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1.
Health Educ Behav ; 50(1): 70-83, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34796747

ABSTRACT

BACKGROUND: There is little understanding of men's weight loss outcomes and behaviors in self-directed contexts, such as digital commercial mobile weight management programs. This is an especially pressing question given that men often express disinterest in weight management programs and it is unknown how that manifests in self-directed environments. Aims. Two studies fill this gap by retrospectively observing how men lose weight and engage in weight loss behaviors (Study 1) and their perceptions of improvements and gained knowledge (Study 2) when participating in the full length of a commercial mobile behavior change program called Noom. METHOD: In Study 1, repeated-measures linear mixed modeling was used to examine whether weight loss was statistically significant from baseline to 16 weeks and how engagement behaviors predicted weight in a sample of 7,495 male Noom users. In Study 2, 971 male Noom users completed an exploratory survey on the impact of the behavior change education in the program. RESULTS: In Study 1, men who remained in the full length of the program lost statistically significant weight from baseline to 16 weeks. 63% achieved clinically meaningful (5% or more) weight loss. Engagement in weight loss behaviors on the program predicted the amount of weight lost. In Study 2, men reported learning most about practical application and psychological aspects relating to food and psychology. DISCUSSION AND CONCLUSION: This is the first study to observe men's weight loss outcomes, behaviors, and perceptions of what they learned in a self-directed behavior change program. Our findings have important implications for more effective health promotion for the many men who choose to self-direct their weight loss.


Subject(s)
Health Promotion , Learning , Humans , Male , Retrospective Studies , Surveys and Questionnaires , Weight Loss
2.
PLOS Digit Health ; 1(6): e0000050, 2022 Jun.
Article in English | MEDLINE | ID: mdl-36812521

ABSTRACT

Behavioral weight loss reduces risk of weight-related health complications. Outcomes of behavioral weight loss programs include attrition and weight loss. There is reason to believe that individuals' written language on a weight management program may be associated with outcomes. Exploring associations between written language and these outcomes could potentially inform future efforts towards real-time automated identification of moments or individuals at high risk of suboptimal outcomes. Thus, in the first study of its kind, we explored whether individuals' written language in actual use of a program (i.e., outside of a controlled trial) is associated with attrition and weight loss. We examined two types of language: goal setting (i.e., language used in setting a goal at the start of the program) and goal striving (i.e., language used in conversations with a coach about the process of striving for goals) and whether they are associated with attrition and weight loss on a mobile weight management program. We used the most established automated text analysis program, Linguistic Inquiry Word Count (LIWC), to retrospectively analyze transcripts extracted from the program database. The strongest effects emerged for goal striving language. In striving for goals, psychologically distanced language was associated with more weight loss and less attrition, while psychologically immediate language was associated with less weight loss and higher attrition. Our results highlight the potential importance of distanced and immediate language in understanding outcomes like attrition and weight loss. These results, generated from real-world language, attrition, and weight loss (i.e., from individuals' natural usage of the program), have important implications for how future work can better understand outcomes, especially in real-world settings.

3.
JMIR Mhealth Uhealth ; 9(11): e30622, 2021 11 08.
Article in English | MEDLINE | ID: mdl-34747706

ABSTRACT

BACKGROUND: There is large variance in weight loss outcomes of digital behavior change interventions (DBCIs). It has been suggested that different patterns of engagement in the program could be responsible for this variance in outcomes. Previous studies have found that the amount of engagement on DBCIs, such as the number of meals logged or articles read, is positively associated with weight loss. OBJECTIVE: This retrospective study extends previous research by observing how important weight loss outcomes (high weight loss: 10% or greater body weight loss; moderate weight loss: between 5% to 10%; stable weight: 0 plus or minus 1%) are associated with engagement on a publicly available mobile DBCI (Noom) from 9 to 52 weeks. METHODS: Engagement and weight data for eligible participants (N=11,252) were extracted from the Noom database. Engagement measures included the number of articles read, meals logged, steps recorded, messages to coach, exercise logged, weigh-ins, and days with 1 meal logged per week. Weight was self-reported on the program. Multiple linear regressions examined how weight loss outcome (moderate and high vs stable) was associated with each engagement measure across 3 study time periods: 9-16 weeks, 17-32 weeks, and 33-52 weeks. RESULTS: At 9-16 weeks, among the 11,252 participants, 2594 (23.05%) had stable weight, 6440 (57.23%) had moderate weight loss, and 2218 (19.71%) had high weight loss. By 33-52 weeks, 525 (18.21%) had stable weight, 1214 (42.11%) had moderate weight loss, and 1144 (39.68%) had high weight loss. Regression results showed that moderate weight loss and high weight loss outcomes were associated with all engagement measures to a significantly greater degree than was stable weight (all P values <.001). These differences held across all time periods with the exception of exercise for the moderate weight loss category at 1 time period of 33-52 weeks. Exercise logging increased from 9 to 52 weeks regardless of the weight loss group. CONCLUSIONS: Our results suggest that these clinically important weight loss outcomes are related to the number of articles read, meals logged, steps recorded, messages to coach, exercise logged, weigh-ins, and days with 1 meal logged per week both in the short-term and long-term (ie, 1 year) on Noom. This provides valuable data on engagement patterns over time on a self-directed mobile DBCI, can help inform how interventions tailor recommendations for engagement depending on how much weight individuals have lost, and raises important questions for future research on engagement in DBCIs.


