Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients.

Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+ CD154+ and CD8+ CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+ CD154+ T cells (P = 0·001) and a low percentage of CD8+ CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+ CD154+ (P = 0·001) and CD8+ CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+ CD154+ , CD8+ CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+ CD154+ and CD8+ CD154+ T cells in parallel with other transplant factors.

Molecular characterisation and antifungal susceptibility of clinical Cryptococcus deuterogattii (AFLP6/VGII) isolates from Southern Brazil.

Cryptococcosis, caused by Cryptococcus gattii sensu lato, is an emerging disease that was initially found in (sub)tropical regions but recently expanded to temperate regions. Cryptococcus gattii s.l. infections are mostly encountered in healthy individuals, frequently affecting both lungs and the central nervous system (CNS). Usually, C. gattii s.l. is less susceptible to antifungal compounds than its counterpart, C. neoformans s.l. We studied 18 clinical C. gattii s.l. isolates with amplified fragment length polymorphism (AFLP) fingerprinting, mating-typing, multi-locus sequence typing (MLST) and antifungal susceptibility testing. All isolates were C. deuterogattii (genotype AFLP6/VGII), 14 were mating-type α and four were type a. Amphotericin B, itraconazole, voriconazole, posaconazole and isavuconazole showed high activity, with minimum inhibitory concentration (MIC) ranges of 0.063-0.25, 0.031-0.25, 0.031-0.25, 0.031-0.25 and <0.016-0.25 µg mL-1, respectively. Fluconazole and flucytosine had high geometric mean MICs of 2.07 and 3.7 µg mL-1, respectively. Most cases occurred in immunocompetent patients (n = 10; 55.6 %) and CNS involvement was the most common clinical presentation (n = 14; 77.8 %). Three patients (16.7 %) showed sequelae, hyperreflexia, dysarthria, diadochokinesia, anosmia and upper limb weakness. In conclusion, all infections were caused by C. deuterogattii (AFLP6/VGII) and the majority of patients were immunocompetent, with the CNS as the most affected site. All antifungal drugs had high in vitro activity against C. deuterogattii isolates, except fluconazole and flucytosine.

Pro- and anti-inflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease.

Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFß [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1ß [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFß, IL10, IL6, IL1α, IL1ß, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFß, IL10, IL6 and IL1α, IL1ß, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development.

Should IFN-γ, IL-17 and IL-2 be considered predictive biomarkers of acute rejection in liver and kidney transplant? Results of a multicentric study.

Acute rejection (AR) remains a major challenge in organ transplantation, and there is a need for predictive biomarkers. In the present multicenter study, we prospectively examined a series of biomarkers in liver and kidney recipients. Intracellular expression of IFN-γ, IL-17 and IL-2 and IL-17 soluble production were evaluated both pre-transplantation and post-transplantation (1st and 2nd week, 1st, 2nd and 3rd month). 142 transplant patients (63 liver/79 kidney) were included in the study. Twenty-eight recipients (14 liver/14 kidney) developed AR. Pre- and post-transplantation intracellular expression of %IFN-γ(+) in CD4(+)CD69(+) and in CD8(+)CD69(+) and soluble IL17 identified liver and kidney transplant patients at high risk of AR. Pre-transplantation, %IL-2(+) in CD8(+)CD69(+) also identified kidney patients at high risk. We constructed pre- and post-transplantation risk prediction models, based on a composite panel of biomarkers, which could provide the basis for future studies and will be a useful tool for the selection and adjustment of immunosuppressive treatments.

Genetic polymorphisms of tumour necrosis factor alpha (TNF-α) promoter gene and response to TNF-α inhibitors in Spanish patients with inflammatory bowel disease.

Tumour necrosis factor alpha (TNF-α) has an important role in inflammatory response. Alterations in the regulation of TNF-α have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF-α inhibitors. Polymorphisms in the TNF-α promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF-α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti-TNF-α treatment. DNA samples from patients with IBD and controls were screened for TNF-α -238G/A (rs361525) and -308G/A (rs1800629) SNPs by PCR-SSOP using a microbeads luminex assay and compared with response to TNF-α inhibitors. There were not statistical differences in -238G/A and -308G/A allele and genotype frequencies between patients. However, we found an increased frequency of -308A allele and -308GA genotype in these nonresponders patients to TNF-α inhibitors with respect to responders patients (Pc < 0.05). This -308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF-α inhibitors. TNF-α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF-α genotypes may be involved in the different responses to TNF-α inhibitor treatment in Spanish patients with IBD.

