[A comparative study of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of primary hyperaldosteronism on left side].

Objective: To compare the therapeutic effect of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of left-sided primary hyperaldosteronism. Methods: From January 2017 to July 2019, the clinical data of 70 patients with left-sided primary hyperaldosteronism (PHA) who underwent surgery in the First Hospital of Lanzhou University and five other hospitals in Gansu Province were retrospectively analyzed. There are 43 male and 27 female patients. Among them,28 patients were performed transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy and 42 patients were performed transperitoneal paracolic sulci approach laparoscopic adrenal tumorectomy. The general information and perioperative data of the two groups were compared. Results: All 70 cases of surgery were successfully completed. As compared with the paracolic sulci approach group, the operation time was significantly shorter in the transmesenteric approach group[(26.7±8.8)vs (38.9±7.1)min,P<0.001)], and the estimated blood loss was less in the transmesenteric approach group[45(30,50) vs 50(40,60)ml,P=0.042]. There was no statistically significant difference in the postoperative hospitalization days between the two groups[(4.4±1.0)vs(4.5±1.0)d, P=0.669)]. The electrolytes and aldosterone to renin ratio returned to a healthy level in the postoperative one month, and the blood pressure also returned to a healthy level in 53 (75.7%) patients. Conclusion: Transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy is safe and feasible, with a short operation time and relatively less estimated blood loss.

Construct validity of the Menopause Rating Scale in Indonesia.

Objective: This study assessed the construct validity of the Menopause Rating Scale (MRS) in Indonesia. Methods: The study included 240 women aged over 45 years in Indonesia. The MRS measures psychological, somatic-vegetative, and urogenital symptoms using 11 items obtained from participants' daily symptom records. The intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were measured to examine the test-retest reliability and internal consistency reliability. The test-retest reliability was evaluated by an extra 30 participants twice at 2-week intervals. For construct validity, exploratory factor analysis (EFA) was employed to assess factor structure and confirmatory factor analysis (CFA) was used to evaluate the structural model fit of the MRS. Results: The ICC for the test-retest reliability ranged between 0.90 and 0.95. The Cronbach alpha coefficients in the somatic-vegetative, psychological, and urogenital dimensions were 0.92, 0.93, and 0.95, respectively. The Kaiser-Meyer-Olkin value was 0.96, and the Bartlett's test of sphericity was statistically significant and adequate for EFA. CFA was tested using the second-order model with three first-order factors and yielded an excellent model fit. Conclusion: Results indicated that the brief questionnaire of the MRS possesses acceptable construct validity for evaluating menopause symptoms in Indonesian women.

Identifying characteristics of an effective fracture liaison service: systematic literature review.

Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.

Modulation of periodontitis progression using pH-responsive nanosphere encapsulating metronidazole or N-phenacylthialzolium bromide.

BACKGROUND AND OBJECTIVE: This study aimed to develop pH-responsive polylactide-glycolic acid co-polymer and chitosan (PLGA/chitosan) nanosphere as an inflammation-responsive vehicle and evaluate the potential of the nanosphere encapsulating metronidazole, an antibiotic, and N-phenacylthiazolium bromide (PTB), a host modulator, for treating periodontitis. MATERIAL AND METHODS: PLGA/chitosan nanospheres were fabricated using oil-in-water emulsion method. Experimental periodontitis was induced on the rat maxillae, and the sites were randomly allocated to four treatment categories, including periodontitis alone (PR), periodontitis with nanospheres alone, nanospheres encapsulating metronidazole (MT) and nanospheres encapsulating PTB (PB). The ligature was retained until the animals were killed, and the treatment outcome was evaluated by the progression of periodontal bone loss (PPBL), inflammatory cell infiltration and collagen deposition. RESULTS: The encapsulated drug was released rapidly from the nanospheres without significant initial burst release at pH 5.5. Compared with group PR, PPBL was significantly reduced in groups MT and PB on day 4 (P<.05). On day 21, PPBL was significantly lower in group PB (P<.05). In groups MT and PB, inflammation was significantly reduced in groups MT and PB relative to groups PR and periodontitis with nanospheres alone (P<.05), and collagen deposition was significantly greater relative to group PR (P<.05). CONCLUSION: PLGA/chitosan nanospheres encapsulating metronidazole or PTB showed potential for modulating periodontitis progression.

The potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy: A preliminary assessment.

BACKGROUND AND OBJECTIVE: The response to nonsurgical periodontal treatment varied among patients. This study assessed the potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy. MATERIAL AND METHODS: This study recruited 34 participants with severe chronic periodontitis (the test group) and 20 participants without periodontal destruction in any teeth (the control group) from September 6, 2013 to August 25, 2017. Participants in the test group received nonsurgical periodontal therapy and were further divided into 2 subgroups of 17 low responders and 17 high responders, based on probing depth reduction. Clinical periodontal parameters were recorded, and saliva samples were harvested before and after nonsurgical periodontal therapy. Salivary biomarkers, including interleukin (IL)-1beta (IL-1ß), IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, platelet-derived growth factor-BB, vascular endothelial growth factor, MMP-8, MMP-9, C-reactive protein, and lactoferrin were analyzed. RESULTS: Compared with participants in the control group, participants in the test group had significantly greater periodontal pocket depth, clinical attachment level, and salivary IL-1ß and MMP-8 levels, and all of these parameters were significantly reduced after nonsurgical periodontal therapy. The pretreatment levels of IL-1ß, MMP-8, and lactoferrin were significantly higher in participants of the high-responder subgroup than participants of the low-responder subgroup.Based on the analysis from a dichotomous table, MMP-8 and lactoferrin showed odds ratios of 5.76, with 71% sensitivity and 71% specificity, and statistical significance (P = .02) for discriminating between the high- and low-responder subgroups. CONCLUSION: Salivary IL-1ß and MMP-8 might be useful for diagnosing periodontitis and monitoring the recovery of periodontitis following nonsurgical periodontal therapy. MMP-8 and lactoferrin showed potential for predicting the sensitivity to the treatment.

Construction of an infectious plasmid clone of Muscovy duck parvovirus by TA cloning and creation of a partially attenuated strain.

Muscovy duck parvovirus (MDPV) infection is a highly contagious and fatal disease of Muscovy ducklings. The infectious clone methodology is a valuable tool to study the pathogenic mechanisms of viruses, but no infectious clone of MDPV is yet available. In this study, a plasmid clone containing the full-length genome of MDPV was constructed using the TA cloning methodology. This MDPV clone was found to be infectious after transfection of primary Muscovy duck embryo fibroblast cells and passage in embryonated Muscovy duck eggs. Site-directed mutagenesis showed that the K75N mutation in the VP1 protein of MDPV resulted in the partial attenuation of the virus. The availability of an MDPV infectious clone can facilitate investigation of the pathogenic mechanisms of MDPV and development of vaccines against diseases caused by MDPV.

Identification and functional analysis of the cytolethal distending toxin gene from Avibacterium paragallinarum.

Avibacterium paragallinarum is the causative agent of infectious coryza, an important respiratory disease of chickens. Cytolethal distending toxins (CDTs) are a family of protein cytotoxins that cause cell cycle arrest and apoptosis in eukaryotic cells. Whole-genome sequencing analysis showed that Av. paragallinarum contains cdtABC genes. Filter-sterilized lysates prepared from Av. paragallinarum or from recombinant Escherichia coli expressing cdtABC genes exhibited CDT activity on HeLa cells and chicken embryo fibroblast (DF-1) cells. In vitro DNase assays showed that purified recombinant CdtB has DNase activity. Polymerase chain reaction and sequencing analysis revealed that the cdtABC genes are present in all strains of Av. paragallinarum examined in this study. This is the first report of the identification and functional analysis of cdtABC genes from Av. paragallinarum. The gene products of cdtABC genes may be involved in the pathogenesis of the disease caused by Av. paragallinarum.

Irradiation by light-emitting diode light as an adjunct to facilitate healing of experimental periodontitis in vivo.

