Risk Factors of Patients with Postpartum Acute Kidney Injury: An Observational Study.

Postpartum acute kidney injury (AKI) is a condition characterized by a sudden and rapid decline in kidney function that occurs shortly after childbirth. Several risk factors may be associated with postpartum acute kidney injury (AKI). Understanding the possible risk factors is essential for timely intervention and improved maternal healthcare. The aim of the study was to assess the risk factors of postpartum acute kidney injury patients. This prospective observational study took place at Mymensingh Medical College Hospital, from March 2020 to April 2021. It was carried out in the Departments of Nephrology and Departments of Obstetrics & Gynecology, where 153 postpartum acute kidney injury (AKI) patients were enrolled through purposive sampling. The study collected data on patient demographics, etiology and presentation. Statistical analysis was conducted using SPSS (Statistical Package for the Social Sciences) version 26.0, with a significance threshold set at p<0.05 for all tests. Among participants, puerperal sepsis (77.8%) and toxemia of pregnancy (58.8%) were prevalent risk factors. Intrauterine death was rare (1.3%). Other risk factors such as postpartum hemorrhage 22.2%, HELLP syndrome 11.1%, and antepartum hemorrhage 15.0% were found. A statistically significant difference in postpartum hemorrhage prevalence (p=0.038) was noted between hemodialysis and non-hemodialysis patients. Puerperal sepsis is the most common risk factor for postpartum acute kidney injury, closely followed by toxemia of pregnancy. Intrauterine death is rare, while postpartum hemorrhage significantly affects subjects, with variations noted between hemodialysis and non-hemodialysis patients.

A randomised, controlled, double blind study to assess mechanistic effects of combination therapy of dapagliflozin with exenatide QW versus dapagliflozin alone in obese patients with type 2 diabetes mellitus (RESILIENT): study protocol.

INTRODUCTION: The newer glucose-lowering therapies for type 2 diabetes (T2D), the glucagon-like peptide-1 receptor agonists (GLP1-RAs) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i), have additional clinical benefits beyond improving glycaemic control; promoting weight loss, addressing associated cardiovascular risk factors and reducing macrovascular and microvascular complications. Considering their independent mechanisms of actions, there is a potential for significant synergy with combination therapy, yet limited data exist. This 32-week randomised, double-blind, placebo-controlled trial will gain mechanistic insight into the effects of coadministration of exenatide QW, a weekly subcutaneous GLP1-RA, with dapagliflozin, a once daily oral SGLT2i, on the dynamic, adaptive changes in energy balance, total, regional and organ-specific fat mass and multiorgan insulin sensitivity. METHODS AND ANALYSIS: 110 obese patients with diagnosed T2D (glycated haemoglobin, HbA1c ≥48 mmol/mol) will be treated for 32 weeks with dapagliflozin (10 mg once daily either alone or in combination with exenatide QW (2 mg once weekly); active treatments will be compared with a control group (placebo tablet and sham injection). The primary objective of the study is to compare the adjusted mean reduction in total body fat mass (determined by dual-energy X-ray absorptiometry, DEXA) from baseline following 32 weeks of treatment with exenatide QW and dapagliflozin versus dapagliflozin alone compared with control (placebo). Secondary outcome measures include changes in (1) energy balance (energy intake and energy expenditure measured by indirect calorimetry); (2) appetite (between and within meals) and satiety quotient; (3) body composition including visceral adipose tissue, subcutaneous adipose tissue, liver and pancreatic fat. Exploratory outcome measures include metabolic changes in hepatic and peripheral insulin sensitivity (using a two-stage hyperinsulinaemic, euglycaemic clamp), central nervous system responses to food images using blood oxygen level-dependent (BOLD) functional MRI (fMRI) and changes in cardiovascular function (using transthoracic echocardiography, cardiac MR and duplex ultrasonography). ETHICS AND DISSEMINATION: This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1147) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice. Results from the study will be published in peer-reviewed scientific and open access journals and/or presented at scientific conferences and summarised for distribution to the participants. TRIAL SPONSOR: University of Liverpool. TRIAL REGISTRATION NUMBER: ISRCTN 52028580; EUDRACT number 2015-005242-60.

Analysis of Noninvasive Ventilation in Subjects With Sepsis and Acute Respiratory Failure.

