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Aims: The present study aims to provide a comprehensive analytical and biological validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for analysis of salivary cortisol and its inactive metabolite cortisone. Variation in cortisol awakening response (CAR) over one week were investigated. Methods: Saliva samples were collected from 19 healthy volunteers. To determine CAR, participants collected saliva samples at three time points: immediately after awakening, 15 and 30 minutes thereafter. The same procedure was repeated each morning over one week period. In addition, all participants filled in diaries containing information about duration of sleep, time of awakening, smoking, and coffee and alcohol intake. Upon collection, the saliva samples were stored at -20°C until analysis. Prior to analysis, the saliva samples were thawed and spiked with internal standard and extracted using solid phase extraction columns (Oasis Prime-HLB). The identification and quantification of cortisol and cortisone were performed using the developed UPLC-MS/MS method, on a Waters Aquity TQ-XS system. Results: The obtained limits of quantification (LoQ) were 1ng/ml for cortisol and 500pg/ml for cortisone. Intra-assay accuracy values of calibration points were between 83-111%. The mean levels of cortisol and cortisone in the total sample were 3.55 ± 1.99 ng/ml and 10.51 ± 3.46 ng/ml, respectively. In the first 30 minutes after awakening, there was a 70% increase in the average cortisol levels (CAR) and a 49% increase in the levels of cortisone. A high intra-individual variability of CAR was observed over the week (CV ranged between 17.9-68.9%), whereas the inter-individual variability of the average CAR equaled 28.2%. Furthermore, the changes in CAR were related to variables from participants’ diaries. Conclusion: The UPLC-MS/MS method has shown to be a sensitive and specific technique for determination of salivary cortisol and cortisone. However, in the clinical context, CAR data should be interpreted with precaution due to high inter- and intra-individual variability.

The benefits of successful kidney transplants for patients with end stage renal disease associated with insulin-dependent diabetes mellitus are well known, and the potential advantages of earlier transplantation have been emphasized in other reports. Cadaver transplants, which are not always available for these patients, have not provided a high degree of success in many centers. This has discouraged the use of transplants unless well matched related donors are available. Most patients do not have well matched family members who are able to donate. We have attempted to increase the availability of related transplants for diabetic patients by using a new protocol in which related donors who are poorly matched by mixed lymphocyte culture (MLC) testing (stimulation index (SI) greater than or equal to 7) can often serve as the source of the transplant. This protocol of pretransplant donor-specific transfusions (DSTs) has been applied to 20 diabetic patients. Sixteen transplants have been performed after serial immunological studies following the DSTs detected no specific evidence of recipient sensitization to the respective transfusion donors. Only one of the transplants has been rejected, and this occurred in a patient who intentionally terminated immunosuppressive therapy. Graft survival for the group of 16 patients is 93 and 84% at 1 and 3 years, respectively. The quality of renal function for most of the patients is very good, with a mean serum creatinine of 1.9 and 1.5 ml/dl for those transplants at risk for 12 and 24 months. This new method has given encouraging results for poorly matched related transplants in diabetic patients and makes earlier transplantation possible by providing an alternative to cadaver transplants.

Between August 1967 and January 1977, 699 cadaver kidneys were preserved and transplanted in our hospital after continuous perfusion with cryoprecipitated plasma. Overall graft survival of primary transplants was 55 ± 2 per cent at one year and 41 ± 2 per cent at four years. The results with ninety-six second transplants were similar. The number of HLA antigens shared and the duration of preservation did not influence graft survival. Patient survival among 426 cadaver graft recipients since September 1972, when lower dose immunosuppression was started, was 91 ± 1 per cent at one year and 84 ± 2 per cent at four years, significantly better than survival before then. Survival of fifty-two recipients of cadaver retransplants since September 1972 was 86 ± 5 per cent at one year and 86 ± 5 per cent at four years, which was better than before. The incidence of posttransplantation dialysis was 30 per cent and did not correlate with the length of preservation. Primary wound infections, primary ureteral extravasation, and vascular complications each occurred with an incidence of 1.1 per cent or less in patients treated with lower dose immunosuppression. Only four kidneys were lost because of complications, and in no instance was the need for transplant nephrectomy directly related to the method of preservation. Perfusion preservation with cryoprecipitated plasma gives excellent results compared with alternative methods.

We assessed immunologic factors determining graft survival in 510 recipients of primary cadaver allografts at one center. The degree of HLA match grade did not directly affect graft survival (54 per cent in no-antigen match, and 42 per cent in three-antigen match, at two years). There was no correlation between the HLA match grade and the degree of stimulation of the mixed lymphocyte culture. Patients receiving more than five blood transfusions had a significantly better graft survival than nontransfused recipients (52 versus 23 per cent, respectively, at two years, P less than 0.001). The beneficial effect of transfusions was noted whether or not lymphocytotoxic antibodies were produced, provided adequate screening was performed before transplantation. Transfusions did not alter the degree of stimulation in the mixed lymphocyte culture. More liberal use of transfusions and frequent screening for cytotoxic antibodies would probably result in more effective cadaver-kidney transplantation.