Dependence on the thermodynamic state of self-diffusion of pseudo-hard-sphere and Lennard-Jones potentials.

Self-diffusion D in a system of particles that interact with a pseudo-hard-sphere or a Lennard-Jones potential is analyzed. Coupling with a solvent is represented by a Langevin thermostat, characterized by the damping time t_{d}. The hypotheses that D=D_{0}φ is proposed, where D_{0} is the small concentration diffusivity and φ is a thermodynamic function that represents the effects of interactions as concentration is increased. Molecular dynamics simulations show that different values of the noise intensity modify D_{0}, but do not have an effect on φ. This result is consistent with the assumption that φ is a thermodynamic function since the thermodynamic state is not altered by the presence of damping and noise.

[Metastatic lung tumor from colon cancer with cavitation: report of a case].

A 55-year-old man underwent rectal amputation for rectal cancer in August 2005. A tiny thin-walled cavity lesion in his left S1+2 was found on computed tomography (CT) of the chest in November 2008. The cavity lesion in the left S1+2 gradually increased in size over 3 months and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) showed FDG accumulation at the lesion. Videoassisted thoracoscopic (VATS) wedge resection was performed to make a definite diagnosis in March 2009. The pathological findings revealed a metastatic lung tumor from the rectal cancer. It is necessary to consider the possibility of metastatic lung tumors in a case with the cavity lesions especially in patients with a history of colon cancer.

Diffusion on a lattice: Transition rates, interactions, and memory effects.

We analyze diffusion of particles on a two-dimensional square lattice. Each lattice site contains an arbitrary number of particles. Interactions affect particles only in the same site, and are macroscopically represented by the excess chemical potential. In a recent work, a general expression for transition rates between neighboring cells as functions of the excess chemical potential was derived. With transition rates, the mean-field tracer diffusivity, D^{MF}, is immediately obtained. The tracer diffusivity, D=D^{MF}f, contains the correlation factor f, representing memory effects. An analysis of the joint probability of having given numbers of particles at different sites when a force is applied to a tagged particle allows an approximate expression for f to be derived. The expression is applied to soft core interaction (different values for the maximum number of particles in a site are considered) and extended hard core.

Primary plasma cell leukemia: a retrospective multicenter study of 73 patients.

BACKGROUND: Epidemiological and clinical information on primary plasma cell leukemia (pPCL) are rarely reported. The aims are to evaluate the clinical features, prognostic factors, and efficacy of treatments in pPCL. PATIENTS AND METHODS: A multicenter retrospective cohort study was carried out from January 2000 to December 2008 in 26 Italian hematology divisions. A total of 128 cases of plasma cell leukemia were collected, and 73 of them (57%) were classified as primary (male/female 43/30). RESULTS: Sixty-four patients had at least 1 sign of end-organ damage and 10 had extramedullary localization. One patient died early; of the remaining patients, 36 (50%) received anthracycline-based regimens as first-line therapy, 17 (24%) single alkylating agents, and 30 (42%) bortezomib or thalidomide as additional (n = 11) or unique treatments (n = 19). Twenty-three patients (31%) underwent autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT). The median overall survival (OS) was 12.6 months; complete or partial response was achieved in 22 (30%) and 18 patients (25%), respectively; the median duration of response (DOR) was 16.4 months. HSCT patients had a longer OS and DOR (median 38.1 and 25.8 months, respectively) compared with nontransplanted patients (9.1 and 7.3 months, respectively, P < 0.001). OS was influenced by nonresponse to treatment, hypoalbuminemia, and HSCT. DOR was favorably influenced only by HSCT. CONCLUSIONS: pPCL is an aggressive disease with a poor prognosis and a low response rate to conventional therapy. HSCT is effective, increasing OS and DOR by 69% and 88%, respectively. The use of bortezomib and thalidomide may improve outcomes.

Application of the Widom insertion formula to transition rates in a lattice.