Subject(s)
Behavior Therapy , Weight Loss , Exercise , Humans , Overweight , Retrospective Studies
4.
Nutrients ; 13(9)2021 Aug 24.
Article in English | MEDLINE | ID: mdl-34578787

ABSTRACT

Maintaining a healthy weight is beneficial for cancer survivors. However, weight loss program effectiveness studies have primarily been in highly controlled settings. This is a retrospective study exploring real-world outcomes (weight loss and program engagement) after use of a digital commercial weight loss program (Noom) in cancer survivors and matched controls. All participants had voluntarily self-enrolled in Noom. Weight and engagement data were extracted from the program. Cancer-related quality of life was secondarily assessed in a one-time cross-sectional survey for survivors. Controls were a sample of Noom users with overweight/obesity who had no history of cancer but 0-1 chronic conditions. Primary outcomes were weight change at 16 weeks and program engagement over 16 weeks. Engagement included frequency of weight, food, and physical activity logging, as well as number of coach messages. Multiple regression controlling for baseline age, gender, engagement, and BMI showed that survivors lost less weight than controls (B = -2.40, s.e. = 0.97, p = 0.01). Survivors also weighed in less (survivors: 5.4 [2.3]; controls: 5.7 [2.1], p = 0.01) and exercised less (survivors: 1.8 [3.2]; controls: 3.2 [4.1], p < 0.001) than controls. However, survivors sent more coach messages (survivors: 2.1 [2.4]; controls: 1.7 [2.0], p < 0.001). Despite controls losing more weight than cancer survivors (-7.0 kg vs. -5.3 kg), survivors lost significant weight in 4 months (M = -6.2%). Cancer survivors can have success on digital commercial programs available outside of a clinical trial. However, they may require additional support to engage in weight management behaviors.


Subject(s)
Cancer Survivors , Obesity/therapy , Overweight/therapy , Weight Reduction Programs/methods , Adult , Aged , Breast Neoplasms/epidemiology , Cross-Sectional Studies , Exercise , Female , Humans , Male , Middle Aged , Neoplasms/epidemiology , Obesity/epidemiology , Overweight/epidemiology , Quality of Life , Retrospective Studies , Surveys and Questionnaires , Treatment Outcome , Weight Loss
5.
Article in English | MEDLINE | ID: mdl-34205282

ABSTRACT

During behavioral weight management, individuals reflect on their progress and barriers through goal pursuit (goal setting and goal striving). Emotions during goal pursuit are largely unknown, and previous investigations of emotions in weight management have primarily relied on self-report. In this retrospective study, we used a well-validated computational text analysis approach to explore how emotion words changed over time during goal setting and striving conversations with a coach in a mobile weight loss program. Linear mixed models examined changes in emotion words each month from baseline to program end and compared emotion words between individuals who set an overall concrete goal for the program (concrete goal setters) and those who set an overall abstract goal (abstract goal setters). Contrary to findings using self-report, positive emotion words were stable and negative emotion words significantly increased over time. There was a marginal trend towards greater negative emotion word use being associated with greater weight loss. Concrete goal setters used more positive words than abstract goal setters, with no differences in negative emotion words and weight loss. Implications include the possibility that individuals may need increasing support over time for negative emotions expressed during goal setting and striving, and concrete goals could boost positive emotion. Future research should investigate these possibilities.


