Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

The relationship between late (≥ 7 days) systemic dexamethasone and functional network connectivity in very preterm infants.

Background: Current evidence shows that systemic dexamethasone administration starting after the first week of age reduces bronchopulmonary dysplasia for very preterm (VPT) infants, but its neurological effects remain obscure. Using resting-state functional magnetic resonance imaging (rs-fMRI), we assessed the changes in functional network connectivity (FNC) in very preterm infants treated with late systemic dexamethasone (≥7 days of age). Methods: VPT infants (GA ≤ 32 weeks) who needed to rely on mechanical ventilation for more than 7 days but fewer than 14 days to maintain vital signs were included in the study. The cohort was divided into two groups according to whether they were given systemic dexamethasone. In addition, 26 healthy term infants were recruited as controls. At term-equivalent age (TEA), rs-fMRI and 3D-T1 data from eligible infants were acquired with a 3.0-T MRI scanner. After the MRI data were preprocessed, group-level independent component analysis (ICA), a technique used for blind source separation, was used to identify the components of resting-state networks (RSNs). Then, the functional connectivity between components and RSNs was compared among different groups. Upon follow-up at 3 months of corrected age, the neurodevelopmental outcomes of enrolled infants were assessed with the Bayley Scales of Infant Development-Chinese Revision (BSID-CR), and the Motor Development Index (MDI) and Psychomotor Development Index (PDI) were measured. Finally, the correlations between resting-state FNC and BSID scores were analysed. Results: Ultimately, 59 infants were included in the final analysis, including 19 preterm infants who received dexamethasone, 20 who did not, and 20 healthy term infants as controls. Based on their data, 11 components were identified, belonging to 5 RSNs: the visual network (VN), the dorsal attention network (DAN), the auditory network (AN), the primary sensorimotor network (SMN), and the default-mode network (DMN). Compared with the term infants, the preterm infants showed significantly weakened functional connectivity between the DAN and VN, as well as the VN and AN (P < 0.05). Among preterm infants, those who were given dexamethasone showed significantly stronger functional connectivity between the DAN and VN, as well as the DMN and AN (P < 0.05), than those who were not. The correlation analysis demonstrated that the connectivity values between the DAN and VN and between the VN and AN were positively correlated with the MDI (r = 0.432, P＜0.001, and r = 0.479, P＜0.001, respectively) and the PDI (r = 0.436, P＜0.001 and r = 0.516, P＜0.001, respectively). Conclusions: Our investigation uncovers a noteworthy link between the administration of late systemic dexamethasone (≥7 days of age) in VPT infants and distinct improvements in FNC. Furthermore, the observed positive correlation between inter-network connectivity and scores on the BSID-CR implies a plausible neuroprotective aspect of this therapeutic approach in this specific group of children.

Occlusion as a predisposing factor for peri-implant disease: A review article.

BACKGROUND: The restoration of dental implants presents a unique challenge due to the intrinsic biomechanical differences between osseointegrated implants and natural teeth, and their subsequent responses to occlusal loading. However, controversy exists regarding the role that occlusion plays in the physiology of the peri-implant complex. PURPOSE: To provide an overview of the scientific literature regarding occlusion as it relates to implant dentistry and peri-implant disease. MATERIALS AND METHODS: This article presents a narrative review on occlusal loading and its potential effects on the peri-implant complex, as well as some generally accepted guidelines for occlusion in implant dentistry. RESULTS AND CONCLUSIONS: Although there is strong evidence linking occlusal factors to mechanical complications of dental implants, the same cannot be said regarding biological complications. There is no clear scientific evidence on the relationship between occlusal overload and peri-implant disease. However, occlusal overload may be an accelerating factor for peri-implant disease in the presence of inflammation. As the biomechanical properties of dental implants differ from that of the natural dentition, modifications to classic concepts of occlusion may be necessary when dental implants are involved. Thus, clinical recommendations are proposed which function to minimize unfavorable occlusal forces on implant restorations and reduce the associated biological and mechanical complications.