BACKGROUND: Acute respiratory failure is among the sequelae of complications that can develop in response to severe sepsis. Research into sepsis-related respiratory failure has focused on ARDS and invasive mechanical ventilation. We studied the factors associated with success and failure of noninvasive ventilation (NIV) in the treatment of sepsis-related acute respiratory failure. METHODS: This retrospective study included 136 subjects with a diagnosis of acute respiratory failure and intrapulmonary or extrapulmonary sepsis who were placed on NIV. Subjects were divided into 2 groups based on the need for intubation from NIV: NIV failure (n = 70) and NIV success (n = 66). Demographic, clinical, and outcome data were collected and compared between groups, with the development of multivariate models to predict NIV failure and mortality. RESULTS: The overall NIV failure rate in subjects with a diagnosis of sepsis was 51%. There were no between-group differences in demographic or baseline characteristics. However, there were significant differences in clinical variables, with higher SOFA scores (NIV failure: 6.4 [± 3.0] vs NIV success: 4.9 [± 2.1]; P = .002), 2nd lactate levels (NIV failure: 2.6 [1.7 - 4.3] vs NIV success: 1.9 [1.4 - 2.6] mmol/L; P = .007), and initial NIV [Formula: see text] settings (NIV failure: 0.50 [0.40 - 0.70] vs NIV failure: 0.40 [0.35 - 0.50]; P = .003) in subjects who failed NIV. There were also more subjects in the NIV failure group who had a lactate ≥ 4 mmol/L prior to NIV start compared to those who succeeded on NIV (33% vs 15%, P = .02). At NIV start, subjects in the NIV failure group had lower mean arterial pressure (85 mm Hg [IQR 74-96] vs 91.7 mm Hg [IQR 78-108], P = .042) and Glasgow coma scale scores (14 [IQR 13-15] vs 15 [IQR 14-15], P < .002), while fewer subjects in the NIV failure group received a fluid bolus in the 24 h prior to NIV start (33% vs 53%, P = .02) or had signs of volume overload (36% vs 64%, P < .001). Multivariate analysis indicated that age (odds ratio 1.05 [95% CI 1.01-1.09], P = .02), SOFA score (odds ratio 1.49 [95% CI 1.15-1.94], P = .002), first systolic blood pressure (odds ratio 0.97 [95% CI 0.95-0.99], P = .02), signs of volume overload (odds ratio 0.23 [95% CI 0.07-0.68], P = .008], fluids prior to NIV (odds ratio 0.08 [95% CI 0.02-0.31], P < .001), and initial [Formula: see text] on NIV (odds ratio 1.04 [95% CI 1.01-1.08, P = .002) independently predicted NIV failure with an area under the curve of 0.88. Only NIV failure independently predicted death in multivariate analysis (area under the curve = 0.70). CONCLUSIONS: NIV failure in sepsis-related acute respiratory failure was independently predicted by patient acuity, first systolic blood pressure after sepsis alert, initial [Formula: see text] settings on NIV, fluid resuscitation, and signs of volume overload. However, only NIV failure independently predicted death in this cohort of subjects.

Evaluation and exploration of a social prescribing initiative: Study protocol.

Attention is being given to healthcare initiatives with the potential to save money and improve lives. One example is social prescribing, which supports patients whose ill-health is exacerbated by loneliness. While evidence has accumulated attesting to social prescribing's efficacy, one limitation has been the lack of a theoretical framework, which limits understanding of how tackling loneliness improves health. In our evaluation of a social prescribing pathway, we adopt a 'Social Cure' approach, which posits that social relations affect health. Our study will evaluate the efficacy of the pathway and determine the extent to which group processes are responsible for health improvements.

Fighting COVID-19 with Agility, Transparency, and Participation: Wicked Policy Problems and New Governance Challenges.

Governments are being put to the test as they struggle with the fast and wide spread of COVID-19. This article discusses the compelling challenges posed by the COVID-19 pandemic by examining how this wicked problem has been managed by the South Korean government with agile-adaptive, transparent actions to mitigate the surge of COVID-19. Unlike many Western countries, South Korea has been able to contain the spread of COVID-19 without a harsh forced lockdown of the epicenter of the virus. This essay argues that an agile-adaptive approach, a policy of transparency in communicating risk, and citizens' voluntary cooperation are critical factors. It also suggests that the South Korean government learned costly lessons from the MERS failure of 2015. This essay suggests ways that Western countries can manage future wicked problems such as COVID-19 without paying too much cost and maintaining quality of life in open and free societies.

