Seasonal meropenem resistance in Acinetobacter baumannii and influence of temperature-driven adaptation.

BACKGROUND: Recognition of seasonal trends in bacterial infection and drug resistance rates may enhance diagnosis, direct therapeutic strategies, and inform preventive measures. Limited data exist on the seasonal variability of Acinetobacter baumannii. We investigated the seasonality of A. baumannii, the correlation between temperature and meropenem resistance, and the impact of temperature on this bacterium. RESULTS: Meropenem resistance rates increased with lower temperatures, peaking in winter/colder months. Nonresistant strain detection exhibited temperature-dependent seasonality, rising in summer/warmer months and declining in winter/colder months. In contrast, resistant strains showed no seasonality. Variations in meropenem-resistant and nonresistant bacterial resilience to temperature changes were observed. Nonresistant strains displayed growth advantages at temperatures ≥ 25 °C, whereas meropenem-resistant A. baumannii with ß-lactamase OXA-23 exhibited greater resistance to low-temperature (4 °C) stress. Furthermore, at 4 °C, A. baumannii upregulated carbapenem resistance-related genes (adeJ, oxa-51, and oxa-23) and increased meropenem stress tolerance. CONCLUSIONS: Meropenem resistance rates in A. baumannii display seasonality and are negatively correlated with local temperature, with rates peaking in winter, possibly linked to the differential adaptation of resistant and nonresistant isolates to temperature fluctuations. Furthermore, due to significant resistance rate variations between quarters, compiling monthly or quarterly reports might enhance comprehension of antibiotic resistance trends. Consequently, this could assist in formulating strategies to control and prevent resistance within healthcare facilities.

Prevalence and molecular characterization of Clostridioides difficile infection in China over the past 5 years: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to provide an overview of the prevalence and molecular characteristics of Clostridioides difficile infection (CDI) in China in the past 5 years. METHODS: A systematic literature review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Nine databases were searched for relevant studies published between January 2017 and February 2022. The Joanna Briggs Institute critical appraisal tool was used to assess the quality of included studies, and R software version 4.1.3 was used for data analysis. Funnel plots and Egger regression tests were also performed to assess publication bias. RESULTS: A total of 50 studies were included in the analysis. The pooled prevalence of CDI in China was 11.4% (2696/26,852). The main circulating C. difficile strains in southern China were ST54, ST3, and ST37, consistent with the overall situation in China. However, the most prevalent genotype in northern China was ST2, which was previously underappreciated. CONCLUSION: Based on our findings, increased awareness and management of CDI is necessary to reduce the prevalence of CDI in China.

Bacteria can drill holes: Salmonella enterica serovar London infection of the leg and heel with colonization of the gut.

Salmonella enterica serovar London is known to colonize the human digestive tract and can cause gastroenteritis and diarrhea. The excretion of S. London in the stool can spread into the environment. However, S. London colonization of the gut is not known to cause infection of the soft tissues. Here, we report a case of S. London infection of the skin and soft tissue of the leg and heel.

Mental health and psychosocial problems among laboratory technicians in response to the COVID-19 pandemic in Hebei, China.

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods: A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians' mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results: A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p < 0.001), more than 10 years of work experience (depression symptoms: OR = 2.350, p = 0.024; anxiety symptoms: OR = 2.642, p = 0.038), frontline work (depression symptoms: OR = 1.761, p = 0.001; anxiety symptoms: OR = 2.619, p < 0.001; hostility symptoms: OR = 1.913, p = 0.001), participant in more than 3 times large-scale SARS-CoV-2 screenings and more than 36 h per week in SARS-CoV-2 nucleic acid testing. Conclusion: A portion of laboratory technicians reported experiencing varying levels of psychological burden. During the COVID-19 pandemic, multiple interventions should be developed and implemented to address existing psychosocial challenges and promote the mental health of laboratory technicians.

