Başkent University

Castell’s book is the first part of his milstone “The Information Age: Economy Society, and Culture” work. The author states that, the triology was prepared to be a single book, but then with the contributions of the editor, it was divided into three books by making each part of the study a separate book. In this particular book, Castells presents an easily understandable and comprehensive analysis by examining the economic, social, and cultural changes that caused by the Network Society. He does this by being as realistic as possible and reaching a clear conclusion by supporting all of his claims with various statistics and examples.

We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance ( p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion ( p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely high-powered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.

AIMS: This European Association Cardiovascular Imaging (EACVI) Expert Consensus document aims at defining the main quantitative information on cardiac structure and function that needs to be included in standard echocardiographic report following recent ASE/EACVI chamber quantification, diastolic function, and heart valve disease recommendations. The document focuses on general reporting and specific pathological conditions such as heart failure, coronary artery and valvular heart disease, cardiomyopathies, and systemic diseases. METHODS AND RESULTS: Demographic data (age, body surface area, blood pressure, and heart rhythm and rate), type (vendor and model) of ultrasound system used and image quality need to be reported. In addition, measurements should be normalized for body size. Reference normal values, derived by ASE/EACVI recommendations, shall always be reported to differentiate normal from pathological conditions. This Expert Consensus document suggests avoiding the surveillance of specific variable using different ultrasound techniques (e.g. in echo labs with high expertise in left ventricular ejection fraction by 3D and not by 2D echocardiography). The report should be also tailored in relation with different cardiac pathologies, quality of images, and needs of the caregivers. CONCLUSION: The conclusion should be concise reflecting the status of left ventricular structure and function, the presence of left atrial and/or aortic dilation, right ventricular dysfunction, and pulmonary hypertension, leading to an objective communication with the patient health caregiver. Variation over time should be considered carefully, taking always into account the consistency of the parameters used for comparison.

International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer. SIGNIFICANCE: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.

Biomaterials currently used in cardiac tissue engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating cardiac cell behavior. Here, the myocardial tissue constructs are engineered based on reduced graphene oxide (rGO)-incorporated gelatin methacryloyl (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhances the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO-GelMA scaffolds exhibit better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes show stronger contractility and faster spontaneous beating rate on rGO-GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO-GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial designs to improve tissue engineering outcomes. The engineered cardiac tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high-fidelity tissue models for drug studies and the investigations of cardiac tissue development and/or disease processes in vitro.

BACKGROUND: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are increasing in frequency and are associated with high mortality rates. Circulation of CTX-M-type ESBLs in the community is of particular concern, because it may confound standard infection-control measures. METHODS: We analyzed the results of epidemiologic studies of infection caused by ESBL-producing Enterobacteriaceae in nonhospitalized patients from 6 centers in Europe, Asia, and North America. Risk factors for infection with an ESBL-producing organism were identified by univariate and multivariate analyses. RESULTS: A total of 983 patient-specific isolates were reviewed (890 [90.5%] of which were Escherichia coli, 68 [6.9%] of which were Klebsiella species, and 25 [2.5%] of which were Proteus mirabilis); 339 [34.5%] of the isolates produced ESBLs. CTX-M types were the most frequent ESBLs (accounting for 65%). Rates of co-resistance to ciprofloxacin among ESBL-producing isolates were high (>70%), but significant variation was seen among centers with respect to rates of resistance to gentamicin, amoxicillin-clavulanate, and trimethoprim-sulfamethoxazole. Similar risk factors for infection with an ESBL-producing organism were found in the different participating centers. Significant risk factors, identified by multivariate analysis, were recent antibiotic use, residence in a long-term care facility, recent hospitalization, age 65 years, and male sex (area under the receiver-operator characteristic [ROC] curve, 0.80). However, 34% of ESBL-producing isolates (115 of 336 isolates) were obtained from patients with no recent health care contact; the area under the ROC curve for the multivariate model for this group of patients was only 0.70, which indicated poorer predictive value. CONCLUSIONS: Community-acquired ESBL-producing Enterobacteriaceae are now prevalent worldwide, necessitating international collaboration. Novel approaches are required to adequately address issues such as empirical treatment for severe community-acquired infection and infection control.

