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Background: Autosomal dominant polycystic kidney disease (ADPKD) is the leading inherited cause of kidney disease. Clinical management has historically focused on symptom control and reducing associated complications. Improved understanding of the molecular and cellular mechanisms involved in kidney cyst growth and disease progression has resulted in new pharmaceutical agents targeting disease pathogenesis and preventing disease progression. However, the role of disease-modifying agents for all people with ADPKD is unclear. This is an update of a review first published in 2015., Objectives: We aimed to evaluate the benefits and harms of interventions to prevent the progression of ADPKD and the safety based on patient-important endpoints, defined by the Standardised Outcomes in NephroloGy-Polycystic Kidney Disease (SONG-PKD) core outcome set, and general and specific adverse effects., Search Methods: We searched the Cochrane Kidney and Transplants Register of Studies up to 13 August 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov., Selection Criteria: Randomised controlled trials (RCTs) comparing any interventions for preventing the progression of ADPKD with other interventions, placebo, or standard care were considered for inclusion., Data Collection and Analysis: Two authors independently assessed study risks of bias and extracted data. Summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Main Results: We included 57 studies (8016 participants) that investigated 18 pharmacological interventions (vasopressin 2 receptor (V2R) antagonists, antihypertensive therapy, mammalian target of rapamycin (mTOR) inhibitors, somatostatin analogues, antiplatelet agents, eicosapentaenoic acids, statins, kinase inhibitors, diuretics, anti-diabetic agents, water intake, dietary intervention, and supplements) in this review. Compared to placebo, the V2R antagonist tolvaptan probably preserves eGFR (3 studies, 2758 participants: MD 1.26 mL/min/1.73 m 2 , 95% CI 0.73 to 1.78; I 2 = 0%) and probably slows total kidney volume (TKV) growth in adults (1 study, 1307 participants: MD -2.70 mL/cm, 95% CI -3.24 to -2.16) (moderate certainty evidence). However, there was insufficient evidence to determine tolvaptan's impact on kidney failure and death. There may be no difference in serious adverse events; however, treatment probably increases nocturia, fatigue and liver enzymes, may increase dry mouth and thirst, and may decrease hypertension and urinary and upper respiratory tract infections. Data on the impact of other therapeutic interventions were largely inconclusive. Compared to placebo, somatostatin analogues probably decrease TKV (6 studies, 500 participants: SMD -0.33, 95% CI -0.51 to -0.16; I 2 = 11%), probably have little or no effect on eGFR (4 studies, 180 participants: MD 4.11 mL/min/1.73 m 3 , 95% CI -3.19 to 11.41; I 2 = 0%) (moderate certainty evidence), and may have little or no effect on kidney failure (2 studies, 405 participants: RR 0.64, 95% CI 0.16 to 2.49; I 2 = 39%; low certainty evidence). Serious adverse events may increase (2 studies, 405 participants: RR 1.81, 95% CI 1.01 to 3.25; low certainty evidence). Somatostatin analogues probably increase alopecia, diarrhoea or abnormal faeces, dizziness and fatigue but may have little or no effect on anaemia or infection. The effect on death is unclear. Targeted low blood pressure probably results in a smaller per cent annual increase in TKV (1 study, 558 participants: MD -1.00, 95% CI -1.67 to -0.33; moderate certainty evidence) compared to standard blood pressure targets, had uncertain effects on death, but probably do not impact other outcomes such as change in eGFR or adverse events. Kidney failure was not reported. Data comparing antihypertensive agents, mTOR inhibitors, eicosapentaenoic acids, statins, vitamin D compounds, metformin, trichlormethiazide, spironolactone, bosutinib, curcumin, niacinamide, prescribed water intake and antiplatelet agents were sparse and inconclusive. An additional 23 ongoing studies were also identified, including larger phase III RCTs, which will be assessed in a future update of this review., Authors' Conclusions: Although many interventions have been investigated in patients with ADPKD, at present, there is little evidence that they improve patient outcomes. Tolvaptan is the only therapeutic intervention that has demonstrated the ability to slow disease progression, as assessed by eGFR and TKV change. However, it has not demonstrated benefits for death or kidney failure. In order to confirm the role of other therapeutic interventions in ADPKD management, large RCTs focused on patient-centred outcomes are needed. The search identified 23 ongoing studies, which may provide more insight into the role of specific interventions., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Dramatic environmental shifts are occuring throughout the Arctic from climate change, with consequences for the cycling of mercury (Hg). This review summarizes the latest science on how climate change is influencing Hg transport and biogeochemical cycling in Arctic terrestrial, freshwater and marine ecosystems. As environmental changes in the Arctic continue to accelerate, a clearer picture is emerging of the profound shifts in the climate and cryosphere, and their connections to Hg cycling. Modeling results suggest climate influences seasonal and interannual variability of atmospheric Hg deposition. The clearest evidence of current climate change effects is for Hg transport from terrestrial catchments, where widespread permafrost thaw, glacier melt and coastal erosion are increasing the export of Hg to downstream environments. Recent estimates suggest Arctic permafrost is a large global reservoir of Hg, which is vulnerable to degradation with climate warming, although the fate of permafrost soil Hg is unclear. The increasing development of thermokarst features, the formation and expansion of thaw lakes, and increased soil erosion in terrestrial landscapes are increasing river transport of particulate-bound Hg and altering conditions for aquatic Hg transformations. Greater organic matter transport may also be influencing the downstream transport and fate of Hg. More severe and frequent wildfires within the Arctic and across boreal regions may be contributing to the atmospheric pool of Hg. Climate change influences on Hg biogeochemical cycling remain poorly understood. Seasonal evasion and retention of inorganic Hg may be altered by reduced sea-ice cover and higher chloride content in snow. Experimental evidence indicates warmer temperatures enhance methylmercury production in ocean and lake sediments as well as in tundra soils. Improved geographic coverage of measurements and modeling approaches are needed to better evaluate net effects of climate change and long-term implications for Hg contamination in the Arctic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The presence of toxic methylmercury (MeHg) in Arctic freshwater ecosystems and foodwebs is a potential health concern for northern Indigenous people. Addressing this issue requires a better understanding of MeHg production, fate during transport, and uptake into foodwebs. We used methylation assays and spatiotemporal surveys of MeHg concentrations, during the ice-covered and open water seasons, across a hydrologic continuum (composed of thaw seeps, lake/ponds, and a wetland) to identify Hg methylation hotspots and seasonal differences in MeHg cycling unique to Arctic ecosystems. Ponds and saturated wetland soils support methylation hotspots during the open water season, but subsequent export of MeHg to downstream ecosystems is limited by particle settling, binding of MeHg on soil organic matter, and/or demethylation in drier wetland soils. During the ice-covered season, MeHg concentrations in lake waters were approximately ten-fold greater than in summer; however, zooplankton MeHg concentrations were paradoxically five times lower at this time. Despite limited evidence of snow-phase methylation, the snowpack is an important MeHg reservoir. Changes in ice-cover duration will alter MeHg production and bioaccumulation in lakes, while increased thaw and surface water flow will likely result in higher methylation rates at the aquatic-terrestrial interface and more efficient downstream transport of MeHg.