Microbial contamination of tattoo and permanent makeup inks marketed in the US: a follow-up study.

In a 2018 survey, U.S. Food and Drug Administration (FDA) identified microbial contamination in 42 (49%) of 85 unopened tattoo and permanent makeup (PMU) inks purchased from 13 manufacturers in the US between November 2015 and April 2016. To confirm the results of our previous survey, we evaluated the level of microbial contamination in an additional 27 samples from 10 manufacturers from September 2017 to December 2017, including 21 unopened tattoo and PMU inks which were selected based on our previous survey results and 6 ink diluents that were not previously analysed. Aerobic plate count and enrichment culture methods from the FDA's Bacteriological Analytical Manual revealed 11 (52%) out of 21 inks, from six manufacturers, were contaminated with micro-organisms, with contamination levels up to 3·6 × 108  CFU per gram, consistent with our previous survey results. We identified 25 bacterial strains belonging to nine genera and 19 species. Strains of Bacillus sp. (11 strains, 44%) were dominant, followed by Paenibacillus sp. (5 strains, 20%). Clinically relevant strains, such as Kocuria rhizophila and Oligella ureolytica, were also identified, as similar to the findings in our previous survey. No microbial contamination was detected in any of the six ink diluents.

Models of transmission of COVID-19 with time under the influence of meteorological determinants

ObjectivesThis work aimed at modeling the progressions of COVID-19 cases in time in relation to meteorological factors in large cities of Brazil, Italy, Spain, and USA, and finding the viability of SARS-CoV-2 virus in different weather conditions based on models. MethodsNew models constructed showing the relationship of the I' (the number of infected individuals divided by the total population of a city) with the independent variables -time, temperature, relative humidity, and wind velocity. The regression models fitting in the data were statistically validated by: 1) plot of observed and predicted response; 2) standardized residual plots showing the characteristics of errors; 3) adjusted [Formula] value; 4) the p value for the parameters associated with the various independent variables; and 5) the predictive power of the model beyond data points. ResultsModels indicate that 1) the transmission of COVID-19 could be relatively high either for elevated temperatures with lower relative humidity or for lower temperatures with higher relative humidity conditions; 2) disease transmission is expected to be reduced more with higher wind velocity; 3) the rate of increase in the number of COVID-19 cases increases in one model with a constant rate and in the other two with varying rates in time. These transmission features seem to have connections with the structural components of the SARS-CoV-2 virus. Under suitable meteorological conditions, the partial natural disappearance of COVID-19 pandemic could be possible. ConclusionNew models for I' may be considered to understand the viability of the virus in the environment and future transmission of COVID-19.

Policy learning and crisis policy-making: quadruple-loop learning and COVID-19 responses in South Korea.

This study aims to analyze how the Korean government has been effective in taming COVID-19 without forced interruptions (i.e. lockdowns) of citizens' daily lives. Extending the theory of organizational learning, we propose the quadruple-loop learning model, through which we examine how a government can find solutions to a wicked policy problem like COVID-19. The quadruple-loop learning model is applied to explain how the Korean government could effectively tame COVID-19 in the initial stage through its agile as well as adaptive approach based on effective interactions of backstage (time, target, and context) and frontstage of policy processes mainly focusing on the initial stage until the highest alert level was announced. Based on the Korean case, this study also examines critical factors to effective learning organizations such as leadership, information and transparency, as well as citizen participation and governance.

Procedural and obstetric outcomes after embryo reduction vs fetal reduction in multifetal pregnancy.