We consider diffusion of particles on a lattice in the so-called dynamical mean-field regime (memory effects are neglected). Interactions are local, that is, only among particles at the same lattice site. It is shown that a statistical mechanics analysis that combines detailed balance and Widom's insertion formula allows for the derivation of an expression for transition rates in terms of the excess chemical potential. The rates reproduce the known dependence of self-diffusivity as the inverse of the thermodynamic factor. Soft-core interactions and general forms of the excess chemical potential (linear, quadratic, and cubic with the density) are considered.

Causes of Death and Survival in Alcoholic Cirrhosis Patients Undergoing Liver Transplantation: Influence of the Patient's Clinical Variables and Transplant Outcome Complications.

BACKGROUND: Clinical and molecular mechanisms involved in the cause and time of death of alcoholic cirrhosis (AC) patients undergoing liver transplantation (LT) are not entirely understood. In sudden death cases, judicial autopsy practice is mandatory for determining the cause and circumstances of death. The medico-legal autopsy data are essential for helping health authorities to guide future public health activities, assess the effectiveness of health systems, and adopt the necessary preventive measures to improve and adapt the treatments in order to increase these patients' survival. OBJECTIVE: Our study aimed to determine the different clinical and sociodemographic causes that influence the different causes of death and the short- and long-term survival of AC patients undergoing liver transplantation. METHODS: A total of 122 deceased AC patients undergoing LT were analyzed at different times post-transplantation. The main pre- and post-transplant complications were analyzed in relation to the cause of death and the patient's survival, as well as the causes and time at which the patient's death occurred. RESULTS: A total of 53.3% of non-sudden death was observed. A large number of the deaths of AC patients undergoing transplantation were due to non-sudden death, sepsis, and graft failure (GF), the main causes of death in the sample being similar in both sexes. In non-sudden deaths, there were no significant differences between the death rates either related or not related to the liver transplant. Sepsis was the main cause, with the highest percentage (21.3%) of mortality, followed by GF (18.9%) and multiorgan failure (15.6%) at ten years. Furthermore, our results showed how pre-transplant clinical complications, such as viral infections and encephalopathy, influence the age at which multiorgan failure occurs in the transplanted patient. CONCLUSION: Multiorgan failure is the leading cause of sudden death, with higher mortality during the first year after transplantation, followed by sepsis and GF. Our results show the vulnerability of AC patients, both in the hospital period after the transplant and outside.

[Simultaneously treated thymoma and lung cancer; report of a case].

A 74-year-old man was admitted to our hospital in order to treat a mediastinal mass and 2 ground-glass attenuations in the right upper lobe detected by chest X-ray and computed tomography (CT). Partial resection of right lung and thymectomy were performed. The mediastinal mass and 2 ground-glass attenuations in the right upper lobe proved to be thymoma and bronchioloalveolar carcinomas, respectively by pathology.

[Sleep and academic performance in university students: a systematic review]. / Sueño y rendimiento académico en estudiantes universitarios: revisión sistemática.

INTRODUCTION: University students tend to suffer from problems of sleep regularity, quantity and quality, which can affect their academic performance. These problems are related to changes typical of the phase of the life cycle in which they find themselves due to maturational, psychosocial development (associated with the processes of individuation and socialisation) and academic factors. The study of the relationship between sleep and academic performance in university students is an area of research of growing interest, which has started to be studied over the last two decades. AIM: To conduct a systematic review of the existing literature on the relationship between sleep and academic performance in university students. SUBJECTS AND METHODS: The articles included in the PubMed database were selected, following the PRISMA guidelines. Studies evaluating samples of subjects with an average age between 18 and 26 years, published in English or Spanish during the period 2000-2019 were included. Subsequently, the quality of the selected articles was evaluated according to the STROBE standard. RESULTS: Thirty studies were identified, which were grouped according to different aspects of sleep: drowsiness, duration, experience of total sleep deprivation, sleep quality, chronotype, regularity and sleep disorders. CONCLUSION: The results of these studies suggest that inadequate sleep has a negative effect on the academic performance of university students.

