Outgroup Research Articles

Assessment of Mental Health and Coping Disparities Among Racial and Ethnic Groups Amid COVID-19 From the "How Right Now" Campaign.

Objectives:How Right Now (HRN) is an evidence-based, culturally responsive communication campaign developed to facilitate coping and resilience among US groups disproportionately affected by the COVID-19 pandemic. To inform the development of this campaign, we examined patterns in emotional health, stress, and coping strategies among HRN’s audiences, focusing on differences among racial and ethnic groups.Methods:We used a national probability panel, AmeriSpeak, to collect survey data from HRN’s priority audience members in English and Spanish at 2 time points (May 2020 and May 2021). We conducted statistical testing to examine differences between time points for each subgroup (Hispanic, non-Hispanic Black, and non-Hispanic White) and differences among subgroups at each time point.Results:We found disparities in COVID-19–related mental health challenges and differences in coping strategies. Non-Hispanic Black respondents were more likely than non-Hispanic White respondents to report challenges related to the social determinants of health, such as affording food and housing (26.4% vs 9.4% in May 2020) and experiencing personal financial loss (46.6% vs 29.2% in May 2020). In May 2021, 30.6% of Hispanic respondents reported being unable to meet basic food or housing needs versus 8.2% of non-Hispanic White respondents, and 51.6% reported personal financial loss versus 26.5% of non-Hispanic White respondents.Conclusions:Our study further illuminates what is needed to build emotional well-being pathways for people who historically have been economically and socially marginalized. Our findings underscore the need for public health interventions to provide culturally responsive mental health support to populations disproportionately affected by COVID-19 during the pandemic and into the future, with a focus on racial and ethnic disparities.

US Generalist Physicians and Groups That Focused Practice in a Single Care Setting: 2014-2017.

Some generalist physicians whose training prepared them for primary care practice increasingly practice in a facility (eg, hospitals, nursing homes); however, whether this trend was accompanied by a complimentary rise in generalist physicians who focused their practice on office-based care is unknown. Our objective in this study was to examine trends in the prevalence of generalist physicians and physician groups that practice in a single setting. This was a retrospective cross-sectional study of generalist physicians trained in family medicine, internal medicine, or geriatrics. We used 2014-2017 billing data for Medicare fee-for-service beneficiaries to measure the proportion of all patient visits made by physicians in the following care settings: office, outpatient hospital department, inpatient hospital, and other sites. From 2014 to 2017, the proportion of generalist physicians who narrowed their practice to a single setting increased by 6.69% (from 62.80% to 67.00%, p for trend <0.001). In 2017, 4.63% of physician groups included more than 1 type of setting-based physicians. Generalist physicians treating older adults increasingly narrowed their practice focus to a single type of health care setting. This trend was not accompanied by growth among physician groups that included different types of setting-based physicians. Further evaluation of the consequences of these trends on the fragmentation of primary care delivery across different health care settings and primary care outcomes is needed.

Melatonin ameliorates diabetic hyperglycaemia-induced impairment of Leydig cell steroidogenic function through activation of SIRT1 pathway