BACKGROUND AND OBJECTIVE: This study evaluated the biostimulatory effect of 660 nm light-emitting diode (LED) as an adjunct in the treatment of experimental periodontitis. MATERIAL AND METHODS: Ninety-six Sprague-Dawley rats underwent experimental periodontitis by placement of a silk ligature followed with or without additive Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) injection. Irradiation with LED light was performed at varying energy densities of 5, 10 and 15 J/cm2, 1 d after debridement and detoxification. Rats were killed at 3, 7 and 14 d after irradiation with LED light, and the effect of irradiation was evaluated by descriptive histology and quantitative measurements of periodontal bone loss, inflammatory infiltration and cellular proliferation. RESULTS: Reduction of inflammation, accelerated collagen deposition and realignment was noted following irradiation with LED light at densities of 10 and 15 J/cm2, and temporary reduction of periodontal bone loss, as well as bundle bone apposition, was noted at day 3 in rats treated with 10 J/cm2 light. The biomodulatory effect was stronger in sites treated with Pg-LPS injection. In sites without Pg-LPS injection, temporary reduction of inflammation was noted in all LED light-irradiated specimens at day 3. No significant change in cellular proliferation was noted in any LED light-treated group. CONCLUSIONS: LED light (660 nm) with an energy density of 10 J/cm2 appeared suitable as an adjunct modality for periodontitis by temporarily reducing inflammation, facilitating collagen realignment and bundle bone deposition. Future studies will aim to amplify the biostimulatory effect of LED light by adding a supplementary medium or repeated irradiation.

Glycated matrix up-regulates inflammatory signaling similarly to Porphyromonas gingivalis lipopolysaccharide.

BACKGROUND AND OBJECTIVE: Hyperglycemia and advanced glycation end-products (AGEs) have been hypothesized as the etiologic factors of diabetic periodontitis. The aim of this study was to clarify in greater detail the patterns of AGE-mediated periodontal inflammation under various physiological conditions. MATERIAL AND METHODS: The deposition of AGEs and expression of the receptor for AGEs (RAGE) were identified by immunohistochemistry in Sprague-Dawley rats with experimentally induced periodontitis or diabetes. Human periodontal ligament cells (PDLCs) and mesenchymal stem cells (MSCs) were cultured under simulated conditions of hyperglycemia, Porphyromonas gingivalis lipopolysaccharide (LPS) stimulation and matrix glycation. Cell viability and expression of toll-like receptors (TLRs), Rage, an inflammatory signaling initiator (nuclear factor kappa light chain enhancer of activator ß cells), an oxidative stressor (heme oxygenase-1) and collagen synthesis (type I and type IV) genes were evaluated. RESULTS: The deposition of AGEs and the expression of Rage were evident in the inflamed periodontal tissues in all rats and appeared to be enhanced in rats with diabetes. Matrix glycation augmented cytotoxicity, up-regulated RAGE and TLRs in both PDLCs and MSCs, and significantly activated downstream inflammatory signaling in MSCs. Oxidative stress was significantly increased under matrix glycation in both PDLCs and MSCs and was significantly increased at a high-glucose concentration in MSCs. A consistent decrease in expression of type I and type IV collagens was observed in MSCs, but a delayed reduction was noted in PDLCs. CONCLUSIONS: Matrix glycation modulated cell behavior to induce inflammation equivalent to that produced by incubation with P. gingivalis LPS. Periodontal inflammation also led to matrix glycation, thus demonstrating a definite interaction between diabetes and periodontitis.

Identification of the lic1ABCD operon that controls the phase-variable expression of phosphorylcholine on lipopolysaccharide from Avibacterium paragallinarum.

