Complete genome sequence of a novel lytic phage of Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen in rice.

Bacteriophage L522, which infects Xanthomonas oryzae pv. oryzae, was isolated from a paddy leaf sample collected in Long An province, Vietnam. The phage shows myovirus morphology based on transmission electron microscopy. It displays a latent period and burst size of approximately 3 h and 63 new virions per infected cell (PFU/infected cell), respectively. The genome of L522 is 44,497 bp in length, with 52% GC content. Of the 63 genes identified, functions were predicted for 26. No virulence or antibiotic-resistance genes were detected. The results of a BLASTn search showed similarity to a previously reported Xanthomonas phage, with 85% average nucleotide sequence identity and 87.15% query coverage. Thus, this L522 is a representative of a new species in the genus Xipdecavirus.

Effectiveness of China-PAR and Framingham risk score in assessment of 10-year cardiovascular disease risk in Chinese hypertensive patients.

OBJECTIVES: Estimating the total risk of cardiovascular disease (CVD) using risk prediction models represents a huge improvement in identifying and treating each of the risk factors. The objective of this study was to evaluate the effectiveness of the China-PAR (Prediction of atherosclerotic CVD risk in China) and Framingham risk score (FRS) in predicting the 10-year risk of CVD in Chinese hypertensive patients. The results of the study can be used to design health promotion strategies. STUDY DESIGN: A large cohort study was used to assess the validity of models by comparing model predictions with actual incidence rates. METHODS: In total, 10,498 hypertensive patients aged 30-70 years in Jiangsu Province, China, participated in the baseline survey that took place between January and December 2010 and were followed up to May 2020. China-PAR and FRS were used to calculate the predicted 10-year risk of CVD. The 10-year observed incidence of new cardiovascular events was adjusted by the Kaplan-Meier method. The ratio of the predicted risk to the actual incidence was calculated to evaluate the effectiveness of the model. The discrimination Harrell's C statistics and calibration Chi-square value were used to evaluate the predictive reliability of the models. RESULTS: Of the 10,498 participants, 4411 (42.02%) were male. During the mean follow-up of 8.30 ± 1.45 years, a total of 693 new cardiovascular events occurred. Both models overestimated the risk of morbidity to varying degrees, and the FRS overestimated to a greater extent. After adjustment for covariates, the results of Cox proportional hazards regression showed that the risk of CVD in the high-risk group was higher than in low-risk group. The degree of discrimination in both models was approximately 0.6, which showed that discrimination was not ideal in the models. In addition, Chi-square calibrations of the two models were <20 in males, which showed that calibration of the models was better for men than women. CONCLUSIONS: The China-PAR and FRS models overestimated the risk of CVD for participants in this study. In addition, the degree of discrimination was not ideal, and both models performed better in males than in females in terms of calibration. The results of this study suggest that a more suitable risk prediction model should be established according to the characteristics of the hypertensive population in Jiangsu Province.

Biological Characterization and Genomic Analysis of Novel Phages DLDT_So2 and BHDT_So9 Against Pseudomonas solanacearum, an Infectious Agent in Tomato in Vietnam.

Tomato (Solanum lycopersicum L.) is an important grown vegetable in Vietnam. Bacterial wilt caused by Pseudomonas solanacearum has been considered to be an important disease resulting in a harvest loss up to 90% and significant economic loss to farmers. In this study, two bacteriophages DLDT_So2 and BHDT_So9 specific to P. solanacearum were isolated. Morphological analysis indicated that DLDT_So2 and BHDT_So9 had podovirus morphology and were classified into Autographiviridae family. The latent period and burst size of DLDT_So2 was found to be approximately 120 min and 20.0 ± 2.4 virions per infected cell. Meanwhile, the latent period of BHDT_So9 was 140 min with a burst size of 11.5 ± 2.8 virions per infected cell. Of the 23 bacterial strains tested, the phages infected 7/11 strains of P. solanacearum and none of the other bacteria tested were susceptible to the phages. Stability of the phages at different temperatures, pHs, solvents was also investigated. The genomes of DLDT_So2 and BHDT_So9 are 41,341 bp and 41,296 bp and long with a total GC content of 63%, contains 48 and 46 predicted protein-encoding CDSs. No virulence or antibiotic resistance genes were found in the genomes, suggesting they would be useful biocontrol agents against P. solanacearum. Classification of the phage using average nucleotide identity, phylogenetic analysis was also carried out. The two phages represented new species when they had overall average nucleotide identity of < 95%. This is first report of the isolation and characterization of P. solanacearum-specific phages from tomato farms in Vietnam. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01090-9.