Study of a Mode Separation Due to Polarization Existing in a Cavity-Enhanced Absorption Spectroscopy.

A special phenomenon of resonance mode separation is observed during the study of a high sensitivity folded-cavity enhanced absorption spectroscopy for the measurement of trace gases. The phenomenon affects the measurement of gas absorption spectrum in the cavity. This resonant mode separation phenomenon of the resonant cavity is different from the resonant modes previously observed in linear-cavity enhanced absorption spectroscopy systems. To explore the mechanism of this phenomenon, a series of hypotheses are proposed. The most likely reason among these hypotheses is based on the different reflectance properties of the plane mirror at the fold of the cavity for S-polarized light and P-polarized light. Based on the matrix calculation method, the different reflectance and phase shift of the plane mirror for S-polarized light and P-polarized light are analyzed theoretically, and the results are in better agreement with the phenomena observed in the experiment. Finally, in order to eliminate the resonant mode separation phenomenon, line polarizers were added. By improving the system, the cavity enhanced absorption spectrum of residual water vapor in the cavity was successfully measured, and a minimum detectable absorption coefficient of αmin = 7.6 × 10-9 cm-1 can be obtained in a single laser scan of 10 s.

Diversity of Extended-Spectrum Cephalosporin-Resistant Escherichia coli in Feces from Calves and Cows on Pennsylvania Dairy Farms.

The global incidence of human infections associated with extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing. Dairy animals are reservoirs of ESBL-producing E. coli, especially, third-generation cephalosporin (3GC)-resistant strains. To further understand the diversity of 3GC-resistant E. coli across animals of different age groups (e.g., pre- and postweaned calves, lactating cows, and dry cows) and farms, we used pulsed-field gel electrophoresis (PFGE) to characterize 70 fecal isolates from 14 dairy farms located in nine Pennsylvania counties. Results of this analysis indicated that 3GC-resistant E. coli were highly diverse and grouped into 27 PFGE clades (80% similarity cutoff) and 24 unique antimicrobial resistance patterns were observed among the isolates. For eight farms, clonal E. coli with the same resistance patterns were isolated from two or more age groups, indicating that strains were carried in both the calves and adult cows within the same herd. However, there were also several isolates with the same resistance pattern that were distributed to different clades, including isolates from different animal age groups on the same farm, suggesting different strains of E. coli within a farm harbored the same resistance-conferring elements. Results of this analysis indicated that 3GC-resistant E. coli were highly diverse, associated with multidrug resistance, and circulated through different (noncommingled) animal groups on individual farms.

Antimicrobial Resistance Among Escherichia coli Isolated from Veal Calf Operations in Pennsylvania.

Antimicrobial resistance (AR) is a pressing public health concern, and agricultural operations such as dairy and beef cattle production have been implicated as potential sources of resistant bacteria or genetic elements. This study aimed to determine the prevalence of antimicrobial-resistant Escherichia coli from calf pens in 6 auction houses (56 manure composite samples) and 12 veal calf operations (240 fecal samples in 2 visits: after the calves arrived at the farm and shortly before the animals were sent to slaughter) in the Commonwealth of Pennsylvania. A total of 1567 generic E. coli were isolated and screened for resistance phenotypes. Resistant E. coli were isolated from all auction houses and farms sampled. Based on nonparametric Kruskal-Wallis tests, incremental prevalence of E. coli resistant to ampicillin, azithromycin, cefoxitin, ceftiofur, ceftriaxone, chloramphenicol, streptomycin, sulfisoxazole, trimethoprim-sulfamethoxazole, and tetracycline in the samples from auction houses and the first and second farm visits was observed (χ2 6.98-15.91, p < 0.05). Multidrug-resistant E. coli (resistant to more than three antimicrobial classes) were identified in 76.8%, 90.8%, and 100% of samples collected from the auction houses, first farm visits, and second farm visits, respectively. The presence of blaCTX-M-E. coli in 11 of the 12 farms presents the possibility of veal production environments being a reservoir for resistant genetic materials that may pose a risk to human health if they are transferred to human pathogens. Additional research on the impact of various management strategies in veal calf rearing is needed for a complete scenario of AR in these production environments.