TITLE: Sueño y rendimiento académico en estudiantes universitarios: revisión sistemática.Introducción. Los estudiantes universitarios tienden a padecer problemas de regularidad, cantidad y calidad de sueño, que pueden afectar a su rendimiento académico. Estos problemas se relacionan con cambios propios de la fase del ciclo vital en la que se encuentran debido a diversos factores: madurativos, del desarrollo psicosocial (asociados con los procesos de individuación y socialización) y académicos. El estudio de la relación entre el sueño y el rendimiento académico en estudiantes universitarios es un área de investigación de interés creciente, que ha empezado a ser objeto de estudio en las últimas dos décadas. Objetivo. Revisión sistemática de la bibliografía existente sobre la relación del sueño y el rendimiento académico en los estudiantes universitarios. Sujetos y métodos. Se seleccionaron los artículos recogidos en la base de datos PubMed, siguiendo las directrices PRISMA. Se incluyeron los estudios que valoraban muestras de sujetos con una edad media entre 18 y 26 años, publicados en inglés o castellano, durante el período 2000-2019. Posteriormente, se evaluó la calidad de los artículos seleccionados siguiendo la normativa STROBE. Resultados. Se identificaron 30 estudios, que fueron agrupados según distintos aspectos del sueño: somnolencia, duración, experiencia de privación total de sueño, calidad de sueño, cronotipo, regularidad y trastornos del sueño. Conclusión. Los resultados de estos estudios sugieren que un sueño inadecuado afecta negativamente al rendimiento académico de los estudiantes universitarios.

MOUNT GRAHAM: Report Finds Squirrels Survived 3 Telescopes.

In 1988 Congress allowed construction of three telescopes on Mount Graham, a desert "sky island" northeast of here, prompting the U.S. Forest Service to order a long-range study to monitor the population of an endangered subspecies of red squirrel that lives here. The results are now in. But the findings--that the work to date has had "no significant effect" on the rare rodents--have done little to resolve a debate that is expected to heat up again next year when the University of Arizona seeks permission to build four more telescopes.

ARCHAEOLOGY: Arizona to Take High Road to Preservation?

State transportation officials have agreed to weigh a proposal to set aside a scientifically valuable parcel of a federal highway project for future research rather than excavating it and selling it to the highest bidder. Should it proceed, Arizona could set a new standard of stewardship for government agencies that determine the fate of ancient relics.

Ecology/paleontology. Colorado River clams provide benchmark.

Conservationists have long contended, largely in impressionistic terms, that 70 years of American dam building and water diversion have destroyed the biological richness of the Colorado River delta, a key nursery of marine life at the end of the Southwest's great watercourse. Now researchers have confirmed those suspicions, using an important ecological player--clams--as a quantitative marker.

[Thymic carcinoma; report of a case].

A 52-year-old woman was admitted to our hospital because of an abnormal shadow on chest X-ray. Chest computed tomography scan and magnetic resonance imaging demonstrated an anterior mediastinal tumor. The tumor was extirpated completely with combined partial resection of the left lung through a median sternotomy. Microscopically, the tumor was diagnosed thymic cancer, basaloid carcinoma. The patient was treated with combination chemotherapy and radiation, postoperatively. We reported a case of thymic carcinoma.

Dynamic vaccination in partially overlapped multiplex network.

In this work we propose and investigate a strategy of vaccination which we call "dynamic vaccination." In our model, susceptible people become aware that one or more of their contacts are infected and thereby get vaccinated with probability ω, before having physical contact with any infected patient. Then the nonvaccinated individuals will be infected with probability ß. We apply the strategy to the susceptible-infected-recovered epidemic model in a multiplex network composed by two networks, where a fraction q of the nodes acts in both networks. We map this model of dynamic vaccination into bond percolation model and use the generating functions framework to predict theoretically the behavior of the relevant magnitudes of the system at the steady state. We find a perfect agreement between the solutions of the theoretical equations and the results of stochastic simulations. In addition, we find an interesting phase diagram in the plane ß-ω, which is composed of an epidemic and a nonepidemic phase, separated by a critical threshold line ß_{c}, which depends on q. As q decreases, ß_{c} increases, i.e., as the overlap decreases, the system is more disconnected, and therefore more virulent diseases are needed to spread epidemics. Surprisingly, we find that, for all values of q, a region in the diagram where the vaccination is so efficient that, regardless of the virulence of the disease, it never becomes an epidemic. We compare our strategy with random immunization and find that, using the same amount of vaccines for both scenarios, we obtain that the spread of disease is much lower in the case of dynamic vaccination when compared to random immunization. Furthermore, we also compare our strategy with targeted immunization and we find that, depending on ω, dynamic vaccination will perform significantly better and in some cases will stop the disease before it becomes an epidemic.