0001) less pronounced, as post-challenge selleck screening library with the homologous

virus A/equine/Otar/764/07 (H3N8). For example, when the animals in the control group were challenged with A/equine/Sydney/2888-8/07 (H3N8), the total score for the clinical symptoms was 27.4 ± 3.5 with duration and 11.6 ± 0.2 days, compared to 36.8 ± 0.8 and 16.3 ± 0.2, respectively for the virus A/equine/Otar/764/07 (H3N8). Neither the prime or booster vaccination did not induced accumulation of detectable antibody titers to the homologous EIV H3N8 in the HAI assay over the entire 12-month observation period (data not shown). In the single vaccinated group, double vaccinated group and control group which were post-challenged at different times PV (up to 12 months),

significant antibody titers against H3N8 were detected in the HAI assay on day 28 post-challenge (Fig. 3 or Supplementary Table 3). The highest antibody titers post-challenge were observed in the double vaccinated group, with significantly (from P = 0.02 to P = 0.0003) higher antibody titers when post-challenged 5 months after the booster vaccination compared to the other single vaccinated and control groups. Here we present new data on the duration of the protective immune Libraries response formed in yearlings after prime and booster immunization with a modified live viral vaccine Gefitinib price against EIV based on the novel Ca reassortant strain A/HK/Otar/6:2/2010. This vaccine was developed in response to a serious epizootic outbreak of equine influenza A (H3N8) in Kazakhstan in 2007 [19], when approximately 200,000 horses became ill, of which 50,000 horses – including 40,000 foals – died. Strain A/equine/Otar/764/2007 Mannose-binding protein-associated serine protease (H3N8)

was isolated from the epizootic outbreak and subsequently used to generate the Ca vaccine strain A/HK/Otar/6:2/2010. Phylogenetic analysis of the HA gene of A/equine/Otar/764/2007 (H3N8) demonstrated that this strain belongs to the American Lineage Florida Clade 2 and has 99.99% homology to the strain A/equine/Richmond/1/2007 (H3N8) [18], which was recommended by the Office International des Epizooties for the production of a vaccine against EIV [20]. One objective of this study was to investigate the safety of our vaccine in yearlings. Both single and double intranasal administration of the live vaccine were harmless to yearlings, as no clinical signs of disease were observed in any animal during the observation period, and viral shedding only occurred at low titers and in less than in 50% of the animals. These results are consistent with our earlier studies [16] and [17], which demonstrated that the reassortant Ca strain A/HK/Otar/6:2/2010 could only replicate in the upper respiratory organs and did not induce any clinical manifestation of EIV (or even of a generalized infectious process) in yearlings or pregnant mares.

The completion of the human genome project,72 the parallel development of the HapMap database of human SNP variation, and the availability of information on more than 3.1 million SNPs across the human genome have paved the way to effectively carry out large-scale GWAS.73-75 Genetic association MK-1775 order studies are based on the common disease common variant hypothesis. This hypothesis proposes that common diseases are a result of interactive contribution of common variants with small Inhibitors,research,lifescience,medical effect sizes, and the susceptibility alleles will be shared by a significant proportion

of unrelated affected individuals. This is the basis of both hypothesis-based candidate gene association studies as well as the hypothesis-free GWAS method. In the past 4 years at least 11 GWAS have attempted to identify susceptibility genes for schizophrenia by genotyping individual samples Inhibitors,research,lifescience,medical as well as using DNA poolingbased methods. GWAS using DNA pooling DNA pooling was initially proposed as a method to reduce genotyping costs in large-scale association studies.76 DNA from cases and controls are pooled into two separate groups, and the differences in allele frequency between the two groups are estimated to assess association. The first pooling-based association study was genecentric, and analyzed 25

494 SNPs present within 10 kb of each of a large set of genes77 (Table II). In the initial discovery sample a significant Inhibitors,research,lifescience,medical association of the marker rs752016 in intron 11 of the Plexin A2 gene (PLXNA2, 1q32; OR = 1.49; P=0.006) was found. A similar association was observed in the replication Inhibitors,research,lifescience,medical case-control as well as family based samples. However, independent replications for this SNP have been mixed.78 – 80 Shifman et al81 conducted a pooling-based GWAS study and observed

female-specific association of the SNP rs7341475 G/A, in the fourth intron of the reelin gene (RELN, ORGG=2.1, 9.8×10-5). This was confirmed in a replication sample of patients of European ancestry from the United Kingdom, but not in samples from three other populations (Irish, Inhibitors,research,lifescience,medical Isotretinoin American, and Chinese). The trend in the last three samples was in the same direction, and was significant in a meta-analysis including all samples ORGG=1.58 (1.31-1.89), P=8.8×10-7. However none of these observations were significant after correcting for multiple testing. The reelin protein is a serine protease that plays an important role in corticogenesis and it is associated with an autosomal recessive form of lissencephaly.82 It has also been implicated in neurotransmitter-related GSK3(3 signaling and regulation of NMDA receptor activation.83 Polymorphisms in the RELN gene have been associated with neurocognitive endophenotypes of schizophrenia (eg, working memory and executive functioning).84,85 Furthermore, the association of the RELN gene with schizophrenia has been replicated in an independent sample.

