The Epidemiology, Management and Therapeutic Outcomes of Subdural Empyema in Neonates with Acute Bacterial Meningitis.

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction.

Helicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A (cagA)-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP_0888, upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA, leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae, selectively enriched in the colons of H. pylori-pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium. IMPORTANCE: Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A (cagA). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies.

Case Report: Neurally adjusted ventilatory assist as an effective rescue treatment for pulmonary interstitial emphysema in extremely low birth weight infants.

Pulmonary interstitial emphysema (PIE) is a complication observed in extremely low birth weight (ELBW) infants on mechanical ventilation. Despite various proposed therapeutic interventions, the success rates have shown inconsistency. Neurally adjusted ventilatory assist (NAVA) stands out as a novel respiratory support mode, offering lower pressure and tidal volume in comparison to conventional ventilation methods. In this case report, we present five ELBW infants with refractory PIE who were transitioned to NAVA ventilation. Following the switch to NAVA, all cases of PIE gradually resolved. In contrast to traditional modes, NAVA provided respiratory support with significantly lower fraction of inspired oxygen, reduced peak inspiratory pressure, diminished mean airway pressure, and decreased tidal volume within 7 days of NAVA utilization (p = 0.042, 0.043, 0.043, and 0.042, respectively). Consequently, we propose that NAVA could serve as a valuable rescue treatment for ELBW infants with PIE.

Correction: Accelerated weight gain, prematurity, and the risk of childhood obesity: A meta-analysis and systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0232238.].

Analgesic Effect of Low-Level Laser Therapy before Heel Lance for Pain Management in Healthy Term Neonates: A Randomized Controlled Trial.

Currently, the prevention, assessment, and management of procedural pain in neonates continues to challenge clinicians and researchers. Objective. To investigate the analgesic effect of low-level laser therapy (LLLT) during heel lance compared to breast milk (BM) feeding in healthy term neonates. In this randomized controlled trial, healthy term neonates who underwent heel lance were randomly assigned to an LLLT or a BM group. The LLLT group received laser therapy to the heel lance site for 20 s before heel lance. The BM group received 5 mL expressed BM via a syringe before heel lance. The primary outcomes were behavioral responses. The secondary outcomes were physiological responses and levels of salivary cortisol and α-amylase. A total of 125 neonates were included, of whom 55 in the LLLT group and 59 in the BM group completed the study. There were no significant differences in latency to first cry and cry duration between the two groups. The squeeze time was significantly shorter in the LLLT group than in the BM group (p = 0.047). There were no significant differences in pain scores, heart rate, respiratory rate, oxygen saturation, and blood pressure before and after heel lance between the two groups. There were no significant differences in salivary cortisol and α-amylase levels in the LLLT group before and after heel lance; however, the differences were significant in the BM group. These findings suggest that the analgesic effect of LLLT is similar to that of BM during heel lance in healthy term neonates. LLLT has potential as an analgesic treatment.

A Three-Arm, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Lactobacillus salivarius AP-32 and Bifidobacterium animalis CP-9 Used Individually in Healthy Infants.

