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Proinflammatory cytokines and their inhibitors are involved in the regulation of multiple immune reactions including response to transplanted organs. In this prospective study, we evaluated changes in serum concentrations of six IL-1 family cytokines (IL-1 alpha, IL-1 beta, IL-1RA, IL-18, IL-18BP, and IL-36 beta) in 138 kidney allograft recipients and 48 healthy donors. Samples were collected before transplantation and then after one week, three months and one year, additional sera were obtained at the day of biopsy positive for acute rejection. We have shown, that concentrations of proinflammatory members of the IL-1 family (IL-1ß, IL-18, IL-36 ß) and anti-inflammatory IL-18BP decreased immediately after the transplantation. The decline of serum IL-1RA and IL-1α was not observed in subjects with acute rejection. IL-18, including specifically its free form, is the only cytokine which increase serum concentrations in the period between one week and three months in both groups of patients without upregulation of its inhibitor, IL-18BP. Serum concentrations of calculated free IL-18 were upregulated in the acute rejection group at the time of acute rejection. We conclude that IL-1 family cytokines are involved mainly in early phases of the response to kidney allograft. Serum concentrations of free IL-18 and IL-18BP represent possible biomarkers of acute rejection, and targeting IL-18 might be of therapeutic value.
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Aloinjertos , Biomarcadores , Rechazo de Injerto , Interleucina-18 , Trasplante de Riñón , Humanos , Interleucina-18/sangre , Masculino , Femenino , Biomarcadores/sangre , Rechazo de Injerto/inmunología , Rechazo de Injerto/sangre , Persona de Mediana Edad , Adulto , Péptidos y Proteínas de Señalización Intercelular/sangre , Interleucina-1/sangre , Estudios Prospectivos , Trasplante Homólogo/métodosRESUMEN
Sterilized processed cheese is a specific dairy product with a prolonged shelf life intended for regular retail offer but also as food provisions for armies during peacetime, as well as during crisis and emergency situations, and for storage in state material reserves. Storage requirements are usually defined as ≤25°C for at least 24 mo. One of the ways to achieve such a shelf life is sterilization. Therefore, the aim of the work was to describe, for the first time in the available scientific literature, in situ changes in the viscoelastic properties of spreadable melt (34% wt/wt DM content, 45% wt/wt fat in DM content, and 14% wt/wt protein content) during an increase in temperature (target temperature 122°C), holding at sterilization temperature (20 min) and subsequent cooling (to ~30°C). While increasing to the target sterilization temperature, a significant decrease occurred in the storage and loss moduli values. Both moduli started to increase again during the target sterilization temperature period and during the whole cooling phase. The values of the storage and loss moduli were significantly higher at the end of the cooling of the sterilized product, and conversely, the phase angle value was lower compared with the melt before sterilization. As a result of sterilization, an increase occurred in the levels of markers of the Maillard reaction complex and lipid oxidation processes. The value of hardness, corrected stress, and elongational viscosity also increased compared with nonsterilized products. As a result of sterilization, the flavor worsened and sterilized processed cheeses showed darker (brownish) color. However, even after sterilization, the products were evaluated as acceptable for consumers and maintained their spreadability.
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Queso , Animales , Queso/análisis , Temperatura , Reacción de Maillard , Frío , Esterilización , Manipulación de AlimentosRESUMEN
BACKGROUND: Tuberculum sellae meningiomas are challenging to treat when accompanied with altered vision due to compression of the optic nerve. These tumors mostly refer to be benign; therefore, gross total removal and excellent functional recovery are desired. METHOD: We describe the microsurgical treatment of tuberculum sellae meningioma with altered vision function on the left eye. Intradural unroofing of the optic canal with gross total resection of the tumor led to immediate excellent recovery. Intraoperative video highlights key steps of our surgical approach. CONCLUSION: Optic canal unroofing is in our opinion safe and mandatory when treating tuberculum sellae meningiomas with compression of optic nerve.