Age-Associated Distribution of Antimicrobial-Resistant Salmonella enterica and Escherichia coli Isolated from Dairy Herds in Pennsylvania, 2013-2015.

Antimicrobial resistance has become a major global public health concern, and agricultural operations are often implicated as a source of resistant bacteria. This study characterized the prevalence of antimicrobial-resistant Salmonella enterica and Escherichia coli from a total of 443 manure composite samples from preweaned calves, postweaned calves, dry cows, and lactating cows from 80 dairy operations in Pennsylvania. A total of 1095 S. enterica and 2370 E. coli isolates were screened and tested for resistance to 14 antimicrobials on the National Antimicrobial Resistance Monitoring System Gram-negative (NARMS GN) panel. Salmonellae were isolated from 67% of dairy operations, and 99% of the isolates were pan-susceptible. Salmonella were isolated more frequently from lactating and dry cow samples than from pre- and postweaned calf samples. Overall, the most prevalent serotypes were Cerro, Montevideo, Kentucky, and Newport. E. coli were isolated from all the manure composite samples, and isolates were commonly resistant to tetracyclines, sulfonamides, and aminoglycosides. Resistance was detected more frequently in the E. coli isolates from pre- and postweaned calf samples than in isolates from dry and lactating cow samples (p < 0.05). Multidrug-resistant E. coli (i.e., resistant to >3 antimicrobial classes) were isolated from 66 farms (83%) with significantly greater prevalence in preweaned calves (p < 0.05) than in the older age groups. The blaCTX-M and blaCMY genes were detected in the cephalosporin-resistant E. coli from 4% and 35% of the farms, respectively. These findings indicate that dairy animals, especially the calf population, serve as significant reservoirs for antimicrobial-resistant bacteria. Additional research on the colonization and persistence of resistant E. coli in calves is warranted to identify potential avenues for mitigation.

Modeling the long-term kinetics of Salmonella survival on dry pet food.

Due to multiple outbreaks and large-scale product recalls, Salmonella has emerged as a priority pathogen in dry pet food and treats. However, little data are available to quantify risks posed by these classes of products to both pets and their owners. Specifically, the kinetics of Salmonella survival on complex pet food matrices are not available. This study measured the long-term kinetics of Salmonella survival on a dry pet food under storage conditions commonly encountered during production, retail, and in households (aw < 0.60, 23 °C). A Salmonella enterica cocktail of 12 strains isolated from dry pet foods and treats was used to inoculate commercial dry dog food. Salmonella was enumerated on non-selective (BHI) and selective (XLD and BS) media. Results at 570 days indicated an initial relatively rapid decline (up to 54 days), followed by a much slower extended decline phase. The Weibull model provided a satisfactory fit for time series of Log-transformed Salmonella counts from all three media (δ: mean 4.65 day/Log (CFU/g); p: mean 0.364 on BHI). This study provides a survival model that can be applied in quantitative risk assessment models.

Dynamics of Escherichia coli Virulence Factors in Dairy Herds and Farm Environments in a Longitudinal Study in the United States.