BackgroundDiabetes mellitus (DM)-related complications are important health problems worldwide. The underlying mechanisms for diabetic male subfertility/infertility are considerably complicated and need to be unveiled for therapeutic intervention. Melatonin treatment was investigated to assess the beneficial effects on injured steroidogenic function in DM due to its regulatory roles in mitochondria and autophagy.MethodsDiabetic hyperglycaemia was induced in rats injected with streptozotocin (STZ, 55 mg/kg/d) or simulated in TM3 Leydig cell line cultured with medium containing 30 mM D-glucose. Then, diabetic rats or the TM3 cells under high glucose were treated with melatonin. The diabetic rats were randomly divided into diabetes mellitus group (DM group), insulin treatment group (DM + INS group) and melatonin treatment group (DM + MT group). The TM3 Leydig cells were divided into a normal glucose control group (NG group), a high glucose treatment group (HG group), and a melatonin treatment group (HG + MT group). Then, Sirt1 (silent mating type information regulation 2 homologue) 1 expression was knocked down by siRNA.ResultsThe results showed that hyperglycaemia induced a decline in steroidogenesis, accompanied by autophagy defects, mitochondrial dysfunction and oxidative stress, in rats in the DM group or TM3 Leydig cells in the HG group. Furthermore, reduced SIRT1 expression levels and hyperacetylation were found in Leydig cells of DM group. Melatonin treatment ameliorated hyperglycaemia-induced impairment of Leydig cell function with simultaneous stimulation of 5’-adenosine monophosphate activated protein kinase (AMPK)/SIRT1 activity and the expression of autophagy-related genes. With regards to mitochondrial function, it promoted mitochondrial biogenesis with elevated PGC-1α, NRF1 and mtTFA, improved mitochondrial morphology, increased BNIP3L-related mitophagy and alleviated oxidative stress. Further results revealed that knockdown of Sirt1 in Leydig cells prevented the protective effects provided by melatonin against high glucose treatment, and interestingly, neutralization of reactive oxygen species (ROS) by N-acetyl-L-cysteine pretreatment abolished the stimulatory effect of melatonin on AMPK/SIRT1 activity in Leydig cells and prevented the induction of autophagy and mitochondrial biogenesis in the context of high glucose, indicating that modulation of SIRT1 pathway by melatonin was closely linked to ROS levels and oxidative stress.ConclusionsThese findings suggest that SIRT1 pathway plays essential roles in the pleiotropic actions of melatonin on Leydig cells and in the prevention of hyperglycaemia-induced steroidogenic dysfunction. The stimulatory action of melatonin on SIRT1 pathway is related to oxidative stress and its antioxidant property. Our data provide new evidence for the relationship of melatonin and SIRT1 pathway in the context of hyperglycaemia, and melatonin as a combination therapy may be useful to combat DM-related complications, especially male reproductive system injury.

A randomized single-blind controlled trial of a prototype digital polytherapeutic for tinnitus.

ObjectiveThis randomized single-blind controlled trial tested the hypothesis that a prototype digital therapeutic developed to provide goal-based counseling with personalized passive and active game-based sound therapy would provide superior tinnitus outcomes, and similar usability, to a popular passive sound therapy app over a 12 week trial period.MethodsThe digital therapeutic consisted of an app for iPhone or Android smartphone, Bluetooth bone conduction headphones, neck pillow speaker, and a cloud-based clinician dashboard to enable messaging and app personalization. The control app was a popular self-help passive sound therapy app called White Noise Lite (WN). The primary outcome measure was clinically meaningful change in Tinnitus Functional Index (TFI) between baseline and 12 weeks of therapy. Secondary tinnitus measures were the TFI total score and subscales across sessions, rating scales and the Client Oriented Scale of Improvement in Tinnitus (COSIT). Usability of the US and WN interventions were assessed using the System Usability Scale (SUS) and the mHealth App Usability Questionnaire (MAUQ). Ninety-eight participants who were smartphone app users and had chronic moderate-severe tinnitus (>6 months, TFI score > 40) were enrolled and were randomly allocated to one of the intervention groups. Thirty-one participants in the USL group and 30 in the WN group completed 12 weeks of trial.ResultsMean changes in TFI for the USL group at 6 (16.36, SD 17.96) and 12 weeks (17.83 points, SD 19.87) were clinically meaningful (>13 points reduction), the mean change in WN scores were not clinically meaningful (6 weeks 10.77, SD 18.53; 12 weeks 10.12 points, SD 21.36). A statistically higher proportion of USL participants achieved meaningful TFI change at 6 weeks (55%) and 12 weeks (65%) than the WN group at 6 weeks (33%) and 12 weeks (43%). Mean TFI, rating and COSIT scores favored the US group but were not statistically different from WN. Usability measures were similar for both groups.ConclusionsThe USL group demonstrated a higher proportion of responders than the WN group. The usability of the USL therapeutic was similar to the established WN app. The digital polytherapeutic demonstrated significant benefit for tinnitus reduction supporting further development.

Exercise testing in heart failure with preserved ejection fraction: an appraisal through diagnosis, pathophysiology and therapy-A clinical consensus statement of the Heart Failure Association and European Association of Preventive Cardiology of the European Society of Cardiology.