Optimization Design of Magnetic Isolation Ring Position in AC Solenoid Valves for Dynamic Response Performances.

Dynamic response characteristics of solenoid valves directly determined their performances. Among numerous parameters, the influence of magnetic isolation ring (MIR) on solenoid valve performance is crucial. Previous optimization studies have not conducted a systematic exploration and analysis of MIR. In this paper, a model of an AC solenoid valve considering the position of the MIR is proposed, and the model's accuracy was verified by simulation and experiments. The electromagnetic force, response time, and magnetic field distribution at different positions of the MIR were analyzed, and the effect of the position of MIR on dynamic response characteristics of the solenoid valve was clarified. The results show that the MIR affects the dynamic response characteristics of the solenoid valve by changing the magnetic circuit. With the positive translation of the position of the MIR along the Z-axis, the electromagnetic force first increases and then decreases, and the response time first decreases and then increases. The position range of MIR with excellent dynamic response performance was obtained from the comprehensive consideration of response time and electromagnetic force. Finally, the optimization design for the dynamic response performance of the solenoid valves is realized.

The prolyl 4-hydroxylase inhibitor GSK360A decreases post-stroke brain injury and sensory, motor, and cognitive behavioral deficits.

There is interest in pharmacologic preconditioning for end-organ protection by targeting the HIF system. This can be accomplished by inhibition of prolyl 4-hydroxylase (PHD). GSK360A is an orally active PHD inhibitor that has been previously shown to protect the failing heart. We hypothesized that PHD inhibition can also protect the brain from injuries and resulting behavioral deficits that can occur as a result of surgery. Thus, our goal was to investigate the effect of pre-stroke surgery brain protection using a verified GSK360A PHD inhibition paradigm on post-stroke surgery outcomes. Vehicle or an established protective dose (30 mg/kg, p.o.) of GSK360A was administered to male Sprague-Dawley rats. Initially, GSK360A pharmacokinetics and organ distribution were determined, and then PHD-HIF pharmacodynamic markers were measured (i.e., to validate the pharmacological effects of the GSK360A administration regimen). Results obtained using this validated PHD dose-regimen indicated significant improvement by GSK360A (30mg/kg); administered at 18 and 5 hours prior to transient middle cerebral artery occlusion (stroke). GSK360A exposure and plasma, kidney and brain HIF-PHD pharmacodynamics endpoints (e.g., erythropoietin; EPO and Vascular Endothelial Growth Factor; VEGF) were measured. GSK360A provided rapid exposure in plasma (7734 ng/ml), kidney (45-52% of plasma level) and brain (1-4% of plasma level), and increased kidney EPO mRNA (80-fold) and brain VEGF mRNA (2-fold). We also observed that GSK360A increased plasma EPO (300-fold) and VEGF (2-fold). Further assessments indicated that GSK360A reduced post-stroke surgery neurological deficits (47-64%), cognitive dysfunction (60-75%) and brain infarction (30%) 4 weeks later. Thus, PHD inhibition using GSK360A pretreatment produced long-term post-stroke brain protection and improved behavioral functioning. These data support PHD inhibition, specifically by GSK360A, as a potential strategy for pre-surgical use to reduce brain injury and functional decline due to surgery-related cerebral injury.

Activation of the Amino Acid Response Pathway Blunts the Effects of Cardiac Stress.

