lmplementation of a national regulatory framework for drinking water safety plans in Uruguay.

The establishment of national strategic frameworks for systematic scaling-up of water safety plans (WSPs) implementation needs to overcome major constraints: lack of legislation and policies, and the need for appropriate monitoring tools. In 2018, the Uruguayan regulator for energy and water services promulgated a regulation intended to ensure an ambitious and pragmatic strategy that supports and promotes WSP implementation and auditing at a national scale. The goal is to have all drinking water supply systems with their WSP implemented by 2030. For this, a demanding schedule was recommended considering the size of the drinking water supplies: (i) large systems serving more than 2,000 inhabitants and (ii) small and very small systems serving fewer than 2,000 inhabitants. A mandatory verification through internal and external audits was also established. This work describes the legal and regulatory framework as well as the challenges and opportunities that open up for the generalization of WSP implementation in Uruguay. Despite the impact of COVID-19 on working conditions for water suppliers, as for the year 2022, WSPs have been successfully implemented in 94 water systems serving more than 2.4 million people. Results of successful implementation and auditing processes are presented and discussed covering methods and outcomes.

A strategic approach for Water Safety Plans implementation in Portugal.

Effective risk assessment and risk management approaches in public drinking water systems can benefit from a systematic process for hazards identification and effective management control based on the Water Safety Plan (WSP) concept. Good results from WSP development and implementation in a small number of Portuguese water utilities have shown that a more ambitious nationwide strategic approach to disseminate this methodology is needed. However, the establishment of strategic frameworks for systematic and organic scaling-up of WSP implementation at a national level requires major constraints to be overcome: lack of legislation and policies and the need for appropriate monitoring tools. This study presents a framework to inform future policy making by understanding the key constraints and needs related to institutional, organizational and research issues for WSP development and implementation in Portugal. This methodological contribution for WSP implementation can be replicated at a global scale. National health authorities and the Regulator may promote changes in legislation and policies. Independent global monitoring and benchmarking are adequate tools for measuring the progress over time and for comparing the performance of water utilities. Water utilities self-assessment must include performance improvement, operational monitoring and verification. Research and education and resources dissemination ensure knowledge acquisition and transfer.

On line high dose static position monitoring by ionization chamber detector for industrial gamma irradiators.

A 1 cm(3) cylindrical ionization chamber was developed to measure high doses on line during the sample irradiation in static position, in a (60)Co industrial plant. The developed ionization chamber showed to be suitable for use as a dosimeter on line. A good linearity of the detector was found between the dose and the accumulated charge, independently of the different dose rates caused by absorbing materials.

Impact of mild acute kidney injury (AKI) on outcome after open repair of aortic aneurysms.

Recently, mild AKI has been considered as a risk factor for mortality in different scenarios. We conducted a retrospective analysis of the risk factors for two distinct definitions of AKI after elective repair of aortic aneurysms. Logistic regression was carried out to identify independent risk factors for AKI (defined as $25% or $50% increase in baseline SCr within 48 h after surgery, AKI 25% and AKI 50%, respectively) and for mortality. Of 77 patients studied (mean age 68 +/- 10, 83% male), 57% developed AKI 25% and 33.7% AKI 50%. There were no differences between AKI and control groups regarding comorbidities and diameter of aneurysms. However, AKI patients needed a supra-renal aortic cross-clamping more frequently and were more severely ill. Overall in-hospital mortality was 27.3%, which was markedly higher in those requiring a supra-renal aortic cross-clamping. The risk factors for AKI 25% were supra-renal aortic cross-clamping (odds ratio 5.51, 95% CI 1.05-36.12, p = 0.04) and duration of operation for AKI 25% (OR 6.67, 95% CI 2.23-19.9, p < 0.001). For AKI 50%, in addition to those factors, post-operative use of vasoactive drugs remained as an independent factor (OR 6.13, 95% CI 1.64-22.8, p = 0.005). The risk factors associated with mortality were need of supra-renal aortic cross-clamping (OR 9.6, 95% CI 1.37-67.88, p = 0.02), development of AKI 50% (OR 8.84, 95% CI 1.31-59.39, p = 0.02), baseline GFR lower than 49 mL/min (OR 17.07, 95% CI 2.00-145.23, p = 0.009), and serum glucose > 118 mg/dL in the post-operative period (OR 19.99, 95% CI 2.32-172.28, p = 0.006). An increase of at least 50% in baseline SCr is a common event after surgical repair of aortic aneurysms, particularly when a supra-renal aortic cross-clamping is needed. Along with baseline moderate chronic renal failure, AKI is an independent factor contributing to the high mortality found in this scenario.