Patients with heart failure with preserved ejection fraction (HFpEF) universally complain of exercise intolerance and dyspnoea as key clinical correlates. Cardiac as well as extracardiac components play a role for the limited exercise capacity, including an impaired cardiac and peripheral vascular reserve, a limitation in mechanical ventilation and/or gas exchange with reduced pulmonary vascular reserve, skeletal muscle dysfunction and iron deficiency/anaemia. Although most of these components can be differentiated and quantified through gas exchange analysis by cardiopulmonary exercise testing (CPET), the information provided by objective measures of exercise performance has not been systematically considered in the recent algorithms/scores for HFpEF diagnosis, by neither European nor US groups. The current clinical consensus statement by the Heart Failure Association (HFA) and European Association of Preventive Cardiology (EAPC) of the European Society of Cardiology (ESC) aims at outlining the role of exercise testing and its pathophysiological, clinical and prognostic insights, addressing the implications of a thorough functional evaluation from the diagnostic algorithm to the pathophysiology and treatment perspectives of HFpEF. Along with these goals, we provide a specific analysis of the evidence that CPET is the standard for assessing, quantifying, and differentiating the origin of dyspnoea and exercise impairment and even more so when combined with echocardiography and/or invasive haemodynamic evaluation. This will lead to improved quality of diagnosis when applying the proposed scores and may also help to implement the progressive characterization of the specific HFpEF phenotypes, a critical step toward the delivery of phenotype‐specific treatments.

A cross-cultural study of visual attention in autism spectrum disorder

ABSTRACT Differences in visual attention have been documented in ASD, and appear linked to clinical symptoms. However, most research has been conducted in Western cultures. Because striking differences in visual attention patterns have been documented in other cultures, it is important to understand how culture may influence attentional patterns in ASD. This study compared differences in visual attention in ASD across Western and East Asian cultures, where differences in attention to contextual and global information have been repeatedly demonstrated, to investigate potential culturally-specific ASD phenotypes. One hundred thirty-two total participants included individuals with ASD (n = 24) and controls (n = 47) from Hong Kong (HK), along with a previously studied group of age- and IQ-comparable participants from the United States (n = 26 ASD; n = 35 control). Gaze was tracked while participants completed two narrative tasks that differed in social-emotional complexity. Proportions of fixations to face, bodies, and setting were examined across groups using linear mixed-effect models and a series of growth curve models. Cultural differences were found across tasks and groups. Both the ASD and control HK groups attended more to global contextual setting information, more to the body regions, and less toward faces of characters compared to US groups. Growth curve models indicated that these differences attenuated over time in certain stimuli. ASD-related effects were only observed in the more complex stimuli depicting characters with ambiguous facial expressions. Findings indicate a notable cultural influence on visual attention patterns in ASD, and underscore the importance of stimuli complexity in differentiating cultural versus diagnostic effects on attentional styles.

Ultrasound-Guided Umbilical Venous Catheter Insertion to Reduce Rate of Catheter Tip Malposition in Neonates: A Randomized, Controlled Trial.

To investigate whether ultrasound-guided umbilical venous catheter (UVC) insertion (US group) reduced the rate of malpositioning of the catheter tip compared to the standard method of insertion (SD group). In this open-label, randomized, controlled trial, neonates admitted to NICU within the first week of life were randomly assigned to the US group (n = 26) or SD group (n = 27). Neonates with major congenital anomalies of the thorax and abdomen were excluded. The primary outcome was the rate of malpositioning of the catheter tip. The rate of malpositioning of the catheter tip was observed in a significantly lower number of neonates in the US group as compared to the SD group (11/26, 42.3% vs. 20/27, 74%; RR = 0.57, 95% CI: 0.34 to 0.94, p = 0.019). As more of the UVCs were positioned optimally in the first attempt in the US group than SD group, the need for repeated attempts at catheter repositioning was reduced, resulting in reduced procedure time (minutes) [mean (SD), 23.96 (6.42) vs. 30 (1.83); mean difference 6.04 (95% CI: 3.46 to 8.62), p = 0.005]. This also led to a reduction in the additional X-ray exposure in the US group (n = 11) compared to the SD group (n = 20) [95% CI: 3.12 to 44.26; p = 0.020]. Ultrasound-guided UVC insertion significantly reduced the rate of catheter tip malposition. It also reduced the number of attempts at catheter manipulation, procedure time, and X-ray exposures. With adequate training, it could be incorporated into routine bedside practice during UVC insertion for optimum placement. Clinical Trial Registry of India ( www.ctri.nic.in ) CTRI/2021/03/031894.