BACKGROUND: The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure. METHODS AND RESULTS: Consistent with its ability to inhibit prolyl-tRNA synthetase, halofuginone elicited a general control nonderepressible 2-dependent activation of the AAR pathway in cardiac fibroblasts as evidenced by activation of known AAR target genes, broad regulation of the transcriptome and proteome, and reversal by l-proline supplementation. Halofuginone was examined in 3 mouse models of cardiac stress: angiotensin II/phenylephrine, transverse aortic constriction, and acute ischemia reperfusion injury. It activated the AAR pathway in the heart, improved survival, pulmonary congestion, left ventricle remodeling/fibrosis, and left ventricular function, and rescued ischemic myocardium. In human cardiac fibroblasts, halofuginone profoundly reduced collagen deposition in a general control nonderepressible 2-dependent manner and suppressed the extracellular matrix proteome. In human induced pluripotent stem cell-derived cardiomyocytes, halofuginone blocked gene expression associated with endothelin-1-mediated activation of pathologic hypertrophy and restored autophagy in a general control nonderepressible 2/eIF2α-dependent manner. CONCLUSIONS: Halofuginone activated the AAR pathway in the heart and attenuated the structural and functional effects of cardiac stress.

Runx2 alleviates high glucose-suppressed osteogenic differentiation via PI3K/AKT/GSK3ß/ß-catenin pathway.

Hyperglycemia is one of the most important pathogenesis of diabetic osteopathy. Several lines of studies indicate Runx2 plays a critical role in the process of osteogenic differentiation. However, little studies have analyzed the effect of Runx2 on osteoblast differentiation of rat bone mesenchymal stem cells (rBMSCs) in high-glucose condition. In this study, the effect of Runx2 on osteoblast differentiation in high-glucose condition was evaluated by the expression of osteogenesis-related maker including Runx2, ALP, OC, and OPN, as well as ALP staining, ALP activity, and Alizarin red S staining. Western blot analysis was performed to detect the protein expression levels of p-AKT, AKT, p-GSK3ß, GSK3ß, and ß-catenin. Immunofluorescence staining analysis was performed to detect subcellular localization of ß-catenin. Our results revealed that high glucose significantly inhibited osteogenic differentiation, hyperosmolarity did not cause a suppression. In addition, Runx2 could upregulate the expression of osteogenic-related genes and increase matrix mineralization, while applying 10 µM PI3K/AKT inhibitor LY294002 abolished the beneficial effect. Collectively, these results indicate that Runx2 alleviates high glucose-induced inhibition of osteoblast differentiation by modulating PI3K/AKT/GSK3ß/ß-catenin pathway.

Toward improved myocardial maturity in an organ-on-chip platform with immature cardiac myocytes.

In vitro studies of cardiac physiology and drug response have traditionally been performed on individual isolated cardiomyocytes or isotropic monolayers of cells that may not mimic desired physiological traits of the laminar adult myocardium. Recent studies have reported a number of advances to Heart-on-a-Chip platforms for the fabrication of more sophisticated engineered myocardium, but cardiomyocyte immaturity remains a challenge. In the anisotropic musculature of the heart, interactions between cardiac myocytes, the extracellular matrix (ECM), and neighboring cells give rise to changes in cell shape and tissue architecture that have been implicated in both development and disease. We hypothesized that engineered myocardium fabricated from cardiac myocytes cultured in vitro could mimic the physiological characteristics and gene expression profile of adult heart muscle. To test this hypothesis, we fabricated engineered myocardium comprised of neonatal rat ventricular myocytes with laminar architectures reminiscent of that observed in the mature heart and compared their sarcomere organization, contractile performance characteristics, and cardiac gene expression profile to that of isolated adult rat ventricular muscle strips. We found that anisotropic engineered myocardium demonstrated a similar degree of global sarcomere alignment, contractile stress output, and inotropic concentration-response to the ß-adrenergic agonist isoproterenol. Moreover, the anisotropic engineered myocardium exhibited comparable myofibril related gene expression to muscle strips isolated from adult rat ventricular tissue. These results suggest that tissue architecture serves an important developmental cue for building in vitro model systems of the myocardium that could potentially recapitulate the physiological characteristics of the adult heart. Impact statement With the recent focus on developing in vitro Organ-on-Chip platforms that recapitulate tissue and organ-level physiology using immature cells derived from stem cell sources, there is a strong need to assess the ability of these engineered tissues to adopt a mature phenotype. In the present study, we compared and contrasted engineered tissues fabricated from neonatal rat ventricular myocytes in a Heart-on-a-Chip platform to ventricular muscle strips isolated from adult rats. The results of this study support the notion that engineered tissues fabricated from immature cells have the potential to mimic mature tissues in an Organ-on-Chip platform.