Single-cell RNA-seq analysis identifies unique chondrocyte subsets and reveals involvement of ferroptosis in human intervertebral disc degeneration.

OBJECTIVE: Nucleus pulposus (NP) plays a central role in disc degeneration pathogenesis, however, as a heterogeneous tissue, cell subsets in NP and their corresponding biological process in intervertebral disc degeneration (IVDD) are unreported. METHOD: Nucleus pulposus were isolated from normal control and IVDD, and then subjected to single-cell RNA sequencing (scRNA-seq). Unsupervised clustering of the cells based on the gene expression profiles using the Seurat package and passed to tSNE for clustering visualization. Rat model of disc degeneration was built to validate the pathways identified by scRNA-Seq. RESULTS: Seven chondrocyte subsets were revealed in NP based on differential gene expression, among which 4 subsets (C1-C4) were reported for the first time. Furthermore, GO and KEGG analyses discovered that ferroptosis pathways were enriched. Rat model of disc degeneration was built (n = 6/group, control vs. model) to validate the pathways identified by scRNA-Seq. Iron levels of NP were significantly higher in model group than control group (means 0.712 vs. 0.248, respectively, mg/gpro, p = 0.0026), and the levels of Heme Oxygenase 1 (HO-1) were also elevated in model group (means 14.33 vs. 5.16 IOD, respectively, p = 0.0002). However, the levels of ferritin light chain (FTL) were significantly decreased in model group compared to control group (means 26.17 vs. 9.00 FTL+ cell number, respectively, p = 0.0011). CONCLUSIONS: Novel chondrocyte subsets in nucleus pulposus were discovered through scRNA-Seq, which provided novel insight to understand the pathological change during the development of IVDD. Ferroptosis participated in disc degeneration pathogenesis and it might serve as a new target for intervening IVDD.

[Current situation of screening, prevention and treatment of bleeding esophageal varices in cirrhotic portal hypertension in Tibet region: a multicenter study].

Objective: To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region. Methods: Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively. Results: 511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective ß-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment. Conclusion: Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

SCD1 methylation in subcutaneous adipose tissue associated with menopausal age.

Objective: This study was designed to investigate associations between menopausal age and the DNA methylation levels of stearoyl-coenzyme A desaturase 1 (SCD1, selected by the Illumina Human Methylation 450 K Bead Chip) and explore the changes in mRNA levels of SCD1 and DNA methyltransferases (DNMTs) in response to estrogen replacement therapy (ERT). Methods: In the human experiment, we performed subcutaneous adipose tissue DNA extraction on 85 menopausal women. Methylation of SCD1 was measured by MethyLight polymerase chain reaction. In the rat experiment, we established models of menopause (ovariectomy group) and ERT (ovariectomy + 17ß-estradiol group). The mRNA levels of SCD1, DNMT1, DNMT3A, and DNMT3B were determined. Results: The results showed that DNA methylation of SCD1 was inversely correlated with menopausal age (r = 0.370, P < 0.001). In the rat study, the mRNA levels of SCD1 decreased (P < 0.001) and those of DNMT3A (P < 0.001) and DNMT3B increased (P < 0.001) after ERT. Conclusion: Methylation levels of SCD1 were significantly associated with menopausal age. DNMT3A and DNMT3B may be involved in the methylation of SCD1.

Comparison of the performance of mental health, drug and alcohol comorbidities based on ICD-10-AM and medical records for predicting 12-month outcomes in trauma patients.

