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The internal behaviour of a population is an important feature to take account of when modelling its dynamics. In line with kin selection theory, many social species tend to cluster into distinct groups in order to enhance their overall population fitness. Temporal interactions between populations are often modelled using classical mathematical models, but these sometimes fail to delve deeper into the, often uncertain, relationships within populations. Here, we introduce a stochastic framework that aims to capture the interactions of animal groups and an auxiliary population over time. We demonstrate the model's capabilities, from a Bayesian perspective, through simulation studies and by fitting it to predator-prey count time series data. We then derive an approximation to the group correlation structure within such a population, while also taking account of the effect of the auxiliary population. We finally discuss how this approximation can lead to ecologically realistic interpretations in a predator-prey context. This approximation also serves as verification to whether the population in question satisfies our various assumptions. Our modelling approach will be useful for empiricists for monitoring groups within a conservation framework and also theoreticians wanting to quantify interactions, to study cooperation and other phenomena within social populations., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Microorganisms from L. terrestris gut previously exposed to different types of plastic (PET, LDPE, LLDPE, and PS) were studied to be used as probiotics of earthworms in plastic-contaminated soils (LDPE, LLDPE and recycled mulching film) at mesocosm-scale trials. The most abundant morphotypes with enzymatic capacities of interest were identified. Pseudomonas alkylphenolica (PL4) and Pseudomonas putida (PL5) strains were selected to be used as inoculants using Morus alba leaves as carriers to strengthen the intestinal microbiota of earthworms. Culture (selective cetrimide agar medium) and molecular (qPCR) techniques were used to trace the presence of the inoculum in the intestine of the earthworms. Additionally, a metataxonomic analysis was carried out to study the biodiversity and functionality of the earthworm microbiome, and their measure of survival and weight. Probiotics improved the survival rates of earthworms exposed to plastics, which also increased the abundance of microbial groups of interest in plastic bioremediation tasks., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Composting is an advantageous and efficient process for recycling organic waste and producing organic fertilizers, and many kinds of microorganisms are involved in obtaining quality compost with suppressive activity against soil-borne pathogens. The aim of this work was to evaluate the main differences in the effects of three composting piles on the whole bacterial and fungal communities of baby-leaf lettuce crops and to determine the specific communities by high-throughput sequencing related to suppressiveness against the soil-borne plant pathogen Pythium irregulare- (P. irregulare). Compost pile A was composed of 47% vineyard pruning waste, 34% tomato waste and 19% leek waste; pile B was composed of 54% vineyard pruning waste and 46% tomato waste; and pile C was composed of 42% vineyard pruning waste, 25% tomato waste and 33% olive mill cake. The temperature and the chemical properties of the piles were monitored throughout the composting process. In addition, the potential suppressive capacity of the three composts (C_A, C_B and C_C) against P. irregulare in baby-leaf lettuce was assessed. We found that the bacterial community changed according to the composting phases and composting pile and was sensitive to chemical changes throughout the composting process. The fungal community, on the other hand, did not change between the composting piles and proved to be less influenced by chemical properties, but it did change, principally, according to the composting phases. All composts obtained were considered stable and mature, while compost C_C showed higher maturity than composts C_A and C_B. During composting, the three piles contained a greater relative abundance of Bacterioidetes, Proteobacterias and Actinobacterias related to the suppression of soil-borne pathogens such as Pythium irregulare. Composts C_A and C_B, however, showed higher suppressiveness against P. irregulare than compost C_C. Deeper study showed that this observed suppressiveness was favored by a higher abundance of genera that have been described as potential suppressive against P. irregulare, such as Aspergillus, Penicillium, Truepera and Luteimonas., 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 © 2021 Elsevier B.V. All rights reserved.)