AIMS: To describe the cardiac abnormalities in patients with COVID-19 and identify the characteristics of patients who would benefit most from echocardiography. METHODS AND RESULTS: In a prospective international survey, we captured echocardiography findings in patients with presumed or confirmed COVID-19 between 3 and 20 April 2020. Patient characteristics, indications, findings, and impact of echocardiography on management were recorded. Multivariable logistic regression identified predictors of echocardiographic abnormalities. A total of 1216 patients [62 (52-71) years, 70% male] from 69 countries across six continents were included. Overall, 667 (55%) patients had an abnormal echocardiogram. Left and right ventricular abnormalities were reported in 479 (39%) and 397 (33%) patients, respectively, with evidence of new myocardial infarction in 36 (3%), myocarditis in 35 (3%), and takotsubo cardiomyopathy in 19 (2%). Severe cardiac disease (severe ventricular dysfunction or tamponade) was observed in 182 (15%) patients. In those without pre-existing cardiac disease (n = 901), the echocardiogram was abnormal in 46%, and 13% had severe disease. Independent predictors of left and right ventricular abnormalities were distinct, including elevated natriuretic peptides [adjusted odds ratio (OR) 2.96, 95% confidence interval (CI) 1.75-5.05) and cardiac troponin (OR 1.69, 95% CI 1.13-2.53) for the former, and severity of COVID-19 symptoms (OR 3.19, 95% CI 1.73-6.10) for the latter. Echocardiography changed management in 33% of patients. CONCLUSION: In this global survey, cardiac abnormalities were observed in half of all COVID-19 patients undergoing echocardiography. Abnormalities were often unheralded or severe, and imaging changed management in one-third of patients.

Cyber-attacks represent a potential threat to information security. As rates of data usage and internet consumption continue to increase, cyber awareness turned to be increasingly urgent. This study focuses on the relationships between cyber security awareness, knowledge and behavior with protection tools among individuals in general and across four countries: Israel, Slovenia, Poland and Turkey in particular. Results show that internet users possess adequate cyber threat awareness but apply only minimal protective measures usually relatively common and simple ones. The study findings also show that higher cyber knowledge is connected to the level of cyber awareness, beyond the differences in respondent country or gender. In addition, awareness is also connected to protection tools, but not to information they were willing to disclose. Lastly, findings exhibit differences between the explored countries that affect the interaction between awareness, knowledge, and behaviors. Results, implications, and recommendations for effective based cyber security training programs are presented and discussed.

Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)--or "neonatal hepatitis" suggesting PFIC--that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or "neonatal hepatitis" suggesting PFIC. Archival liver were retrieved and immunostained for BSEP. Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents. Among the 11 nonrelated children studied aged 13-52 months at diagnosis of HCC, 9 (and a full sibling, with neonatal hepatitis suggesting PFIC, of a tenth from whom liver was not available) had immunohistochemical evidence of BSEP deficiency; the eleventh child did not. Mutations in ABCB11 were demonstrated in all patients with BSEP deficiency in whom leukocyte DNA could be studied (n = 7). These mutations were confirmed in the parents (n = 14). With respect to the other 3 children with BSEP deficiency, mutations in ABCB11 were demonstrated in all 5 parents in whom leukocyte DNA could be studied. Thirteen different mutations were found. In conclusion, PFIC associated with BSEP deficiency represents a previously unrecognized risk for HCC in young children. Immunohistochemical evidence of BSEP deficiency correlates well with demonstrable mutation in ABCB11.

BACKGROUND: High-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF). MATERIALS AND METHODOLOGY: The European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF. RESULTS: The task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF. CONCLUSIONS: HFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings.

We drop the complexification procedure from the Newman-Janis algorithm and introduce more physical arguments and symmetry properties, and we show how one can generate regular and singular rotating black hole and non-black-hole solutions in Boyer-Lindquist coordinates. We focus on generic rotating regular black holes and show that they are regular on the Kerr-like ring, but physical entities are undefined there. We show that rotating regular black holes have much smaller electric charges, and, with increasing charge, they turn into regular non-black-hole solutions well before their Kerr-Newman counterparts become naked singularities. No causality violations occur in the region inside a rotating regular black hole. The separability of the Hamilton-Jacobi equation for neutral particles is also carried out in the generic case, and the innermost boundaries of circular orbits for particles are briefly discussed. Other, but special, properties pertaining to the rotating regular counterpart of the Ay\'on-Beato--Garc\'{\i}a regular static black hole are also investigated.

AIM: This paper is a report of a study conducted to describe the prevalence and risk factors for lower back pain amongst a variety of Turkish hospital workers including nurses, physicians, physical therapists, technicians, secretaries and hospital aides. BACKGROUND: Hospital workers experience more low back pain than many other groups, the incidence varies among countries. Work activities involving bending, twisting, frequent heavy lifting, awkward static posture and psychological stress are regarded as causal factors for many back injuries. METHOD: A 44-item questionnaire was completed by 1600 employees in six hospitals associated with one Turkish university using a cross-sectional survey design. Data were collected over nine months from December 2005 to August 2006 and analysed using Chi square and multivariate logistic regression techniques. FINDINGS: Most respondents (65.8%) had experienced low back pain, with 61.3% reporting an occurrence within the last 12 months. The highest prevalence was reported by nurses (77.1%) and the lowest amongst secretaries (54.1%) and hospital aides (53.5%). In the majority of cases (78.3%), low back pain began after respondents started working in the hospital, 33.3% of respondents seeking medical care for 'moderate' low back pain while 53.8% (n = 143) had been diagnosed with a herniated lumbar disc. Age, female gender, smoking, occupation, perceived work stress and heavy lifting were statistically significant risk-factors when multivariate logistic regression techniques were conducted (P < 0.05). CONCLUSION: Preventive measures should be taken to reduce the risk of lower back pain, such as arranging proper rest periods, educational programmes to teach the proper use of body mechanics and smoking cessation programmes.