BACKGROUND: Many outcome studies capture the presence of mental health, drug and alcohol comorbidities from administrative datasets and medical records. How these sources compare as predictors of patient outcomes has not been determined. The purpose of the present study was to compare mental health, drug and alcohol comorbidities based on ICD-10-AM coding and medical record documentation for predicting longer-term outcomes in injured patients. METHODS: A random sample of patients (n = 500) captured by the Victorian State Trauma Registry was selected for the study. Retrospective medical record reviews were conducted to collect data about documented mental health, drug and alcohol comorbidities while ICD-10-AM codes were obtained from routinely collected hospital data. Outcomes at 12-months post-injury were the Glasgow Outcome Scale - Extended (GOS-E), European Quality of Life Five Dimensions (EQ-5D-3L), and return to work. Linear and logistic regression models, adjusted for age and gender, using medical record derived comorbidity and ICD-10-AM were compared using measures of calibration (Hosmer-Lemeshow statistic) and discrimination (C-statistic and R2). RESULTS: There was no demonstrable difference in predictive performance between the medical record and ICD-10-AM models for predicting the GOS-E, EQ-5D-3L utility sore and EQ-5D-3L mobility, self-care, usual activities and pain/discomfort items. The area under the receiver operating characteristic (AUC) for models using medical record derived comorbidity (AUC 0.68, 95% CI: 0.63, 0.73) was higher than the model using ICD-10-AM data (AUC 0.62, 95% CI: 0.57, 0.67) for predicting the EQ-5D-3L anxiety/depression item. The discrimination of the model for predicting return to work was higher with inclusion of the medical record data (AUC 0.69, 95% CI: 0.63, 0.76) than the ICD-10-AM data (AUC 0.59, 95% CL: 0.52, 0.65). CONCLUSIONS: Mental health, drug and alcohol comorbidity information derived from medical record review was not clearly superior for predicting the majority of the outcomes assessed when compared to ICD-10-AM. While information available in medical records may be more comprehensive than in the ICD-10-AM, there appears to be little difference in the discriminative capacity of comorbidities coded in the two sources.

The prevalence of pre-existing mental health, drug and alcohol conditions in major trauma patients.

Objective Capturing information about mental health, drug and alcohol conditions in injury datasets is important for improving understanding of injury risk and outcome. This study describes the prevalence of pre-existing mental health, drug and alcohol conditions in major trauma patients based on routine discharge data coding. Methods Data were extracted from the population-based Victorian State Trauma Registry (July 2005 to June 2013, n=16096). Results Seventeen percent of major trauma patients had at least one mental health condition compared with the Australian population prevalence of 21%. The prevalence of mental health conditions was similar to the Australian population prevalence in men (19% v. 18%), but lower in women (14% v. 25%) and across all age groups. Mental health conditions were more prevalent in intentional self-harm cases (56.3%) compared with unintentional (13.8%) or other intentional (31.2%) cases. Substance use disorders were more prevalent in major trauma patients than the general population (15% v. 5%), higher in men than women (17% v. 10%) and was highest in young people aged 25-34 years (24%). Conclusions Under-reporting of mental health conditions in hospital discharge data appears likely, reducing the capacity to characterise the injury population. Further validation is needed. What is known about the topic? Medical record review, routine hospital discharge data and self-report have been used by studies previously to characterise mental health, drug and alcohol conditions in injured populations, with medical record review considered the most accurate and reliance on self-report measures being considered at risk of recall bias. The use of routinely collected data sources provides an efficient and standardised method of characterising pre-existing conditions, but may underestimate the true prevalence of conditions. What does this paper add? No study to date has explored the prevalence of Abbreviated Injury Scale and International Classification of Diseases and Health Related Problems, Tenth Revision, Australian Modification (ICD-10-a.m)-coded mental health, alcohol and drug conditions in seriously injured populations. The results of this study show the incidence of mental health conditions appeared to be under-reported in major trauma patients, suggesting limitations in the use of ICD-10-a.m. to measure mental health comorbidities. What are the implications for practitioners? In order to achieve improvements in measuring mental health, drug and alcohol comorbidities, we suggest the use of a series of different diagnostic systems to be used in conjunction with ICD-10-a.m., such as medical record review and self-reporting as well as linkage to other datasets. When applied simultaneously, diagnosis and outcomes of mental health may be compared and validated across diagnostic systems and deviations in diagnoses could be more readily accounted for.

Blockade of Interleukin-17 Restrains the Development of Acute Lung Injury.

The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Here, we explored the association between IL-17 and development of ALI using LPS-induced murine model. We found that IL-17 level was elevated in bronchoalveolar lavage (BAL) fluid of ALI mice. Upregulation of IL-17 resulted in increased severity of ALI as evidenced by decreased body weight and survival rate, elevated level of total protein and albumin in BAL fluid, as well as more apparent histopathology changes of lung. Induction of ALI was impaired in IL-17-deficient mice. Management of IL-17 could modulate LPS-induced pulmonary inflammation, as reflected by the total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in BAL fluid. Of note, blockade of IL-17 effectively inhibited the lung inflammation and alleviated ALI severity. Finally, we confirmed the clinical relevance and found that IL-17 expression was elevated and associated with the disease severity in patients with ARDS. In essence, IL-17 was crucial for development of ALI, suggesting a potential application for IL-17-based therapy in clinical practice.