Subject(s)
Weight Reduction Programs , Emotions , Goals , Humans , Motivation , Retrospective Studies
6.
Front Public Health ; 9: 604937, 2021.
Article in English | MEDLINE | ID: mdl-34178911

ABSTRACT

Mobile health (mHealth) interventions are ubiquitous and effective treatment options for obesity. There is a widespread assumption that the mHealth interventions will be equally effective in other locations. In an initial test of this assumption, this retrospective study assesses weight loss and engagement with an mHealth behavior change weight loss intervention developed in the United States (US) in four English-speaking regions: the US, Australia and New Zealand (AU/NZ), Canada (CA), and the United Kingdom and Ireland (UK/IE). Data for 18,459 participants were extracted from the database of Noom's Healthy Weight Program. Self-reported weight was collected every week until program end (week 16). Engagement was measured using user-logged and automatically recorded actions. Linear mixed models were used to evaluate change in weight over time, and ANOVAs evaluated differences in engagement. In all regions, 27.2-33.2% of participants achieved at least 5% weight loss by week 16, with an average of 3-3.7% weight loss. Linear mixed models revealed similar weight outcomes in each region compared to the US, with a few differences. Engagement, however, significantly differed across regions (P < 0.001 on 5 of 6 factors). Depending on the level of engagement, the rate of weight loss over time differed for AU/NZ and UK/IE compared to the US. Our findings have important implications for the use and understanding of digital weight loss interventions worldwide. Future research should investigate the determinants of cross-country engagement differences and their long-term effects on intervention outcomes.


Subject(s)
Weight Loss , Australia/epidemiology , Canada , Humans , Ireland/epidemiology , New Zealand , Retrospective Studies , United Kingdom , United States
7.
Nutrients ; 13(5)2021 May 20.
Article in English | MEDLINE | ID: mdl-34065277

ABSTRACT

Little is known about nutritional factors during weight loss on digital commercial weight loss programs. We examined how nutritional factors relate to weight loss for individuals after 4 and 18 months on a mobile commercial program with a food categorization system based on energy density (Noom). This is a two-part (retrospective and cross-sectional) cohort study. Two time points were used for analysis: 4 months and 18 months. For 4-month analyses, current Noom users who met inclusion criteria (n = 9880) were split into 5% or more body weight loss and stable weight loss (0 ± 1%) groups. Individuals who fell into one of these groups were analyzed at 4 months (n = 3261). For 18-month analyses, individuals from 4-month analyses who were still on Noom 18 months later were invited to take a one-time survey (n = 803). At 18 months 148 participants were analyzed. Noom has a system categorizing foods as low-, medium-, and high-energy-dense. Measures were self-reported proportions of low-, medium-, and high-energy-dense foods, and self-reported nutritional factors (fruit and vegetable intake, dietary quality, nutrition knowledge, and food choice). Nutritional factors were derived from validated survey measures, and food choice from a novel validated computerized task in which participants chose a food they would want to eat right now. ANOVAs compared participants with 5% or more body weight loss and participants with stable weight (0 ± 1%) at 4 months on energy density proportions. Analyses at 18 months compared nutritional factors across participants with >10% (high weight loss), 5-10% (moderate weight loss), and less than 5% body weight loss (low weight loss), and then assessed associations between nutritional factors and weight loss. Individuals with greater weight loss reported consuming higher proportions of low-energy-dense foods and lower proportions of high-energy-dense foods than individuals with less weight loss at 4 months and 18 months (all ps < 0.02). Individuals with greater weight loss had higher fruit and vegetable intake (p = 0.03), dietary quality (p = 0.02), nutrition knowledge (p < 0.001), and healthier food choice (p = 0.003) at 18 months. Only nutrition knowledge and food choice were associated with weight loss at 18 months (B = -19.44, 95% CI: -33.19 to -5.69, p = 0.006; B = -5.49, 95% CI: -8.87 to -2.11, p = 0.002, respectively). Our results highlight the potential influence of nutrition knowledge and food choice in weight loss on a self-managed commercial program. We also found for the first time that in-the-moment inclination towards food even when just depicted is associated with long-term weight loss.