Phosphorylcholine (ChoP) is an important virulence factor found on the surface of many mucosal pathogens and its expression enhances bacterial colonization on mucous membranes and reduces susceptibility to antimicrobial peptides. Whole-genome sequencing analyses showed that Avibacterium paragallinarum contained an operon with strong sequence similarity to the lic1ABCD operon from Haemophilus influenzae and the pcgDABC operon from Pasteurella multocida; both operons are involved in metabolism and addition of ChoP on bacterial lipopolysaccharide (LPS). Western immunoblot analysis with ChoP-specific monoclonal antibody showed that ChoP is present on LPS of Av. paragallinarum and the expression of ChoP is controlled by phase variation mediated by the number of 5'-CAAT-3' tetranucleotide tandem repeats within the coding region of the lic1A gene. The number of tetranucleotide repeats varied widely among strains, and variation in the number of repeats was observed following in vivo passage but not in vitro passage. Antimicrobial susceptibility assays showed that ChoP expression decreased susceptibility of Av. paragallinarum to chicken antimicrobial peptide fowlicidin-1. This is the first report showing that ChoP is present on LPS from Av. paragallinarum and that Av. paragallinarum contains a phase-variable gene. These results could be valuable for understanding the mechanism of pathogenicity of Av. paragallinarum.

Regions Important for Hemagglutination Activity and Serotypes of Avibacterium paragallinarum HMTp210 Protein.

Avibacterium paragallinarum is an important respiratory pathogen of domestic chickens. Avibacterium paragallinarum has been subtyped into three serogroups and nine serovars according to the Page and revised Kume schemes. The major hemagglutinin antigen of A. paragallinarum is HMTp210, which is a large protein of about 2000 amino acids (aa), including a 70-aa signal peptide at its N-terminal end. However, the regions important for the hemagglutination (HA) activity and serotypes of HMTp210 remain unclear. In this study we constructed a series of A. paragallinarum strains expressing HMTp210 in-frame deletion mutants and determined their HA titers to identify the regions important for the HA activity and serotypes of HMTp210. Two distinct types of HA activities were found in HMTp210. The type 1 HA activity resided in the region spanning the full-length HA (aa 71-2084), whereas the type 2 resided in the region spanning aa 1003-2084. The putative ligand binding of the type 1 HA activity was located at aa 176-360, which had a structure similar to YadA of Yersinia enterocolitica. The putative ligand binding site of the type 2 HA activity was located at aa 1003-1125, which had a structure similar to UspA1 from Moraxella catarrhalis. The type 1 HA activity appeared to be Page serogroup specific, whereas type 2 appeared to be Kume serovar specific. Finally, sequence analyses of the regions spanning aa 1-400 and aa 1100-1600 of HMTp210 could be useful for the molecular serotyping (the Page and revised Kume schemes) of A. paragallinarum isolates.

Regiones importantes para la actividad de hemaglutinación y serotipos de la proteína HMTp210 de Avibacterium paragallinarum. La bacteria Avibacterium paragallinarum es un patógeno respiratorio importante de los pollos domésticos. Avibacterium paragallinarum se subtipificó en tres serogrupos y nueve serovares de acuerdo con los esquemas revisados de Page y Kume. El principal antígeno de la hemaglutinina de A. paragallinarum es la proteína HMTp210, que es una proteína grande de unos 2000 aminoácidos (aa), que incluye un péptido señal de 70 aminoácidos en su extremo N-terminal. Sin embargo, las regiones importantes para la actividad de hemaglutinación (HA) y de los serotipos de la proteína HMTp210 siguen sin estar determinados. En este estudio, se construyó una serie de cepas de A. paragallinarum que expresaban mutantes de deleción en marco de lectura de HMTp210 y se determinaron sus títulos de hemaglutinación para identificar las regiones importantes para la actividad de hemaglutinación y de los serotipos de HMTp210. Se encontraron dos tipos distintos de actividades hemaglutinación en la proteína HMTp210. La actividad de hemaglutinación de tipo 1 residía en la región que abarcaba la longitud completa (aminoácidos 71­2084), mientras que la de tipo 2 residía en la región que abarcaba entre los aminoácidos 1003­2084. El sitio supuesto de unión al ligando de la actividad de hemaglutinación tipo 1 se ubicó entre los aminoácidos 176­360, que tenía una estructura similar a la proteína YadA de Yersinia enterocolitica. El supuesto sitio de unión del ligando de la actividad de hemaglutinación tipo 2 se ubicó entre los aminoácidos 1003­1125, que tenía una estructura similar a la proteína UspA1 de Moraxella catarrhalis. La actividad de hemaglutinación tipo 1 parecía ser específica del serogrupo Page, mientras que la hemaglutinación tipo 2 parecía ser específica del serovar Kume. Finalmente, los análisis de secuencias de las regiones que abarcan los aminácidos 1­400 y aminoácidos 1100­1600 de HMTp210 podrían ser útiles para la serotipificación molecular (por el esquema revisado de Page y Kume revisado) de aislamientos de A. paragallinarum.