Detection of disseminated tumor cells in aspirative drains after neck dissection.

The dissemination of individual tumor cells is a common phenomenon in solid cancers. Detection of tumor cells in bone marrow disseminated tumor cells (DTC) and in peripheral blood circulating tumor cells (CTC) in nonmetastatic situation is of high prognostic significance. Compared to breast, colon and prostate cancers, the studies on CTC and DTC in head and neck cancers are sparse. The objective of our study was to detect DTC in drains after neck dissection. Fourteen patients undergoing surgery for stages III and IV head and neck cancers were enrolled in this study--twelve presenting with squamous cell carcinoma and two with adenocarcinoma. Redon drain analysis was performed by the Cellsearch method using immunomagnetic and fluorescence approaches. A positivity threshold value was set at 2DTC/7.5 ml of the sample. Tumor cells were detected in drains of 69 % of patients a few days after surgery. The range of quantification was 3-2,094 DTC/5 ml and we showed morphological differences between the two types of carcinoma cells. DTC were detected after neck dissection both in squamous cell carcinoma and in adenocarcinoma. Potential clinical significance of tumor cells needs to be further investigated as their presence could affect pre-surgical and post-operative treatments.

[Clinical comparison of modified laparoscopic and conventional placement of peritoneal dialysis catheters].

Objective: To explore the clinical efficacy of the modified laparoscopic placement of peritoneal dialysis catheters by nephrologists. Methods: A total of 188 patients diagnosed as end-stage renal disease (ESRD) were enrolled, who received catheter and continuous ambulatory peritoneal dialysis (CAPD) therapy from January 2011 to May 2016 in Zhejiang Provincial People's Hospital. They were divided into group A (with modified laparoscopic placement of peritoneal dialysis catheters, n=59) and group B (with conventional placement of peritoneal dialysis catheter, n=129). The demographic and clinical characteristics, past abdominal operation history, surgery time, hospital stay after operation, expenses for surgery and hospitalization, early and late complications including bleeding, pain, leakage, peritonitis and catheter displacement were observed. Results: Patients with previous abdominal surgery accounted for 11.9% in group A and 0 in group B(χ2=15.897, P<0.001). The duration of the operation was (38.9±12.8)min in group A and (64.1±12.7)min in group B(t=-6.466 6, P=0.000 0). The cost of the operation was (5 488.4±156.1) yuan in group A and (1 602.7±48.92) yuan in group B (t=257.129, P=0.000 0). Catheter displacement within one month was observed in 0 and 11.6%(χ2=7.455 3, P=0.003), pain in 15.3% and 41.9% (χ2=12.862 2, P=0.000), and catheter displacement after one month in 0 and in 16.3% (χ2=10.812 4, P=0.000) of the patients, respectively in group A and group B. The incidences of peritonitis within one month and beyond one month, leakage, bleeding and so on showed no difference between the two groups(P>0.05). Conclusions: Placement of PD catheter with laparoscope is suitable for renal failure patients with abdominal operation history and replacement PD catheter. It also has the advantages of shorter surgery time, less pain and lower incidences of catheter displacement, expanding the application of PD. However, bleeding, leakage, hernia and other complications are frequently seen.

CARD11 blockade suppresses murine collagen-induced arthritis via inhibiting CARD11/Bcl10 assembly and T helper type 17 response.

The scaffold protein caspase recruitment domain-containing protein 11 (CARD11) is implicated in the regulation of inflammation and autoimmunity. The present study aimed to explore the role of CARD11 in the pathogenesis of rheumatoid arthritis (RA). Mice with collagen-induced arthritis (CIA) were treated with either CARD11-targeted interfering RNA (CARD11 siRNA) or control siRNA by intraperitoneal injection every 3 days after CIA establishment. The clinical score of arthritis was recorded every other day. Synovial inflammation and cartilage erosion were evaluated by histology and microcomputed tomography (micro-CT). Serum anti-type II collagen (anti-CII) antibodies and cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The CARD11/Bcl10 formation and nuclear factor-kappa B (NF-κB) activation was assessed by immunoprecipitation and immunoblotting, and the percentage of T helper type 17 (Th17) cells was determined by flow cytometry. Systemic administration of CARD11 siRNA significantly reduced the clinical score of CIA severity. As indicated by the histology, joint inflammation and destruction were attenuated by CARD11 siRNA treatment. Micro-CT demonstrated less severe joint destruction in CARD11 siRNA-treated mice than in control mice. CARD11 siRNA treatment resulted in inhibition of CARD11/Bcl10 formation and the subsequent NF-κB activation. In addition, treatment with CARD11 siRNA resulted in a pronounced decrease in proinflammatory cytokines interleukin (IL)-1ß, IL-6 and IL-17. Serum anti-CII antibody and the percentage of Th17 cells were also significantly reduced. CARD11 is involved in the pathogenesis of CIA by formation of the CARD11/Bcl10 complex and enhancement of the Th17 cell response. Targeting CARD11 provides a novel research direction in the development of therapeutic strategies for RA.