OBJECTIVE: To compare the obstetric outcome and incidence of procedure-related adverse events after embryo reduction (ER) vs fetal reduction (FR), in multifetal pregnancies undergoing reduction to twins or singletons. METHODS: We analyzed retrospectively data from multifetal pregnancies that underwent transvaginal ER (n = 181) at a mean gestational age of 7.6 weeks or transabdominal FR (n = 115) at a mean gestational age of 12.9 weeks between December 2006 and January 2017. FR was performed after a detailed fetal anomaly scan. The two groups were compared with respect to obstetric outcomes, such as incidence of miscarriage, early or late preterm delivery, maternal complications and fetal loss, and procedure-related adverse events, including incidence of subchorionic hematoma and procedure-related fetal loss. RESULTS: Compared with pregnancies that underwent ER, the incidence of procedure-related fetal loss was lower in the FR group (7.2% vs 0.9%; P = 0.039; odds ratio (OR), 0.12; 95% CI, 0.02-0.89). Mean gestational age at delivery for twins was 34.2 weeks in the ER group and 35.7 weeks in the FR group (P = 0.014). Compared with the ER group, the FR group had lower miscarriage (8.8% vs 2.6%; P = 0.045; OR, 0.28; 95% CI, 0.08-0.97) and overall fetal loss (13.3% vs 5.2%; P = 0.031; OR, 0.36; 95% CI, 0.14-0.91) rates. CONCLUSIONS: The FR procedure is, overall, a better and safer approach to reducing morbidity and mortality in multifetal pregnancies. Spontaneous demise of one fetus may occur after ER, and FR has the advantage that chorionic villus sampling and ultrasound screening for increased nuchal translucency and anatomical defects can be conducted before the procedure. The ER approach is still reasonable when a patient's religious or other ethical concerns are of primary importance. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Microbiological survey of commercial tattoo and permanent makeup inks available in the United States.

AIMS: Tattooing and use of permanent makeup (PMU) has dramatically increased over the last decade, with a concomitant increase in ink-related infections. The aim of this study was to determine whether micro-organisms are present, and if so, the number and their identification in the commercial tattoo and PMU inks available in the United States. METHODS AND RESULTS: We surveyed 85 unopened tattoo and PMU inks, purchased from 13 companies. We incubated 100 µl of ink samples on trypticase soy agar plates for bacterial growth, 7H10 Middlebrook medium for mycobacterial growth, and Sabouraud dextrose medium for fungal growth. In total, 42 inks were contaminated with micro-organisms (49%). Thirty-three inks were contaminated with bacteria, 2 inks with fungi, and 7 inks had both bacterial and fungal growth. Mycobacteria were not detected in any of the examined tattoo and PMU inks. In 26 inks, microbial concentrations ranged between 101 and 103 CFU per ml, but higher counts (>103 CFU per ml) were recorded in 16 inks. We identified 83 bacteria by their 16S rDNA sequences, including 20 genera and 49 species. Strains of Bacillus spp. (53%) were dominant, followed by Lysinibacillus fusiformis (7%) and Pseudomonas aeruginosa (5%). Thirty-four (41%) possibly clinically relevant strains were identified, including P. aeruginosa, Dermacoccus barathri and Roseomonas mucosa, some of which have been previously reported to be associated with human skin infections. CONCLUSIONS: The results indicate that commercial tattoo and PMU inks on the US market surveyed in this study contain a wide range of micro-organisms, including pathogenic bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial contaminants in tattoo and PMU inks are an emerging safety concern for public health. This study provides evidence that microbial contamination of tattoo and PMU inks available in the United States is more common than previously thought and highlights the importance of monitoring these products for potentially pathogenic micro-organisms.

Experimental results from an X-ray imaging crystal spectrometer utilizing multi-wire proportional counter for KSTAR.

The inconsistency of the first experimental results from the X-ray imaging crystal spectrometer for the Korea Superconducting Tokamak Advanced Research device utilizing a multi-wire proportional counter (MWPC) is clarified after improving the photon-count rate of the data acquisition system for the MWPC and ground loop isolator for the whole spectrometer system. The improved MWPC is successfully applied to pure Ohmic plasmas as well as plasmas with high confinement modes.