Subject(s)
Food/classification , Obesity/therapy , Self-Management/psychology , Weight Loss , Weight Reduction Programs/methods , Cross-Sectional Studies , Diet, Healthy/psychology , Diet, Healthy/statistics & numerical data , Eating/psychology , Female , Food Preferences/psychology , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Mobile Applications , Nutritive Value , Obesity/physiopathology , Obesity/psychology , Retrospective Studies , Self Report , Self-Management/methods , Time Factors , Treatment Outcome
8.
Nutr Metab Cardiovasc Dis ; 31(7): 2165-2172, 2021 06 30.
Article in English | MEDLINE | ID: mdl-34039503

ABSTRACT

BACKGROUND AND AIMS: Food preferences are often modified in populations during stressful, unanticipated events. We examined how a U.S. population's food choices changed during the beginning of the COVID-19 stay-at-home orders, specifically during the spring of 2020. METHODS AND RESULTS: Daily dietary intake data from a digital behavior change weight loss program, which includes an interface for logging meals, beverages, and snacks, were analyzed to assess self-reported food choices from March 5-March 11, 2020 ("Start-COVID") and during the first week of the COVID-19 lockdown (March 12-March 18, 2020; "during-COVID"). The final sample consisted of 381,564 participants: 318,076 (83.4%) females, the majority who were aged 45-65 years (45.2%). Results indicate that self-reported servings of fresh fruit and vegetable intake decreased from start-to during-COVID, while intake of red meat and starchy vegetables increased. More men than women increased their intake of red meat and processed meat. Less overall change in fruit and vegetable consumption was seen in those 66 and older, compared to aged 18-35. Lean meat and starchy vegetable intake increased in older participants, but the change was negligible in younger subjects. More subjects aged 18-35 years reduced their intake of caffeine, desserts, lean meat, and salads compared to older participants. No changes were observed in snack or alcohol intake logged. CONCLUSION: This study revealed that particular food groups were altered according to age and gender during the first weeks of COVID lockdown. Understanding changes in food choices during a crisis may be useful for preparing supply chains and public health responses.


Subject(s)
COVID-19 , Choice Behavior , Diet, Healthy , Feeding Behavior , Weight Loss , Weight Reduction Programs , Adolescent , Adult , Age Factors , Aged , Energy Intake , Female , Humans , Internet-Based Intervention , Male , Middle Aged , Nutritive Value , Patient Compliance , Serving Size , Time Factors , United States , Young Adult
9.
Article in English | MEDLINE | ID: mdl-33578975

ABSTRACT

There is substantial variability in weight loss outcomes. Psychosocial characteristics underlying outcomes require better understanding, particularly on self-managed digital programs. This cross-sectional study examines differences in psychosocial characteristics by weight loss and engagement outcome, and which characteristics are most associated with weight loss, on a self-managed digital weight loss program. Some underexplored psychosocial characteristics are included, such as flourishing, or a sense of meaning and purpose in life. A questionnaire was emailed to a random sample of 10,000 current users at week 5 in the program and 10,000 current users at week 17. The questionnaire was completed by 2225 users, and their self-reported weight and recorded program engagement data were extracted from the program's database. Multiple comparison tests indicated that mental health quality of life, depression, anxiety, work-life balance, and flourishing differed by weight loss outcome at program end (week 17; ≥5%, 2-5%, below 2%) and by engagement tertile at program beginning and end (weeks 5 and 17). Only anxiety was associated with weight loss in a backward stepwise regression controlling for engagement and sociodemographic characteristics. Flourishing did not predict weight loss overall but predicted the weight loss outcome group. Our findings have implications for creating more effective interventions for individuals based on psychosocial characteristics and highlight the potential importance of anxiety in underexplored self-managed digital programs.


Subject(s)
Self-Management , Anxiety Disorders , Cross-Sectional Studies , Humans , Quality of Life , Weight Loss
10.
Medicine (Baltimore) ; 100(4): e23627, 2021 Jan 29.
Article in English | MEDLINE | ID: mdl-33530164

