Subinhibitory concentrations of phloretin repress the virulence of Salmonella typhimurium and protect against Salmonella typhimurium infection.

Phloretin, a natural component of many fruits, exhibits anti-virulence effects and provides a new alternative to counter bacterial infection. The aim of this study was to determine the effect of subinhibitory concentrations of phloretin on the virulence of Salmonella typhimurium. At concentrations where growth of Salmonella was not inhibited, phloretin significantly inhibited bacteria biofilm formation and motility. Subinhibitory concentrations of phloretin repressed eight genes involved in the Salmonella pathogenicity island 1 and 3 genes involved in flagella production. Furthermore, subinhibitory concentrations of phloretin inhibited the adhesion and invasion of Salmonella in IEC-6 cells and reduced the LDH levels of S. typhimurium-infected IEC-6 cells. Additionally, phloretin significantly decreased the cecum bacterial loads of the mice infected with live S. typhimurium containing subinhibitory concentrations of phloretin by gavage. These results suggested that subinhibitory concentrations of phloretin attenuate the virulence of S. typhimurium and protect against S. typhimurium infection.

Genetic diagnosis of autism spectrum disorders: the opportunity and challenge in the genomics era.

A genetic etiology for autism spectrum disorders (ASDs) was first suggested from twin studies reported in the 1970s. The identification of gene mutations in syndromic ASDs provided evidence to support a genetic cause of ASDs. More recently, genome-wide copy number variant and sequence analyses have uncovered a list of rare and highly penetrant copy number variants (CNVs) or single nucleotide variants (SNVs) associated with ASDs, which has strengthened the claim of a genetic etiology for ASDs. Findings from research studies in the genetics of ASD now support an important role for molecular diagnostics in the clinical genetics evaluation of ASDs. Various molecular diagnostic assays including single gene tests, targeted multiple gene panels and copy number analysis should all be considered in the clinical genetics evaluation of ASDs. Whole exome sequencing could also be considered in selected clinical cases. However, the challenge that remains is to determine the causal role of genetic variants identified through molecular testing. Variable expressivity, pleiotropic effects and incomplete penetrance associated with CNVs and SNVs also present significant challenges for genetic counseling and prenatal diagnosis.

A Virtual-Reality System Integrated With Neuro-Behavior Sensing for Attention-Deficit/Hyperactivity Disorder Intelligent Assessment.

Attention-deficit/Hyperactivity disorder(ADHD) is a common neurodevelopmental disorder among children. Traditional assessment methods generally rely on behavioral rating scales (BRS) performed by clinicians, and sometimes parents or teachers. However, BRS assessment is time consuming, and the subjective ratings may lead to bias for the evaluation. Therefore, the major purpose of this study was to develop a Virtual Reality (VR) classroom associated with an intelligent assessment model to assist clinicians for the diagnosis of ADHD. In this study, an immersive VR classroom embedded with sustained and selective attention tasks was developed in which visual, audio, and visual-audio hybrid distractions, were triggered while attention tasks were conducted. A clinical experiment with 37 ADHD and 31 healthy subjects was performed. Data from BRS was compared with VR task performance and analyzed by rank-sum tests and Pearson Correlation. Results showed that 23 features out of total 28 were related to distinguish the ADHD and non-ADHD children. Several features of task performance and neuro-behavioral measurements were also correlated with features of the BRSs. Additionally, the machine learning models incorporating task performance and neuro-behavior were used to classify ADHD and non-ADHD children. The mean accuracy for the repeated cross-validation reached to 83.2%, which demonstrated a great potential for our system to provide more help for clinicians on assessment of ADHD.

HIV prevalence in suspected Ebola cases during the 2014-2016 Ebola epidemic in Sierra Leone.