Probiotics are considered safe and beneficial to human health. However, the safety of Lactobacillus salivarius AP-32 and Bifidobacterium animalis CP-9 in infants has not been confirmed. This study was to assess the safety of long-term oral administration of L. salivarius AP-32 and B. animalis CP-9 in healthy infants compared with placebo. A three-arm, randomized, double-blind, placebo-controlled trial was conducted in healthy, full-term infants. Eighty-eight infants between 7 days and 2 months (60 ± 7 days) of age were selected and randomized to treatment with L. salivarius AP-32, B. animalis CP-9 or placebo for 4 months. The unblinding indicated subjects were randomized to receive B. animalis CP-9 (N = 28), L. salivarius AP-32 (N = 29), or placebo (N = 31). A total of 76 infants completed the 4-month treatment with fully compliance. The primary outcome was weight gain, with no significant difference in infant weight at 4 months when comparing AP-32 or CP-9 group with the placebo group, either. The head circumference and recumbent length of the CP-9 group were not significantly different from those of the placebo group. The recumbent length of the AP-32 group was slightly lower than that in the placebo group at month 4, but there was no difference between the two groups in head circumference. Overall, the growth trend of all treatments was similar without significant difference. Furthermore, there were no apparent differences between each group in digestive tolerance, the occurrence of adverse events, crying/fussing time and episodes, alpha diversity, and beta diversity. The CP-9 group showed a significant increase in the abundance of the Bacteroides genus, while the AP-32 group demonstrated a significant increase in the abundance of the Lactobacillus genus when comparing the two probiotic groups. Our study findings indicate that the oral administration of both AP-32 and CP-9 strains has a positive impact on the maintenance of a healthy gut flora in infants. Long-term use of L. salivarius AP-32 or B. animalis CP-9 is safe for infants from 7 days to 6 months of age.

The Clinical Characteristics, Microbiology and Risk Factors for Adverse Outcomes in Neonates with Gram-Negative Bacillary Meningitis.

Background: We aimed to describe the clinical features of Gram-negative bacillary (GNB) meningitis in neonates and investigate the risk factors associated with final adverse outcomes of neonatal GNB meningitis. Methods: From 2003 to 2020, all neonates (aged ≤ 90 days old) with bacterial meningitis who were hospitalized in four tertiary-level neonatal intensive care units (NICUs) of two medical centers in Taiwan were enrolled. Neonates with GNB meningitis were compared with those with Streptococcus agalactiae (group B streptococcus, GBS) meningitis. Results: During the study period, a total of 153 neonates with bacterial meningitis were identified and enrolled. GNB and GBS accounted for 40.5% (n = 62) and 35.3% (n = 54) of all neonatal bacterial meningitis, respectively. In neonates with GNB meningitis, the final mortality rate was 6.5% (4 neonates died); 48 (77.4%) had neurological complications, and 26 (44.8%) of 58 survivors had neurological sequelae at discharge. Although the final outcomes were comparable between neonates with GNB meningitis and those with GBS meningitis, neonates with GNB meningitis were more likely to have more severe clinical manifestations initially and have ventriculomegaly at follow-up. After multivariate logistic regression analysis, neonates with seizure at onset, early onset sepsis, and requirement of surgical intervention for neurological complications were independently associated with final adverse outcomes. Conclusions: GNB meningitis was associated with a high risk of neurological complications and sequelae, although it did not significantly increase the final mortality rate. Close monitoring of the occurrence of neurological complications and advanced therapeutic strategies to optimize the outcomes are urgently needed in the future.

Perinatal Characteristics and the Sensitization to Cow Milk, Egg Whites and Wheat in Children up to 3 Years of Age.

Food sensitization in early life identifies children at risk of developing allergic diseases. We investigated the sensitization to cow milk (CM), egg whites, and wheat. Newborns and infants under 3 years of age with available specific immunoglobulin E (sIgE) data were identified. A retrospective survey was conducted using data from the Chang Gung Research Database. Perinatal characteristics, such as singleton or multiples in a single pregnancy, parity, meconium staining, maternal age, spontaneous delivery or cesarean section, meconium passage, weeks of gestation, birth length, body weight, head and chest circumferences, and season, were obtained. The data on sIgE were collected, and a logistic regression model was used to determine the odds of sensitization. Positive sIgE for CM and egg whites was more likely to occur in boys than in girls. Early-life egg white and wheat sensitization was associated with increased birth body length and weight. A multivariate analysis indicated an association between egg white sIgE positivity and logarithmic total IgE. Higher total IgE levels and younger age were associated with egg white sensitization, and elevated weight and length at birth were linked to food sensitization, particularly to egg whites and wheat.