During the last two decades, the method most widely used to manage olive mill wastewater (OMW) derived from olive oil production has been its disposal in evaporation ponds. Long-term storage of OMW leads to the accumulation of toxic sediments (OMWS) rich in recalcitrant compounds with phytotoxic and antimicrobial properties, which limit their use for agronomic purpose. The aim of this study was to compare the effect of two in situ bioremediation strategies (composting and a combination of composting followed by vermicomposting) to remove the potential toxicity of the sediments derived from long-term stored OMW. The results obtained showed that the composting method assisted with the earthworms enhanced the depletion of phenolic compounds and OMWS ecotoxicity more than composting, especially during the maturation stage. Moreover, vermicomposting was more effective in the reduction of the OMWS salinity. However, a pre-composting process to the OMWS is necessary prior to vermicomposting to provide the suitable conditions for earthworms survival and activity. Furthermore, the final compost showed a phytostimulating effect. Therefore, these in situ bioremediation strategies can be considered potential tools for decontamination and recovery of long-term stored OMWS in evaporation ponds, which currently poses an unsolved environmental problem., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The common method for the disposal of olive oil mill wastewater (OMW) has been its accumulation in evaporation ponds where OMW sediments concentrate. Due to the phytotoxic and antimicrobial effect of OMW, leaks from ponds can pollute soils and water bodies. This work focuses on the search for microorganisms that can be used as inocula for bioremediation of polluted matrices in OMW ponds by means of in situ composting. Two fungi isolated from OMW sediments, Aspergillus ochraceus H2 and Scedosporium apiospermum H16, presented suitable capabilities for this use as a consortium. Composting eliminated the phyto- and ecotoxicity of OMW sediments by depleting their main toxic components. Inoculation with the fungal consortium improved the bioremediation efficacy of the technique by hastening the decrease of phytotoxicity and ecotoxicity and enhancing phytostimulant property of compost produced. This procedure constitutes a promising strategy for bioremediation of OMW polluted sites., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To assess the impact of a training program targeted to Primary Care (PC) professionalson the acquisition of communication skills, attitudes, and knowledge about the prevention and management of unhealthy alcohol use., Methods: A quasi-experimental, pre- and post-intervention study was performed in PC centers of Cordoba (Spain). Family doctors, residents and nurses participated in the study. The intervention was based on a motivational interviewing training program, which consisted in a workshop on learning skills, attitudes and knowledge about the alcohol management. PC providers were videotaped with a standardized patient in order to check the clinical and communication competencies acquired. A descriptive, bivariate and multivariate analysis was carried out (p < 0.05)., Results: PC providers' communication skills and attitudes showed significant improvements in the variables studied (p < 0.001), as well as in the clinical interview evaluation parameters., Conclusion: The present study reveals the impact of a training program targeted to PC professionals on communication skills, attitudes, and knowledge about the prevention and management of patients with unhealthy alcohol use., Practice Implications: Training activities targeted to PC providers represent a valuable strategy to improve communication skills, attitudes and knowledge of these professionals in their clinical practice., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a biological level, between the tumours of asymptomatic and symptomatic patients. Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening., Study Method: A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010-2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained., Results: A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p < 0.05). However, no significant differences were found regarding the markers of tumour biology: Ki67 (proliferation), CD105 (angiogenesis) and the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (apoptosis). The patients with asymptomatic tumours had a lower mortality at five years than those diagnosed presenting symptoms., Conclusions: The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: To increase medical students' ability to detect contextual and emotional cues and to respond empathetically to patients., Methods: a training course in communication skills and patient-centered care with different teaching activities (didactic, reflective and interactive: workshops and encounters with simulated patients) was delivered to third-year medical students just before their clerkships. The program was evaluated by an external observer (OE) and simulated patients (SP) in 2 or 3 videotaped encounters., Results: Students improved significantly from baseline to 3rd interview in all communicative skills and domains explored both in OE (32.4%) and SP (38.3%) measurement. At the end of the course students detected significantly more clues and made more empathetic expressions., Conclusions: The course seems to improve the ability of students to explore the illness experience, showing more empathy in a more genuine way. This was carried out in consultations lasting 10min., Practical Implications: The program is effective and feasible to be applied as a regular formative activity. Further research is needed to assess whether this training program is applicable to students in more advanced educational levels and if it has any additional outcomes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