Transcription factor and bone marrow stromal cells in osseointegration of dental implants.

Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs) with forced expression of special AT-rich sequence-binding protein 2 (SATB2) on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2) and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twenty-one days after implantation, the femora were isolated for immunohistochemical (IHC) staining, haematoxylin eosin (H&E) staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and micro-computed tomography (µCT) analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2-overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. µCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks post-operatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.

Diverse Bacteriophages Infecting the Bacterial Striped Catfish Pathogen Edwardsiella ictaluri.

Bacteriophages infecting Edwardsiella ictaluri have been less investigated, although the host bacterium is one of the most important fish pathogens causing enteric septicemia of catfish (ESC). We present here two distinctly novel bacteriophages vB_EiM_PVN06 and vB_EiA_PVN09 infecting Edwardsiella ictaluri E1, with their geographical origins from the Mekong Delta, Vietnam. Bacteriophage vB_EiM_PVN06 native to a mud sample reveals complete differences of biological properties with the phage vB_EiA_PVN09 originated from a viscus of a healthy catfish (Pangasianodon hypophthalmus) cultured in the same area. Morphological analyses combined with genomic data indicate that phage vB_EiM_PVN06 is classified to Myoviridae family and shares high similarity with E. ictaluri phage PEi21 genome, while vB_EiA_PVN09 is a member of Teseptimavirus genus, Autographiviridae family, and mostly closes to phage vB_EcoP_IME390. The vB_EiA_PVN09 is a T7-like bacteriophage, which has been firstly found infecting to E. ictaluri, and host range analysis also evidences for the cross-infection of this phage to Escherichia coli K12 and Escherichia coli DH5α. Together, our research highlights the diversity of bacteriophages infecting the pathogen E. ictaluri and suggests further explorations of lytic phages in environmental niches, to be exploited in feasible strategies of phage therapy in ESC disease control.

Effects of blood glucose fluctuation on skin biophysical properties, structure and antioxidant status in an animal model.

BACKGROUND: Intermittent blood-glucose fluctuation (BGF) can accelerate diabetes and its complications, but it is still unknown whether BGF can damage the skin of patients with diabetes. AIM: To investigate the effects of repetitive fluctuation in blood glucose concentration on the biophysical properties, structure and antioxidant capacity of diabetic mouse skin. METHODS: Mice with alloxan-induced diabetes were injected with glucose three times daily to induce repetitive BGF. Six weeks later, skin elasticity and skin hydration were measured to evaluate skin water-holding capacity and contraction function. The histological changes of skin were also studied, using haematoxylin and eosin. In addition, we compared levels of blood sugar and advanced glycation end products (AGEs), the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) and hydroxyproline in the skin of normal mice and diabetic mice with or without BGF. RESULTS: The diabetic mice with BGF displayed an 18.6% increase in blood sugar level, an 11.3% increase in AGEs content and a 13.1% increase in MDA content compared with the diabetic mice (P < 0.01). There was a greater reduction in skin elasticity, skin hydration, hydroxyproline content and SOD activity in the diabetic mice with BGF (P < 0.01). Histological examination showed that BGF enhanced skin lesions in diabetic mice. CONCLUSIONS: Repetitive fluctuation in blood-glucose concentration produced a marked detrimental effect on skin structure and function in diabetic mice. The deleterious effects of BGF on skin appeared to due at least partly to the oxidative stress.

Effects of dl-praeruptorin A on cultured neonatal rat ventricular cardiomyocytes with hypertrophy induced by endothelin-1.