Neurally adjusted ventilatory assist for rapid weaning in preterm infants.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a new mode of subject-triggered ventilation. Experience with the use of NAVA in preterm infants is limited. This study compared the effects of invasive mechanical ventilation with NAVA to conventional intermittent mandatory ventilation (CIMV) in terms of reducing the duration of oxygen requirement and invasive ventilator support in preterm infants. METHODS: This was a prospective study. We enrolled infants of less than 32 weeks' gestation who were then randomized to receive either NAVA or CIMV support during hospitalization. We recorded and analyzed data on the maternal history during pregnancy, use of medications, neonatal data at admission, neonatal diseases, and respiratory support in the neonatal intensive care unit. RESULTS: There were 26 preterm infants in the NAVA group and 27 preterm infants in the CIMV group. Significantly fewer infants in the NAVA group received supplemental oxygen at 28 days of age (12 [46%] vs. 21 [78%], p = 0.0365), and they required significantly fewer days of invasive ventilator support: 7.73 (± 2.39) vs. 17.26 (± 3.65), p = 0.0343. CONCLUSIONS: Compared with CIMV, NAVA appears to allow for more rapid weaning from invasive ventilation and decreases the incidence of bronchopulmonary dysplasia, especially in preterm infants with severe respiratory distress syndrome treated with surfactants.

Influences of Initial Empiric Antibiotics with Ampicillin plus Cefotaxime on the Outcomes of Neonates with Respiratory Failure: A Propensity Score Matched Analysis.

Background: Empiric antibiotics are often prescribed in critically ill and preterm neonates at birth until sepsis can be ruled out. Although the current guideline suggests narrow-spectrum antibiotics, an upgrade in antibiotics is common in the neonatal intensive care unit. The impacts of initial broad-spectrum antibiotics on the outcomes of critically ill neonates with respiratory failure requiring mechanical intubation have not been well studied. Methods: A total of 1162 neonates from a tertiary level neonatal intensive care unit (NICU) in Taiwan who were on mechanical ventilation for respiratory distress/failure at birth were enrolled, and neonates receiving ampicillin plus cefotaxime were compared with those receiving ampicillin plus gentamicin. Propensity score-matched analysis was used to investigate the effects of ampicillin plus cefotaxime on the outcomes of critically ill neonates. Results: Ampicillin plus cefotaxime was more frequently prescribed for intubated neonates with lower birth weight, higher severity of illness, and those with a high risk of early-onset sepsis. Only 11.1% of these neonates had blood culture-confirmed early-onset sepsis and/or congenital pneumonia. The use of ampicillin plus cefotaxime did not significantly contribute to improved outcomes among neonates with early-onset sepsis. After propensity score-matched analyses, the critically ill neonates receiving ampicillin plus cefotaxime had significantly worse outcomes than those receiving ampicillin plus gentamicin, including a higher risk of late-onset sepsis caused by multidrug-resistant pathogens (11.2% versus 7.1%, p = 0.027), longer duration of hospitalization (median [IQR], 86.5 [47-118.8] days versus 78 [45.0-106.0] days, p = 0.002), and a significantly higher risk of in-hospital mortality (14.2% versus 9.6%, p = 0.023). Conclusions: Ampicillin plus cefotaxime should not be routinely prescribed as the empiric antibiotics for critically ill neonates at birth because they were associated with a higher risk of infections caused by multidrug-resistant pathogens and final worse outcomes.

Bile Duct Stone Size May Influence the Efficacy of Endoscopic Sphincterotomy With or Without Large-Balloon Dilation: A Meta-Analysis.