Pathogenic Escherichia coli or its associated virulence factors have been frequently detected in dairy cow manure, milk, and dairy farm environments. However, it is unclear what the long-term dynamics of E. coli virulence factors are and which farm compartments act as reservoirs. This study assessed the occurrence and dynamics of four E. coli virulence factors (eae, stx1, stx2, and the gamma allele of the tir gene [γ-tir]) on three U.S. dairy farms. Fecal, manure, water, feed, milk, and milk filter samples were collected from 2004 to 2012. Virulence factors were measured by postenrichment quantitative PCR (qPCR). All factors were detected in most compartments on all farms. Fecal and manure samples showed the highest prevalence, up to 53% for stx and 21% for γ-tir in fecal samples and up to 84% for stx and 44% for γ-tir in manure. Prevalence was low in milk (up to 1.9% for stx and 0.7% for γ-tir). However, 35% of milk filters were positive for stx and 20% were positive for γ-tir. All factors were detected in feed and water. Factor prevalence and levels, expressed as qPCR cycle threshold categories, fluctuated significantly over time, with no clear seasonal signal independent from year-to-year variability. Levels were correlated between fecal and manure samples, and in some cases autocorrelated, but not between manure and milk filters. Shiga toxins were nearly ubiquitous, and 10 to 18% of the lactating cows were potential shedders of E. coli O157 at least once during their time in the herds. E. coli virulence factors appear to persist in many areas of the farms and therefore contribute to transmission dynamics.

Enhancement effect of ultrasound-induced microbubble cavitation on branched polyethylenimine-mediated VEGF(165) transfection with varied N/P ratio.

One isoform of the vascular endothelial growth factor, VEGF(165), has been reported to be a dominant mediator and regulator of angiogenic process, which plays an important role in treating cardiovascular diseases and chronically ischemic wounds. Branched polyethylenimine (bPEI) has been widely used as a non-viral delivery vector for gene therapy. Although bPEI-mediated DNA transfection efficiency can be raised by increasing the PEI nitrogen:DNA phosphate (N/P) ratio, cytotoxicity increases as well. In this study, the enhancement effect of microbubble inertial cavitation (IC) on bPEI-mediated VEGF(165) transfection was investigated, in an effort to optimize transfection efficiency using low N/P ratios. HEK 293T cells, mixed with bPEI:VEGF(165) complexes, were exposed to 1-MHz ultrasound pulses. The results show that: (1) IC activity induced by microbubble destruction can be quantified as an IC "dose" (ICD) and will increase with increasing acoustic driving pressure; (2) larger sonoporation pores can be generated by increasing ICD; (3) the transfection efficiency can be enhanced by increasing ICD until reaching a saturation level; and (4) microbubble IC activity has less cytotoxicity than bPEI, although a combinatorial effect of microbubble IC activity and bPEI could be observed on cell viability. The results suggest that, with appropriate ultrasound parameters, it is possible to optimize bPEI-mediated VEGF transfection efficiency using relatively low N/P ratios by employing ultrasound-induced microbubble inertial cavitation.

[Efficacy of recombinant hepatitis B vaccine and low-dose hepatitis B immune globulin in preventing mother-infant transmission of hepatitis B virus infection].

OBJECTIVE: To determine the efficacy of recombinant hepatitis B (rHB) vaccine and low-dose hepatitis B immune globulin (HBIG) in the prevention of mother-infant transmission of hepatitis B virus (HBV) infection. METHODS: rHB vaccine was administered to two groups of healthy neonates born to mothers with both hepatitis B surface antigen and e antigen positive in Guangxi, Hunan and Hebei province. Two hundred eighty-nine subjects were included in active immunization group, receiving triple doses of rHB vaccine given i.m. at 0, 1 and 6 month intervals; while 186 subjects receiving 50 IU HBIG at birth with triple doses of rHB vaccine in the low-dose HBIG group. RESULTS: Efficacy of active immunization alone was 87.8% (95% CI: 83.6 - 91.9). Efficacy of rHB vaccine and HBIG was 91.2% (95% CI: 86.7 - 95.6). No significant differences in efficacy by type of rHB vaccine (P = 0.707 2), immunoprophylaxis programs (P = 0.295 5) and regions of living (P = 0.998 7) were noticed. Seroprotection rates (anti-HBs >or= 10 mIU/ml) were detected in 91.1% and 93.5% in rHB vaccine alone recipients and rHB vaccine plus HBIG recipients, with geometric mean titer (GMT) of 153 mIU/ml and 164 mIU/ml at 1 year of age, respectively. Anti-rHBs decreased significantly with years after vaccination (chi(2) = 60.47, P = 0.000 1). Seroprotection rates of anti-rHBs antibodies decreased to 65.0% and 66.6% at 4 years of age in rHB vaccine alone recipients and rHB vaccine plus HBIG recipients, with GMT of 55 mIU/ml and 56 mIU/ml, respectively. CONCLUSION: These results suggested that the effectiveness of rHB vaccine plus low-dose HBIG was much better than only active plasma-derived vaccine; however, methods used for anti-rHBs assay need to be evaluated and verified.