BACKGROUND: The 2014-2016 Ebola virus epidemic in West Africa was the largest outbreak of Ebola virus disease (EVD) in history. Clarifying the influence of other prevalent diseases such as human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) will help improve treatment and supportive care of patients with EVD. CASE PRESENTATION: We examined HIV and hepatitis C virus (HCV) antibody prevalence among suspected EVD cases from the Sierra Leone-China Friendship Biological Safety Laboratory during the epidemic in Sierra Leone. HIV and HCV antibodies were tested in 678 EVD-negative samples by enzyme-linked immunosorbent assay. A high HIV prevalence (17.6%) and low HCV prevalence (0.22%) were observed among the suspected cases. Notably, we found decreased HIV positive rates among the suspected cases over the course of the epidemic. This suggests a potentially beneficial effect of an improved public health system after assistance from the World Health Organization and other international aid organizations. CONCLUSIONS: This EVD epidemic had a considerable impact on the public health system and influenced the prevalence of HIV found among suspected cases in Sierra Leone, but also provided an opportunity to establish a better surveillance network for infectious diseases.

Sub-optimal function of the auditory brainstem in term infants with transient low Apgar scores.

OBJECTIVES: To assess functional integrity of the auditory brainstem in neonates with transient low Apgar scores. METHODS: Forty-two term infants were studied with brainstem auditory evoked response (BAER) using the maximum length sequence during the first month of life. All had transient low Apgar scores but no clinical signs of hypoxic-ischaemic encephalopathy (HIE). RESULTS: The latencies of BAER waves I and III in these infants were similar to those of age-matched normal controls at all click rates (91/s, 227/s, 455/s and 910/s) during the period studied. Wave V latency was increased at 910/s on day 1 (P<0.01), but did not differ from that in the controls on any other days. I-V interval was increased significantly at 455/s and 910/s on day 1 (P<0.01 and 0.001) and day 3 (P<0.05 and 0.01). On days 5 and 7, BAER wave latencies and intervals were similar to those in the controls. On day 30, all latencies and intervals reached the values in the controls. No abnormalities were seen in BAER wave amplitude variables on any days. CONCLUSIONS: Neonates with transient low Apgar scores but without HIE had a significant increase in I-V interval at very high click rates on the first three days of life. SIGNIFICANCE: Brainstem auditory function is sub-optimal during the first few days in neonates with transient low Apgar scores.

Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5-fluorouracil alone in human colon cancer cell lines.

AIM: Our previous studies showed increased sensitivity to 5-FU in colon cancer cell lines with microsatellite instability, and considered that mutations of TGFbeta-R II, IGF IIR, RIZ gene might enhance the potentials of cell growth and proliferation, which increased the sensitivity to 5-FU. Here we compared the distribution of cell cycle and P53 status between two human colon cancer cell lines with different sensitivity to 5-FU. Because mechanistic differences exist between 5-FU and CDDP, we also analyzed the efficacy of CDDP and combination therapy on two human colon cancer cell lines. METHODS: We compared the sensitivity to CDDP of these two cell lines by MTT assay. Distribution of cell cycle under treatment of 5-FU, CDDP alone or both was analyzed by Flow Cytometry, and expression of P53 was detected by immunocytochemical staining. RESULTS: SW480 cells were more sensitive to CDDP than LoVo cells at the concentrations above 16 micromol/l (Ratio of absorption is 0.64 and 0.79 at 16 micromol/l, respectively; P<0.01). Efficacy of combination therapy was conversely lower than that of single-therapy of 5-FU (Ratio of absorption in LoVo+5-FU, SW480+5-FU, LoVo+5-FU+CDDP and SW480+5-FU+CDDP is 0.53, 0.54, 0.72, 0.78, respectively; P<0.01). LoVo cells were negative whereas SW480 cells positive in P53 expression. 5-FU induced G1-phase arrest in both cell lines, but LoVo cells peaked 24 hours earlier than SW480 cells, and 48 hours earlier for an apparent hypodiploid DNA. However, CDDP showed the contrary, inducing S-phase arrest, and SW480 cells peaking 36 hours earlier. Both cell lines showed hypodipliod nuclei 48 hours after CDDP treatment. Percentage of cells in G1-phase and S-phase dominated alternatively under combination therapy in both cell lines. CONCLUSION: These results suggest that colon cancer cells with microsatellite instability are more sensitive to 5-FU, whereas more resistant to CDDP. Combination therapy of 5-FU and CDDP shows fewer efficacies than 5-FU single-therapy, although it can render a cell cycle arrest. P53 may be involved in the shift of G1-phase to S-phase, but inessentially.