Inflammation and premature aging in advanced chronic kidney disease

Systemic inflammation in end-stage renal disease (ESRD) is an established risk factor for mortality and a catalyst for other complications which are related to a premature aging phenotype, including muscle wasting, vascular calcification and other forms of premature vascular disease, depression, osteoporosis and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have direct effect on cellular and tissue function. In addition to uremia-specific causes such as abnormalities in the phosphate- Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect are abnormal or misplaced protein structures as well as abnormalities in tissue homeostasis, which evoke danger signals through damage associated molecular patters (DAMPS) as well as the senescence associated secretory phenotype (SASP). Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserve, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relation between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences are discussed

Temporal Recurrent Networks for Online Action Detection

Most work on temporal action detection is formulated as an offline problem, in which the start and end times of actions are determined after the entire video is fully observed. However, important real-time applications including surveillance and driver assistance systems require identifying actions as soon as each video frame arrives, based only on current and historical observations. In this paper, we propose a novel framework, Temporal Recurrent Network (TRN), to model greater temporal context of a video frame by simultaneously performing online action detection and anticipation of the immediate future. At each moment in time, our approach makes use of both accumulated historical evidence and predicted future information to better recognize the action that is currently occurring, and integrates both of these into a unified end-to-end architecture. We evaluate our approach on two popular online action detection datasets, HDD and TVSeries, as well as another widely used dataset, THUMOS'14. The results show that TRN significantly outperforms the state-of-the-art

One year effectiveness of an app-based treatment for urinary incontinence in comparison to care as usual in Dutch general practice:A pragmatic randomised controlled trial over 12 months

OBJECTIVE: To assess the long-term effectiveness of app-based treatment for female stress, urgency, or mixed urinary incontinence (UI) compared to care-as-usual in primary care. DESIGN: A pragmatic, randomised controlled, superiority trial. SETTING: Primary care in the Netherlands from 2015 to 2018, follow-up at 12 months. POPULATION: Women with ≥2 UI-episodes per week, access to mobile apps, wanting treatment. 262 women randomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended one year follow-up. INTERVENTIONS: The standalone app included conservative management for UI with motivation aids (e.g., reminders). Care-as-usual delivered according to the Dutch GP guideline for UI. MAIN OUTCOME MEASURES: Effectiveness assessed by the change in symptom severity score (ICIQ-UI-SF) and the change in quality of life (ICIQ-LUTS-QoL) with linear regression on an intention-to-treat basis. RESULTS: Clinically relevant improvement of UI severity for both app (-2.17 ± 2.81) and care-as-usual (-3.43 ± 3.6), with a non-significant mean difference of 0.903 (-0.66 to 1.871). CONCLUSION: App-based treatment is a viable alternative to care-as-usual for UI in primary care in terms of effectiveness after one year

Cost-effectiveness of an app-based treatment for urinary incontinence in comparison with care-as-usual in Dutch general practice:a pragmatic randomised controlled trial over 12 months

OBJECTIVE: To assess the cost-effectiveness of app-based treatment for female stress, urgency, or mixed urinary incontinence (UI) compared to care-as-usual in Dutch primary care. DESIGN: A pragmatic, randomised controlled, superiority trial. SETTING: Primary care in the Netherlands from 2015 to 2018, follow-up at 12 months. POPULATION: Women with ≥2 UI-episodes per week, access to mobile apps, wanting treatment. INTERVENTIONS: The standalone app included conservative management for UI with motivation aids (e.g., reminders). Care-as-usual delivered according to the Dutch GP guideline for UI. MAIN OUTCOME MEASURES: Costs and cost-effectiveness and -utility were assessed from a societal perspective, based on Incontinence Impact Adjusted Life Years (IIALYs), Quality Adjusted Life years (QALYs) and medical, non-medical and productivity costs. Information on costs was obtained with the iMCQ and iPCQ questionnaires (Medical Consumption and Productivity Cost Questionnaires). RESULTS: 262 women randomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended follow-up. Costs were lower for app-based treatment with €-161 (95%CI: -180 to -151) per year. Cost-effectiveness showed small mean differences in effect for IIALY (0.04) and QALY (-0.03) and thus larger ICER (-€3,696) and ICUR (€6,379) (Incremental Cost-Effectiveness and Cost-utility Ratios). CONCLUSION: App-based treatment is a cost-effective alternative to care-as-usual for women with UI in Dutch primary care

App-Based Treatment in Primary Care for Urinary Incontinence:A Pragmatic, Randomized Controlled Trial

PURPOSE: Electronic application (app)-based treatment is promising for common diseases with good conservative management options, such as urinary incontinence (UI) in women, but its effectiveness compared with usual care is unclear. This study set out to determine if app-based treatment for women with stress, urgency, or mixed UI was noninferior to usual care in the primary care setting. METHODS: The URinControl trial is a pragmatic, noninferiority randomized controlled trial in Dutch primary care including adult women with 2 episodes of UI per week. From July 2015 to July 2018, we screened 350 women for eligibility. A stand-alone app-based treatment with pelvic floor muscle and bladder training (URinControl) was compared with usual care according to the Dutch general practitioner guideline for UI treatment. Outcomes measured were change in symptom severity score from baseline to 4 months (primary outcome), impact on disease-specific quality of life, patient-perceived improvement, and number of UI episodes. Noninferiority (<1.5 points) was assessed with linear regression analysis. RESULTS: A total of 262 eligible women were randomized equally; 195 of them had follow-up through 4 months. The change in symptom severity with app-based treatment (-2.16 points; 95% CI, -2.67 to -1.65) was noninferior to that with usual care (-2.56 points; 95% CI, -3.28 to -1.84), with a mean difference of 0.058 points (95% CI, -0.776 to 0.891) between groups. Neither treatment was superior to the other, and both groups showed improvements in outcome measures after treatment. CONCLUSIONS: App-based treatment for women with UI was at least as effective as usual care in the primary care setting. As such, app-based treatments, with their potential advantages of privacy, accessibility, and lower cost, may provide women with a good alternative to consultation