Effect of acute kidney injury on weaning from mechanical ventilation in critically ill patients.

OBJECTIVES: Acute kidney injury (AKI) worsens outcome in various scenarios. We sought to investigate whether the occurrence of AKI has any effect on weaning from mechanical ventilation. DESIGN AND SETTING: Observational, retrospective study in a 23-bed medical/surgical intensive care unit (ICU) in a cancer hospital from January to December 2003. PATIENTS: The inclusion criterion was invasive mechanical ventilation for > or =48 hrs. AKI was defined as at least one measurement of serum creatinine of > or =1.5 mg/dL during the ICU stay. Patients were then separated into AKI and non-AKI patients (control group). The criterion for weaning was the combination of positive end-expiratory pressure of < or =8 cm H2O, pressure support of < or =10 cm H2O, and Fio2 of < or =0.4, with spontaneous breathing. The primary end point was duration of weaning and the secondary end points were rate of weaning failure, total length of mechanical ventilation, length of stay in the ICU, and ICU mortality. RESULTS: A total of 140 patients were studied: 93 with AKI and 47 controls. The groups were similar in regard to age, sex, and type of tumor. Diagnosis of acute lung injury/acute respiratory distress syndrome as cause of respiratory failure and Simplified Acute Physiology Score II at admission did not differ between groups. During ICU stay, AKI patients had markers of more severe disease: increased occurrence of severe sepsis or septic shock, higher number of antibiotics, and longer use of vasoactive drugs. The median (interquartile range) duration of mechanical ventilation (10 [6-17] vs. 7 [2-12] days, p = .017) and duration of weaning from mechanical ventilation (41 [16-97] vs. 21 [7-33.5] hrs, p = .018) were longer in AKI patients compared with control patients. Cox regression analysis demonstrated that a > or =85% increase in baseline serum creatinine (hazard rate, 2.30; 95% confidence interval, 1.30-4.08), oliguria (hazard rate, 2.51; 95% confidence interval, 1.24-5.08), and the number of antibiotics (hazard rate, 2.64; 95% confidence interval, 1.51-4.63) predicted longer duration of weaning. The length of ICU stay and ICU mortality rate were significantly greater in the AKI patients. After adjusting for Simplified Acute Physiology Score II, oliguria (odds ratio, 30.8; 95% confidence interval, 7.7-123.0) remained as a strong risk factor for mortality. CONCLUSION: This study shows that renal dysfunction has serious consequences in the duration of mechanical ventilation, weaning from mechanical ventilation, and mortality in critically ill cancer patients.

Chronic inhibition of nuclear factor-kappaB attenuates renal injury in the 5/6 renal ablation model.

Recent studies indicated that the nuclear transcription factor, NF-kappaB, activates a number of proinflammatory genes in subjects with progressive nephropathies. We investigated whether NF-kappaB inhibition limits progressive renal injury in the 5/6 renal ablation model (Nx). Adult male Munich-Wistar rats were subdivided in four groups: S (n = 16), subjected to sham operation; S+PDTC (n = 18), sham-operated rats receiving the NF-kappaB inhibitor pyrrolidine-dithiocarbamate (PDTC; 60 mg x kg(-1) x day(-1)) in drinking water; Nx (n = 16), Nx rats receiving vehicle only; and Nx+PDTC (n = 19), Nx rats given PDTC as above. Thirty days after renal ablation, Nx rats exhibited systemic and glomerular hypertension. Only the former was attenuated by PDTC treatment. Sixty days after renal ablation, Nx rats exhibited marked hypertension, albuminuria and creatinine retention, as well as glomerulosclerosis and cortical interstitial expansion/inflammation. Immunohistochemical analysis of Nx rats showed renal interstitial infiltration by macrophages and by cells staining positively for ANG II and its receptor, AT(1). Glomerular and interstitial cells expressing the p65 subunit of the NF-kappaB system were also found. PDTC treatment attenuated renal injury and inflammation, as well as the density of cells staining positively for the p65 subunit. Activation of the NF-kappaB system plays an important role in the pathogenesis of renal injury in the Nx model. Inhibition of this system may represent a new strategy to prevent the progression of chronic kidney disease.

