagnosed with PID (ICD-9-CM 614.0 [N70.01-03], 614.1[N70.11-13], 614.9 [N73.5, N73.9]) at our hospital from October 2014 to March 2020. Patients were divided into three groups according to age: the age <25 years, age 25-44 years, and the ≥ 45 years group. Chi-square test, ANOVA and logistic regression were used for statistical analysis. In subgroup analysis, endocervical pathogens were further stratified into vaginal, respiratory, enteric, skin, oral, and other. RESULTS: A total of 96 patients were included in the study. There were 31 patients in the age ≥ 45 years group, 52 patients in the age 25-44 years group, and 13 patients in the age <25 years group. Vagina and enteric pathogens were the most common pathogens among all groups. The isolated respiratory and other pathogens were more in the age ≥ 45 years group than in the other two groups. Prevotella bivia was more common in the age <25 years and 25-44 years groups. CONCLUSIONS: This may be due to different pathogeneses of PID in the age ≥ 45 years patients. Our study can be used as a reference for antibiotic choice of non-sexually transmitted PID and to prevent long-term sequelae of PID.

Primary inguinal subcutaneous endometriosis accompanied with an inguinal hernia: A case report.

RATIONALE: We report a case with inguinal subcutaneous endometriosis without typical cyclic dysmenorrhea and accompanied with a hernia sac treated with resection of the tumor and herniorrhaphy. PATIENT CONCERNS: A 40-year-old woman had a painless enlarged inguinal nodule for 3 months. DIAGNOSES: Subcutaneous endometriosis accompanied with a hernia sac. INTERVENTIONS: Ultrasonography showed a hypoechoic lesion (3.0 cm × 2.0 cm), and an inguinal subcutaneous tumor was first suspected. After surgical exploration, a cystic lesion was excised and the hernia hole was repaired by herniorrhaphy. The immunohistochemical analysis of the small endometriotic cyst-like lesion revealed calretinin (-) in epithelial cells and CD10 (+) in stromal cells, indicative of subcutaneous endometriosis accompanied with a hernia sac. OUTCOMES: The patient was followed up for 1 year and without recurrence. LESSONS: Cutaneous endometriosis accompanied with a hernia sac can be presented without typical endometriosis-associated symptoms such as dysmenorrhea. Inguinal endometriosis might be the differential diagnosis of inguinal painless nodules.

Supplementation of nanofiltrated deep ocean water ameliorate the progression of osteoporosis in ovariectomized rat via regulating osteoblast differentiation.

Magnesium was reported to be necessary for bone formation. Previous study indicated nanofiltrated deep ocean water (DOW) rich in magnesium. This study investigated the potential mechanisms of DOW in ameliorating osteoporosis. Briefly, female Sprague-Dawley rat was ovariectomized and fed with 0.35, 0.7, or 1.4 ml/kg of DOW daily for 8 weeks. In the results, DOW increased bone density, decreased trabecular bone loss, and decreased bone adiposity. DOW improved bone mass by examining structure in micro-computed tomography. About 0.35 and 0.7 ml/kg of DOW can increase protein expression of runt-related transcription factor 2 (RUNX2), an essential transcription factor for regulating osteoblast differentiation, by 9.4% or 12.9%. In human osteoblast, DOW increased the levels of osteocalcin, RUNX2, and alkaline phosphatase; all the proteins can regulate osteoblast differentiation. Considering the results of in vivo and in vitro study, DOW can ameliorate ovareictomy-caused osteoporosis via regulating the osteoblast differentiation, thereby, maintenance of bone structure. PRACTICAL APPLICATIONS: In addition to calcium, magnesium is essential to promoting the deposition of calcium in bones and regulating its transport; it may also slow the progression of osteoporosis. Nanofiltrated DOW contains abundant magnesium along with several microelements and peptides. In this study, a product was developed for decelerating osteoporosis by using an estrogen depletion model. DOW regulates osteoblast differentiation and thus prevents osteoporosis. This finding provides an alternative healthy source of bone supplements. In addition to tablets or capsules, aqueous supplements can be produced to achieve osteoporosis prevention. This finding is beneficial to the health-care industry for developing sustainable supplements.

High Serum Fibroblast Growth Factor 23 Level Is Associated With Metabolic Syndrome in Kidney Transplantation Patients.

BACKGROUND: Fibroblast growth factor 23 (FGF23), an important regulator of phosphate and vitamin D metabolism, has also been suggested to perform metabolic functions. This retrospective study evaluated the relationship between metabolic syndrome (MetS) and fasting FGF23 levels in patients undergoing kidney transplantation (KT). METHODS: Serum carboxyl-terminal FGF23 levels were measured in fasting blood samples of 74 KT patients using a commercially available enzyme-linked immunosorbent assay. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation. RESULTS: Twenty-four KT patients (32.4%) had MetS. Hypertension (P = .008); diabetes (P = .002), body weight (P < .001); body mass index (P < .001); waist circumference (P < .004); body fat mass (P < .001); systolic blood pressure (P = .008); and levels of triglycerides (P = .003), blood urea nitrogen (P = .007), and insulin (P = .004); homeostasis model assessment of insulin resistance (P = .001); and FGF23 (P = .002) were higher, whereas high-density lipoprotein cholesterol (P = .049) levels were lower in KT patients with MetS. Multivariable logistic regression analysis including significant variables revealed that FGF23 (odds ratio 1.030, 95% confidence interval [CI] 1.000-1.060, P = .048) was an independent predictor of MetS in KT patients. The area under the receiver operating characteristic curve to evaluate the ability of serum FGF23 in discriminating KT patients with MetS was 0.727 (95% CI 0.611-0.824, P = .0005). CONCLUSION: These results revealed that a high serum FGF23 level was positively associated with MetS in KT patients.

Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice.

OBJECTIVE: The gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance. DESIGN: A pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation. RESULTS: The OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT. CONCLUSION: The OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment. TRIAL REGISTRATION NUMBER: NCT02838732; Results.

An outbreak of norovirus gastroenteritis associated with asymptomatic food handlers in Kinmen, Taiwan.

BACKGROUND: In February 2015 an outbreak of gastroenteritis occurred in a distillery in Kinmen, Taiwan. At least 450 affected employees developed the symptoms of diarrhea and vomiting after attending a lunch banquet on 6 February. Epidemiological, laboratory and environmental investigations were conducted to identify the agent and source of this outbreak. METHODS: A case-control study was carried out among lunch attendees from the distillery. Using a semi-structured questionnaire, food and beverage consumption in the lunch banquet was assessed, as well as demographic and clinical data of the exposed people. An outbreak case was defined as a diner who developed at least three following symptoms: diarrhea, vomiting, abdominal pain, nausea, chills and/or weakness in the 72 h following the lunch. Controls were defined as lunch attendees who did not have any of the above symptoms. Rectal swabs or stool samples of the symptomatic exposed diners and food handlers as well as food and environmental samples were collected to test potential bacteria and viruses. Norovirus was detected by reverse transcription-polymerase chain reaction and sequence analysis. An environmental assessment, including environmental inspection of the restaurant and a review of work practices of food workers, was undertaken. RESULTS: Of 363 respondents with complete data, 169 met the case definition and 111 met the control definition. Consumption of pork liver in cold appetizers (adjusted odd ratio (aOR) 3.23; 95 % confidence interval (CI): 1.26-8.30) and lamb chops (aOR: 3.98, 95 % CI: 1.74-9.11) were each associated with increased risk of illness. No cases but two asymptomatic food handlers who prepared or cooked the implicated foods tested positive for norovirus genotype I.6. Food and environmental samples were negative for any bacteria. Environmental assessment indicated that hand washing facilities were not properly accessible to food handlers. Inappropriate hygiene practices in food handlers may have contributed to food contamination. CONCLUSION: Our investigation suggests that etiological agent of this outbreak was norovirus. The food vehicles were pork liver and lamb chops, which may have been contaminated by asymptomatic infected food handlers. Strict adherence to hand hygiene practices and access to hand washing facilities should be reinforced to prevent such foodborne outbreaks.

Antimicrobial susceptibilities of Proteus mirabilis: a longitudinal nationwide study from the Taiwan surveillance of antimicrobial resistance (TSAR) program.

BACKGROUND: Longitudinal nationwide data on antimicrobial susceptibility in Proteus mirabilis from different sources are rare. The effects of the revised Clinical and Laboratory Standards Institute (CLSI) ß-lactam breakpoints on susceptibility rates and on detecting extended-spectrum ß-lactamase (ESBL) and AmpC ß-lactamase-producers in this species are also seldom evaluated. The present study analyzed data from the Taiwan Surveillance of Antimicrobial Resistance program to address these issues. METHODS: Isolates were collected biennially between 2002 and 2012 from 25 to 28 hospitals in Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. All isolates with aztreonam, ceftazidime, or cefotaxime MIC ≥ 2 mg/L were checked for the presence of ESBL by CLSI confirmatory test and subjected to ESBL and AmpC ß-lactamases gene detection by PCR. Univariate and multivariate analyses were performed. RESULTS: Between 2002 and 2012, a total of 1157 P. mirabilis were studied. Susceptibility to cefotaxime, ceftazidime, and ciprofloxacin decreased significantly during the past decade, from 92.6% to 81.7%, 100% to 95.2%, and 80.1% to 53.8%, respectively (P < 0.01). The revised CLSI breakpoints had significant impact on susceptibility to cefazolin (2009 vs. current breakpoints, 71.9% vs. 0.9%) and imipenem (99.8% vs. 55.1%) (P < 0.001 for both). However, using the 2014 cefazolin breakpoints for urinary tract infections, 81.2% of the urine isolates were susceptible. Susceptibilities of isolates from different specimen types were mostly similar but outpatient isolates were more susceptible than inpatient isolates. The overall prevalence of ESBL- and AmpC- producers was 8.2% and 4.7%, respectively, but AmpC carriage increased significantly over the years (from 0 to 7.0%, P < 0.001). ESBL and AmpC ß-lactamase-producers were more likely to be found in elderly and ICU patients. The predominant ESBL and AmpC ß-lactamase genes were CTX-M- and CMY- types, respectively. CONCLUSIONS: A significant decrease in susceptibility to 3rd-generation cephalosporins and ciprofloxacin occurred in P. mirabilis from Taiwan in the past decade. The prevalence of ESBL remained stable but AmpC ß-lactamase-producing P. mirabilis increased significantly. Cefotaxime was a better surrogate than ceftazidime for predicting the presence of these ß-lactamases. Continuous surveillance on antimicrobial resistance and associated resistance mechanisms in P. mirabilis is warranted.