Cellular Mechanisms Underlying the Laxative Effect of Flavonol Naringenin on Rat Constipation Model

BACKGROUND & AIMS: Symptoms of constipation are extremely common, especially in the elderly. The present study aim to identify an efficacious treatment strategy for constipation by evaluating the secretion-promoting and laxative effect of a herbal compound, naringenin, on intestinal epithelial anion secretion and a rat constipation model, respectively. METHODS/PRINCIPAL FINDINGS: In isolated rat colonic crypts, mucosal addition of naringenin (100 microM) elicited a concentration-dependent and sustained increase in the short-circuit current (I(SC)), which could be inhibited in Cl- free solution or by bumetanide and DPC (diphenylamine-2-carboxylic acid), but not by DIDS (4, 4'- diisothiocyanatostilbene-2, 2'-disulfonic acid). Naringenin could increase intracellular cAMP content and PKA activity, consisted with that MDL-12330A (N-(Cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride) pretreatment reduced the naringenin-induced I(SC). In addition, significant inhibition of the naringenin-induced I(SC) by quinidine indicated that basolateral K+ channels were involved in maintaining this cAMP-dependent Cl- secretion. Naringenin-evoked whole cell current which exhibited a linear I-V relationship and time-and voltage- independent characteristics was inhibited by DPC, indicating that the cAMP activated Cl- conductance most likely CFTR (cystic fibrosis transmembrane conductance regulator) was involved. In rat constipation model, administration of naringenin restored the level of fecal output, water content and mucus secretion compared to loperamide-administrated group. CONCLUSIONS: Taken together, our data suggest that naringenin could stimulate Cl- secretion in colonic epithelium via a signaling pathway involving cAMP and PKA, hence provide an osmotic force for subsequent colonic fluid secretion by which the laxative effect observed in the rat constipation model. Naringenin appears to be a novel alternative treatment strategy for constipation

Barriers and opportunities to increase PD incidence and prevalence: Lessons from a European Survey.

INTRODUCTION: Peritoneal dialysis (PD) remains underutilised and unplanned start of dialysis further diminishes the likelihood of patients starting on PD, although outcomes are equal to haemodialysis (HD). METHODS: A survey was sent to members of EuroPD and regional societies presenting a case vignette of a 48-year-old woman not previously known to the nephrology department and who arrives at the emergency department with established end-stage kidney disease (unplanned start), asking which dialysis modality would most likely be chosen at their respective centre. We assessed associations between the modality choices for this case vignette and centre characteristics and PD-related practices. RESULTS: Of 575 respondents, 32.8%, 32.2% and 35.0% indicated they would start unplanned PD, unplanned HD or unplanned HD with intention to educate patient on PD later, respectively. Likelihood for unplanned start of PD was only associated with quality of structure of the pre-dialysis program. Structure of pre-dialysis education program, PD program in general, likelihood to provide education on PD to unplanned starters, good collaboration with the PD access team and taking initiatives to enhance home-based therapies increased the likelihood unplanned patients would end up on PD. CONCLUSIONS: Well-structured pre-dialysis education on PD as a modality, good connections to dedicated PD catheter placement teams and additional initiatives to enhance home-based therapies are key to grow PD programs. Centres motivated to grow their PD programs seem to find solutions to do so

Assisted peritoneal dialysis across Europe: Practice variation and factors associated with availability