Purpose: Endoscopic sphincterotomy (EPT) combined with endoscopic papillary large balloon dilatation (EPBD) are used to remove large common bile duct (CBD) stones. This meta-analysis compared the efficacy and safety of EPT+EPBD versus EPT alone in the removal of stones based on stone size. Materials and Methods: Twenty-two studies (11 randomized control trials [RCTs] and 11 non-RCTs) were identified and reviewed based on searches of Embase, PubMed, and Web of Science. CBD stone's size was measured with reference to diameter of the duodenoscope (13 mm) and size of the large dilatation balloon (17 mm) seen on cholangiogram. The stone clearance rate, required mechanical lithotripsy (ML), procedure time, and pancreatitis were compared according to the mean stone size, and further divided into Groups A (small) 10-13 mm, B (medium) 13-17 mm, and C (large) >17 mm. Results: Subgroup analysis according to CBD stone size showed EPT + EPBD had a significantly better initial stone clearance rate than EPT in Groups B (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.20-4.77) and C (OR = 3.05, 95% CI: 1.86-5.03), but not for Group A (OR = 1.41, 95% CI: 0.90-2.21). EPT+EPBD also required significantly less ML than EPT in Groups B (OR = 0.34, 95% CI: 0.15-0.77) and C (OR = 0.31, 95% CI: 0.13-0.73). EPT+EPBD had significantly shorter procedure time than EPT in Group B (standardized mean difference = -1.20, 95% CI: -2.08 to 0.32). In meta-regression analysis, Group B had a better OR in initial stone clearance rate and less ML usage rate correlation with the size of CBD stone, but not for Group C with larger stones. Conclusions: EPT+EPBD had a significantly better initial stone clearance rate, and required less ML with shorter procedure time than EPT for removing medium-sized CBD stones, but the efficacy was limited to large CBD stones. The study protocol and trial registration had been registered in PROSPERO (Registration No. CRD42020171689).

HLA Risk Alleles in Aromatic Antiepileptic Drug-Induced Maculopapular Exanthema.

To characterize human leukocyte antigen (HLA) loci as risk factors in aromatic antiepileptic drug-induced maculopapular exanthema (AED-MPE). A case-control study was performed to investigate HLA loci involved in AED-MPE in a southern Han Chinese population. Between January 2007 and June 2019, 267 patients with carbamazepine (CBZ), oxcarbazepine (OXC), or lamotrigine (LTG) associated MPE and 387 matched drug-tolerant controls from six centers were enrolled. HLA-A/B/C/DRB1 genotypes were determined using sequence-based typing. Potential risk alleles were validated by meta-analysis using data from different populations and in silico analysis of protein-drug interactions. HLA-DRB1*04:06 was significantly associated with OXC-MPE (p = 0.002, p c = 0.04). HLA-B*38:02 was associated with CBZ-MPE (p = 0.03). When pooled, HLA-A*24:02, HLA-A*30:01, and HLA-B*35:01 additionally revealed significant association with AED-MPE. Logistic regression analysis showed a multiplicative interaction between HLA-A*24:02 and HLA-B*38:02 in CBZ-MPE. Meta-analysis of data from different populations revealed that HLA-24*:02 and HLA-A*30:01 were associated with AED-MPE (p = 0.02 and p = 0.04, respectively). In silico analysis of protein-drug interaction demonstrated that HLA-A*24:02 and HLA-A*30:01 had higher affinities with the three aromatic AEDs than the risk-free HLA-A allele. HLA-DRB1*04:06 showed relatively specific high affinity with S-monohydroxy derivative of OXC. HLA-DRB1*04:06 is a specific risk allele for OXC-induced MPE in the Southern Han Chinese. HLA-A*24:02, possibly HLA-A*30:01, are common risk factors for AED-MPE. The multiplicative risk potential between HLA-A*24:02 and HLA-B*38:02 suggests that patients with two risk alleles are at greater risk than those with one risk allele. Inclusion of these HLA alleles in pre-treatment screening would help estimating the risk of AED-MPE.

Correlations between serum BDNF levels and neurodevelopmental outcomes in infants of mothers with gestational diabetes.