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Neoplasias Meníngeas , Meningioma , Neoplasias de la Base del Cráneo , Humanos , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Meningioma/complicaciones , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Procedimientos Neuroquirúrgicos , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Nervio Óptico/cirugía , Estudios Retrospectivos , Silla Turca/diagnóstico por imagen , Silla Turca/patología , Silla Turca/cirugía , Neoplasias de la Base del Cráneo/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVES: Evaluation of the impact of surgical treatment on malignant transformation (MT) of adult supratentorial infiltrative grade II gliomas (G2G) in a series of chemotherapy and radiotherapy-naïve patients. BACKGROUND: Despite G2G are slow-growing tumours, they typically undergo MT with a subsequent fatal disease course. An extensive resection alone likely changes their biological behaviour and defers MT; however, this impact is not unequivocally confirmed. METHODS: Thirty-eight chemotherapy and radiotherapy-naïve adult patients operated from 2005 till 2014 for a G2G were investigated. Based on postoperative magnetic resonance imaging (MRI) and/or positron emission tomography follow-up (FU) scans, the patients were classified as "transformers" (15 patients in whom MT occurred during the FU-period) and "non-transformers" (23 patients). RESULTS: The follow-up period of "non-transformers" was longer (p <0.0001). After adjustment for known risk factors - age, male sex, astrocytoma histology, preoperative tumour volume, preoperative contrast enhancement and positive isocitrate dehydrogenase 1 gene mutation status - a larger log postoperative tumour volume (p=0.031) and a smaller extent of resection (p=0.0086) were associated with a shorter MT-free survival. CONCLUSION: In our series, less extensive resections were associated with a shorter time to MT. Our data support an adoption of techniques enabling extensive G2G resections, such as intraoperative imaging and awake resections, into everyday routine (Tab. 1, Fig. 2, Ref. 40).
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Neoplasias Encefálicas , Glioma , Adulto , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Progresión de la Enfermedad , Glioma/diagnóstico por imagen , Glioma/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasia Residual , Carga TumoralRESUMEN
INTRODUCTION: Endometriosis is defined as the presence of endometrial tissue, endometrial glands or endometrial stroma outside the uterine cavity causing chronic inflammatory response. The prevalence of abdominal wall endometriosis is less than 1%. Cesarean scar endometriosis is the most common type of abdominal wall endometriosis. Chronic lower abdominal pain amplified during menstruation and palpable mass in the area of scar are the main symptoms. Generally, surgical resection with negative resection margins offers the best chance for definitive treatment of abdominal wall endometriosis. CASE REPORT: The authors present two female patients in fertile age with chronic pain in the area of Cesarean scar. The preoperatively assumed endometriosis was histologically confirmed after complete surgical excision. CONCLUSION: Abdominal wall endometriosis is rare. However, it is a possible cause of constant lower abdominal pain, impacting quality of life of the patient.
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Pared Abdominal , Endometriosis , Pared Abdominal/cirugía , Cesárea/efectos adversos , Cicatriz/etiología , Cicatriz/patología , Endometriosis/etiología , Endometriosis/patología , Endometriosis/cirugía , Femenino , Humanos , Embarazo , Calidad de VidaRESUMEN
INTRODUCTION: Peritoneal carcinomatosis (PK) of colorectal origin is a malignant tumour of the peritoneum caused by spreading of colorectal carcinoma (KRK) over the peritoneal surface of the abdominal cavity and its organs. PK occurs as a synchronous tumour in 1520% of patients, and as metachronous disease in 2550% of patients. METHODS: A group of 66 patients operated on for PK was retrospectively evaluated; 18 patients were excluded due to insufficient data. We evaluated 48 patients in total (22 men and 26 women) with mean age of 58 and 53 years, respectively; 12 patients (25%) were aged over 65 years. The patients were operated on between 2000 and 2019 using the Sugarbaker´s method of maximal cytoreduction (CRS) + HIPEC (Hyperthermic Intraoperative Peritoneal Chemotherapy). We evaluated the length, median survival, the incidence of complications and lethality in relation to the Peritoneal Carcinoma Index (PCI) and the Completeness of Cytoreduction (CC) score. The patients were divided into two subgroups according to the PCI score (012 and >12, respectively) and the CC score (CC 01 and CC 23, respectively). RESULTS: The mean survival was 26.3 months in the group with PCI up to 12 and 21.4 months in patients with PCI above 12 (p=0.02). In the group with CC 01 the mean survival was 27.1 months, while in the patients with the CC 23 it reached 12.6 months (p=0.06). The morbidity rate requiring an intervention was 18.7% and the lethality rate was 6.25% in the entire group. The median survival of the entire group was 22 months (1334 months). CONCLUSION: Literary references and our results are comparable, confirming the high efficiency of this method both in our country and worldwide. The use of CRS and HIPEC, associated with acceptable mortality and morbidity in selected patients with PK of colorectal origin, results in a significant extension of overall survival (OS).