On-farm anaerobic digestion (AD) has been promoted due to its improved environmental performance, which is based on a number of life cycle assessments (LCA). However, the influence of site-specific conditions and practices on AD performance is rarely captured in LCA studies and the effects on C and N cycles are often overlooked. In this paper, a new model for AD (SIMS WASTE-AD ) is described in full and tested against a selection of available measured data. Good agreement between modelled and measured values was obtained, reflecting the model capability to predict biogas production (r 2 =0.84) and N mineralization (r 2 =0.85) under a range of substrate mixtures and operational conditions. SIMS WASTE-AD was also used to simulate C and N flows and GHG emissions for a set of scenarios exploring different AD technology levels, feedstock mixtures and climate conditions. The importance of post-digestion emissions and its relationship with the AD performance have been stressed as crucial factors to reduce the net GHG emissions (-75%) but also to enhance digestate fertilizer potential (15%). Gas tight digestate storage with residual biogas collection is highly recommended (especially in temperate to warm climates), as well as those operational conditions that can improve the process efficiency on degrading VS (e.g. thermophilic range, longer hydraulic retention time). Beyond the effects on the manure management stage, SIMS WASTE-AD also aims to help account for potential effects of AD on other stages by providing the C and nutrient flows. While primarily designed to be applied within the SIMS DAIRY modelling framework, it can also interact with other models implemented in integrated approaches. Such system scope assessments are essential for stakeholders and policy makers in order to develop effective strategies for reducing GHG emissions and environmental issues in the agriculture sector., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: We analyzed the toxicity and cosmetic outcomes for patients who had undergone 3-dimensional conformal radiotherapy with a hypofractionated schedule and identified the risk factors associated with such a schedule., Materials and Methods: A total of 143 patients were treated for breast cancer (stage 0-III) with a hypofractionated radiation schedule after breast-conserving surgery from 2006 to 2011. Most patients received 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction to the whole breast plus an additional simultaneous integrated or sequential boost to the tumor bed., Results: The median follow-up period was 36 months. Mild acute skin toxicity was observed in 62%; 7% of the patients developed moderate skin toxicity, but no grade 4 toxicity was observed. The prevalence of fibrosis within the boost area was 5%, but no grade ≥ 2 was observed. The prevalence of fibrosis of any grade was greater in the nonboost (23%) than in the boost area. Of all the patients, 91% had good or excellent cosmetic outcomes. From the multivariate analysis, the incidence of epithelitis correlated with the patient's treated volume (P = .044). The incidence of acute toxicity correlated with the boost type to the tumor bed and the total treatment dose (P = .012 and P = .002, respectively). Also, a poor to fair cosmetic outcome was significantly associated statistically with the surgery type (P = .05), boost type (P = .004), and total dose (P = .001)., Conclusion: Delivering whole-breast irradiation with a hypofractionated schedule of 42.4 Gy plus a simultaneous integrated boost to the tumor bed appears to be a safe and effective technique, with good cosmetic results and lower toxicity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Mannose-binding lectin (MBL) is a protein of the innate immune system that participates in host defense and the tissue injury/repair process, enhancing the clearance of apoptotic cells by macrophages. The aim is to characterize the relationship between pre-transplant MBL levels, histological lesions and number of apoptotic cells in early surveillance renal allograft biopsies., Patients and Methods: Consecutive renal transplant recipients were recruited and MBL levels were classified into tertiles. The first tertile was considered the low MBL group. Surveillance biopsies were done during the first 6 months and were evaluated according to Banff criteria. Renal inflammatory infiltrates were studied by immunohistochemical techniques. Apoptosis was studied using morphological methods in renal tubular cells and was expressed as the number of apoptotic cells/mm(2)., Results: MBL was determined in 126 patients and a surveillance biopsy with sufficient tissue was obtained in 41 of them. Patients with low pre-transplant MBL levels showed a higher acute Banff index (3.14 ± 1.96 vs. 1.88 ± 1.56, p = 0.044) and an increased proportion of biopsies with tubular cell apoptosis The proportion of biopsies with tubular cell apoptosis was higher in patients with low pre-transplant MBL levels in comparison with patients with high MBL levels (4.3 ± 3.6 versus 0.2 ± 0.9 p = 0.012) and increased interstitial number of inflammatory cells and significantly the macrophages/mm(2) (109 ± 118 vs. 32 ± 46; p = 0.04)., Conclusion: Low pre-transplant serum MBL levels are associated with more severe inflammation and increased apoptosis in early surveillance renal allograft biopsies suggesting that MBL modulates renal inflammation after transplantation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Sewage sludge application to agricultural soils is a common practice in several countries in the European Union. Nevertheless, the application dose constitutes an essential aspect that must be taken into account in order to minimize environmental impacts. In this study, near infrared reflectance spectroscopy (NIRS) was used to estimate in sewage sludge samples several parameters related to agronomic and environmental issues, such as the contents in organic matter, nitrogen and other nutrients, metals and carbon fractions, among others. In our study (using 380 biosolid samples), two regression models were fitted: the common partial least square regression (PLSR) and the penalized signal regression (PSR). Using PLSR, NIRS became a feasible tool to estimate several parameters with good goodness of fit, such as total organic matter, total organic carbon, total nitrogen, water-soluble carbon, extractable organic carbon, fulvic acid-like carbon, electrical conductivity, Mg, Fe and Cr, among other parameters, in sewage sludge samples. For parameters such as C/N ratio, humic acid-like carbon, humification index, the percentage of humic acid-like carbon, the polymerization ratio, P, K, Cu, Pb, Zn, Ni and Hg, the performance of NIRS calibrations developed with PLSR was not sufficiently good. Nevertheless, the use of PSR provided successful calibrations for all parameters., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Composting is an environmentally friendly alternative for the recycling of organic wastes and its use is increasing in recent years. An exhaustive monitoring of the composting process and of the final compost characteristics is necessary to certify that the values of compost characteristics are within the limits established by the legislation in order to obtain a safe and marketable product. The analysis of these parameters on each composting batch in the commercial composting plant is time-consuming and expensive. So, their estimation in the composting facilities based on the use of near infrared reflectance spectroscopy (NIRS) could be an interesting approach in order to monitor compost quality. In this study, more than 300 samples from 20 different composting procedures were used to calibrate and validate the NIRS estimation of compost properties (pH, electrical conductivity (EC), total organic matter (TOM), total organic carbon (TOC), total nitrogen (TN) and C/N ratio, macronutrient contents (N, P, K) and potentially pollutant element concentrations (Fe, Cu, Mn and Zn)). The composts used were elaborated using different organic wastes from agroindustrial activities (GS: grape stalk; EGM: exhausted grape marc; GM: grape marc; V: vinasse; CJW: citrus juice waste; Alpeorujo: olive-oil waste; AS: almond skin; EP: exhausted peat; TSW: tomato soup waste; SMS: spent mushroom substrate) co-composted with manures (CM: cattle manure; PM: poultry manure) or urban wastes (SS: sewage sludge) The estimation results showed that the NIRS technique needs to be fitted to each element and property, using specific spectrum transformations, in order to achieve an acceptable accuracy in the prediction. However, excellent prediction results were obtained for TOM and TOC, successful calibrations for pH, EC, Fe and Mn, and moderately successful estimations for TN, C/N ratio, P, K, Cu and Zn.

Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 +/- 117), SCR (202 +/- 145), IF/TA (208 +/- 151) and IF/TA + SCR (307 +/- 180 cells/mm(2)), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23-7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

Objective: To explore the communicative behaviours as used by specialty physicians, and their patients' perception of the communicative act as well as their satisfaction with the encounter., Methods: Cross-sectional study involving 27 specialty physicians and 257 outpatients. Encounters were video-recorded and analysed through the GATHA-ESP scale. Patients rated the quality of the interaction and their satisfaction with it in a questionnaire., Results: Most specialist doctors use a "managerial" style where there is no exploration of their patients' emotions (22%), expectations (28%) or psychosocial aspects (10-20%). Less than one doctor out of every four ever gave the patient an opportunity to participate in any type of decision making at the surgery. Patients were more satisfied with those encounters they felt more patient-centred (F: 11.37; p<0.001); higher scores on the GATHA-ESP characterised these visits., Conclusions: Specialty physicians show a limited range of communicative skills as they use a doctor-centred style that allows for little patient participation. Patients' perceptions of patient-centeredness are linked to satisfaction more than the analysis of doctors' behaviour at the consultation does., Practice Implications: It seems important to foster training in communication skills in the different specialist vocational training programs. Studies on physician-patient communication should deal with the perceived and observed perspectives on this domain.