Renal transplantation is superior to hemodialysis in terms of rehabilitation and cost, but it is offered to only a minority of patients with end-stage renal failure because of complications related to immunosuppression therapy. To reduce morbidity, we modified out therapy of patients with transplant rejection from high dose intravenous methylprednisolone (group A: January 1968--September 1972) to lower dose oral prednisone (group B: September 1972--December 1977). Patient survival in group B was significantly improved over that in group A, both in recipients of cadaver transplants (91 per cent versus 81 per cent, respectively, at one year, p less than 0.0009) and in recipients of transplants from living related donors (99 per cent versus 86 per cent, respectively, at one year p less than 0.001). The improvement in patient survival was the result of a significant decrease in the incidence of infections. Patients with multiple rejection episodes, a very high risk group, experienced an 18 per cent increase in patient survival in group B. With reduction and rapid tapering of corticosteroids for the treatment of patients with acute rejection and curtailment of the therapy of patients with multiple rejection episodes, survival after renal transplantation becomes comparable to that following hemodialysis; in addition, graft function is not compromised.

Blood transfusions prior to first cadaver kidney transplants have a significant beneficial effect on graft survival and, in this sense, appear to enhance the possibility of a compatible transplant. This desirable effect, however, occurs concomitantly with an increased degree of sensitization, which in turn reduces the likelihood of identifying a compatible kidney by direct crossmatch testing. This report illustrates that the beneficial effect is achieved with one to five transfusions prior to transplantation, but that more transfusions afford no additional benefits. In addition, the presence of cytotoxic antibodies per se does not have an adverse influence on graft survival. Liberal transfusion policies are therefore indicated in cadaver transplant candidates, but more than five transfusions prior to transplantation should probably be avoided unless clinically necessary.

Summary From analysis of results of more than 1,500 renal transplants has evolved a plan for donor selection and immunosuppressive management whereby patients with end-stage renal disease can obtain maximum graft and patient survival. With superior results in both patient and graft survival with living-related transplantation, this modality should be considered initially. Pretreatment with third party blood transfusions appears effective in all donor categories. Donor-specific blood transfusions have afforded 1-haplotype mixed lymphocyte culture-incompatible recipients enhanced opportunity for successful transplantation. Current results with living-related transplantation suggest realistic expectations of 1 and 2 year graft survival rates of greater than 90 percent. Curtailment of steroid therapy has resulted in improved patient survival at 1 and 2 years: 98 and 97 percent for recipients of living-related grafts, and 91 and 88 percent for recipients of cadaver grafts. These results, in combination with proper donor selection and appropriate recipient pretreatment with blood transfusions, have made renal transplantation a very effective therapeutic method in patients with end-stage renal disease.

In order to select MLC incompatible one-haplotype related donor-recipient pairs that would achieve better graft survival and in an effort to alter the recipient immune response, 45 patients received three fresh blood transfuions from their prospective kidney donors. Recipient sensitization was evaluated by cross-match testing weekly sera obtained during and after the blood transfusions against donor T- and B-lymphocytes at 5 C (cold) and 37 C (warm). Thirteen (29%) of the 45 potential related recipients developed a positive warm T-cell cross-match or a persistent warm B-cell cross-match to their blood donor and related transplantation was not performed. Thirty-two (71%) patients had an appropriate negative cross-match to their blood donor. Thirty of these patients subsequently received kidneys from their blood donor. Ninety-seven per cent of the kidneys are functioning from one to 25 months with a single graft failure due to a patient discontinuing immunosuppressive medication. In addition to the excellent graft survival there was an unusually low incidence of rejection episodes in the recipients of kidneys from their blood donor so that the posttransplant course paralleled that of HLA-identical siblings. This approach may have future application with two-haplotype mismatched donor-recipient pairs, both related and unrelated.

In an analysis of 632 cadaver transplants, the early renal transplant course gave important prognostic information depending on temporal and/or renofunctional characteristics of rejection episodes. Two transplant rejections occurring within the first 2 mo posttransplant were associated with either 37%, 27%, or 6% 1-yr graft survivals depending on whether these episodes were separate, temporally back-to-back, or were without interrejection renofunctional recovery, respectively. This compares to 1-yr graft survivals of 89% or 73% in those patients who had no rejection or one with recovery early posttransplant. Patient survival in groups with multiple early rejections was also associated with a poor prognosis. Ninety to 93% 1-yr patient survival was noted when there was no or one rejection. There was only a 74%–83% 1-yr patient survival with two early treated rejections. Transplant rejection therapy must be individualized or even withheld in order to ensure optimum graft and patient survival.

The chance of achieving successful kidney transplants in diabetic patients was previously limited because few of them had optimally-matched (2-haplotype) related donors. Hence, transplants were usually not carried out until renal failure had already occurred. The application of donor-specific transfusions (DSTs) prior to transplantation to poorly matched donor-recipient pairs (1-haplotype) has been associated with a high success rate for type-I diabetic recipients in our center. The rate of graft survival for 35 consecutive transplants in this category was 88%, 80%, and 73% at 1, 2, and 5 years, respectively. Furthermore, the rate of patient survival was 94%, 90%, and 90% at 1, 2, and 5 years. These patient and graft survival data were without significant difference when compared with the corresponding data for 142 optimally-matched (2-haplotype) related transplants performed without DSTs for nondiabetic recipients, and also when compared with the corresponding data for 130 poorly matched (1 or 0-haplotype) related transplants involving nondiabetic recipients who were prepared for transplantation with DSTs. These good results with DSTs in diabetic recipients emphasize that earlier transplantation utilizing poorly matched related donors should be seriously considered for diabetic patients even before the onset of renal failure, as long as the transplants are carried out in association with DSTs.

Accuracy of ultrasonography (US), quantitative scintigraphy, and magnetic resonance (MR) imaging in diagnosis of acute renal allograft rejection was studied in 46 patients who underwent renal biopsy. Thirty-three patients had acute rejection ; six, cyclosporine nephrotoxicity, as shown by biopsy, clinical findings, and follow-up study ; two, acute tubular necrosis ; and five, normal biopsy findings and renal function. Accuracy in demonstrating rejection was 72% for US and 73 for scintigraphy, indicating no signifincant difference between the two. MR imaging imaging was significantly more accurate, reaching a level of 98%. Howeever, accuracy of MR in demonstrating acute tubular necrosis in a larger number of patients is not known, and its accuracy in indicating recurrent glomerulopathy or infectious disease has not been adressed. The definitive role of MR in evaluating posttransplant renal failure is currently not established, but because of its high sensitivity in detecting renal abnormality, MR can used for cases when results of US or scintigraphy are equivocal or contradict clinical impressions or then biopsy cannot be performed for medical reasons.

A cost increase of more than 900% for medical services to dialysis patients and transplant recipients has been projected during the decade 1974 to 1984. To evaluate the role of renal transplantation in the End-Stage Renal Disease Program, we analyzed direct costs and patient outcomes in 466 consecutive transplants at our center. A successful transplant from either a living related or cadaver donor cost less than $7,000 per year for two years of graft function. The cost of transplants rejected during the second year also proved cost-effective when compared with the yearly costs of maintenance-facility hemodialysis. Patient survival was 100% at two years for recipients of a transplant from a living related donor and 84% at two years for recipients of a transplant from a cadaver. Renal transplantation can reduce the rising costs for end-stage renal disease patient care, without reducing life expectancy. (JAMA241:1469-1473, 1979)

Biochemical and bone scintigraphic studies were performed in nondiabetic and diabetic patients receiving hemodialysis at the time of kidney transplantation to assess the degree of secondary hyperparathyroidism. Despite lower serum calcium concentrations, diabetic patients had significantly lower parathyroid hormone (PTH) levels than nondiabetic patients. In addition, diabetic patients had lower graded total-skeletal scintigraphic scores than nondiabetic patients. The PTH levels showed positive correlations with bone scan scores and with alkaline phosphatase in nondiabetic patients but not in diabetic patients. Avascular necrosis occurred in 17% of nondiabetic patients and in only 2% of diabetic patients. Patients with avascular necrosis had significantly higher PTH levels than patients without avascular necrosis. Diabetes mellitus seems to confer a protective effect from the skeletal manifestations of secondary hyperparathyroidism, including avascular necrosis. ( JAMA 1981;245:930-933)

Two-hundred three children 1 to 16 years of age received kidney transplants during a 20-year period, 100 from living donors and 103 from cadaver donors. The overall survival rate was 79%. Actuarial patient and kidney survival rates at 15 years were 79% and 52%, respectively, for recipients of living donor kidneys and 57% and 19%, respectively, for recipients of cadaver donor kidneys. One of two children who received transplants in 1964 was alive 20½ years later. Twenty-nine children had kidneys that had functioned more than 10 years; their mean serum creatinine concentration was 1.7 mg/dL and 24 were fully rehabilitated. Eighteen were more than 2 SD below the mean height of normal chidren, however. Comparison of survival rates during successive 5-year intervals showed significant improvement in patient survival during the 20-year period and smaller improvements in kidney survival after 1979. Patient survival after living donor transplants during the last 10 years was 100%, and kidney survival during the last 5 years was 92%. Improvement was attributed to the effect of experience, as well as to changes in immunosuppressive therapy in 1972 and the introduction of donor-specific transfusions in 1978.