[Transfer and Fate of Polybrominated Diphenyl Ethers in an Electrical Equipment Dismantling Area Using a Multimedia Fugacity Model].

The multimedia fugacity model (Ⅲ) was used to simulate the distribution, transfer and fate of typical polybrominated diphenyl ethers (PBDEs) in air, water, soil and sediment in an electrical equipment dismantling area in eastern China. The modeling data were compared with monitored values in air, soil and sediment for validation purpose. Moreover, the transfer fluxes between different compartments were analyzed in order to infer the main transfer process. Parameters of the model were tested and the key parameters were identified using sensitivity analysis method for BDE47 and BDE209.The results of sensitivity analysis indicated that vapor pressure, the lgKow value and half-life had significant influence on concentrations of PBDEs in different media. The results showed that when the system reached equilibrium, most of the PBDEs would be accumulated in soil and sediment. The air advection outflow and soil degradation were the major routes for PBDEs to disappear in the area. The results will provide the basis for the risk management of PBDEs contamination.

[Open-top Chamber for in situ Research on Response of Mercury Enrichment in Rice to the Rising Gaseous Elemental Mercury in the Atmosphere].

In situ research was conducted on the response of mercury enrichment in rice organs to elevated gaseous elemental mercury (GEM) with open-top chambers (OTCs) fumigation experiment and soil Hg enriched experiment. The results showed that Hg concentrations in roots were generally correlated with soil Hg concentrations (R = 0.9988, P < 0.05) but insignificantly correlated with air Hg concentrations (P > 0.05), indicating that Hg in rice roots was mainly from soil. Hg concentrations in stems increased linearly (R(B) = 0.9646, R(U) = 0.9831, P < 0.05) with elevated GEM, and Hg concentrations in upper stems were usually higher than those in bottom stems in OTCs experiment. Hg concentrations in bottom stems were generally correlated with soil Hg concentrations (R = 0.9901, P < 0.05) and second-order polynomial (R = 0.9989, P < 0.05) was fitted for Hg concentrations in upper stems to soil Hg concentrations, and Hg concentrations in bottom stems were usually higher than those in upper stems in soil Hg enriched experiment, indicating the combining impact of Hg from air and soil on the accumulation of mercury in stems. Hg concentrations in foliage were significantly correlated (P < 0.05) with air Hg and linearly correlated with soil Hg (R = 0.9983, P = 0.0585), implying that mercury in foliage was mainly from air and some of Hg in root from soil was transferred to foliage through stem. Based on the function in these filed experiments, it was estimated that at least 60%-94% and 56%-77% of mercury in foliage and upper-stem of rice was from the atmosphere respectively, and yet only 8%-56% of mercury in bottom-stem was attributed to air. Therefore, mercury in rice aboveground biomass was mainly from the atmosphere, and these results will provide theoretical basis for the regional atmospheric mercury budgets and the model of mercury cycling.

[Regional difference of NPK fertilizers application and environmental risk assessment in Jiangsu Province, China].