ABSTRACT

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common complication in the third trimester of pregnancy, which may result in premature delivery, fetal distress, stillbirth, and other adverse pregnancy outcomes. Ursodeoxycholic acid (UDCA) is a first-line treatment for ICP and has been controversial in improving adverse pregnancy outcomes. The purpose of this protocol is to systematically evaluate the effect of UDCA on pregnancy outcomes in patients with intrahepatic cholestasis during pregnancy. METHODS: To search the databases PubMed, Embase, Web of Science, the Cochrane Library, CNKI, WanFang, VIP, CBMDIsc by computer, then to include randomized controlled clinical studies on UDCA for treatment of intrahepatic cholestasis during pregnancy from the establishment of the database to October 1, 2020. Two researchers independently extract and evaluate the data of the included studies, and meta-analysis is conducted on the included literatures using RevMan5.3 software. RESULTS: This protocol evaluates the outcome of UDCA in improving ICP by incidence of postpartum hemorrhage in pregnant women preterm birth rates meconium contamination rate in amniotic fluid incidence of fetal distress scale of newborns scoring <7 in 5-min Apgar incidence of neonatal admission to neonatal intensive care unit. CONCLUSION: This protocol will provide an evidence-based basis for clinical use of UDCA in the treatment of intrahepatic cholestasis during pregnancy. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605 / OSF.IO / BE67H.


Subject(s)
Cholagogues and Choleretics/therapeutic use , Cholestasis, Intrahepatic/drug therapy , Pregnancy Complications/drug therapy , Pregnancy Outcome/epidemiology , Prenatal Care/methods , Ursodeoxycholic Acid/therapeutic use , Female , Fetal Distress/epidemiology , Fetal Distress/etiology , Humans , Incidence , Infant, Newborn , Meta-Analysis as Topic , Pregnancy , Premature Birth/epidemiology , Premature Birth/etiology , Research Design , Stillbirth/epidemiology , Systematic Reviews as Topic , Treatment Outcome
11.
J Womens Health (Larchmt) ; 30(11): 1645-1652, 2021 11.
Article in English | MEDLINE | ID: mdl-33481655

ABSTRACT

Background: Mobile health (mHealth) technology can circumvent barriers to participation in weight loss programs faced by new mothers. The objective of this study was to assess weight change and program engagement in postpartum women (n = 130) participating in a 24-week behavior change mHealth weight-loss intervention. Materials and Methods: Participants were recruited through a program offered on a commercial mHealth application that provided evidence-based lifestyle interventions. To meet inclusion criteria, women had to be 18-45 years of age, and given birth within 2 years before the start of the study. Participants signed up for the Noom Healthy Weight program between January and March of 2019 and were offered the program free of charge. Linear mixed models were conducted; the primary outcome was weight change from baseline at 16 and 24 weeks. Secondary outcomes were program engagement and their relationship with completion status. Results: Results showed that time was a significant predictor of weight at week 16 [t(-3.94) = -9.40; p < 0.001] and week 24 [t(-4.08) = -9.74; p < 0.001]; users lost 3.94 kgs at week 16 and 4.08 kgs at week 24, compared with baseline. In addition, body mass index significantly decreased at week 24 [t(112) = 7.33, p < 0.0001] with the majority of participants (80%) experiencing reductions by more than 2 units. On average, subjects who completed the program (completers) lost more weight compared with those who did not complete the program [t(-5.09) = -2.94; p = 0.004], losing 5.09 kgs (95% CI -8.48 to -1.69) throughout the 24 weeks. Conclusion: This cohort study shows that a uniquely mobile, behavior change intervention for weight management is effective at producing significant weight loss with potential to address postpartum weight retention.


Subject(s)
Gestational Weight Gain , Telemedicine , Cohort Studies , Data Analysis , Female , Humans , Retrospective Studies , Weight Loss
12.
Contemp Clin Trials Commun ; 16: 100468, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31701042

ABSTRACT

Many people with HIV (PWH) experience chronic pain that limits daily function and quality of life. PWH with chronic pain have commonly been prescribed opioids, sometimes for many years, and it is unclear if and how the management of these legacy patients should change in light of the current US opioid epidemic. Guidelines, such as the Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain (CDCG), provide recommendations for the management of such patients but have yet to be translated into easily implementable interventions; there is also a lack of strong evidence that adhering to these recommendations improves patient outcomes such as amount of opioid use and pain levels. Herein we describe the development and preliminary testing of a theory-based intervention, called TOWER (TOWard SafER Opioid Prescribing), designed to support HIV primary care providers in CDCG-adherent opioid prescribing practices with PWH who are already prescribed opioids for chronic pain. TOWER incorporates the content of the CDCG into the theoretical and operational framework of the Information Motivation and Behavioral Skills (IMB) model of health-related behavior. The development process included elicitation research and incorporation of feedback from providers and PWH; testing is being conducted via an adaptive feasibility clinical trial. The results of this process will form the basis of a large, well-powered clinical trial to test the effectiveness of TOWER in promoting CDCG-adherent opioid prescribing practices and improving outcomes for PWH with chronic pain.