Canadian Cardiovascular Society/Canadian Society of Cardiac Surgeons/Canadian Society for Vascular Surgery Joint Position Statement on Open and Endovascular Surgery for Thoracic Aortic Disease

In 2014, the Canadian Cardiovascular Society (CCS) published a position statement on the management of thoracic aortic disease addressing size thresholds for surgery, imaging modalities, medical therapy, and genetics. It did not address issues related to surgical intervention. This joint Position Statement on behalf of the CCS, Canadian Society of Cardiac Surgeons, and the Canadian Society for Vascular Surgery provides recommendations about thoracic aortic disease interventions, including: aortic valve repair, perfusion strategies for arch repair, extended arch hybrid reconstruction for acute type A dissection, endovascular management of arch and descending aortic aneurysms, and type B dissection. The position statement is constructed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and has been approved by the primary panel, an international secondary panel, and the CCS Guidelines Committee. Advent of endovascular technology has improved aortic surgery safety and extended the indications of minimally invasive thoracic aortic surgery. The combination of safer open surgery with endovascular treatment has improved patient outcomes in this rapidly evolving subspecialty field of cardiovascular surgery.

Linking Emotional Labor, Public Service Motivation, and Job Satisfaction: Social Workers in Health Care Settings.

This study examines the determinants of emotional laborers'--social workers in health care organizations--job satisfaction and their public service motivation in using a structural equation model and provides empirical evidence regarding what contributes to job satisfaction or burnout in these workers. Among several latent variables, this study confirmed that false face significantly decreases the job satisfaction of social worker and is positively associated with burnout. In addition, commitment to public interest increases social workers' job satisfaction significantly. This study has implications for the management of emotional labor. By educating emotional laborers to reappraise situations to increase their job satisfaction and avoid burnout, reappraisal training and education are expected to result in increases in positive emotions and decreases in negative emotions, and to improve employees' performance in their organizations.

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM.

CR6-interacting factor 1 is a key regulator in Aß-induced mitochondrial disruption and pathogenesis of Alzheimer's disease.

Mitochondrial dysfunction, often characterized by massive fission and other morphological abnormalities, is a well-known risk factor for Alzheimer's disease (AD). One causative mechanism underlying AD-associated mitochondrial dysfunction is thought to be amyloid-ß (Aß), yet the pathways between Aß and mitochondrial dysfunction remain elusive. In this study, we report that CR6-interacting factor 1 (Crif1), a mitochondrial inner membrane protein, is a key player in Aß-induced mitochondrial dysfunction. Specifically, we found that Crif1 levels were downregulated in the pathological regions of Tg6799 mice brains, wherein overexpressed Aß undergoes self-aggregation. Downregulation of Crif1 was similarly observed in human AD brains as well as in SH-SY5Y cells treated with Aß. In addition, knockdown of Crif1, using RNA interference, induced mitochondrial dysfunction with phenotypes similar to those observed in Aß-treated cells. Conversely, Crif1 overexpression prevented Aß-induced mitochondrial dysfunction and cell death. Finally, we show that Aß-induced downregulation of Crif1 is mediated by enhanced reactive oxygen species (ROS) and ROS-dependent sumoylation of the transcription factor specificity protein 1 (Sp1). These results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying Aß-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. We propose that Crif1 may serve as a novel therapeutic target in the treatment of AD.

Crucial role of calbindin-D28k in the pathogenesis of Alzheimer's disease mouse model.

Calbindin-D28k (CB), one of the major calcium-binding and buffering proteins, has a critical role in preventing a neuronal death as well as maintaining calcium homeostasis. Although marked reductions of CB expression have been observed in the brains of mice and humans with Alzheimer disease (AD), it is unknown whether these changes contribute to AD-related dysfunction. To determine the pathogenic importance of CB depletions in AD models, we crossed 5 familial AD mutations (5XFAD; Tg) mice with CB knock-out (CBKO) mice and generated a novel line CBKO·5XFAD (CBKOTg) mice. We first identified the change of signaling pathways and differentially expressed proteins globally by removing CB in Tg mice using mass spectrometry and antibody microarray. Immunohistochemistry showed that CBKOTg mice had significant neuronal loss in the subiculum area without changing the magnitude (number) of amyloid ß-peptide (Aß) plaques deposition and elicited significant apoptotic features and mitochondrial dysfunction compared with Tg mice. Moreover, CBKOTg mice reduced levels of phosphorylated mitogen-activated protein kinase (extracellular signal-regulated kinase) 1/2 and cAMP response element-binding protein at Ser-133 and synaptic molecules such as N-methyl-D-aspartate receptor 1 (NMDA receptor 1), NMDA receptor 2A, PSD-95 and synaptophysin in the subiculum compared with Tg mice. Importantly, this is the first experimental evidence that removal of CB from amyloid precursor protein/presenilin transgenic mice aggravates AD pathogenesis, suggesting that CB has a critical role in AD pathogenesis.