Lack of protection of N-acetylcysteine (NAC) in acute renal failure related to elective aortic aneurysm repair-a randomized controlled trial.

BACKGROUND: N-acetylcysteine (NAC) is an antioxidant drug largely tested in different clinical situations. Recently, NAC has been employed with variable success in the prevention of radiocontrast nephropathy. Since aortic aneurysm surgical repair is a condition that is frequently accompanied by acute renal failure (ARF), we sought to investigate whether NAC has any role in preventing ARF in this scenario. METHODS: A randomized, placebo-controlled, double-blind trial with the following inclusion criteria: elective aortic aneurysm repair in patients with stable renal function. The groups were randomly matched for age, gender, presence of diabetes and pre-existent renal failure. NAC or placebo (control) was administered p.o. for 24 h before operation and maintained i.v. for 48 h after operation. The dose of NAC was 1200 mg b.i.d. the day before surgery and 600 mg b.i.d. after. The primary endpoint was the development of ARF up to the third post-operative day, defined as an increase in SCr > or = 25% from baseline. Secondary endpoints were: ICU mortality and ICU length of stay. RESULTS: Forty-two patients (n = 18 for NAC group and n = 24 for control) were studied. The baseline SCr and calculated GFR did not differ between the groups (1.19 +/- 0.33 vs 1.37 +/- 0.49 mg/dl; and 64.6 +/- 26.22 vs 65.7 +/- 28.32 ml/min, NAC vs control, respectively, P = 0.17 and P = 0.90). Need for suprarenal aortic cross-clamping and its duration, occurrence of major bleeding, intra-operative hypotension and the post-operative peak of CPK did not differ between NAC and control groups. The overall incidence of ARF in the study was 36% (13/36), but it was not significantly different between groups (7/14, 50% in NAC vs 6/22, 27.3% in control, P = 0.16). The overall mortality was 23% (10/42) and was not different (P = 0.209) in NAC group (33.3%) when compared with control (16.7%), the same occurring with the length of ICU stay (2.93 +/- 1.53 vs 2.52 +/- 1.36 days, P = 0.40). CONCLUSION: This study suggests that the putative beneficial effects of NAC on radiocontrast nephropathy might not be applicable to other situations, such as ARF associated with elective aortic aneurysm repair.

Coordination of the cell cycle is an important determinant of the syndrome of acute renal failure.

Recovery from injury is usually accompanied by cell replication, in which new cells replace those irreparably damaged. After acute renal failure, normally quiescent kidney cells enter the cell cycle, which in tubule segments is accompanied by the induction of cell cycle inhibitors. We found that after acute renal failure induced by either cisplatin injection or renal ischemia, induction of the p21 cyclin-dependent kinase (cdk) inhibitor is protective. Mice lacking this gene developed more widespread kidney cell death, more severe renal failure, and had reduced survival, compared with mice with a functional p21 gene. Here, we show induction of 14-3-3sigma, a regulator of G(2)-to-M transition, after acute renal failure. Our findings, using both in vivo and in vitro models of acute renal failure, show that this protein likely helps to coordinate cell cycle activity to maximize recovery of renal epithelial cells from injury and reduce the extent of the injury itself. Because in terminally differentiated cells, these proteins are highly expressed only after injury, we propose that cell cycle coordination by induction of these proteins could be a general model of tissue recovery from stress and injury.