It is of great importance to have a deep understanding of the spatial distribution of NPK fertilizers application and the potential threat to the ecological environment in Jiangsu Province, which is helpful for regulating the rational fertilization, strengthening the fertilizer use risk management and guidance, and preventing agricultural non-point pollution. Based on the environmental risk assessment model with consideration of different impacts of N, P, K fertilizers on environment, this paper researched the regional differentiation characteristic and environmental risk of intensity of NPK fertilizer usages in Jiangsu. Analystic hierarchy process ( AHP) was used to determine the weithts of N, P, K. The environmental safety thresholds of N, P, K were made according to the standard of 250 kg · hm(-2) for the construction of ecological counties sponsered by Chinese government and the proportion of 1:0.5:0.5 for N:P:K surposed by some developed countries. The results showed that the intensity of NPK fertilizer application currently presented a gradually increasing trend from south to north of Jiangsu, with the extremum ratio of 3.3, and the extremum ratios of nitrogen fertilizer, phosphorus fertilizer and potassium fertilizer were 3.3, 4.5 and 4.4, respectively. The average proportion of nitrogen fertilizer, phosphorus fertilizer and potassium fertilizer of 13 cities in Jiangsu was 1:0.39:0.26. Their proportion was relatively in equilibrium in southern Jiangsu, but the nutrient structure disorder was serious in northern Jiangsu. In Jiangsu, the environmental risk index of fertilization averaged at 0.69 and in the middle-range of environmental risk. The environmental risk index of fertilizer application in southern and central Jiangsu was respectively at the low and moderate levels, while that of cities in northern Jiangsu was at the moderate, serious or severe level. In Jiangsu, the regional difference of fertilizer application and environmental risk assessment were affected by many factors, including physical and economic conditions, government policy, management system, technology, and management methods.

[Effect of premolar extractions on third molar angulation changes: a meta-analysis].

OBJECTIVE: To assess the effect of premolar extractions on third molar angulation changes in orthodontic patients. METHODS: The Cochrane library, PubMed, Embase, China Science and Technology Periodical Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang database were searched from January 1, 1990 to May 20, 2014 to identify all the studies about third molar angulation changes in orthodontic patients with or without premolars extraction, which was assigned as a extraction group and a control group. Th e extraction group was further divided into a fi rst premolar extraction subgroup and a second premolar extraction subgroup. Literature filtering, data extraction and methodological quality evaluation were finished independently by two researchers. After cross checking, the disagreements were solved by discussion. Meta-analysis was carried out by RevMan 5.3.3 software. RESULTS: Ten studies involving 712 patients were included. Meta-analysis revealed that: compared with the control group, the changes of third molar angulation in maxillary and mandible in the extraction group were statistically significantly different (all P<0.05); the difference in angulation between the two groups was about 5.19° in maxillary and 3.55° in mandibul. As for the premolar extraction subgroups, there was no significant difference in mandibular third molar angulation between them (P>0.05). CONCLUSION: The orthodontic treatment involving first or second premolar extractions can improve the maxillary third molar angulation, and the second premolar extraction is the best option.

Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease.

Hypoxia inducible factor (HIF) stabilization by HIF-prolyl hydroxylase (PHD) inhibitors may improve ischemic conditions such as peripheral artery disease (PAD). This multicenter, randomized, placebo-controlled study evaluated the safety and efficacy of GSK1278863 (an oral PHD inhibitor) in subjects with PAD. The study assessed two active treatment paradigms: single dosing and subchronic daily dosing (300 mg single dose and 15 mg daily for 14 days, respectively). Neither regimen improved exercise performance compared with placebo (change from baseline in the 6-minute walk test (6MWT; feet), (GSK1278863, placebo): single dose (-46, -44), p=0.96; repeat dose (9, 8), p=0.99; change in number of contractions to onset of claudication (goniometry): single dose (4, -1), p=0.053; repeat dose (-2, 1), p=0.08). A calf-muscle biopsy substudy showed no increases in mRNA or protein levels of HIF target genes. More subjects receiving GSK1278863 than placebo experienced adverse events, particularly following the 300 mg single dose. Thus, assessing the safety of GSK1278863 in this setting would require a larger population exposed to the agent for a longer duration. These data do not support a benefit of GSK1278863 in PAD using the regimens tested. CLINICALTRIALSGOV IDENTIFIER NCT01673555:

Association between interleukin-1ß C (3953/4)T polymorphism and chronic periodontitis: evidence from a meta-analysis.