A case-controlled, retrospective, comparative study on the use of biodegradable synthetic polyurethane foam versus polyvinyl acetate sponge after nasal fracture reduction.

One of the most frequently used packing materials in closed reduction of a nasal bone fracture is the hydroxylated polyvinyl acetate sponge (PVAS; Merocel(®)); however this may cause synechia, epistaxis, and pain. Synthetic polyurethane foam (SPF; Nasopore(®) Forte) has recently been used in septoplasty to prevent synechia or restenosis and haematoma formation. The purpose of this study was to compare the effects of PVAS and SPF on postoperative appearance and discomfort following the reduction of nasal bone fractures. We retrospectively reviewed all patient questionnaires and medical histories, and clinical photographs and computed tomography scans obtained before and after surgery. Outcomes were assessed using the Global Aesthetic Improvement Scale (GAIS) score and visual analogue scale (VAS) scores, which were used to assess discomfort during the 6-month follow-up period. Postoperatively, there was no statistically significant difference in the GAIS for the two packing materials (P > 0.05). Postoperative epistaxis was observed at a significantly lower rate in the SPF group than in the PVAS group, whereas anterior rhinorrhea and posterior nasal drip occurred at significantly higher rates following removal of packing in the SPF group (P < 0.05). The results of this study suggest that synthetic dissolvable polyurethane may be a reliable alternative material for nasal packing and postoperative management following the reduction of nasal bone fractures.

Efficiency disparities among community hospitals in Tennessee: do size, location, ownership, and network matter?

This study examined the impact of ownership, size, location, and network on the relative technical efficiency of community hospitals in Tennessee for the 2002-2006 period, by applying data envelopment analysis (DEA) to measure technical efficiency (decomposed into scale efficiency and pure technical efficiency). Data envelopment analysis results indicate that medium-size hospitals (126-250 beds) are more efficient than their counterparts. Interestingly, public hospitals are significantly more efficient than private and nonprofit hospitals in Tennessee, and rural hospitals are more efficient than urban hospitals. This is the first study to investigate whether hospital networks with other health care providers affect hospital efficiency. Results indicate that community hospitals with networks are more efficient than non-network hospitals. From a management and policy perspective, this study suggests that public policies should induce hospitals to downsize or upsize into optional size, and private hospitals and nonprofit hospitals should change their organizational objectives from profit-driven to quality-driven.

SIRT1, a class III histone deacetylase, regulates TNF-α-induced inflammation in human chondrocytes.

OBJECTIVE: The present study was performed to elucidate the possible role of SIRT1 signaling in joint inflammation in human articular chondrocytes. DESIGN: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect gene products and proteins involved in tumor necrosis factor α (TNF-α)-induced inflammation and cartilage degradation in human primary chondrocytes. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was evaluated by gelatin zymography. Overexpression and knockdown of SIRT1 were also performed to investigate whether SIRT1 is associated with the anti-inflammatory activity of resveratrol in chondrocytes. RESULTS: Resveratrol dose-dependently inhibited TNF-α-induced cyclooxygenase-2 (COX-2), MMP-1, MMP-3, MMP-13 and PGE(2) production in human chondrocytes. Moreover, MMP-2 and MMP-9 activity was increased by treatment with TNF-α; however, SIRT1 activation decreased the proinflammatory effects induced by TNF-α. In addition, treatment of SIRT1 activator and overexpression of SIRT1 inhibited the expression and activation of the main proinflammatory regulator NF-κB, which was increased by TNF-α. When SIRT1 was overexpressed in chondrocytes, the anti-inflammatory action of SIRT1 was similar to that exerted by resveratrol. CONCLUSIONS: SIRT1 activation deacetylates and inactivates NF-κB, and thereby, exerts an anti-inflammatory effect on chondrocytes, suggesting that SIRT1 activators could be explored as potential treatments for arthritis.

Vitamin D-binding protein interacts with Aß and suppresses Aß-mediated pathology.

The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (Aß), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced Aß aggregation in vitro. DBP also prevented Aß-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Aß-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Aß into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Aß by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD.