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Lipocalin 2 (Lcn2) is rapidly produced by damaged nephron epithelia and is one of the most promising new markers of renal injury, delayed graft function and acute allograft rejection (AR); however, the functional importance of Lcn2 in renal transplantation is largely unknown. To understand the role of Lcn2 in renal AR, kidneys from Balb/c mice were transplanted into C57Bl/6 mice and vice versa and analyzed for morphological and physiological outcomes of AR at posttransplantation days 3, 5, and 7. The allografts showed a steady increase in intensity of interstitial infiltration, tubulitis and periarterial aggregation of lymphocytes associated with a substantial elevation in serum levels of creatinine, urea and Lcn2. Perioperative administration of recombinant Lcn2:siderophore:Fe complex (rLcn2) to recipients resulted in functional and morphological amelioration of the allograft at day 7 almost as efficiently as daily immunosuppression with cyclosporine A (CsA). No significant differences were observed in various donor–recipient combinations (C57Bl/6 wild‐type and Lcn2−/−, Balb/c donors and recipients). Histochemical analyses of the allografts showed reduced cell death in recipients treated with rLcn2 or CsA. These results demonstrate that Lcn2 plays an important role in reducing the extent of kidney AR and indicate the therapeutic potential of Lcn2 in transplantation., The authors demonstrate the function of lipocalin 2 as an upregulated marker during acute rejection and as a therapeutic agent to reduce acute rejection in a murine kidney transplantation model, supporting a possible future application of lipocalin 2 as an early biomarker as well as an immunosuppressive agent in kidney transplantation.

This study examines the efficiency of EPI cluster sampling in assessing the prevalence of diarrhoea and dysentery. A computer was used to simulate fieldwork carried out by a survey taker. The bias and variance of prevalence estimates obtained using EPI cluster sampling were compared with those obtained using simple random sampling and cluster (stratified random) sampling. Efficiency ratios, calculated as the mean square error divided by total distance travelled, were used to compare EPI cluster sampling to simple random sampling and standard cluster sampling. EPI cluster sampling may be an appropriate low-cost tool for monitoring trends in the prevalence of diarrhoea and dysentery over time. However, it should be used with caution when estimating the prevalence of diarrhoea at a single point in time because of the bias associated with this cluster sampling method.Diarrhea is one of the major causes of morbidity and mortality among children in developing countries, and more than 12,000 people are estimated to die per day from diarrheal disease in such countries. Diarrhea has also been shown to affect child growth and is an important cause of malnutrition which can adversely affect child mortality. The infectious nature of diarrhea suggests that fecal contamination of water and food contributes to its transmission. That is, a contaminated source of water, if serving several families, can cause a cluster of illness. Simple random sampling and cluster sampling are discussed as examples of strategies which can be used to measure the prevalence of diarrhea and dysentery in a community. The authors investigated the cost of conducting World Health Organization (WHO) Expanded Program on Immunization (EPI) cluster sample surveys, expressed as the distance travelled to visit the sample subjects, and the bias and variance of the estimates derived with that design. The efficiency of EPI cluster sampling was specifically evaluated with regard to the assessment of the prevalence of diarrhea and dysentery. A computer was used to simulate fieldwork conducted by a survey taker. The bias and variance of prevalence estimates obtained using EPI cluster sampling were compared with those obtained using simple random sampling and cluster sampling. EPI cluster sampling was determined to be an appropriate low-cost tool with which to monitor trends in the prevalence of diarrhea and dysentery over time. It should, however, be used with caution when estimating the prevalence of diarrhea at a single point in time because of bias.

Pharmacokinetics; Liposomal irinotecan; Safety Farmacocinética; Irinotecán liposomal; Seguridad Farmacocinètica; Irinotecan liposomal; Seguretat Liposomal irinotecan is a liposomal formulation of irinotecan, which prolongs circulation of irinotecan and its active metabolite SN-38. A population pharmacokinetic (PK) model was developed based on data from seven studies (N = 440). Adequacy of the model was assessed using multiple methods, including visual predictive check. Associations between PK exposure and the incidence of diarrhea (grade ≥3) and neutropenia adverse events (AEs) (grade ≥3) at first event in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) were investigated using logistic regression based on data from two studies (the phase III NAPOLI-1 [N = 260] and phase I/II NCT02551991 [N = 56] trials). The PKs of total irinotecan was described by a two-compartment model with first-order elimination, with SN-38 formed directly by a first-order constant from the central compartment of irinotecan or after using a transit compartment. Clearance was 17.9 L/week (0.107 L/h) and 19,800 L/week (118 L/h) for total irinotecan and SN-38, respectively. The UGT1A1*28 7/7 homozygous genotype had no significant impact on SN-38 clearance. Model evaluation was satisfactory for both irinotecan and SN-38. The incidence of diarrhea (grade ≥3) at first event was significantly higher with increasing average concentrations of total irinotecan and SN-38; there was no significant association between an increased risk of neutropenia AEs (grade ≥3) at first event and average SN-38 concentrations. In summary, the PKs of total irinotecan and SN-38 after administration of liposomal irinotecan were well-described by the model. The UGT1A1*28 status had no significant impact on the PKs of liposomal irinotecan.