13.
Cancer Chemother Pharmacol ; 80(3): 507-516, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28707013

ABSTRACT

PURPOSE: To determine the efficacy and safety of sunitinib in Chinese patients with unresectable or metastatic pancreatic neuroendocrine tumors (pNETs) and the clinical significance of steady-state sunitinib serum concentrations. METHODS: We conducted a multicenter retrospective study including six centers from across China. A total of 60 patients with unresectable or metastatic pNETs who were treated with sunitinib were evaluated retrospectively. RESULTS: The median overall survival (OS) was 47.5 months and the median time to progression (TTP) was 15.3 months. The objective response rate was 5.0%, and the stable disease (SD) rate was 81.7%. About 35.2% of patients required a dosage decrease from 37.5 to 25 mg/day due to adverse events, which in most cases were alleviated or disappeared with the dosage reduction. In 14 patients who experienced sunitinib-related hypertension, 2 achieved a partial response (PR) and 11 had SD. The median OS and TTP of these 14 patients experienced hypertension were both not reached. The median Css of sunitinib was similar between patients treated with sunitinib 37.5 and 25 mg/day (P = 0.955), but higher in patients who had PR than in those who achieved SD or progressive disease, although no statistically significant difference was found (P = 0.173). CONCLUSIONS: Sunitinib had similar treatment efficacy to western patients with pNET in China. A 25 mg/day dosage was better tolerated than 37.5 mg/day in Chinese patients, and there were no significant differences in sunitinib Css between the two dosage groups. Patients with higher sunitinib Css seem to have better efficacy. Sunitinib-related hypertension may be a predictor of a better treatment effect.


Subject(s)
Indoles/therapeutic use , Neuroendocrine Tumors/drug therapy , Pyrroles/therapeutic use , Adult , Aged , China , Female , Humans , Indoles/administration & dosage , Indoles/pharmacology , Male , Middle Aged , Pyrroles/administration & dosage , Pyrroles/pharmacology , Retrospective Studies , Sunitinib , Young Adult
14.
Mol Med Rep ; 12(1): 45-54, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25695625

ABSTRACT

The present study aimed to investigate whether klotho gene delivery attenuated renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats. A recombinant adeno-associated virus (rAAV) carrying mouse klotho full-length cDNA (rAAV.mKL), was constructed for in vivo investigation of klotho expression. Diabetes was induced in rats by a single tail vein injection of 60 mg/kg streptozotocin. Subsequently, the diabetic rats received an intravenous injection of rAAV.mKL, rAAV.green fluorescent protein (GFP) or phosphate-buffered saline (PBS). The Sprague-Dawley rat group received PBS and served as the control group. After 12 weeks, all the rats were sacrificed and ELISA, immunohistochemical and histological analyses, fluorescence microscopy, semi-quantitative reverse transcription-polymerase chain reaction and western blottin were performed. A single dose of rAAV.mKL was found to prevent the progression of renal hypertrophy and fibrosis for at least 12 weeks (duration of study). Klotho expression was suppressed in the diabetic rats, but was increased by rAAV.mKL delivery. rAAV.mKL significantly suppressed diabetes-induced renal hypertrophy and histopathological changes, reduced renal collagen fiber generation and decreased kidney hypertrophy index. In addition, rAAV.mKL decreased the protein expression levels of fibronectin and vimentin, while it downregulated the mRNA expression and activity of Rho-associated coiled-coil kinase (ROCK)I in the kidneys of the diabetic rats. These results indicated that klotho gene delivery ameliorated renal hypertrophy and fibrosis in diabetic rats, possibly by suppressing the ROCK signaling pathway. This may offer a novel approach for the long-term control and renoprotection of diabetes.