The aim of this study was to perform a meta-analysis to evaluated the association between interleukin-1ß (IL-1ß) C(3953/4)T polymorphism and chronic periodontitis (CP). Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase and Web of Science. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Publication bias was tested by Begg's funnel plot and Egger's regression test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy-Weinberg equilibrium (HWE) or high quality (score ≥ 7). Data analyses were carried out by Stata 11.0. There were significant associations between IL-1ß C(3953/4)T polymorphism and CP (for T allele vs. C allele: OR = 1.30, 95%CI = 1.05-1.60, p = 0.02; for T/T vs. C/C: OR = 1.66, 95%CI = 1.12-2.45, p = 0.01; for C/T+T/T vs. C/C: OR = 1.28, 95%CI = 0.99-1.65; and for T/T vs. C/T+C/C: OR = 1.62, 95%CI = 1.15-2.29, p = 0.006). When stratified by ethnicity, statistically significantly elevated risk was found for Caucasians, but not for Asians. When stratified by study design, evidences of significant association was observed between IL-1ß C(3953/4)T polymorphism and CP in both population-based studies and hospital-based studies. This meta-analysis indicates that there is strong evidence for association between IL-1ß C(3953/4)T polymorphism and CP.

[Spatial distribution and evaluation of nitrogen, phosphorus and organic matter in surface sediments from western lakeside belt of Lake Taihu].

The surface sediments in western lakeside belt of Taihu Lake were collected. The spatial distribution of nutrients and pollution evaluation were studied. The results showed that concentration of the nitrogen, phosphorus and organic matter in the surface sediments had an increasing tendency from inshore to the far shore. The concentration of organic matter in the sediments ranged from 2261.78 mg x kg(-1) to 11963.10 mg x kg(-1), with the average of 7 124.00 mg x kg(-1). Total nitrogen concentration in the sediments ranged from 343.20 mg x kg(-1) to 1 390.12 mg x kg(-1), with the average of 819.20 mg x kg(-1). The total phosphorus concentration in the sediments ranged from 197.46 mg x kg(-1) to 570.85 mg x kg(-1), with the average of 379.39 mg x kg(-1). The C/N ratio in the lake sediment was 9.5. Organic matter and nutrient were from alga and aquatic plant in lake. Based on the organic index and organic nitrogen, we can concluded that the surface sediments in western lakeside belt of Taihu Lake still belong to less clean category. The average values of organic index and organic nitrogen were 0.037% and 0.044%, respectively. The organic index and organic nitrogen in offshore were high, which indicated the risk of organic pollution.

An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure.

Pulmonary edema resulting from high pulmonary venous pressure (PVP) is a major cause of morbidity and mortality in heart failure (HF) patients, but current treatment options demonstrate substantial limitations. Recent evidence from rodent lungs suggests that PVP-induced edema is driven by activation of pulmonary capillary endothelial transient receptor potential vanilloid 4 (TRPV4) channels. To examine the therapeutic potential of this mechanism, we evaluated TRPV4 expression in human congestive HF lungs and developed small-molecule TRPV4 channel blockers for testing in animal models of HF. TRPV4 immunolabeling of human lung sections demonstrated expression of TRPV4 in the pulmonary vasculature that was enhanced in sections from HF patients compared to controls. GSK2193874 was identified as a selective, orally active TRPV4 blocker that inhibits Ca(2+) influx through recombinant TRPV4 channels and native endothelial TRPV4 currents. In isolated rodent and canine lungs, TRPV4 blockade prevented the increased vascular permeability and resultant pulmonary edema associated with elevated PVP. Furthermore, in both acute and chronic HF models, GSK2193874 pretreatment inhibited the formation of pulmonary edema and enhanced arterial oxygenation. Finally, GSK2193874 treatment resolved pulmonary edema already established by myocardial infarction in mice. These findings identify a crucial role for TRPV4 in the formation of HF-induced pulmonary edema and suggest that TRPV4 blockade is a potential therapeutic strategy for HF patients.