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Neoplasias Colorrectales , Neoplasias Peritoneales , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Femenino , Hospitales , Humanos , Masculino , Neoplasias Peritoneales/terapia , Peritoneo , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare malignant disease with various grades of malignancy, producing mucinous and gelatinous masses. The origin of PMP is usually connected with the rupture of appendiceal mucinous tumours, other mucinous tumours of the gastrointestinal tract or of the ovary. The staging of this disease is determined by the PCI score (peritoneal cancer index), and the efficiency of surgical procedure by the CC score. Clinical presentation is very variable and depends on the stage of the disease. Many patients are asymptomatic with a minimal clinical finding, presented only with abdominal discomfort. A typical finding of the “jelly belly“ syndrome expands with progression of the disease. The diagnosis consists in preoperative determination of the tumour characteristics and PCI based on imaging methods, especially CT imaging. METHODS: The Sugarbaker technique of complete tumour removal or the so-called cytoreductive surgery (CRS) was used, including hyperthermic intraperitoneal chemotherapy (HIPEC) or alternatively early postoperative intraperitoneal chemotherapy (EPIC). We performed retrospective evalu-ation of 73 patients with pseudomyxoma peritonei undergoing surgery, 39 males and 34 females, mean age 50.6 and 56.4 years, respectively. Surgical revision was performed in 18 patients, 14 males and 4 females. The mean age of this group was 48.8 for the males and 47 for the females. The surgical procedures were performed between 1999 and 2018. Survival rates, median survival, complications based on Clavien-Dindo classification, lethality rates, and PCI and CC scores were assessed in the patient group. RESULTS: 96 surgeries were performed in 73 patients with pseudomyxoma peritonei at our surgical department between 19992018. The surgery had to be repeated in 18 patients (24.6%). High grade (HG) pseudomyxoma was diagnosed in 29 patients (39.7%), and low grade (LG) pseudomyxoma in 44 patients (60.3%). Overall morbidity was 27.3%, and the mortality rate was 5.4%. The mean overall survival (OS) was 139.5 months in the LG pseudomyxoma group and 71.5 months in the HG pseudomyxoma group. Median survival was 86 months in the entire group and 72 in the HG pseudomyxoma group; the median was not reached in the LG pseudomyxoma group. CONCLUSIONS: Results in the literature and our results are comparable, confirming the high efficiency of this method both in the world and in the Czech republic. The results indicate a highly statistically significant improvement of the OS with acceptable mortality and morbidity. These results confirm this method as a gold standard therapy for selected patients.
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Intervención Coronaria Percutánea , Neoplasias Peritoneales/cirugía , Seudomixoma Peritoneal , Terapia Combinada , República Checa , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The possibility of using a quantum computer D-Wave 2X with more than 1000 qubits to determine the global minimum of the energy landscape of trained restricted Boltzmann machines is investigated. In order to overcome the problem of limited interconnectivity in the D-Wave architecture, the proposed RBM embedding combines multiple qubits to represent a particular RBM unit. The results for the lowest-energy (the ground state) and some of the higher-energy states found by the D-Wave 2X were compared with those of the classical simulated annealing (SA) algorithm. In many cases, the D-Wave machine successfully found the same RBM lowest-energy state as that found by SA. In some examples, the D-Wave machine returned a state corresponding to one of the higher-energy local minima found by SA. The inherently nonperfect embedding of the RBM into the Chimera lattice explored in this work (i.e., multiple qubits combined into a single RBM unit were found not to be guaranteed to be all aligned) and the existence of small, persistent biases in the D-Wave hardware may cause a discrepancy between the D-Wave and the SA results. In some of the investigated cases, introduction of a small bias field into the energy function or optimization of the chain-strength parameter in the D-Wave embedding successfully addressed difficulties of the particular RBM embedding. With further development of the D-Wave hardware, the approach will be suitable for much larger numbers of RBM units.