Subject(s)
Diabetic Retinopathy/therapy , Fibrosis/therapy , Glucuronidase/genetics , Hypertrophy/therapy , rho-Associated Kinases/biosynthesis , Animals , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/therapy , Diabetic Retinopathy/genetics , Diabetic Retinopathy/pathology , Fibrosis/etiology , Fibrosis/genetics , Gene Expression Regulation , Gene Transfer Techniques , Glucuronidase/therapeutic use , Humans , Hypertrophy/etiology , Hypertrophy/genetics , Kidney/metabolism , Kidney/physiopathology , Klotho Proteins , Mice , Rats , Signal Transduction/drug effects , rho-Associated Kinases/genetics
15.
Medicine (Baltimore) ; 93(27): e247, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25501094

ABSTRACT

Chromogranin A (CgA) not only plays an important role in pathologic diagnosis, but is also used as a circulating biomarker in patients with gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). However, the relationship between immunohistochemistry (IHC) expression and serum levels of CgA has not been investigated. The value of CgA for evaluating treatment response and prognosis is still not well understood. We conducted this study to assess the significance of CgA in GEP-NEN in terms of diagnosis, curative effects evaluation and prognosis. One hundred forty-five patients comprising 88 patients with active disease and 57 disease-free patients were enrolled in this study from January 2011 to November 2013. The expression of CgA was assessed by IHC, and serial serum CgA levels were measured by enzyme linked immunosorbent assay. The overall expression rate of CgA was 69.0% (100/145). CgA expression was associated with tumor site and stage (P < 0.05), but not correlated with prognosis (P = 0.07). Serum CgA levels were significantly higher in GEP-NEN patients with active disease when compared with disease-free patients (P = 0.001) or healthy participants (P < 0.001). A CgA cutoff value of 95 ng/ml discriminated between healthy subjects or disease-free patients and patients with active disease (sensitivity 51.2% and specificity 87.5%, respectively). There was a correlation between the CgA IHC expression and high serum CgA levels (R = 0.320, P = 0.002). Serum CgA levels were much higher in patients who classified as neuroendocrine carcinoma, mixed adenoendocrine carcinoma (P = 0.035) and who were on stage IV (P = 0.041). Changes in CgA levels normalization or ≥ 30% decrease suggested that patients had tumor response. Furthermore, patients with serum CgA levels higher than 95 ng/ml had a significantly shorter survival compared with patients with levels lower than 95 ng/ml (P < 0.001). CgA is a reliable pathologic and circulating maker for diagnosis of GEP-NEN. We further confirmed that serial measurement of CgA may be useful for evaluating the efficacy of different kinds of therapies in patients during follow-up, and serum CgA level ≥ 95 ng/ml may serve as a predictor of overall survial.


Subject(s)
Chromogranin A/blood , Digestive System Neoplasms/blood , Neuroendocrine Tumors/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , China/epidemiology , Digestive System/pathology , Digestive System Neoplasms/mortality , Digestive System Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/pathology , Survival Analysis , Young Adult
16.
Int J Clin Exp Pathol ; 7(7): 4204-12, 2014.
Article in English | MEDLINE | ID: mdl-25120800

ABSTRACT

O(6)-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O(6)-alkylating agents. Until now, we know only little about the expression of MGMT in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen University during October 1995 to November 2013, 22 specimens came from Peking Union Medical College Hospital during September 2004 to April 2010. MGMT protein was detected with EnVision immunohistochemical staining method. Clinicopathological factors were also collected and analyzed. We observed that the overall expression rate of MGMT was 83.9%. Over expression of MGMT protein was not associated with sex, age, functional status, primary tumor location, grading, classification, TNM stage and metastasis (P > 0.05). Kaplan-Meier analysis revealed that there was no significant difference in survival between MGMT-positive and MGMT-negative tumors of GEP-NEN patients (χ(2) = 0.887, P = 0.346). In multivariate analyses carried out by Cox proportional hazards regression model, MGMT expression was also not an independent predictors of survival. These results demonstrated that MGMT protein was highly expressed in GEP-NEN. MGMT deficiency rate was similar in pancreatic NEN and in gastrointestinal NEN. MGMT expression was not correlated with prognosis of GEP-NEN.


Subject(s)
DNA Modification Methylases/biosynthesis , DNA Repair Enzymes/biosynthesis , Digestive System Neoplasms/enzymology , Digestive System Neoplasms/pathology , Neuroendocrine Tumors/enzymology , Neuroendocrine Tumors/pathology , Tumor Suppressor Proteins/biosynthesis , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , DNA Modification Methylases/analysis , DNA Repair Enzymes/analysis , Digestive System Neoplasms/mortality , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Neuroendocrine Tumors/mortality , Prognosis , Proportional Hazards Models , Tumor Suppressor Proteins/analysis , Young Adult
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