The Clinical Application of Combined Ultrasound, Mammography, and Tumor Markers in Screening Breast Cancer among High-Risk Women.

In order to explore the clinical application value of color Doppler ultrasound (CDUS), mammography (MAM), and serum tumor marker carbohydrate antigen 153 (CA153) in screening breast cancer (BC) for high-risk women, a total of 38,241 women were surveyed by epidemiological questionnaire on BC high-risk factors. A total of 10,821 cases were screened, accounting for 28.30%. They were randomly divided into US, MAM, and CA153 and combined examination group which has no significant difference in high-risk factors. Breast cancer in high-risk population was screened by CDUS, MAM, and CA153 and combined examination. CA153 was detected by electroluminescence method. The positive detection rate of BC was 360.41/100,000 (39/10,821). The overall difference in the positive detection rate of BC among 10,821 cases in all age groups was statistically significant. The sensitivity and negative predictive value of combined examination were significantly improved compared with each single examination. Combined examination for BC screening can significantly improve the sensitivity of BC early diagnosis and reduce the missed diagnosis rate.

APJS-1 International trial activity of AGITG

The Australasian Gastrointestinal Trials Group (AGITG) is the main cooperative trials group performing multidisciplinary gastrointestinal clinical trials in Australia and New Zealand. The group has a strong history of international collaboration and has undertaken trials with US and European trial groups. More recently AGITG has had more of a focus in the Asian region and has developed strong relationships with several key Asian partners including within Japan. This relationship has developed primarily in the gastric cancer space through the INTEGRATE gastric cancer trials program.

PI3K/Akt pathway mediates the positive inotropic effects of insulin in Langendorff-perfused rat hearts

Insulin exerts positive inotropic effects on cardiac muscle; however, the relationship between cardiac contractility and phosphoinositol-3-kinase/Akt (PI3K/Akt) activation remains unclear. We hypothesized that the positive inotropic effects of insulin are dose-dependent and mediated via the PI3K/Akt pathway in isolated normal rat hearts. The Institutional Animal Investigation Committee approved the use of hearts excised from rats under pentobarbital anesthesia. The hearts were perfused at a constant pressure using the Langendorff technique. After stabilization (baseline), the hearts were randomly divided into the following four insulin (Ins) groups: 1) Ins0 (0 IU/L), 2) Ins0.5 (0.5 IU/L), 3) Ins5 (5 IU/L), and 4) Ins50 (50 IU/L) (n = 8 in each group). To clarify the role of the PI3K/Akt pathway in insulin-dependent inotropic effects, we also treated the insulin groups with the PI3K inhibitor wortmannin (InsW): 5) InsW0 (0 IU/L), 6) InsW0.5 (0.5 IU/L), 7) InsW5 (5 IU/L), and 8) InsW50 (50 IU/L). Hearts were perfused with Krebs–Henseleit buffer solution with or without wortmannin for 10 min, followed by 20 min perfusion with the solution containing each concentration of insulin. The data were recorded as the maximum left ventricular derivative of pressure development (LV dP/dt max). Myocardial p-Akt levels were measured at 3 min, 5 min, and at the end of the perfusion. In the Ins groups, LV dP/dt max in Ins5 and Ins50 increased by 14% and 48%, respectively, 3 min after insulin perfusion compared with the baseline. Tachyphylaxis was observed after 10 min in the Ins5 and Ins50 treatment groups. Wortmannin partially inhibited the positive inotropic effect of insulin; although insulin enhanced p-Akt levels at all time points compared with the control group, this increase was suppressed in the presence of wortmannin. The positive inotropic effect of insulin is dose-dependent and consistent with Akt activation. This effect mediated by high doses of insulin on cardiac tissue was temporary and caused tachyphylaxis, potentially triggered by Akt overactivation, which leads beta 1 deactivation.

A Preliminary Study on the Effects of Black Cohosh Preparations on Bone Metabolism of Rat Models With GnRH-a-Induced Peri-Menopausal Symptoms.

A Preliminary Study on the Effects of Black Cohosh Preparations on Bone Metabolism of Rat Models With GnRH-a-Induced Peri-Menopausal Symptoms.