Background/aims: The effect of interferon on the reduction of liver fibrosis is controversial. We aimed to compare semiquantitative methods with a quantitative digital image analysis system to assess liver fibrosis in biopsies from patients with chronic hepatitis and different responses to interferon., Methods: We studied 98 liver biopsies with chronic hepatitis C before and after recombinant interferon alfa-2 treatment, using conventional histological assessment, grading of histological activity, scoring/staging of fibrosis (Knodell and Scheuer), and quantification of fibrosis with image analysis (FibroQuant)., Results: Sustained-responders to interferon showed a significant reduction in histological lesions and in their Knodell and Scheuer activity indexes. The semiquantitative systems showed no reduction in fibrosis. The FibroQuant application showed a significant reduction in porto-periportal and septal areas among sustained-responders (P < 0.001) and non-responders (P < 0.05), and in porto-periportal and septal fibrosis areas only in sustained-responders (P < 0.001), whereas the percentage of fibrosis increased in non-responders (P < 0.001)., Conclusions: The Scheuer system is useful for the daily evaluation of fibrosis, but the FibroQuant application provides more objective data on the anti-fibrogenic effects of interferon, which include a reduction in the porto-periportal area in sustained-responders and non-responders, accompanied by a reduction in the area of fibrosis only when the viral replication has ceased.

Background/aims: Liver fibrosis is one of the most important and characteristic histologic alterations in progressive and chronic liver diseases. Thus, in both clinical and experimental practice, it is fundamental to have a reliable and objective method for its precise quantification. Several semi-quantitative scoring systems have been described. All are time-consuming and produce partially subjective fibrosis evaluations that are not very precise. This paper describes the design and validation of an original image analysis-based application, FibroQuant, for automatically and rapidly quantifying perisinusoidal, perivenular and portal-periportal and septal fibrosis and portal-periportal and septal morphology in liver histologic specimens., Methods: The implemented image-processing algorithms automatically segment interstitial fibrosis areas, while extraction of portal-periportal and septal region is carried out with an automatic algorithm and a simple interactive step. For validation, all automatically extracted areas were also manually segmented and quantified., Results: Statistical analysis showed significant intra- and interoperator variability in manual segmentation of all areas. Automatic quantifications did not significantly differ from mean manual evaluations of the same areas. Comparison of our image analysis quantifications with staging histologic evaluations of liver fibrosis showed significant correlations (Spearman's, 0.72

P-glycoprotein (P-gp) expels hydrophobic substances from the cell, including chemotherapeutic agents and immunosuppressants such as cyclosporin A (CsA) and FK506. Exposure of cultured renal tubular cells to CsA induces P-gp overexpression in cell membranes. Angiotensin II has recently been implicated as the principal factor responsible for progression of interstitial fibrosis induced by CsA. To investigate the in vivo relationships between histological lesions, P-gp overexpression, and intrarenal angiotensin II deposits, we developed a model of chronic CsA toxicity in Sprague-Dawley rats treated with 25 mg/kg/day CsA for 28 and 56 days and fed either a standard maintenance diet or a low-salt diet. Immunohistochemical methods were used to study the expression of P-gp in renal tubular cells and the appearance of intrarenal angiotensin II deposits. Rats treated with CsA developed chronic nephrotoxicity lesions that were more evident in the group fed the low-salt diet. Treatment with CsA induced overexpression of P-gp in tubular cells of the kidney that increased with time. We found that immunohistochemical expression of P-gp was slightly more severe in rats fed a low-salt diet. Intrarenal deposits of angiotensin II were more evident in rats treated with CsA; these deposits also increased with time. This finding was also more relevant in rats given the low-salt diet. The up-regulation of P-gp was inversely related to the incidence of hyaline arteriopathy (r = -0.65; P < 0.05), periglomerular (r = -0.58; P < 0.05) and peritubular fibrosis (r = -0.63; P < 0.05), and intrarenal angiotensin H deposits in animals with severe signs of nephrotoxicity (r = -0.65; P < 0.05). These results support the hypothesis that the role of P-gp as a detoxicant in renal cells may be related to mechanisms that control the cytoplasmic removal of both toxic metabolites from CsA and those originating from the catabolism of signal transduction proteins (methylcysteine esters), which are produced as a result of ras activation in presence of angiotensin II.