Visible light communication (VLC) is a promising candidate to face the bandwidth limitation problems of traditional radio communication system. The use of a light emitting diode (LED), directly modulated, as a transmitter of the wireless telecommunication link permits the installation of VLC-based systems in practically all human-attended settings (home, office, markets). However, a drawback of VLC systems remains the receiver side, due to the lack of photovoltaic devices for this specific application. Organic electronics based on solution processed technologies has the great potential to be applied in VLC systems, building effective, scalable and low-cost photodetectors. We have investigated the effect of the device architecture on optical and electrical device performance, using both P3HT:PCBM and PTB7:PC70BM bulk-heterojunction active layers. We have established that both materials and structures could affect greatly the device properties, and we have provided an analytical representation of the spectral matching between light source and detector. In particular, the most promising device, based on a P3HT:PCBM blend, has demonstrated high performance, especially using an inverted structure. In this configuration, a device cut-off frequency of ~1.0 MHz has been achieved, paying the way to organic photodetector application on VLC-based telecommunication systems in 5G scenarios.

INTRODUCTION: Phthalates, a group of ubiquitous industrial chemicals, have been widely used in occupational settings, mainly as plasticizers in a variety of applications. Occupational exposure to different phthalates has been studied in several occupational settings using human biomonitoring (HBM). AIM: To provide a comprehensive review of the available literature on occupational exposure to phthalates assessed using HBM and to determine future data needs on the topic as part of the HBM4EU project. METHODS: A systematic search was carried out in the databases of Pubmed, Scopus, and Web of Science for articles published between 2000 and September 4, 2019 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 22 studies on the occupational HBM of phthalates was considered suitable for review. RESULTS AND DISCUSSION: Among the reviewed studies, 19 (86%) focused on DEHP, an old phthalate that is now subject to authorization and planned to be restricted in the EU. Concentrations of MEHHP, one of its metabolites, varied up to 13-fold between studies and across sectors when comparing extreme geometric means, ranging from 11.6 (similar to the general populations) to 151 μg/g creatinine. Only 2 studies focused on newer phthalates such as DiNP and DPHP. Concerning the geographical distribution, 10 studies were performed in Europe (including 6 in Slovakia), 8 in Asia, and 4 in North America, but this distribution is not a good reflection of phthalate production and usage levels worldwide. Most HBM studies were performed in the context of PVC product manufacturing. Future studies should focus on: i) a more uniform approach to sampling timing to facilitate comparisons between studies; ii) newer phthalates; and iii) old phthalates in waste management or recycling. CONCLUSION: Our findings highlight the lack of recent occupational HBM studies on both old and new phthalate exposure in European countries and the need for a harmonized approach. Considering the important policy actions taken in Europe regarding phthalates, it seems relevant to evaluate the impact of these actions on exposure levels and health risks for workers. ispartof: INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH vol:229 ispartof: location:Germany status: published

Occupational exposure to hexavalent chromium (Cr(VI)) can cause serious adverse health effects such as lung cancer and irritation of the skin and airways. Although assessment of chromium (Cr) in urine is not specific for Cr(VI) exposure, the total amount of Cr in urine is the most used marker of exposure for biomonitoring of Cr(VI). The purpose of this systematic review was fourfold: (1) to assess current and recent biomonitoring levels in subjects occupationally exposed to Cr(VI), with a focus on urinary Cr levels at the end of a working week, (2) to identify variables influencing these biomonitoring levels, (3) to identify how urinary Cr levels correlate with other Cr(VI) exposure markers and (4) to identify gaps in the current research. To address these purposes, unpublished and published biomonitoring data were consulted: (i) unpublished biomonitoring data comprised urinary Cr levels (n = 3799) of workers from different industries in Belgium collected during 1998–2018, in combination with expert scores indicating jobs with Cr exposure and (ii) published biomonitoring data was extracted by conducting a systematic literature review. A linear mixed effect model was applied on the unpublished biomonitoring data, showing a decreasing time trend of 30% in urinary Cr levels. Considering the observed decreasing time trend, only articles published between January 1, 2010 and September 30, 2020 were included in the systematic literature search to assess current and recent biomonitoring levels. Twenty-five studies focusing on human biomonitoring of exposure to Cr(VI) in occupational settings were included. Overall, the results showed a decreasing time trend in urinary Cr levels and the need for more specific Cr(VI) biomarkers. Furthermore, this review indicated the importance of improved working conditions, efficient use of personal protective equipment, better exposure control and increased risk awareness to reduce Cr levels in biological matrices. Further investigation of the contribution of the different exposure routes is needed, so that better guidance on the use of control measures can be provided. In addition, this review support the call for more harmonization of human biomonitoring.