Pulmonary function over 2 years in diabetic patients treated with prandial inhaled Technosphere Insulin or usual antidiabetes treatment: a randomized trial.

AIMS: Development of inhaled insulin has increased the need to understand its pulmonary safety. This study evaluated pulmonary function changes in diabetes patients receiving inhaled Technosphere Insulin (TI) or usual antidiabetes treatment (usual care). METHODS: This randomized, open-label study was conducted at 220 sites (25 July 2005 to 29 August 2008). Pulmonary function tests [forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC) and lung diffusion capacity for carbon monoxide (DL(CO))] were prospectively followed over 2 years in patients with type 1 or type 2 diabetes receiving TI (n = 730) or usual care (n = 824), along with a cohort without diabetes not receiving any specific therapy (n = 145). RESULTS: Baseline demographics and pulmonary function were similar between diabetes treatment groups. Lung function declined from baseline in all groups. TI was non-inferior to usual care for mean change in FEV(1) from baseline to month 24 [mean (s.e.m.) 0.037 (0.0119) l; 95% CI 0.014 to 0.060] using mixed-model repeated-measure with a pre-specified non-inferiority margin of 50 ml/year. After a greater initial decline at month 3 with TI, rate of change (slope) in FEV(1), FVC and DL(CO) (months 3-24) was not statistically different between treatment groups. TI was well tolerated; no serious safety concerns emerged. The most common respiratory event associated with TI was mild, transient cough, occurring within minutes of inhalation. CONCLUSIONS: Observed changes in lung function with TI were small, occurred early after therapy initiation, remained non-progressive over 2 years and were unlikely to be clinically meaningful.

CNS activation maps in awake rats exposed to thermal stimuli to the dorsum of the hindpaw.

Imaging pain pathways in rats offers a tool to investigate CNS systems in acute and chronic rodent models of pain, neural plasticity associated with the latter, and the opportunity to evaluate pharmacological effects of analgesics on these systems. Furthermore, the evaluation of CNS circuits (e.g., sensory, emotional, endogenous analgesic) offers the potential for defining the complexity of circuit-based behaviors that are difficult to evaluate in current preclinical behavioral models of pain. In these studies, we performed functional MRI in trained, acclimated, awake rats to define neural systems activated by noxious thermal stimuli. Analysis revealed activation in response to a 48°C stimuli in cortical, subcortical and brainstem areas, known to be substrates of the pain pathways. Our results demonstrate the ability to characterize CNS patterns of activation in response to pain in rodents while avoiding the potential complicating effects of anesthesia.

Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial.