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BACKGROUND: Ovarian cancer is the most lethal gynecological cancer, almost 80% of all patients succumb the disease within 5 years of diagnosis. High mortality is caused especially by nonspecific symptoms, diagnosis in late stages and the absence of a specific biomarker. Currently, the most common diagnostic biomarkers are the membrane glycoprotein Cancer Antigen 125 (CA 125), the Human Epididymal Protein 4 (HE4) and the Carcinoembryonic Antigen (CAE). None of these biomarkers is specific only for ovarian cancer and increased levels may be caused by other diseases. Therefore, current research is focused on finding new biomarkers for diagnosis and prognosis of ovarian cancer. Interesting clinical material is ascites, the fluid accumulated in abdominal cavity, which is typical for ovarian cancer and it is present in almost 90% of all cases of stage III and IV. MATERIAL AND METHODS: For this study, samples of ascites from patients with benign and malignant ovarian tumors were used. For full glycomic and proteomic analysis, only 5 µL of ascites were used. Glycans were released from proteins by the enzyme PNGase F and proteins were digested to peptides by trypsin. Samples were purified and measured using a mass spectrometer. RESULTS: Glycan and protein profiles of patients with benign and malignant ovarian cancer were compared. In patient with a benign tumor, more simple glycans with lowm/z were increased while in the patient with a malignant tumor, higher, more complex glycans were increased. In the malignat tumor in comparison to benign tumor, 127 unique proteins were identified, especially proteins of the annexin, mucin and peroxiredoxin families. CONCLUSION: This investigation is a pilot study focused on comparison of protein and glycan composition of ascites in patients with benign and malignant ovarian cancer. Significant differences were found on both glycan and protein levels. Results will be verified on a larger set of patients and compared with a set of control samples.Key words: glycomics - proteomics - ascitic fluid - ovarian cancer This study was supported by projects of the Ministry of Education Youth and Sports - National Sustainability Program I - LO1413; Ministry of Health, Czech Republic - conceptual development of research organization (MMCI, 00209805); Czech Science Foundation 16-04496S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 3. 2017Accepted: 26. 3. 2017.
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Ascitis/metabolismo , Biomarcadores de Tumor/análisis , Neoplasias Ováricas/diagnóstico , Polisacáridos/análisis , Proteínas/análisis , Femenino , Humanos , Proyectos Piloto , Proteómica/métodosRESUMEN
BACKGROUND: Visual clinical methods of skin color evaluation for diagnostic purposes are so far mostly subjective and thus inaccurate. We present a modified method of melanin amount measurement based on diffuse reflectance spectroscopy (DRS). This method is non-invasive and objective, and allows easy quantification and comparison of melanin levels. MATERIAL AND METHODS: Skin pigmentation was measured by DRS method in 0-18 year old patients at the Department of Pediatric Dermatovenerology, School of Medicine Comenius University Bratislava. Patients were treated for their vitiligo by Balneo PUVA treatment twice weekly. Each patient had measured his remittance spectra from the treated vitiliginous skin before the treatment was started, after 10 irradiations of Balneo PUVA and at the end of the treatment after 25 irradiations of Balneo PUVA. In our study as a reference skin for spectroscopic assessment of melanin in vivo was used the averaged remittance spectra (measured on the inner arm) from the sample of 10 albino patients. The remittance spectra obtained from the vitiligo patients were ratioed against the newly described remittance reference albino skin. We exploited the linear behavior of the spectral curve in the 620-720 nm interval (significant for melanin absorption) and used the slope of the regression line to compute the quantification index α. RESULTS: By clinical examination before the Balneo PUVA therapy, after the 10th dose of Balneo PUVA therapy as well as at the end of the complete course of Balneo PUVA therapy (after 25 irradiations) we recorded a marked increase of pigmentation in all treated patients for their vitiligo. In each patient the values of melanin quantification angle α were calculated. Statistically we found a significant difference between the melanin quantification angle α in vitiliginous skin before, during the 10th dose of treatment and after the treatment. Similar significant difference was also observed between treated and non-involved skin. We could confirm a clear association between clinical visual examination of treated vitiligo lesions, objective data collected by DRS and melanin quantification angle α. CONCLUSIONS: By using a new standard for the reference skin (albino skin) we could more exactly compare melanin levels in different subjects. Our proposed melanin quantification angle α expresses the extent of the difference in melanin levels between the examined skin lesions. We successfully used this index to quantify the variations of melanin (progress of repigmentation) throughout different stages of treatment of the same lesion and also to objectively evaluate the final effect of the therapy. In the present study, we showed that the diffuse reflectance spectroscopy (DRS) may be suitable method to measure skin colour and the content of human skin melanin in vivo.