Previous studies have shown that in non-Hodgkin's lymphomas and others neoplasms, tumoral progression, treatment response, and outcome are related to the expression of different oncogenic and tumor suppressor proteins. This study aimed to determine the prognostic significance of the expression of p53, bcl2, retinoblastoma protein (Rb), Ki67, CD15, and latent membrane protein 1-Epstein-Barr Virus (LMP1-EBV) proteins in Hodgkin's disease. A retrospective study was performed on 140 patients collected at the 11 participating centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. A highly sensitive immunohistochemical method with previous microwave-induced antigen retrieval technique was used for the demonstration of the above-mentioned proteins. A Cox's multivariate analysis was performed to evaluate the impact of the variables in the overall survival, together with a logistic regression model for the achievement of complete remission. Univariate statistical analysis confirmed the prognostic significance of the alredy known clinical parameters: stage, age over 60 years, and B symptoms. High proliferation index (Ki67) and loss of Rb expression were also found to be adverse prognostic factors influencing respectively lower overall survival and failure to achieve complete remission. Multivariate analysis confirmed the independent significance of these two parameters and additionally identifies LMP1-EBV expression as a favorable prognostic marker, in relation with overall survival. Histopathological type, p53, bcl2, and CD15 expression lack significant influence on the outcome of this series. The progression of the disease or the response to treatment in HD patients is the consequence of the interrelationship of different factors, among which LMP1 expression, loss of Rb, and high growth fraction seems to play a more relevant role.

Recent studies suggest that apoptotic cell death regulates the cell complement in glomerular diseases. However, little is-known about the factors that promote glomerular cell apoptosis. Activation of the Fas receptor by the Fas ligand or agonistic antibodies triggers apoptosis in some cell types that express Fas. Cultured human mesangial cell are among the cells that undergo apoptosis upon Fas activation, but it is unclear whether mesangial cells are sensitive to death induced by Fas in vivo. We have now explored the role of Fas in experimental glomerular injury. Murine mesangial cells in culture express fas and undergo apoptosis when stimulated with the Jo2 agonistic anti-Fas mAb. A fas mRNA transcript is present in normal murine kidney and freshly isolated glomeruli. Balb-c mice developed hematuria and proteinuria within 24 hours of the intraperitoneal injection of 10 micrograms Jo2 anti-Fas mAb. In addition to liver cell apoptosis, glomerular cell apoptosis and mesangial cell depletion were evident in the kidney at three hours and more pronounced at 24 hours. Glomerular and liver injury were not prevented by decomplementation. These data suggest that Fas activation in vivo by specific antibodies induces glomerular and mesangial cell apoptosis in mice.

P-glycoprotein (P-gp), encoded in humans by the mdr-1 gene, acts physiologically as an efflux pump to expel hydrophobic substances from cells. This glycoprotein is closely related to multidrug resistance in tumor cells and can be modulated by cyclosporin A (CsA). We investigated the relationship between CsA and P-gp in 52 renal allograft biopsies and in cultures of Madin-Darby canine kidney (MDCK) renal tubule cells to determine whether the intrarenal accumulation of CsA or chronic stimulation with the drug modified the expression of P-gp. Expression of P-gp and CsA was analyzed by immunohistochemistry. Immunostaining was evaluated semiquantitatively. Modulation of P-gp in MDCK cells after chronic stimulation with CsA for 7, 30, and 60 days was analyzed by flow cytometry. P-gp and CsA immunostaining in renal post-transplant biopsies showed considerable overlap in all cases (Spearman's test, r = 0.577, P < 0.001). After 7 days in vitro, the number of cells expressing P-gp increased progressively; a further increase in mean fluorescence was found after 60 days (P < 0.001, Student's t-test). Our findings suggest that in non-neoplastic cells, CsA may stimulate P-gp as a mechanism of detoxification. Individual differences in the adaptive responses to glycoprotein may be responsible for the appearance of nephrotoxicity or a CsA-resistant rejection reaction in cases of overexpression on lymphocytes and macrophages.

Xyloglucan was purified from water-soluble hemicelluloses extracted with 24% KOH from pine cell walls using ion-exchange chromatography and iodine precipitation. Linkage analysis showed that pine xyloglucan was highly substituted with 80% of the glucosyl residues substituted at position 6. The presence of terminal-fucosyl residues in pine xyloglucan confirm that the primary cell walls of gymnosperms are more closely related to those of dicots than to graminaceous monocot cell walls.