BACKGROUND: Insulin therapy is often a delayed strategy in patients with type 2 diabetes mellitus because it is associated with weight gain, hypoglycaemia, and the need for subcutaneous injections. We aimed to assess the efficacy and safety of prandial Technosphere inhaled insulin compared with twice daily biaspart insulin. METHODS: In this randomised, open-label, parallel-group study, adult patients with type 2 diabetes mellitus and poor glycaemic control despite insulin therapy, with or without oral antidiabetes drugs, were enrolled from ten countries between Feb 23, 2006, and Aug 8, 2007. Patients were randomly allocated in a 1:1 ratio to receive 52 weeks' treatment with: prandial Technosphere inhaled insulin powder plus bedtime insulin glargine; or twice daily premixed biaspart insulin (70% insulin aspart protamine suspension and 30% insulin aspart of rDNA origin). The primary endpoint was a comparison of change in glycosylated haemoglobin (HbA(1c)) from baseline to week 52 between treatment groups; the non-inferiority margin was 0.4%. Analysis was by per protocol for non-inferiority testing of the primary endpoint. This study is registered with ClinicalTrials.gov, number NCT00309244. FINDINGS: 334 patients were allocated to inhaled insulin plus insulin glargine, and 343 to biaspart insulin; 107 patients on inhaled insulin plus insulin glargine and 85 on biaspart insulin discontinued the trial. 211 patients on inhaled insulin plus insulin glargine and 237 on biaspart insulin were included in per-protocol analyses. Change in HbA(1c) with inhaled insulin plus insulin glargine (-0.68%, SE 0.077, 95% CI -0.83 to -0.53) was similar and non-inferior to that with biaspart insulin (-0.76%, 0.071, -0.90 to -0.62). The between-group difference was 0.07% (SE 0.102, 95% CI -0.13 to 0.27). Patients had significantly lower weight gain and had fewer mild-to-moderate and severe hypoglycaemic events on inhaled insulin plus insulin glargine than on biaspart insulin. The safety and tolerability profile was similar for both treatments, apart from increased occurrence of cough and change in pulmonary function in the group receiving inhaled insulin plus insulin glargine. INTERPRETATION: This study is part of a large clinical development programme addressing the efficacy and tolerability of use of Technosphere inhaled insulin in a wide variety of patients. FUNDING: MannKind.

Evaluation of a novel index by tissue Doppler imaging in patients with advanced heart failure: relation to functional class and prognosis.

BACKGROUND: Despite the ability of tissue Doppler imaging (TDI) to detect left ventricular (LV) systolic and diastolic myocardial functions in patients with heart failure, the added value of TDI to clinical variables and conventional echocardiography in predicting the symptoms and outcome of advanced heart failure has not been clearly defined. METHODS AND RESULTS: Two hundred and thirty adult patients diagnosed with congestive heart failure were assigned to study groups based on the New York Heart Association functional classes. Pulsed-wave TDI (PWTDI), including average of peak systolic (Sm), early (Em) and late diastolic (Am) velocities from six mitral annular sites was evaluated. PWTDI was also calculated to create a combined index (EAS index) of diastolic and systolic performances. All patients were followed up for cardiac-related death and hospitalisation as a result of heart failure. Patients with functional class III-IV had a significantly higher EAS index (0.21 ± 0.19 vs. 0.13 ± 0.08, p < 0.05) than those with class I-II and the control (0.10 ± 0.04, p < 0.05). Except for Sm and Em, all conventional echocardiographic Doppler parameters and TDI variables significantly correlated with functional class. Moreover, according to multiple stepwise analysis, EAS index and percentage of chronic renal insufficiency (CRF) were the only two independent predictors of functional class (EAS index, p = 0.006; CRF, p = 0.019). During follow-up (median, 30 months), 93 participants had cardiac events. EAS index, LV mass index and CRF were significant predictors of cardiac mortality and hospitalisation [EAS index, hazard ratio (HR) 4.962, p = 0.006; LV mass index, HR 1.007, p = 0.003; CRF, HR 1.616, p = 0.040]. CONCLUSIONS: The EAS index, which reflects systolic and diastolic performances, is a highly effective means of differentiating between patients with functional class I-II and those with III-IV. The index also correlates with cardiac mortality and hospitalisation for worsening heart failure, thus providing additional value to conventional echocardiographic measures.

Relationship Between the Serotypes and Hemagglutinin Gene Sequences of Avibacterium paragallinarum.

Avibacterium paragallinarum has been subtyped into three serogroups (A, B, and C) and nine serovars (A-1, A-2, A-3, A-4, B-1, C-1, C-2, C-3, and C-4) according to the Page and Kume schemes. Both schemes use the hemagglutination inhibition test for serotyping. However, the relationship between the hemagglutinin gene (HMTp210) sequences and serotypes of A. paragallinarum is still unclear. This problem is partly due to the lack of information on the complete HMTp210 sequence from the formal reference strain of Page serogroup B (strain 0222 or Spross). In this study, we determined the complete HMTp210 sequence of strain Spross. The sequence of Spross and those of other HMTp210 sequences retrieved from GenBank were used to conduct phylogenetic analyses to investigate the relationship between the serotypes and HMTp210 sequences of A. paragallinarum. Four phylogenetic clusters, designated clusters A-1, A-2, B, and C, were identified. Clustering based on complete HMTp210 sequences correlates with serotyping based on hemagglutination inhibition tests. Serovar A-2 was found to contain a chimeric HMTp210 gene that might have resulted from recombination between serovar A-1 and serovar C-1. In addition, phylogenetic analysis based on partial sequences (approximately nucleotides 1-1200) of HMTp210 was sufficient to discriminate between serogroups A, B, and C. These findings could be valuable for developing a molecular method for serotyping of A. paragallinarum.