Characterization of soil microbial community activity and structure for reducing available Cd by rice straw biochar and Bacillus cereus RC-1

The combination of biochar and specific bacteria has been widely applied to remediate Cadmium-contaminated soil. But little is known about how such composites affect the dynamic distribution of metal fractions. This process is accompanied by the alternations of soil properties and microbial community structures. Composite of rice straw biochar and Bacillus cereus RC-1 were applied to investigate its impacts on Cd alleviation and soil microbial diversity and structure. The bacterial/biochar composite treatment decreased the fraction of HOAc-extractable Cd by 38.82%, and increased residual Cd by 23.95% compared to the untreated control. Moreover, compared with the untreated control, the composite treatment significantly increased the soil pH by about 1.5 units, and the activities of catalase, urease and invertase enzymes were increased by 42.39%, 30.50% and 31.20%, respectively. Composite treatment increased soil bacterial and fungal alpha diversity, the relative abundance of Bacillus, Streptomyces, Arthrobacter, and Aspergillus species were also increased. Mantel test and correlation analysis indicated that the effects associated with fungal communities in influencing soil properties were lower than that those of bacterial communities by different treatment. Aggregated boosted tree (ABT) models analysis showed that soil chemical proprieties (as determined by SOM, CEC, AN, etc.,) contributed over 50% of the changes in bacterial and fungal communities by the composite treatment. The co-occurrence network results showed that all treatments enhanced the correlation between OUT groups and improved the possible relationships in the bacterial and fungal communities, especially the interrelationships between bacteria and fungi after the Cd fractions stabilized. These findings provide a new insight to optimal strategies for the remediation of Cd-contaminated soil.

Concomitant treatment with insulin and sodium–glucose cotransporter 2 inhibitors was associated with the renal composite outcome in Japanese patients with type 2 diabetes and chronic kidney disease: A propensity score‐matched analysis

ABSTRACTAims/IntroductionWe previously reported that sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment was associated with an improvement of the albumin‐to‐creatinine ratio in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. The present study clarified how concomitant insulin treatment (IT) with SGLT2i therapy influences the renal composite outcome (RCO).Materials and MethodsWe retrospectively evaluated 624 Japanese patients with type 2 diabetes mellitus and chronic kidney disease who underwent SGLT2i treatment. The renal composite outcome was set as progression of the stage of albuminuria or a ≥15% decrease in the estimated glomerular filtration rate per year. We developed a cohort model of patients managed with and without IT (Ins [+], Ins [−]) using propensity score matching methods. Furthermore, all patients in our study population were stratified into quintiles according to their propensity score.ResultsThe incidence of the RCO was in Ins (+) patients significantly higher than that in Ins (−) (P = 0.033). The estimated hazard ratio for the RCO was 1.55 (P = 0.035) in Ins (+) patients. The change in the estimated glomerular filtration rate and albumin‐to‐creatinine ratio in the groups was not statistically significant. The analysis, which was based on the quintiles, showed a statistically significant difference between the Ins (+) and Ins (−) groups (P = 0.01); the odds ratio for the RCO in patients managed with IT was 2.20 (P = 0.01).ConclusionsConcomitant administration of IT with SGLT2is influenced the RCO in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. We might need to consider the influence of concomitant agents on the renoprotective effects of SGLT2i therapy.

Ultrasound responsive Gd-DOTA/doxorubicin-loaded nanodroplet as a theranostic agent for magnetic resonance image-guided controlled release drug delivery of melanoma cancer

Theranostic agents use simultaneous for diagnostic and therapeutic procedures. In the present study, the effect of Gd-DOTA/doxorubicin-loaded perfluorohexane nanodroplets as a theranostic nanoparticle for control released drug delivery and ultrasound/MR imaging was investigated on B16F10 melanoma cancer cells. The intracellular uptake was performed by inductively coupled plasma optical emission spectrometry (ICP-OES) that indicated sonicated Gd-DOTA/DOX@PFH NDs uptake by cancer cells was approximately 1.5 times more than the non-sonicated nanodroplets after 12 h. In vitro and in vivo toxicity assays revealed that synthesized NDs are biocompatible and do not have organ toxicity. Ultrasound exposure significantly enhanced the release of doxorubicin from NDs (P-value< 0.05). Ultrasound echogenicity and T1-MRI relaxometry indicated that synthesized NDs have strong ultrasound signal intensity and high r1 relaxivity (6.34 mM−1 S−1). The concentration of DOX in mice vital organs for Gd-DOTA/DOX NDs was significantly lower than that of free DOX. Doxorubicin concentration after 150 min in the tumor region for the DOX-loaded Gd-NDs+US group reached 14.8 μg/g followed by sonication, which was 2.3 fold higher than that of the non-sonicated group. According to the obtained results, the synthesized nanodroplets, with excellent diagnostic (ultrasound/MRI) and therapeutic properties, could be promising theranostic agents in cancer imaging and drug delivery for chemotherapeutic application.