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

OBJECT: Hydatidosis is both a medical and an economic problem in Turkey. The aim of this study was to analyze central nervous system (CNS) involvement in this disease, the related problems the disease causes, and its diagnostic and therapeutic aspects. METHODS: The authors conducted an extensive literature survey of the subject, in which papers published by Turkish authors in international and domestic journals were carefully analyzed. In addition, the authors conducted a cooperative study in which data were gathered from 47 neurosurgery departments across the country. The purpose was to determine the current status of the disease in Turkey; thus, each unit was questioned about their experience over the past 5 years. Contrary to common belief, the incidence of hydatidosis has not decreased significantly in Turkey. However, computerized tomography and magnetic resonance imaging have tremendously increased diagnostic specificity. Incidences of morbidity and mortality have improved over time, according to the results of the cooperative study, although these changes are not statistically significant. This may be attributed to experience that has been gained and to more frequent use of chemotherapy, as reflected by the cooperative study data. The two statistically significant findings of that study were expanded use of chemotherapy in the management of hydatidosis, and a higher rate of extraneural involvement in the disease. The cooperative study revealed that chemotherapy was being used more often and that there was a wider range of indications for this treatment than previously reported. The higher rate of extraneural involvement was predictable because lesions in the CNS are typically secondary in this disease. With regard to the studies' findings on cases of spinal hydatid cysts, the authors found that administration of chemotherapeutic drugs was the only statistically significant parameter (t = 3.78, p < 0.05), with the rate of chemotherapy higher in the cooperative study. CONCLUSIONS: Morbidity, mortality, and recurrence rates of hydatidosis uncovered by the cooperative study and the literature survey were not statistically significant.

OBJECTIVE: To assess the efficacy and tolerability of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, for the treatment of acute gouty arthritis. METHODS: In this 8-week, single-blind, double-dummy, dose-ranging study, patients with acute gouty arthritis whose disease was refractory to or who had contraindications to nonsteroidal antiinflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg; n = 143) or an intramuscular dose of triamcinolone acetonide (40 mg; n = 57). Patients assessed pain using a 100-mm visual analog scale. RESULTS: Seventy-two hours after treatment, a statistically significant dose response was observed for canakinumab. All canakinumab doses were associated with numerically less pain than triamcinolone acetonide; thus, a dose with equivalent efficacy to triamcinolone acetonide 72 hours after treatment could not be determined. The reduction from baseline in pain intensity with canakinumab 150 mg was greater than with triamcinolone acetonide 24, 48, and 72 hours after treatment (differences of -11.5 mm [P = 0.04], -18.2 mm [P = 0.002], and -19.2 mm [P < 0.001], respectively), and 4, 5, and 7 days after treatment (all P < 0.05). Canakinumab significantly reduced the risk of recurrent flares versus triamcinolone acetonide (P ≤ 0.01 for all doses) (relative risk reduction 94% for canakinumab 150 mg versus triamcinolone acetonide). The overall incidence of adverse events was similar for canakinumab (41%) and triamcinolone acetonide (42%); most were mild or moderate in severity. CONCLUSION: Our findings indicate that canakinumab 150 mg provides rapid and sustained pain relief in patients with acute gouty arthritis, and significantly reduces the risk of recurrent flares compared with triamcinolone acetonide.

The coronavirus disease 2019 (COVID-19) pandemic has created new and unpredictable challenges for modern medicine and healthcare systems. Preliminary reports have demonstrated that older age, previous cardiovascular disease, diabetes, and hypertension are risk factors for increased mortality.1 Data on the cardiac affinity of the virus and its potential to harm the cardiovascular system and the mechanisms by which this occurs are sparse.2,3A systemic infection generally increases demand on the heart, and can exacerbate underlying cardiac conditions. When the lungs are heavily involved, as seen in COVID-19 patients, this may have a major impact on cardiac function, particularly that of the right ventricle. Finally, COVID-19 may have direct effects on the heart, as may some drugs being used in its treatment. [...]