[Long-term efficacy of infant hepatitis B immunization program].

OBJECTIVE: To evaluate the long-term efficacy of infant hepatitis B (HB) immunization program on preventing hepatitis B virus (HBV) infection, and to assess its impact on the incidence of HB in children. METHODS: Since 1986, the universal HB vaccination for newborn babies with standard, pediatric dose had been launched without serologic prescreening of pregnant women for HBsAg, in a high endemic county of Long-An. A hepatitis surveillance system was set up to evaluate the possible impact on the incidence of hepatitis B. To serologically evaluate the effectiveness of the program, a stratified random sampling of 1000 children in 1987 birth cohorts, who received plasma-derived HB vaccine, was recruited for long-term follow up at the age of 1 to 13 years. A cross-sectional seroepidemiological survey was conducted in the county in 1985, before the program, and in 2001, for 1551 children born in 1996-2000 who were administered yeast recombinant HB vaccine. RESULTS: During the 1 to 13 years after the program, the rates of HBsAg-positive were 0.7% to 2.9% with an average of 1.7% and the protective rates were 83.5% to 96.6%. HBV infection rates were 1.1% tp 5.1% with an average of 2.4% and the protective rates were 93.5% to 98.4%. For the population aged 1 to 4 years who were immunized with recombinant HB vaccine, HBsAg positive rates were 1.8% to 2.4% with an average of 2.0% and the protective rates were 78.4 to 85.2%. 14 years after the program, the cumulative incidence of acute hepatitis B in the children aged 1 to 14 years fell to 1.5 cases per 100,000 children, down 91.8% as compared with that in 1985 to 1987. However, the cumulative incidence of 14.4 cases per 100,000 population in unvaccinated children was not significantly different from that in the history controls. Acute hepatitis B children had not been reported, showing that the vaccination program was 100% protective in children. CONCLUSION: The universal infant HB vaccination program in a hyperendemic area has proved to be effective in controlling HBV infection and decreasing the incidence of acute hepatitis B in children. Booster dose is unnecessary in 13 years after the immunization. The protective efficacy of yeast recombinant HB vaccine is similar to that of plasma-derived HB vaccine.

[Long-term efficacy and persistence of Chinese infants after receiving only active plasma-derived hepatitis B vaccine].

BACKGROUND: To determine the long-term efficacy and persistence of Chinese infants after receiving only active plasma-derived hepatitis B vaccine, and to evaluate if providing booster vaccination after basic hepatitis B immunization is necessary. METHODS: Infants who were born in 1986-1988 in four demonstrative hepatitis B immunization trial areas of Hunan, Guangxi, Hebei and Shanghai after receiving only active plasma-derived hepatitis B vaccination, had been randomly followed up for 15 years. HBsAg,anti-HBs and anti-HBc in 21 680 person-times were tested using commercial SPRIA kits. RESULTS: Prevalence of HBV carriers was less than 1.66% among all children vaccinated with only active plasma-derived hepatitis B vaccine in 4 clinical trial areas. Prevalence of HBsAg did not increase with years after vaccination,90%(95% Cl:83.1%-97.2%) effectiveness of hepatitis B vaccine persisted for 15 years in preventing chronic HBV infection. Carriage, HBV infection and efficacy were not different among all age groups (P>0.05). Seroprotection rate (anti-HBs?10 mIU/ml) and quantity of anti-HBs were significantly decreased with years after vaccination. Seroprotection rates of anti-HBs were 40%-50% and 30%-42% during the 9th-10th year and the 13th-14th ear of vaccination, respectively. Titer of anti-HBs declined?by 90% after 14 years. CONCLUSIONS: These results showed that long-term efficacy of only active plasma-derived hepatitis B vaccination, which was not affected by decline in seroprotection rate and titer of anti-HBs. For children and adults whose immune status is normal, booster doses of vaccine are not recommended.