Exogenous gonadotropin-releasing hormone counteracts the adverse effect of scrotal insulation on testicular functions in bucks

This study determined the effects of scrotal insulation on testicular functions in bucks and evaluated the impact of exogenous gonadotropin-releasing hormone (GnRH) administration before scrotal insulation on sperm production and testicular vascular dynamics. Twelve bucks were randomly divided into three groups: scrotal-insulated animals without GnRH treatment (INS), scrotal-insulated animals treated previously with GnRH (GnRH + INS), and animals without insulation as controls (CON). Doppler ultrasonography was used to evaluate testicular vascular changes, and semen samples were collected to assess seminal parameters. Testicular samples were collected from slaughtered bucks at the end of the experiment for histological investigations and immunohistochemical analysis for caspase 3 (apoptotic marker), and a vascular endothelial growth factor (VEGF; hypoxic marker) evaluation. Sperm motility drastically decreased (33%) in the INS group on day 8 compared with those in the GnRH + INS and CON groups (58% and 85%, respectively). Testicular blood flow significantly decreased for 3 and 2 weeks in the INS and GnRH + INS groups, respectively. The pulsatility index (PI) reached pretreatment values at 5 and 4 weeks after insulation in the INS and GnRH + INS groups, respectively. The resistance index (RI) values increased in both insulated groups for the first 2 weeks and decreased to control values 4 weeks after insulation. However, the maximum velocity (VP) started to increase reaching pretreatment values by the 5th and 3rd weeks after insulation in the INS and GnRH + INS groups, respectively. Histological investigations showed a marked reduction in lipid inclusions in Sertoli cells in the GnRH + INS group compared with those in the INS group. The distributions of both caspase 3 and VEGF decreased in the GnRH + INS group compared with those in the INS group. This study showed that the administration of a single dose of GnRH delayed the negative effects of scrotal insulation on different seminal traits and revealed the pivotal role of GnRH in compensating testicular insulation in bucks.

MO718: Urgent, Early and Planned Start Peritoneal Dialysis—Does the Initiation Modality Matter to Patient's Outcomes?