The present study investigated whether dl-praeruptorin (Pd-Ia) prevents endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and the potential pathways that underlie such an effect. We assessed cardiomyocyte surface area, protein synthesis, the expression of Bax/Bcl2 and Jun genes, the expression of atrial natriuretic factor (ANF) and Ca2+/calmodulin-dependent kinase II (CaMK-II) activity in cultured neonatal rat ventricular cardiomyocytes with ET-1-induced hypertrophy. It was found that Pd-Ia decreased the surface area and protein synthesis rate in cardiomyocytes exposed to ET-1. Additionally, the expression of Bcl2 and Bax was increased in both the ET-1-exposed and Pd-Ia+ET- 1-treated groups compared with the control group, although this was not significant. In cardiomyocytes incubated with ET-1, the expression of ANF (Nppa) significantly increased relative to the control and Pd-Ia groups. The expression of Jun significantly increased in cardiomyocytes incubated with ET-1, but not in the Pd-Ia group, where Jun levels were similar to those found for the control group. Moreover, it was found that Pd-Ia inhibited the ET-1-induced increase in intracellular Ca(2+) concentration. The results showed that Pd-Ia could conceivably be an effective therapeutic drug for treating the contractile defects associated with cardiac hypertrophy and failure. This activity may be associated with its Ca2+-antagonist effect and modulation of the expression of immediate-early genes that play important roles in the mitogen-activated protein (MAP) kinase pathway.

An Adiponectin Receptor Agonist Reduces Type 2 Diabetic Periodontitis.

Periodontitis is twice as prevalent in diabetics as in nondiabetics, and type 2 diabetes (T2D)-associated periodontitis is severe in many cases due to the altered and aberrant functions of bone cells in hyperglycemic conditions. Therefore, developing an effective method to halt the disease process, as well as restore and regenerate lost alveolar bone to reserve the natural teeth in diabetics, is critically important. In the current study, we applied a newly discovered adiponectin receptor agonist AdipoRon (APR) in experimental periodontitis in diabetic animal models and demonstrated the underlying molecular mechanisms. We found that when APR systemically quenched the blood sugar level in diet-induced obesity (DIO) diabetic mice, it reduced osteoclast numbers and alveolar bone loss significantly due to APR's inhibition on osteoclast differentiation shown in our in vitro studies. APR also decreased the production of proinflammatory molecules CC chemokine ligand 2 and interleukin 6 in diseased gingival tissues. On the other hand, APR promoted alveolar bone regeneration through enhancing osteogenic differentiation and decreasing stromal cell-derived factor 1 in the bone marrow that facilitates stem cell migration. Same results were achieved by APR treatment of periodontitis induced in adiponectin (APN) knockout mice, indicating the ability of APR to activate the endogenous APN receptors to exert osteoanabolic effects. In summary, our study supports the notion that APR could be used as an effective multipronged approach to target T2D-associated periodontitis.

Level of agreement between medical record and ICD-10-AM coding of mental health, alcohol and drug conditions in trauma patients.

BACKGROUND: Despite the reliance on administrative data in epidemiological studies, there is little information on the completeness of co-morbidities in administrative data coded from medical records. OBJECTIVE: The aim of this study was to quantify the agreement between the International Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) administrative coding of mental health, drug and alcohol co-morbidities and medical records in a severely injured patient population. METHOD: A random sample of patients (n = 500) captured by the Victorian State Trauma Registry and definitively managed at the state's adult major trauma services was selected for the study. Retrospective medical record review was conducted to collect data about documented co-morbidities. The agreement between ICD-10-AM data generated from routine hospital coding and medical record-based co-morbidities was determined using Cohen's κ and prevalence-adjusted bias-adjusted kappa (PABAK) statistics. RESULTS: The percentage of agreement between the medical record and ICD-10-AM coding for mental health, drug and alcohol co-morbidities was 72.8%, and the PABAK showed moderate agreement (PABAK = 0.46; 95% confidence interval (CI): 0.37, 0.54). There was no difference in agreement between unintentional injury patients (PABAK = 0.52; 95% CI: 0.42, 0.62) compared with intentional injury patients (PABAK = 0.36, 95% CI: 0.23, 0.49), and no change in agreement for patients admitted before (PABAK = 0.40; 95% CI: 0.30, 0.50) and after the introduction of mandatory co-morbidity coding (PABAK = 0.46; 95% CI: 0.37, 0.54). CONCLUSION: Despite documentation in the medical record, a large proportion of mental health, drug and alcohol conditions were not coded in ICD-10-AM. Acknowledgement of these limitations is needed when using ICD-10-AM coded co-morbidities in research studies and health policy development. IMPLICATIONS: This work has implications for researchers of drug and alcohol abuse; mental health; accidents and injuries; workers' compensation; health workforce; health services; and policy decisions for healthcare, emergency services, insurance industry, national productivity and welfare costings reliant on those research outcomes.