BACKGROUND: Diabetes during pregnancy is associated with an increased risk of foetal and neonatal complications and long-term complications in the offspring. Brain-derived neurotrophic factor (BDNF), a neurotrophin that has a crucial role in neurogenesis modulation and neural pathway maturation during neurodevelopment, may have a role in protecting neurons against injury and diseases by modulating glucose metabolism. The aim of this study was to investigate the possible relationship between the serum BDNF levels of infants of mothers with gestational diabetes (IMGD) and neurodevelopmental outcomes of the children after birth. METHODS: A total of 24 candidates, including 8 IMGD and 16 healthy infants, were recruited for the study. Medical records were reviewed. Serum BDNF levels of the study participants were collected at birth and at 6 and 12 months of age. Developmental outcomes of each candidate were assessed using the Bayley Scales of Infant Development III (BSID III) at 6 and 12 months of corrected age. RESULTS: Compared to non-IMGD, IMGD had greater mean body weight (p = 0.04) and height (p < 0.01) at age 12 months. The language composite score was significantly lower in IMGD at 12 months of age (p = 0.038). The BDNF content was significantly higher in the non-IMGD than in the IMGD group at 12 months of age (p = 0.013). CONCLUSION: In this study, we demonstrated that infants of mothers with gestational diabetes do worse in language development and have lower BDNF levels at 12 months of age. There may be a close correlation between language outcomes and serum BDNF levels at 12 months of age. A follow-up study on future developmental status is warranted.

The appropriate frequency of dressing for percutaneous central venous catheters in preventing catheter-related blood stream infection in NICU - A randomized controlled trial.

BACKGROUND: Complications of percutaneous central venous catheters (PCVCs) include catheter-related blood stream infection (CRBSI), occlusion, leakage, and phlebitis, which may lead to sepsis or prolonged hospitalization. The primary objective of this randomized controlled trial was to determine the appropriate frequency of dressing for percutaneous central venous catheters in preventing CRBSI, every week regularly vs. non-regularly, in premature neonates in NICU. METHODS: Patients in NICU requiring PCVCs from March 2019-May 2020 were enrolled. Enrolled patients were randomly assigned into 2 groups: regular dressing group (RD), for which dressings were changed every week regularly, or additionally when oozing was noticed; and non-regular dressing group (ND), for which dressings were changed only when oozing was visible. The incidence of CRBSI, occlusion, leakage, and phlebitis were compared between the two groups using the Chi-squared test. The incidence of catheter-related complications was defined as numbers of episodes per 1000 catheter-days. RESULTS: A total of 197 PCVCs were enrolled. The ND and RD groups had 99 and 98 PCVCs, respectively. The average CD interval was 9.3 days in ND group and 5.8 days in RD group. The incidence of CRBSI in RD group was 0‰, which was significantly lower than that of ND group, which was 2.0‰ (p = 0.048), but no significant differences were found between groups in the incidence of occlusion, leakage, and phlebitis of PCVCs. CONCLUSION: Regular dressing changes every week and when oozing occurs while maintaining the protocol of maximum sterile barrier precautions is the best method and frequency of dressings of PCVCs.

The role of ultrasonography for detecting tip location of percutaneous central venous catheters in neonates-a single-center, prospective cohort study.

BACKGROUND: Percutaneous central venous catheters (PCVCs) are used commonly and widely in the neonatal intensive care unit (NICU). Malposition of PCVCs may cause life-threatening complications and prolong hospitalization. In Taiwan, conventional chest-abdomen radiography (CXR) has been used widely and routinely for assessing tip location of PCVCs. Compared to ultrasonography (US), CXR cannot provide real-time assessment, and patients are exposed to radiation. Therefore, this study aimed to analyze the role of US in detecting PCVC tip location in the lower extremities. METHODS: Neonates who received PCVC insertion in the lower extremities in NICU from March 2019 to April 2020 were enrolled in this prospective cohort study. PCVC tip location was confirmed finally by conventional CXR after US examination and patients were included in the sono group; those not assessed by US formed the non-sono group. In addition, PCVCs inserted in 2018 for which tip location was evaluated only by CXR, were reviewed retrospectively and these cases were included in the non-sono group. Withdrawal rates between the two groups were analyzed using Chi-square test. RESULTS: The sono group included 166 neonates with PCVCs and 141 were in the non-sono group. Median gestational age at date of PCVC insertion was 33.21 and 32.71 weeks in sono and non-sono groups, respectively (p = 0.37). Withdrawal rates were 10.84% and 65.95% (p < 0.001) and duration for catheter location confirmation were 2-4.75 min and 75-247.25 min (p < 0.001), respectively. CONCLUSION: US provides more reliable images than conventional radiography alone for identifying PCVC tip locations in the lower extremities. It can effectively reduce catheter insertion duration, and was associated with fewer manipulations.

Accelerated weight gain, prematurity, and the risk of childhood obesity: A meta-analysis and systematic review.

The purpose of this systematic review and meta-analysis of the literature was to analyze and evaluate the impact of prematurity and accelerated weight gain on the risk of childhood and adolescent obesity. CINAHL, Embase, PubMed, and Web of Science databases were searched until December 2019 which yielded 19 studies with a total of 169,439 children enrolled were systematically reviewed. The results revealed that preterm infants had a greater likelihood of childhood obesity (defined as BMI ≥95th percentile for age-sex), than term infants (OR = 1.19, 95% CI [1.13, 1.26]). However, no difference of childhood obesity was found between "small for gestational age"(SGA) and "appropriate for gestational age"(AGA) among preterms. Accelerated weight gain (defined as weight gain velocity during first two years after birth) significantly increased the likelihood of subsequent childhood obesity among preterms (aOR = 1.87, 95% CI [1.57, 2.231]). In conclusion, accelerated weight gain at infancy among preterm children may be a critical contributor to obesity in later life. Establishing optimal growth trajectories and timely referral to health care providers may be of clinical importance.

Enantiomeric effect of paclobutrazol on the microorganism composition during wine fermentation.

Pesticide residues in food can bring potential risks to human health and has been widely concerned in recent years. In the current study, the influence of paclobutrazol, which resided in raw material (grape) on wine fermentation process, were investigated. The degradation kinetic results indicated that the enantiomers of paclobutrazol not be degraded during 30 days of fermentation process. In order to achieve the fermented microorganism information of diversity, community composition, and function, the analysis of 16S rRNA and ITS sequencing were performed. Results demonstrated that the dominant microorganisms multiplied and the microbial diversity in the samples decreased as the fermentation process progresses. Furthermore, the paclobutrazol stimulated the growth of Pichia, which was observed during wine fermentation and which may have an underlying impact on the quality of the wine. The above results inferred that paclobutrazol residue could disturb the microbial community stability during wine fermentation, and the stable existence of paclobutrazol will cause potential risks to food safety and human health. In this work, we have successfully devised a method to investigate the influences of pesticide residues in raw materials during food processing and conclusions from this study could provide basis for dietary risk assessment.

A novel method to detect bacterial infection in premature infants: Using a combination of inflammatory markers in blood and saliva.

BACKGROUND: Opportunistic infection leads to high morbidity and mortality in premature babies due to their immature immune system. Biomarkers in blood have been reported to detect bacterial infection in neonates. However, serial blood exams pose iatrogenic anemia in premature babies. Thus, this study aimed to identify cytokines in saliva, which can help to diagnose bacterial infection in premature babies via a non-invasive method. METHODS: Premature neonates were enrolled from Aug. 2012 to Feb. 2015 after completing informed consent. Babies with congenital anomalies, bronchopulmonary dysplasia, necrotizing enterocolitis and any surgical indicated diseases were excluded. Salivary samples collection and septic work-up were performed when bacterial infection was clinically suspected, as well as one week after antimicrobial treatment. The level of salivary cytokines was detected by MILLPLEX® MAP and analyzed by Mann-Whitney U test. RESULTS: There were 16 episodes of bacterial infection in 10 cases. Culture-positive group had significantly higher levels of salivary Interleukin (IL) 6, IL-8, macrophage inflammatory protein (MIP)1α, MIP-1ß and tumor necrosis factor (TNF)-α than that in the culture-negative group (p = 0.002, 0.006, 0.001, <0.001, 0.009), and blood C-reactive protein and sugar as well (p < 0.001, 0.026). After adjusting postmenstrual age by logistic regression, blood sugar level was the most significant biomarker (p = 0.019). In combination of blood and salivary biomarkers, blood sugar higher than 67 mg/dL and salivary IL-6 higher than 367.25 pg/mL concurrently, would accurately detect bacterial infection in premature babies. CONCLUSION: This non-invasive method might help us to accurately diagnose bacterial infection in premature babies.