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Melaninas/metabolismo , Terapia PUVA/métodos , Piel/metabolismo , Análisis Espectral/métodos , Vitíligo/tratamiento farmacológico , Vitíligo/metabolismo , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Piel/efectos de los fármacos , Piel/efectos de la radiación , Distribución Tisular , Resultado del TratamientoRESUMEN
We investigated whether early postnatal over-nutrition affects normal course of skin wound healing. To induce over-nutrition the litter size was adjusted on the first day after birth to four pups/nest (small litters). In parallel, as a control, normal nests of 10 pups/nest (normal litters) were used. For the wound healing experiment 30 male Sprague-Dawley rats, 15 from normal nests and 15 from small nests, were used. Two parallel full-thickness skin incisions and two full-thickness excisions were performed on the back of each rat. Samples for histological examination (excisions) and wound tensile strength measurement (incisions) were collected on days 2, 6, and 14 after surgery. Our study demonstrates that rats from the small nests had enhanced plasma levels of insulin and enhanced body weight/fat parameters. Furthermore, in small nests, rats that expressed the above-mentioned symptoms displayed slight improvement of epidermis regeneration, accelerated demarcation line formation, and increased wound tensile strength. From this point of view the small nest model used in the present experiment is helpful for exploration whether these acquired changes might be considered as a sufficient essential factor involved in the regulation of metabolic homeostasis and wound repair in juvenile obese male rats. Nevertheless, further studies need to be performed to verify the present findings also on other animal models and humans and to describe the exact underlying mechanism.
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Obesidad/genética , Piel/patología , Cicatrización de Heridas , Ciencias de la Nutrición Animal , Animales , Animales Recién Nacidos , Peso Corporal , Modelos Animales de Enfermedad , Homeostasis , Insulina/metabolismo , Tamaño de la Camada , Masculino , Síndrome Metabólico/genética , Ratas , Ratas Sprague-Dawley , Resistencia a la Tracción , DesteteRESUMEN
INTRODUCTION: The clinical method of evaluating the color of the skin based on visual assessment is subjective and thus inaccurate. The objective determination of skin phototypes and levels of melanin in the skin is important for diagnosing the pigment disorders and also for adequate photoprotection. Diffuse reflectance spectroscopy (DRS) is a non-invasive, precise and objective method for quantifying the melanin levels. OBJECTIVE: The aim of this study is to assess the characteristic DRS spectrum of healthy skin in children and to detect the differences between them based on age, gender and skin phototype. MATERIAL AND METHODS: Skin pigmentation was measured by DRS in 73 children patients with experimental spectrophotometer UM-ES600. The amount of melanin is quantified from the obtained DRS spectra by proposed melanin quantification angle α obtained by comparing the reflectance properties of skin sample and universal depigmented sample (albino skin). RESULTS: We evaluated spectroscopic characteristics of children's healthy skin depending on age, gender and phototype. The value of melanin quantification angle α grew proportionally from phototype I to phototype IV, without any correlation to age or gender. We confirmed a clear association between clinical determination of Fitzpatrick's skin phototypes and objective data collected by DRS and related angle α. CONCLUSIONS: Our proposed index quantifies the difference in melanin levels in healthy children skin and also for different skin phototypes. The proposed method and melanin quantification angle α can further be used for the objectification of the progress of pigmentary diseases or for monitoring the effect of their therapy (Tab. 5, Fig. 4, Ref. 29).
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Melaninas/análisis , Pigmentación de la Piel , Espectrofotometría/métodos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Valores de Referencia , Análisis EspectralRESUMEN
Glycomics and glycoproteomics represent relatively new directions in detail analyses of complex bio-logical media. These areas of increasing importance to cancer research complement the more established genomic profiling and proteomics. Glycoproteins are being increasingly recognized as important in cellular interactions and adhesion. Structural alterations of their glycan moieties seem to occur in different cancer conditions. We review current directions in glycomic profiling and glycoproteomic investigations of bio-logical fluids and tissues pertaining to cancer. The used methods rely on capillary separation techniques, mass spectrometry, and the glycan and lectin arrays. They all show considerable promise for new diagnostic and prognostic measurements.