Abstract BACKGROUND AND AIMS Peritoneal dialysis (PD) has been used as a renal replacement therapy for end-stage kidney disease patients in different initiation patterns: urgent, early and planned start PD. The indication of PD initiation is mainly based on the presence or not of signs and symptoms that would indicate dialysis urgent initiation and in the possibility of patients receive pre-dialysis when they would plan RRT initiation when necessary. Our aim was to evaluate if the PD initiation modality interfere in patients’ 30- and 180-day outcomes and in the technique survival. METHOD This is a single-center retrospective study that included incident adult patients starting PD between October 2016 and March 2021. Exclusion criteria were: (i) have done previously PD, (ii) patients younger &amp;lt; 18 years old and (iii) missing data related to main outcomes analysed. US-PD group was considered those incident patients starting therapy with some urgent indication and within 3 days after Tenckhoff catheter implantation, ES-PD group was those patients who had previously received urgent hemodialysis (HD) and started PD between 3 and 14 days and, Plan-PD group consisted of patients who started therapy after the breaking period (15 days). Complications and hospitalization due to all cause were compared 30 and 180 days from PD initiation. Technique survival during the first 180 days on PD were assessed by Kaplan–Meier curves. RESULTS During the period mentioned earlier 280 patients started PD. In these analyses 201 patients were included. Mean age was 58.4 ± 15.2 years old, most part of patients were female (51.7%) and considered themselves as white race (92%). The most common etiology for kidney disease was diabetes (32%). Most part of patients had arterial hypertension and diabetes as main comorbidities (88.6% and 48.3%). Considering the PD initiation, 62 (30.8%) patients started PD urgently, 84 (41.8%) patients had an earlier start and 55 (27.4%) started PD planned. Patients have similar characteristics regarding demographics, comorbidities, and cause of renal disease. Patients in the ES-PD group had higher prevalence of heart failure and coronary arterial disease compared to the others (P = 0.03 and 0.08, respectively). Regarding complications in the first 30 days on PD, the most common complication was mechanical ones such as leakage and catheter tip migration and the incidence of these did not differ from PD initiation modalities. The US and ES-PD groups presented a greater incidence of hospitalization events in the first 30 days compared with the Plan-PD group [8 (13.6%) events US-PD, 16 (19.3%) ES-PD and 1 (0.5%) Plan-PD—P = 0.04], most part of them not related to PD. Complication and hospitalization events were similar in all groups in 180 days on therapy. Patients on the ES-PD group had a higher percentage of transfer to HD during the first 180 days. Technique survival was similar between groups (US-PD 85.2%, ES-PD 77.1% and Plan-PD 88.7%—log-rank P = 0.18) in 180 days follow-up (Fig. 1). Death and transfer to HD were the most common causes for dropout, mainly in the ES-PD group [9 (10.7% deaths and 12 (14.3%) transfer to HD]. CONCLUSION The study demonstrates similar complications after 30 days PD initiation regardless of type of PD initiation, greater hospitalization events in the ES-PD group after 30 days, which can be related to the patients’ characteristics. Similar complications, hospitalizations, and technique survival after 180 days on PD we found for both groups.

Mechanism and effects of artesunate on the liver function of rats with type 1 diabetic periodontitis.

Periodontitis is an inflammatory disease of the gums. Periodontitis in diabetic patients can aggravate insulin resistance; however, its molecular and biological mechanism remains unclear. This study aimed to explore the effects of diabetic periodontitis on liver function and determine the mechanism by which artesunate improves liver function. Rats with streptozotocin-induced diabetes were divided into five groups: normal control (NC), diabetic periodontitis (DM+PD), artesunate intervention (ART), insulin intervention (INS), and combined medication intervention (ART+INS) groups. Drug interventions were then administered to the rats in each group as follows: 50mg/kg artesunate to the ART group, 6U/kg insulin to the INS group, and 50mg/kg artesunate + 6U/kg insulin to the ART+INS group. Blood samples, liver tissues, and the maxillary alveolar bone were collected postsacrifice. ART was found to significantly ameliorate hyperglycemia, blood lipid concentrations, and liver function. The levels of inflammatory factors reduced; the effect was more pronounced in the ART+INS group. Artesunate presumably inhibits the TLR4/NF-κB signaling pathway and expression of downstream inflammatory factors, thereby exerting a protective effect on diabetes-related liver function. This offers a fresh approach to treat diabetes mellitus.

Slicing the Pie: Quantifying the Aggregate and Distributional Effects of Trade

Abstract We develop a multi-sector gravity model with heterogeneous workers to quantify the aggregate and group-level welfare effects of trade. The model generalizes the specific-factors intuition to a setting with labour reallocation, leads to a parsimonious formula for the group-level welfare effects from trade, and nests the aggregate results in Arkolakis, Costinot and Rodríguez-Clare (2012, “New Trade Models, Same Old Gains?”, American Economic Review, 102, 94–130). We estimate the model using the structural relationship between China-shock driven changes in manufacturing employment and average earnings across US groups defined as commuting zones. We find that the China shock increases average welfare but some groups experience losses as high as four times the average gain. However, adjusting for plausible measures of inequality aversion barely affects the welfare gains. We also develop and estimate an extension of the model that endogenizes labour force participation and unemployment, finding similar welfare effects from the China shock.