Relación entre los serotipos y las secuencias génicas de hemaglutinina de Avibacterium paragallinarum. Avibacterium paragallinarum se ha subtipificado en tres serogrupos (A, B y C) y nueve serovares (A-1, A-2, A-3, A-4, B-1, C-1, C-2, C- 3 y C-4) de acuerdo con los esquemas Page y Kume. Ambos esquemas utilizan la prueba de inhibición de la hemaglutinación para la serotipificación. Sin embargo, la relación entre las secuencias del gene de la hemaglutinina (HMTp210) y los serotipos de A. paragallinarum aún no está clara. Este problema se debe en parte a la falta de información sobre la secuencia completa del gene HMTp210 de la cepa de referencia formal del serogrupo B de Page (cepa 0222 o Spross). En este estudio, se determinó la secuencia completa de HMTp210 de la cepa Spross. La secuencia de Spross y las de otras secuencias del gene HMTp210 obtenidas de GenBank se utilizaron para realizar análisis filogenéticos para investigar la relación entre los serotipos y las secuencias de HMTp210 de A. paragallinarum. Se identificaron cuatro agrupaciones filogenéticas, denominadas grupos A-1, A-2, B y C. La agrupación basada en las secuencias completas del gene HMTp210 se correlaciona con la serotipificación basada en pruebas de inhibición de la hemaglutinación. Se encontró que el serovar A-2 contenía un gene HMTp210 quimérico que podría haber resultado de la recombinación entre el serovar A-1 y el serovar C-1. Además, el análisis filogenético basado en secuencias parciales (aproximadamente nucleótidos 1-1200) del gene HMTp210 fue suficiente para discriminar entre los serogrupos A, B y C. Estos hallazgos podrían ser valiosos para desarrollar un método molecular para la serotipificación de A. paragallinarum.

Degradable RGD-Functionalized 3D-Printed Scaffold Promotes Osteogenesis.

To establish an ideal microenvironment for regenerating maxillofacial defects, recent research interests have concentrated on developing scaffolds with intricate configurations and manipulating the stiffness of extracellular matrix toward osteogenesis. Herein, we propose to infuse a degradable RGD-functionalized alginate matrix (RAM) with osteoid-like stiffness, as an artificial extracellular matrix, to a rigid 3D-printed hydroxyapatite scaffold for maxillofacial regeneration. The 3D-printed hydroxyapatite scaffold was produced by microextrusion technology and showed good dimensional stability with consistent microporous detail. RAM was crosslinked by calcium sulfate to manipulate the stiffness, and its degradation was accelerated by partial oxidation using sodium periodate. The results revealed that viability of bone marrow stem cells was significantly improved on the RAM and was promoted on the oxidized RAM. In addition, the migration and osteogenic differentiation of bone marrow stem cells were promoted on the RAM with osteoid-like stiffness, specifically on the oxidized RAM. The in vivo evidence revealed that nonoxidized RAM with osteoid-like stiffness upregulated osteogenic genes but prevented ingrowth of newly formed bone, leading to limited regeneration. Oxidized RAM with osteoid-like stiffness facilitated collagen synthesis, angiogenesis, and osteogenesis and induced robust bone formation, thereby significantly promoting maxillofacial regeneration. Overall, this study supported that in the stabilized microenvironment, oxidized RAM with osteoid-like stiffness offered requisite mechanical cues for osteogenesis and an appropriate degradation profile to facilitate bone formation. Combining the 3D-printed hydroxyapatite scaffold and oxidized RAM with osteoid-like stiffness may be an advantageous approach for maxillofacial regeneration.

PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.

Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5 x 10(8) or 5.5 x 10(9) pfu ml(-1)), Ad encoding luciferase (Ad-Luc; 5.5 x 10(9) pfu ml(-1); control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg ml(-1)). Bone repair and osseointegration were measured through backscattered scanning electron microscopy, histomorphometry, micro-computed tomography and biomechanical assessments. Furthermore, a panel of local and systemic safety assessments was performed. Results indicated that bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared with Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B shows regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable with rhPDGF-BB protein delivery in vivo.

Combined central retinal artery and vein occlusion in a patient with systemic lupus erythematosus and anti-phospholipid syndrome.

Combined central retinal artery occlusion and central retinal venous occlusion have been rarely reported in patients with systemic lupus erythematosus and anti-phospholipid syndrome. The impact of this severe vaso-occlusive disease on vision is usually devastating and permanent in spite of vigorous treatment. We report herein a 35-year-old female patient displaying a transient and reversible process. Her best-corrected visual acuity improved from 6/60 to 6/8.6 1 day later, before the initiation of systemic corticosteroid and anticoagulant treatment. The retina regained a normal appearance with her vision recovering to 6/6 2 weeks after the episode of temporary vision loss. Her rapid recovery suggests that continued anti-coagulation therapy and close follow-up to prevent severe complications and recurrent thrombosis is warranted.

Serotypes and Hemagglutinin Gene Sequences of Avibacterium paragallinarum Isolated in Taiwan.

Despite routine vaccine use, sporadic outbreaks of infectious coryza in poultry continue to occur in Taiwan. This study was designed to determine the serotypes and the complete nucleotide sequences of a hemagglutinin gene (HMTp210) of Avibacterium paragallinarum isolated in Taiwan between 1994 and 2017. Hemagglutination inhibition tests showed that these isolates belong to serogroups B and C. Sequence analyses of the HMTp210 gene showed that Taiwanese serogroup B isolates are most similar (94.7%-98.2% identity) to strain FARPER-174 isolated in Peru in 2015. In contrast, Taiwanese serogroup C isolates are most similar (96.3%-99.8% identity) to strain H-18 isolated in Japan in 1976. This is the first report showing the presence of A. paragallinarum of serogroup B in Taiwan. In addition, one Taiwanese isolate showed cross-reactivity with serogroup B and C antisera. This isolate contains a chimeric HMTp210 gene that might result from recombination between serogroups B and C. These findings could be valuable for the epidemiologic study and molecular serotyping of A. paragallinarum.

Serotipos y secuencias de genes de hemaglutinina de Avibacterium paragallinarum aislados en Taiwán. A pesar del uso rutinario de vacunas, en Taiwán continúan ocurriendo brotes esporádicos de coriza infecciosa en avicultura. Este estudio fue diseñado para determinar los serotipos y las secuencias de nucleótidos completas de un gene de hemaglutinina (HMTp210) de Avibacterium paragallinarum aislado en Taiwán entre 1994 y 2017. Las pruebas de inhibición de la hemaglutinación mostraron que estos aislamientos pertenecen a los serogrupos B y C. El análisis de secuencias del gene HMTp210 mostró que los aislamientos del serogrupo B taiwaneses son más similares (94.7% ­98.2% de identidad) a la cepa FARPER-174 aislada en Perú en el año 2015. En contraste, los aislamientos del serogrupo C taiwaneses son más similares (96.3% ­99.8% de identidad) a la cepa H -18 aislada en Japón en 1976. Este es el primer reporte que muestra la presencia de A. paragallinarum del serogrupo B en Taiwán. Además, un aislado taiwanés mostró reactividad cruzada con los antisueros del serogrupo B y C. Este aislado contiene un gene HMTp210 quimérico que podría resultar de la recombinación entre los serogrupos B y C. Estos hallazgos podrían ser valiosos para el estudio epidemiológico y la serotipificación molecular de A. paragallinarum.