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Glicoproteínas/análisis , Neoplasias/química , Cromatografía Liquida , Electroforesis Capilar , Glicómica , Glicosilación , Humanos , Espectrometría de Masas , Polisacáridos/análisis , Análisis por Matrices de ProteínasRESUMEN
The aim of this work is to produce 2D plasmonic and diffractive structures in Ag films with sharp features for which both a deeper understanding of laser induced transformation upon modulated laser intensity and a correlation between structural and optical properties are required. We compare results obtained by exposing silver films to an excimer laser operating at 193 nm whose intensity is either modulated or homogeneous. In all cases, one laser exposure is enough to break the film into nanoparticles (NPs). The use of the modulated beam intensity leads to diffractive 2D patterns that are formed by rectangular regions of untransformed material surrounded by transformed regions covered by NPs. The former have sharp edges that are consistent with the absence of significant mass transport that is discussed in terms of the thermal gradient induced. The latter contain NPs whose diameter increases as the initial film effective thickness increases. The surface plasmons associated with the NPs in the transformed regions dominate the reflectivity spectrum and the 2D array formed by the untransformed regions is responsible for the diffractive properties. Evidence for spinodal dewetting is only observed in our case for the steep gradient conditions achieved at the border of the homogeneously irradiated regions.
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Investigating the impact of parasitism on host phenotype is key to understanding parasite transmission ecology, host behavioural ecology and host-parasite coevolution. Previous studies have provided evidence that avian odour is one such phenotypic trait, as mosquitoes that vector the haemosporidian blood parasite Plasmodium tend to prefer birds that are already infected. Preen oil is a major source of avian odour, yet studies to date have not identified differences in preen oil odour based on the presence or absence of haemosporidian infection. Because preen oil can vary with physiological dynamics, we predicted that the composition of preen oil odours might vary according to parasite load, rather than solely by the presence or absence of infection. We used gas chromatography-mass spectrometry to characterize the composition of volatile compounds in preen oil taken from female dark-eyed juncos, Junco hyemalis carolinensis, and asked whether their composition varied with relative haemosporidian parasite load, which we assessed using quantitative PCR. We identified a subset of volatile compounds (a 'blend') and two specific compounds that varied with increasing parasite load. Importantly, the quantity of these compounds did not vary based on parasite presence or absence, suggesting that birds with low parasite loads might be phenotypically indistinguishable from uninfected birds. The volatile blend associated with parasite load also varied with sampling date, suggesting a possible seasonal relapse of chronic infections triggered by shifts in junco host reproductive state. Furthermore, we found a positive relationship between parasite load and a volatile blend shown in a previous study to predict reproductive success in juncos. This is the first study to demonstrate quantitative differences in avian host odour based on haemosporidian parasite load. Our findings highlight the importance of focusing on parasite load, rather than solely presence or absence, in investigating host-parasite interactions.
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Tumor cells exhibit at least two distinct modes of migration when invading the 3D environment. A single tumor cell's invasive strategy follows either mesenchymal or amoeboid patterns. Certain cell types can use both modes of invasiveness and undergo transitions between them. This work outlines the signaling pathways involved in mesenchymal and amoeboid types of tumor cell motility and summarizes the molecular mechanisms that are involved in transitions between them. The focus is on the signaling of the Rho family of small GTPases that regulate the cytoskeleton-dependent processes taking place during the cell migration. The multiple interactions among the Rho family of proteins, their regulators and effectors are thought to be the key determinants of the particular type of invasiveness. Mesenchymal and amoeboid invasive strategies display different adhesive and proteolytical interactions with the surrounding matrix and the alterations influencing these interactions can also lead to the transitions.
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Movimiento Celular , Invasividad Neoplásica , Línea Celular Tumoral , Citoesqueleto , Humanos , Transducción de Señal , Proteínas de Unión al GTP rac/metabolismoRESUMEN
Antibody-mediated rejection (ABMR) is a major obstacle to the long-term success in kidney transplantation. Diagnosis of ABMR is determined according to the internationally recognized Banff criteria. However, a significant proportion of patients does not meet all the defined criteria, and the outcome of such cases remains poorly understood. The histology of ABMR frequently lacks sensitivity and specificity. More importantly, mixed forms of ABMR and T cell-mediated rejection as well as findings of nonspecific injury are common in clinical settings. Donor-specific anti-HLA antibodies (DSA) are detectable only in half of the ABMR cases by histology. Prognostic role of non-HLA antibodies against various endothelial proteins has been discussed. Antibody independent NK cell activation reflecting killer-cells' inhibitory receptor incompatibility is suggested in microvascular inflammation in DSA negative patients. Molecular assessment of ABMR has been prioritized to overcome high interobserver variability and improve diagnostics in mixed forms of rejections and in DSA negative cases. Finally, donor-derived cell-free DNA detected in a recipient's peripheral blood sample has been proposed as a noninvasive marker for diagnosis of graft rejection, and thus might serve as a liquid biopsy in the near future. Despite all achievements, diagnosing ABMR in kidney allografts remains to be a challenge in a significant number of cases.