[Immediate immunological effect of China-made recombinant hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line].

OBJECTIVE: To understand the protective efficacy of China-made recombinant hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line among newborns. METHODS: 2 969 newborns in seven townships in Zhengding County, Hebei Province, were vaccinated with 10 microgram x 3 doses of China-made recombinant hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line according to the 0 - 1 - 6 month schedule from 1 January 1997 to 31 August 1999. The newborns were to be vaccinated with the first dose within 24 hours after they were born. 1906 serum samples were selected in April 2000 to detect the hepatitis B infection markers, including HBsAg, HBsAb and HbcAb by RIA kits. RESULTS: 2 783 of the 2 969 newborns (93.74%) were vaccinated with three doses, 2 833 of them (95.42%) were vaccinated with the first dose within 24 hours after they were born. The anti-HBs positive rate was 98.25% (S/N >/= 2.1) or 94.26% (S/N >/= 10.0), and the geometric mean titer (GMT) value of antibody was 77.64 within the first year after the whole course vaccination. Then the antibody level decreased gradually with the lapse of time. The HBsAb positive rate was 92.31% (S/N >/= 2.1) or 68.96% (S/N >/= 10.0), and GMT value was 22.86 within the third year after vaccination. The HBsAg positive rates remained less than 1%, the HBcAb positive rates and HBV infection rates remained 1% approximately 3% within 3 years after vaccination. CONCLUSION: The protective efficacy of China-made recombinant hepatitis B vaccine is satisfactory.

A 12-year cohort study on the efficacy of plasma-derived hepatitis B vaccine in rural newborns.

AIM:To understand the anti HBs persistence and the long-term preventive efficacy in rural newborns after vaccination with plasma-derived hepatitis B vaccine.METHODS:In the time of expanded program on immunization (EPI), the newborns were vaccinated with 10&mgr;gcenter dot3 doses of hepatitis B vaccine and 762 newborns who were HBsAg negative after primary immunization were selected for cohort observation from 1986 to 1998. Their serum samples were detected qualitatively and quantitatively for hepatitis B infecting markers, including HBsAg, anti-HBs and anti-HBc by SPRIA Kits. The annual HBsAg positive conversion rate was counted by life-table method.RESULTS:(1)The anti-HBs positive rate was 94.44% for the babies born to HBsAg negative mothers and 84.21% for those born to HBsAg positive mothers in the 1st year after immunization, and dropped to 51.31% and 52.50% in the 12th year respectively.GMT value was dropped from 31.62 to 3.13 and 23.99 to 3.65 in the 2nd to the 12th year respectively. There was a marked drop in GMT at the 3rd to the 5th year, and in anti HBs positive rate at the 9th to the 10th year. (2) In the period of 12 years observation, the person-year HBsAg positive conversion rates were 0.12% (5/4150.0) in newborns born to HBsAg negative mothers and 0.20% (1/508.0) in those born to HBsAg positive mothers, and none of the HBsAg positive converted children became HBsAg chronic carriers. Compared with the baseline before immunization, the protective rates were 97.19% and 95.32% respectively.CONCLUSION:The protective efficacy of plasma-derived hepatitis B vaccine persisted at least 12 years, and a booster dose seems not necessary within at least 12 years after the primary three-doses immunization to newborns born to HBsAg negative mothers.