Lake Hazen, the High Arctic's largest lake, has received an approximately 10-fold increase in glacial meltwater since its catchment glaciers shifted from net mass gain to net mass loss in 2007 common era (CE), concurrent with recent warming. Increased glacial meltwater can alter the ecological functioning of recipient aquatic ecosystems via changes to nutrient budgets, turbidity and thermal regimes. Here, we examine a rare set of five high-resolution sediment cores collected in Lake Hazen between 1990 and 2017 CE to investigate the influence of increased glacial meltwater versus alterations to lake ice phenology on ecological change. Subfossil diatom assemblages in all cores show two major shifts over the past approximately 200 years including: (i) a proliferation of pioneering, benthic taxa at approximately 1900 CE from previously depauperate populations; and (ii) a rise in planktonic taxa beginning at approximately 1980 CE to present-day dominance. The topmost intervals from each sequentially collected core provide exact dates and demonstrate that diatom regime shifts occurred decades prior to accelerated glacial inputs. These data show that diatom assemblages in Lake Hazen are responding primarily to intrinsic lake factors linked to decreasing duration of lake ice and snow cover rather than to limnological impacts associated with increased glacial runoff.

We determined the genetic variability among water isolates of Campylobacter jejuni by using amplified-fragment length polymorphism (AFLP) and multilocus sequence typing (MLST). Across a highly diverse collection of isolates, AFLP clusters did not correlate with MLST clonal complexes, suggesting that AFLP is not reliable for deciphering population genetic relationships and may be problematic for larger epidemiologic analyses.