MiR-129 Regulates Cell Viability in Alzheimer’s Disease Through Targeting Amyloid Precursor Protein (APP)

This study intends to explore miR-129’s effect on cell viability of Alzheimer’s disease by regulating the target gene APP. The hippocampal neurons were assigned into model group (MO group); mimetic group (SI group); inhibitor group (IN group) followed by analysis of hippocampal neuronal cell proliferation and activity, APP protein content, miR-129 expression and cell apoptosis by CCK-8 assay, Western blot method, MTT assay, qRT-PCR and flow cytometry. miR-129 expression of hippocampal neurons in IN group was lowest. Compared with IN and MO groups, SI group had significantly increased miR-129 level and reduced number of hippocampal neuron apoptosis (P &lt; 0.05). Compared with IN group, MO group had significantly reduced cell apoptosis (P &lt; 0.05). SI group had highest number of hippocampal neurons proliferation followed by IN group. SI group had highest OD value followed by MO group and IN group. The cell activity of SI group was higher than that of IN group and MO group (both P &lt; 0.05). Compared with SI group, rat neuron activity in MO group was significantly higher than IN group (P &lt; 0.05). The APP protein expression of hippocampal neuron cells in SI group was lowest followed by MO group and IN group (P &lt; 0.05). In conclusion, the low miR-129 expression can inhibit the activity of hippocampal neurons possibly through up-regulation of APP protein content.

A228 A FERMENTABLE FIBRE FREE DIET ACCELERATES SPONTANEOUS COLITIS DEVELOPMENT AND ALTERS THE GUT MICROBIOME IN MUC2-/- MICE

Abstract Background A key feature of ulcerative colitis (UC) is a defective colonic mucus layer. As Muc2-/- mice lack intestinal mucus, they’re often used to model UC. In these mice, luminal bacteria translocate from the gut lumen, triggering spontaneous colitis by 12–16 weeks of age. Notably, mucus defects are also seen in wildtype mice fed a fermentable fibre free (FF-free) diet. Aside from thinner mucus, FF-free fed mice show increased susceptibility to bacterial infections and a microbiome shift from fibre-utilizing to mucus-degrading bacteria. Indeed, a recent clinical study found that a microbiome shift towards proteolytic bacteria preceded clinical diagnosis of UC Aims To determine whether feeding newly weaned Muc2-/- mice a FF-free versus chow or inulin-enriched diet leads to - more rapid development of spontaneous colitis - shifts in the gut microbiota towards protein fermentation Methods Newly weaned Muc2-/- mice (3–4 weeks old) were fed 1 of 3 diets: 1) usual chow (Chow; 14.7% fibre mix), 2) FF-free (10% cellulose – poorly fermented) and 3) inulin-enriched (IN; same nutritional content as FF-free, with 10% inulin instead of cellulose). Body weight, diet intake and disease activity were monitored daily. By day 10, mice in the FF-free group developed severe colitis requiring euthanization. At this time, cecal contents (short-chain fatty acid [SCFA] analysis) and colonic tissue from all mice were collected for alcian blue/PAS staining and histopathological scoring. Stool was collected for 16S rRNA sequencing Results FF-free fed mice consumed fewer calories (p=0.0073), experienced less body weight gain (p=0.002), had colonic shortening (p&amp;lt;0.0001) and higher disease activity scores (p&amp;lt;0.0001) than mice fed the IN diet. Histopathological scores were higher in FF-free versus Chow (p&amp;lt;0.0001) and IN (p&amp;lt;0.0001) fed mice. Goblet cell mucin staining was reduced in FF-free compared to Chow and IN fed mice. Beta-diversity analysis showed clear differences in microbiome composition between groups. Acetate, product of fibre fermentation, was higher in the Chow (p&amp;lt;0.0001) and IN (p=0.0195) groups whereas branched-chain fatty acids (BCFA), product of protein fermentation, was higher in the FF-free group (p&amp;lt;0.0001) Conclusions Spontaneous colitis development in FF-free fed Muc2-/- mice was observed within 10 days (5–6 weeks old) of weaning whereas Chow or IN fed mice showed minimal to no signs of colitis, respectively. A diet devoid of fibre also led to less mucin staining and a gut microbiome shift that favoured BCFA over SCFA production, suggesting the microbiota of FF-free fed Muc2-/- mice are targeting mucosal proteins concurrent with disease exacerbation. These findings support future studies examining whether consumption of low fibre diets in UC patients worsen disease outcomes whereas diets rich in fibre and/or inulin prove beneficial Funding Agencies CCC, CIHRMSFHR Trainee Award, CH.I.L.D foundation