PURPOSE: To determine angiographically the origins and variations of renal arteries. MATERIALS AND METHODS: The study included 855 consecutive patients (163 females, 692 males; mean age, 61 years) living in the Cukurova region of Turkey, who underwent either aortofemoropopliteal (AFP) angiography for the investigation of peripheral arterial disease, or renal angiography for renovascular hypertension, and were prospectively evaluated. Renal arteries were visualized by non-selective catheterization during AFP angiography and by selective or non-selective catheterization during renal angiography. Locations of renal artery origins and renal artery variations, including the presence of extra renal arteries and division patterns were analyzed on angiograms. RESULTS: The origin of main renal arteries off the aorta was between the upper margin of L1 and lower margin of L2 vertebra in 98% of the patients, and in 74%, this was the origin of extra renal arteries. The most common location for renal artery origin was the L1-L2 intervertebral disc level. A single renal artery was present in both kidneys in 76% of patients. Renal artery variations included multiple arteries in 24%, bilateral multiple arteries in 5%, and early division in 8% of the cases. Additional renal arteries on the right side were found in 16% and on the left side in 13% of cases. Of all the extra renal arteries, the percentage of accessory and aberrant renal arteries were 49% and 51%, respectively. CONCLUSION: Renal arteries originated between the first and the second lumbar vertebral levels in most patients. Extra renal arteries were quite frequent. These results should be kept in mind when a non-invasive diagnostic search is performed for renal artery stenosis, or when renal surgery related to renal arteries is performed.

OBJECTIVE: To evaluate trunk muscle strength in unihemispheric stroke patients and to assess how it relates to body balance and functional disability in this patient group. DESIGN: This prospective case-comparison study investigated isometric and isokinetic reciprocal trunk flexion and extension strength at angular velocities in 38 unihemispheric stroke patients and 40 healthy volunteers. The Berg balance scale was used to assess balance and stability, and the FIM instrument was used to evaluate functional disability in the patient group. Patients were evaluated as soon as they were able to stand long enough for testing. RESULTS: Peak torque values for trunk flexion and extension were lower in the stroke patients than in the controls. The differences were significant for trunk flexion and for trunk extension. In both groups, peak torque values for trunk flexors were greater than peak torque values for trunk extensors. There was a significant positive correlation between trunk muscle strength and Berg balance scale score at discharge. Trunk muscle strength was not correlated with FIM total score or FIM motor score, but the locomotion-transfers FIM subscore at discharge was positively correlated with trunk muscle torque values, except for isometric extension. CONCLUSION: The findings indicate trunk flexion and extension muscle weakness in unihemispheric stroke patients, which can interfere with balance, stability, and functional disability.

The orphan nuclear receptor steroidogenic factor-1 (SF-1, NR5A1) regulates the transcription of multiple genes involved in steroidogenesis, reproduction, and male sexual differentiation. A heterozygous loss-of-function SF-1 mutation (G35E) has been described in a patient with adrenal failure and complete 46XY sex-reversal, indicating that haploinsufficiency of this factor is sufficient to cause a severe clinical phenotype. This mutation in the P-box region of the DNA-binding domain markedly impairs SF-1 binding to most response elements. In an infant with a similar clinical phenotype, we identified an SF-1 mutation (R92Q) in a highly conserved residue of the A-box, a region that functions as a secondary DNA-binding domain. Strikingly, the affected infant was homozygous for the R92Q mutation, but three relatives (parents, sister) were phenotypically normal despite being heterozygous for the mutation. In functional assays, the R92Q mutant exhibited partial loss of DNA binding and transcriptional activity when compared with the G35E P-box change, consistent with its phenotypic expression only when transmitted as a homozygous trait. Taken together, these two naturally-occurring SF-1 mutations reveal the relative functional importance of the P-box and A-box regions for monomeric binding by nuclear receptors. In addition, these patients reveal the exquisite sensitivity of SF-1-dependent developmental pathways to gene dosage and function in humans.

The Injury Hypothesis, first published in 1994 and modified several times between 1996 and 2002, holds that the reactive oxygen species-mediated reperfusion injury to allografts initiates and induces the alloimmune response and contributes to alloatherogenesis. Recent experimental and clinical evidence in support of the concept is presented suggesting that (1) reactive oxygen species-mediated allograft injury activates the innate immune system of the donor and recipient; (2) injury-induced putative endogenous ligands of Toll-like receptors (TLRs) of host origin such as heat shock proteins interact with and activate TLR4-bearing dendritic cells that mature and induce the adaptive alloimmune response (acute rejection), and interact with and activate TLR4-bearing vascular cells contributing to the development of alloatherosclerosis (chronic rejection); and (3) TLR4-triggered signaling, involved in the establishment of a reperfusion injury, seems to use myeloid differentiation marker 88-independent, Toll/interleukin-1 receptor domain containing adaptor inducing interferon-beta-dependent pathways that are associated with the maturation of dendritic cells and induction of interferon-inducible genes.