This study evaluated alternative protocols for culturing thermophilic campylobacters in environmental water. All samples were filtered through a sterile 0.45μm pore-size membrane, which was then incubated in Preston enrichment broth. Four variables were compared: water sample volume (2000mL vs. 500mL), enrichment broth volume (25mL vs. 100mL), enrichment incubation duration (24h vs. 48h), and number of enrichment passages (one vs. two). In addition, DNA extracts were prepared from all final broths and analyzed using three rRNA PCR assays. River water was collected at 3 sampling sites weekly for 9 weeks. Among these 27 collections, 25 (93%) yielded Campylobacter spp. under at least one of the 16 culture conditions. By univariate analysis, yields were significantly better for the 2000mL sample volume (68.5% vs. 43.0%, p<0.0001) and the 25mL enrichment broth volume (64.5% vs. 47.0%, p<0.0004). Neither of the enrichment period had a significant effect, although there was a trend in favor of 48h incubation (59.5% vs. 52.0%, p=0.13). The three PCR methods gave concordant results for 66 (33%) of the culture-negative samples and 103 (50%) of the culture-positive samples. Compared with culture results, Lubeck's 16S PCR assay had the best performance characteristics, with a sensitivity of 82% and a specificity of 94%. Of the 12 culture-negative samples positive by Lubeck's PCR assay, 11 (92%) samples were also positive by Denis' 16S PCR assay, suggesting that in these cases the culture might have been falsely negative. Based on our results, we conclude that the optimal conditions for detecting Campylobacter spp. in natural waters include 2000mL sample volume and a single enrichment broth of 25mL PB incubated for 48h., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: Intractable constipation in children is an uncommon but debilitating condition. When medical therapy fails, surgery is warranted; but the optimal surgical approach has not been clearly defined. We reviewed our experience with operative management of intractable constipation to identify predictors of success and to compare outcomes after 3 surgical approaches: antegrade continence enema (ACE), enteral diversion, and primary resection., Methods: A retrospective review of pediatric patients undergoing ACE, diversion, or resection for intractable, idiopathic constipation from 1994 to 2007 was performed. Satisfactory outcome was defined as minimal fecal soiling and passage of stool at least every other day (ACE, resection) or functional enterostomy without abdominal distension (diversion)., Results: Forty-four patients (range = 1-26 years, mean = 9 years) were included. Sixteen patients underwent ACE, 19 underwent primary diversion (5 ileostomy, 14 colostomy), and 9 had primary colonic resections. Satisfactory outcomes were achieved in 63%, 95%, and 22%, respectively. Of the 19 patients diverted, 14 had intestinal continuity reestablished at a mean of 27 months postdiversion, with all of these having a satisfactory outcome at an average follow-up of 56 months. Five patients underwent closure of the enterostomy without resection, whereas the remainder underwent resection of dysmotile colon based on preoperative colonic manometry studies. Of those undergoing ACE procedures, age younger than 12 years was a predictor of success, whereas preoperative colonic manometry was not predictive of outcome. Second manometry 1 year post-ACE showed improvement in all patients tested. On retrospective review, patient noncompliance contributed to ACE failure., Conclusions: Antegrade continence enema and enteral diversion are very effective initial procedures in the management of intractable constipation. Greater than 90% of diverted patients have an excellent outcome after the eventual restoration of intestinal continuity. Colon resection should not be offered as initial therapy, as it is associated with nearly 80% failure rate and the frequent need for additional surgery., (Copyright 2010 Elsevier Inc. All rights reserved.)

This study aimed to assess the importance of quantitatively detecting Campylobacter spp. in environmental surface water. The prevalence and the quantity of Campylobacter spp., thermotolerant coliforms, and Escherichia coli in 2,471 samples collected weekly, over a 2-year period, from 13 rivers and 12 streams in the Eastern Townships, Québec, Canada, were determined. Overall, 1,071 (43%), 1,481 (60%), and 1,463 (59%) samples were positive for Campylobacter spp., thermotolerant coliforms, and E. coli, respectively. There were weak correlations between the weekly distributions of Campylobacter spp. and thermotolerant coliforms (Spearman's rho coefficient = 0.27; P = 0.008) and between the quantitative levels of the two classes of organisms (Kendall tau-b correlation coefficient = 0.233; P < 0.0001). Well water samples from the Eastern Townships were also tested. Five (10%) of 53 samples from private surface wells were positive for Campylobacter jejuni, of which only 2 were positive for thermotolerant coliforms. These findings suggest that microbial monitoring of raw water by using only fecal indicator organisms is not sufficient for assessing the occurrence or the load of thermophilic Campylobacter spp. Insights into the role of environmental water as sources for sporadic Campylobacter infection will require genus-specific monitoring techniques.

A trichobezoar represents a mass of accumulated hair within the gastrointestinal tract. Isolated gastric trichobezoars, those with extension into the duodenum, and small intestinal trichobezoars have all been described. However, the presence of discrete gastric and intestinal trichobezoars has been rarely presented in the literature. This case report describes synchronous trichobezoars in the stomach and jejunum in a 9-year-old girl presenting with abdominal pain, anorexia, and vomiting. This case emphasizes the role of radiographic imaging in the diagnosis of trichobezoars and the importance of a complete clinical evaluation of the small bowel at the time of removal of an obstructing gastric bezoar.