Background: In Europe, the number of elderly end-stage kidney disease patients is increasing. Few of those patients receive peritoneal dialysis (PD), as many cannot perform PD autonomously. Assisted PD programmes are available in most European countries, but the percentage of patients receiving assisted PD varies considerably. Hence, we assessed which factors are associated with the availability of an assisted PD programme at a centre level and whether the availability of this programme is associated with proportion of home dialysis patients. Methods: An online survey was sent to healthcare professionals of European nephrology units. After selecting one respondent per centre, the associations were explored by chi (2) tests and (ordinal) logistic regression. Results: In total, 609 respondents completed the survey. Subsequently, 288 respondents from individual centres were identified; 58% worked in a centre with an assisted PD programme. Factors associated with availability of an assisted PD programme were Western European and Scandinavian countries (OR: 5.73; 95% CI: 3.07-10.68), non-academic centres (OR: 2.01; 95% CI: 1.09-3.72) and centres with a dedicated team for education (OR: 2.87; 95% CI: 1.35-6.11). Most Eastern & Central European respondents reported that the proportion of incident and prevalent home dialysis patients was 30% for both incident and prevalent home dialysis patients. Availability of an assisted PD programme was associated with a higher incidence (cumulative OR: 1.91; 95% CI: 1.21-3.01) and prevalence (cumulative OR: 2.81; 95% CI: 1.76-4.47) of patients on home dialysis. Conclusions: Assisted PD was more commonly offered among non-academic centres with a dedicated team for education across Europe, especially among Western European and Scandinavian countries where higher incidence and prevalence of home dialysis patients was reported

Healthcare professional education in shared decision making in the context of chronic kidney disease: A Scoping Review

Rationale & Objective: Shared decision making (SDM) is a collaborative effort between healthcare professionals, individuals with CKD whereby clinical evidence, expected out-comes and potential side-effects are balanced with individual values and beliefs to provide the best mutually decided treatment option. Meaningful SDM is supported by effective train-ing and education We aimed to identify the available evidence on SDM training and educa-tion of healthcare professionals caring for people with chronic kidney disease. We aimed to identify existing training programs and to explore what means are used to evaluate the quality and effectiveness of these educational efforts. Methodology: We performed a scoping review to study the effectiveness of training or edu-cation about shared decision making of healthcare professionals treating patients with kid-ney disease. EMBASE, MEDLINE, CINAHL and APA PsycInfo were searched. Results: After screening of 1190 articles, 24 articles were included for analysis, of which 20 were suitable for quality appraisal. These included 2 systematic reviews, 1 cohort study, 7 qualitative studies, and 10 studies using mixed methods. Study quality was varied with high quality (n= 5), medium quality (n= 12), and low quality (n= 3) studies. The majority of studies (n= 11) explored SDM education for nurses, and physicians (n= 11). Other HCP profiles in-cluded social workers (n= 6), dieticians (n= 4), and technicians (n= 2). Topics included educa-tion on SDM in withholding of dialysis, modality choice, patient engagement, and end-of-life decisions. Limitations: We observed significant heterogeneity in study design and varied quality of the data. As the literature search is restricted to evidence published between January 2000 and March 2021, relevant literature outside of this time window has not been taken into ac-count. Conclusions: Evidence on training and education of SDM for healthcare professionals taking care of patients with CKD is limited. Curricula are not standardized, and educational and training materials do not belong to the public domain. The extent to which interventions have improved the process of shared-decision making is tested mostly by pre-post testing of healthcare professionals, whereas the impact from the patient perspective for the most part remains untested.

A 5–50 GHz sige BiCMOS linear transimpedance amplifier with 68 dbΩ differential gain towards highly integrated quasi-coherent receivers

Quasi-coherent optical receivers have recently emerged targeting access networks, offering improved sensitivity and reach over direct-detection schemes at the expense of a higher receiver bandwidth. Higher levels of system integration together with sufficiently wideband front-end blocks, and in particular high-speed linear transimpedance amplifiers (TIAs), are currently demanded to reduce cost and scale up receiver data rates. In this article, we report on the design and testing of a linear TIA enabling high-speed quasi-coherent receivers. A shunt-feedback loaded common-base topology is adopted, with gain control provided by a subsequent Gilbert cell stage. The circuit was fabricated in a commercial 130 nm SiGe BiCMOS technology and has a bandpass characteristic with a 3 dB bandwidth in the range of 5–50 GHz. A differential transimpedance gain of 68 dBΩ was measured, with 896 mVpp of maximum differential output swing at the 1 dB compression point. System experiments in a quasi-coherent receiver demonstrate an optical receiver sensitivity of −30.5 dBm (BER = 1 × 10−3) at 10 Gbps, and −26 dBm (BER = 1 × 10−3) at 25 Gbps. The proposed TIA represents an enabling component towards highly integrated quasi-coherent receivers