HLA-B*13:01 as a Risk Allele for Antiepileptic Drugs-Induced Cutaneous Adverse Reactions: Higher Risk for Cross-Reactivity?

Antiepileptic drugs frequently cause cutaneous adverse reactions (cADRs). Numerous studies have reported associations between human leukocyte antigen (HLA) alleles and cADRs caused by single antiepileptic drug in Southern Han Chinese people. However, the relationship between the HLA allele and cADRs sequentially induced by two or more antiepileptic drugs (AEDs-induced cross-reactivity) is unclear. To explore the associations between HLA alleles and AEDs-induced cross-reactivity, we prospectively recruited patients with AEDs-induced cross-reactivity from 2009 to 2017 and performed high-resolution genotyping to detect the HLA-A, B, C, and DRB1 alleles in patients for comparison with normal controls. To verify the important genotype, we compared its presence in patients with cross-reactivity to enlarged normal controls, and its presence in patients with carbamazepine (CBZ)-induced maculopapular exanthema (MPE) to CBZ-tolerant controls. Further, the important allele was replicated by meta-analysis. Twenty-three patients with AED-induced cross-reactivity and 500 healthy individuals were enrolled from Southern China. All patients had a mild rash without mucosal or systemic involvement. The HLA-B*13:01 allele was present in 34.78% (8/23) of patients, 14.60% (73/500) of healthy individuals, and 14.5% (763/5,270) healthy individuals, revealing a significant association (8/23 vs. 73/500; P = 0.02; OR: 3.12; 95% CI: 1.28-7.62; 8/23 vs. 763/5,270; P = 0.014; OR: 3.15; 95% CI: 1.33-7.46). HLA-B*13:01 was presented numerically higher in CBZ-induced MPE than that in CBZ-tolerant individuals without statistical significance (33/145, 22.76%, vs. 28/179, 15.64%; P = 0.103). Meta-analysis revealed an association between HLA-B*13:01 and cADRs induced by single AEDs or/and non-AEDs in Chinese and Thai populations (P = 0.000). This study suggests that HLA-B*13:01 is potentially associated with AED-cADRs in general, possibly with stronger effect in cross-reactivity. Screening for HLA-B*13:01 prior to starting AEDs therapy may help to avoid cADRs. However, this association requires further analysis in a multi-center study with a larger sample size.

Magnetic polydopamine modified with deep eutectic solvent for the magnetic solid-phase extraction of sulfonylurea herbicides in water samples.

A novel magnetic solid-phase extraction (MSPE) technique coupled with ultra performance liquid chromatography (UPLC) has been developed for the determination of four sulfonylurea herbicides (sulfosulfuron, bensulfuron-methyl, pyrazosulfuron-ethyl and halosulfuron-methyl) in aqueous samples. The key point of this method was the application of a novel magnetic nanomaterial (Fe3O4 @ PDA-DES). The functional groups, morphology, and magnetic properties of this magnetic nanomaterial were investigated through fourier transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM), and X-ray diffraction (XRD) respectively. The main factors which could affect the experiment results were optimized. Under the optimum conditions, the linearity of this method ranged from 5.0-200 µg L-1 for all analytes, with correlation coefficients (r) ≥0.9901. The enrichment factors were between 495 and 630, and the relative standard deviations (RSDs) were less than 3.6%. The limits of detections (LODs) varied from 0.0098 to 0.0110 µg L-1. In the final experiment, the developed method has been successfully applied to the determination of sulfonylurea herbicides in environment and drinking water samples, and the obtained recoveries were between 61.3% and 108.6%.