Variations in dental and alveolar arch dimensions among different malocclusion groups in a sample of untreated patients.

This study compares the different transverse relationships of the upper and lower arches in the 4 different malocclusion groups and describes the origin of these transverse discrepancies. Knowledge of dental and alveolar arch dimensions will help the clinician in diagnosis and treatment planning of patients with different malocclusions.

[A longitudinal study of mandible growth of Angle Class II division 2 malocclusion from mixed dentition to permanent dentition].

OBJECTIVE: To determine the longitudinal growth changes of mandible from mixed dentition to permanent dentition on Angle Class II division 2 malocclusion. METHODS: The sample consisted of 95 students with Angle Class II division 2 malocclusion and 75 students with normal occlusion. Cephalometric radiographs and hand-wrist radiographs were obtained for all the samples. And analysis of all the cephalograms was carried out. RESULTS: The study of growth changes of mandible from mixed dentition to permanent dentition showed that: 1) angle: The control group showed an increase in SNB and S-Ba-Go and a decrease in Ar-Go-Me, SN-MP and NSGn. In the experimental group, the changes in SNB, Ar-Go-Me, Cd-Go-Me, SN-MP, S-Ar-Go, S-Ba-Go were not of statistical significance, however, Y angle and NSGn were increased. In the control group, there was no statistically significant change in the Y angle. 2)chin: In the experimental group, chin concavity increased. The changes were not statistically significant for the other index. In the control group, chin curvature decreased. The chin height, chin depth, chin concavity, chin depth/chin height, SL and Pog to NB increased. 3)spacing: The growth of Cd-Go, Gn-Cd, Go-Me, Ar-Pog, Ar-Go in the control group was more than that of the experimental group. CONCLUSION: The present finding will help the clinicians to come to a diagnosis and reasonable treatment plan in Angle Class II division 2 patients.

Chronic inhibition of hypoxia-inducible factor prolyl 4-hydroxylase improves ventricular performance, remodeling, and vascularity after myocardial infarction in the rat.

BACKGROUND: Hypoxia inducible factors (HIFs) are transcription factors that are regulated by HIF-prolyl 4-hydroxylases (PHDs) in response to changes in oxygen tension. Once activated, HIFs play an important role in angiogenesis, erythropoiesis, proliferation, cell survival, inflammation, and energy metabolism. We hypothesized that GSK360A, a novel orally active HIF-PHD inhibitor, could facilitate local and systemic HIF-1 alpha signaling and protect the failing heart after myocardial infarction (MI). METHODS AND RESULTS: GSK360A is a potent (nanomolar) inhibitor of HIF-PHDs (PHD1>PHD2 = PHD3) capable of activating the HIF-1 alpha pathway in a variety of cell types including neonatal rat ventricular myocytes and H9C2 cells. Male rats treated orally with GSK360A (30 mg x kg x d) had a sustained elevation in circulating levels of erythropoietin and hemoglobin and increased hemoxygenase-1 expression in the heart and skeletal muscle. In a rat model of established heart failure with systolic dysfunction induced by ligation of left anterior descending coronary artery, chronic treatment with GSK360A for 28 days prevented the progressive reduction in ejection fraction, ventricular dilation, and increased lung weight, which were observed in the vehicle-treated animals, for up to 3 months. In addition, the microvascular density in the periinfarct region was increased (>2-fold) in GSK360A-treated animals. Treatment was well tolerated (survival was 89% in the GSK360A group vs. 82% in the placebo group). CONCLUSIONS: Chronic post-myocardial infarction treatment with a selective HIF PHD inhibitor (GSK360A) exerts systemic and local effects by stabilizing HIF-1 alpha signaling and improves long-term ventricular function, remodeling, and vascularity in a model of established ventricular dysfunction. These results suggest that HIF-PHD inhibitors may be suitable for the treatment of post-MI remodeling and heart failure.