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Trasplante de Riñón , Aloinjertos , Rechazo de Injerto/diagnóstico , Humanos , Isoanticuerpos , Riñón/patología , Trasplante de Riñón/efectos adversosRESUMEN
Peripheral blood monocytes, which serve as precursors for tissue macrophages and dendritic cells (DC), play a key role in the immune response to kidney allograft, reparation processes and homeostasis regulation. In this prospective study, we used multicolor flow cytometry to monitor the phenotypic patterns of peripheral monocytes in subjects with uncomplicated outcomes and those with acute rejection. We found a reciprocal increase in the proportion of "classical monocytes" (CD14+CD16-) along with a decline in pro-inflammatory "intermediary" (CD14+CD16+) and "non-classical" (CD14lowCD16+) monocytes in subjects with normal outcomes. In subjects with acute rejection, we observed no reduction in "intermediary" monocytes and no increase in "classical" monocytes. Patients with uncomplicated outcomes exhibited downregulated HLA-DR in all three monocyte subpopulations. However, non-classical monocytes were unaffected in subjects with acute rejection. Expression of CD47 was downregulated after transplantation, while patients with antibody-mediated rejection and donor-specific antibodies showed higher pre-transplant values. In monocytes isolated at the time of biopsy, CD47 expression was higher in individuals with acute rejection compared to patients with normal outcomes one year post-transplant. Expression of CD209 (DC-SIGN) and the proportion of CD163+CD206+ subpopulations were upregulated during the first week after kidney transplantation. CD209 was also upregulated in samples taken on the day of biopsy confirming acute rejection. Our data demonstrate that kidney allograft transplantation is associated with phenotypic changes in peripheral blood monocytes during acute rejection.
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Rechazo de Injerto/patología , Trasplante de Riñón/efectos adversos , Monocitos/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Rechazo de Injerto/etiología , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Prospectivos , Adulto JovenRESUMEN
Based on large-scale molecular dynamics simulations, we propose a new charging method that should be capable of charging a lithium-ion battery in a fraction of the time needed when using traditional methods. This charging method uses an additional applied oscillatory electric field. Our simulation results show that this charging method offers a great reduction in the average intercalation time for Li(+) ions, which dominates the charging time. The oscillating field not only increases the diffusion rate of Li(+) ions in the electrolyte but, more importantly, also enhances intercalation by lowering the corresponding overall energy barrier.
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BACKGROUND: Although tissue adhesives and traditional sutures were compared in numerous studies during the early stages of healing, it has to be clarified, from the histological and biomechanical point of view, how the differences develop during the later phases. METHODS: Twenty-four male Sprague-Dawley rats were used and divided into 2 groups: the IRS (intradermal running suture) and G (glue) groups. Two parallel full-thickness skin incisions were made on the back of each rat. Wounds in the IRS group were closed by an IRS, whereas wounds in the G group were closed using tissue adhesive (n-butylcyanoacrylate). Rats were sacrificed 7 and 22 days after surgery. RESULTS: Similar wound tensile strengths of glued and sutured wounds were measured on days 7 (IRS = 10.3 ± 1.7 g/mm(2) vs. G = 12.9 ± 4.0 g/mm(2), p = 0.9612) and 22 (IRS = 95.6 ± 15.7 g/mm(2) vs. G = 85.6 ± 16.4 g/mm(2), p = 0.2502) after surgery. Histology revealed a significantly increased amount of granulation tissue formation in glued wounds on day 7. The difference in granulation tissue formation was reduced until day 22. CONCLUSIONS: Tissue adhesive based on n-butylcyanoacrylate presents a fair alternative to traditional suture wound closure techniques.