Porphyromonas Gingivalis and E-coli induce different cytokine production patterns in pregnant women

OBJECTIVE: Pregnant individuals of many species, including humans, are more sensitive to various bacteria or their products as compared with non-pregnant individuals. Pregnant individuals also respond differently to different bacteria or their products. Therefore, in the present study, we evaluated whether the increased sensitivity of pregnant women to bacterial products and their heterogeneous response to different bacteria was associated with differences in whole blood cytokine production upon stimulation with bacteria or their products. METHODS: Blood samples were taken from healthy pregnant and age-matched non-pregnant women and ex vivo stimulated with bacteria or LPS from Porphyromonas Gingivalis (Pg) or E-coli for 24 hrs. TNFα, IL-1ß, IL-6, IL-12 and IL-10 were measured using a multiplex Luminex system. RESULTS: We observed a generally lower cytokine production after stimulation with Pg bacteria or it's LPS as compared with E-coli bacteria. However, there was also an effect of pregnancy upon cytokine production: in pregnant women the production of IL-6 upon Pg stimulation was decreased as compared with non-pregnant women. After stimulation with E-coli, the production of IL-12 and TNFα was decreased in pregnant women as compared with non-pregnant women. CONCLUSION: Our results showed that cytokine production upon bacterial stimulation of whole blood differed between pregnant and non-pregnant women, showing that the increased sensitivity of pregnant women may be due to differences in cytokine production. Moreover, pregnancy also affected whole blood cytokine production upon Pg or E-coli stimulation differently. Thus, the different responses of pregnant women to different bacteria or their products may result from variations in cytokine production

New insights into the kinetics and variability of egg excretion in controlled human hookworm infections

Four healthy volunteers were infected with 50 Necator americanus infective larvae (L3) in a controlled human hookworm infection trial and followed for 52 weeks. The kinetics of fecal egg counts in volunteers was assessed with Bayesian multilevel analysis, which revealed an increase between weeks 7 and 13, followed by an egg density plateau of about 1000 eggs/g of feces. Variation in egg counts was minimal between same-day measurements but varied considerably between days, particularly during the plateau phase. These analyses pave the way for the controlled human hookworm model to accelerate drug and vaccine efficacy studies

Primary prevention of diabetes mellitus type 2 and cardiovascular diseases using a cognitive behavior program aimed at lifestyle changes in people at risk: Design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The number of people with cardiovascular disease (CVD) and diabetes mellitus type 2 (T2DM) is growing rapidly. To a large extend, this increase is due to lifestyle-dependent risk factors, such as overweight, reduced physical activity, and an unhealthy diet. Changing these risk factors has the potential to postpone or prevent the development of T2DM and CVD. It is hypothesized that a cognitive behavioral program (CBP), focused in particular on motivation and self-management in persons who are at high risk for CVD and/or T2DM, will improve their lifestyle behavior and, as a result, will reduce their risk of developing T2DM and CVD.</p> <p>Methods</p> <p>12,000 inhabitants, 30-50 years of age living in several municipalities in the semi-rural region of West-Friesland will receive an invitation from their general practitioner (n = 13) to measure their own waist circumference with a tape measure. People with abdominal obesity (male waist ≥ 102 cm, female waist ≥ 88 cm) will be invited to participate in the second step of the screening which includes blood pressure, a blood sample and anthropometric measurements. T2DM and CVD risk scores will then be calculated according to the ARIC and the SCORE formulae, respectively. People with a score that indicates a high risk of developing T2DM and/or CVD will then be randomly assigned to the intervention group (n = 300) or the control group (n = 300).</p> <p>Participants in the intervention group will follow a CBP aimed at modifying their dietary behavior, physical activity, and smoking behavior. The counseling methods that will be used are <it>motivational interviewing </it>(MI) and <it>problem solving treatment </it>(PST), which focus in particular on intrinsic motivation for change and self-management of problems of the participants. The CBP will be provided by trained nurse practitioners in the participant's general practice, and will consists of a maximum of six individual sessions of 30 minutes, followed by 3-monthly booster sessions by phone. Participants in the control group will receive brochures containing health guidelines regarding physical activity and diet, and how to stop smoking. The primary outcome measures will be changes in T2DM and CVD risk scores. Secondary outcome measures will be changes in lifestyle behavior and cost-effectiveness and cost-utility ratios. All relevant direct and indirect costs will be measured, and there will be a follow-up of 24 months.</p> <p>Discussion</p> <p>Changing behaviors is difficult, requires time, considerable effort and motivation. Combining the two counseling methods MI and PST, followed by booster sessions may result in sustained behavioral change.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN59358434</p