167 In contrast to these states, the effectiveness of a representation system is characterized by high variability with minimal interactions among the constituents, furthermore improvement of behavioral performance in behavioral tasks is often characterized by increased interspike variability and reduced spike correlation among neurons.109,165,168-172 This view appears to be at striking odds with suggestions that neuronal oscillations enhance the coding ability of neurons.4,5,17,58,122 There seems to be a compromise between the information processing capacity of neuronal networks and the need for some level of synchronization

of their neurons for efficient Inhibitors,research,lifescience,medical communication. Fast communication among pyramidal neurons in the cortex is established by AMPA-type glutamate receptors, which are weak and have high probability of transmission failures.173 Therefore, in order to convey information to peer neurons, pyramidal cells should come together in transient coalitions, or cell assemblies.46,53 As discussed Inhibitors,research,lifescience,medical above, the goal of the temporal assembly formation is

to discharge the downstream neurons. Thus, for effective communication there is a requirement for a minimum level of synchrony and it may be that γ cycle-defined cell assemblies represent a useable packet of information, which contain varying Inhibitors,research,lifescience,medical specific content.53 Cross-frequency coupling between local γ oscillations and the more global slower rhythms is established by phase synchrony.

However, this coupling mechanism does not imply that the slower oscillation magnifies the synchrony in the γ period. Quite the contrary, γ cycle-embedded cell assemblies are distributed across the phase space of the modulating slow oscillation, as demonstrated Inhibitors,research,lifescience,medical above for θ oscillations. In inhibition-based oscillations, the recruitment of assemblies is deliberately protracted over time. Instead of narrowing the Inhibitors,research,lifescience,medical time window of synchronization, multiple assemblies are separated in nested γ cycles within the slower, modulating θ cycle. In contrast to the intuitive “oscillations-enhance-synchrony” PF01367338 picture, temporal synchrony among principal neurons is lowest during θ oscillations and highest during slow-wave sleep. Another counterintuitive observation is that the coefficient of variation (CV) of the interspike intervals of hippocampal principal cells is also largest during θ-associated exploration through behaviors and smallest during slow-wave sleep.174 The potential mechanism underlying such “paradoxical” asynchrony and spike variability-promoting functions of θ oscillation is its ability to temporally coordinate excitatory and inhibitory synaptic inputs to neurons.12,31,175 Modeling studies have demonstrated that temporally precise correlated fluctuations of excitatory and inhibitory currents can reduce or cancel each others’ action and decorrelate the synaptic current of postsynaptic neurons.

The patients were included on admission. All contacts were recorded, and each poisoning episode was traced through different levels of care using of each patient’s unique personal identification number. This

also included those found dead and subjected to medico-legal examination. Thus, a complete one-year picture of all patients in the capital of Norway who were in contact with health care Inhibitors,research,lifescience,medical services because of acute poisoning was obtained. The catchment area had a total population of 521 886, of which 428 198 were older than 16 years (1st January 2004). Data on fatal poisoning is presented here. The intention behind the fatal intake, the history of substance use disorder, and previous suicide attempts were assessed. Furthermore, the main toxic agents in fatal and non-fatal acute poisonings in the same geographical area and period were compared, and case-fatality Inhibitors,research,lifescience,medical rates were calculated. Epidemiological data on the non-fatal poisonings has been presented previously [12,13]. Data collection The inclusion Inhibitors,research,lifescience,medical criterion for the selleck chemicals llc present part of the study was exposure to a toxic substance in an amount leading to death in subjects ≥16 years, i.e. a primary diagnosis of acute poisoning. Deaths both in and outside hospitals

were included. Furthermore, both deliberate acute poisonings and accidental poisonings were included. Exclusion criteria were chronic poisoning and admission to hospital or the Institute of Forensic Medicine

with another primary diagnosis, such as trauma, even if intoxication (mostly from ethanol) was the underlying reason for the accident. Medico-legal autopsies were performed at the Institute of Forensic Inhibitors,research,lifescience,medical Medicine, University of Oslo. The Institute of Forensic Medicine examines all deaths due to poisoning, according to Norwegian law. Forensic pathologists at the Institute perform the autopsies. Police records are available if relevant. In all forensic cases, Inhibitors,research,lifescience,medical toxicological analyses were performed at the Norwegian Institute of Public Health, Division of Forensic Toxicology and Drug Abuse. For deaths occurring in hospitals where a medico-legal isothipendyl autopsy was not performed, physicians obtained data by completing a standardized registration form based on medical files. If the patient had been conscious during the hospital stay, the form was completed based on a clinical interview. Classification of toxic agents Toxic agents were recorded and classified as main or additional agents. Toxicologists at the Institute of Forensic Toxicology and the forensic pathologist did the determination of the toxic agents responsible for the death in the fatal cases. However, for patients who survived, and for fatal poisonings in hospital not subjected to medico-legal autopsy, the treating physician made the determination of the toxic agents leading to hospitalization.

Number, viability, and purity of the cells were evaluated by Trypan Blue exclusion. The isolated cells were analyzed using FACS Aria II, and the fluorescence intensity was compared with that of U-937 cells incubated with 0, 10, 100, or 1000ng/mL Hoechst 33342 as a control. Fluorescence intensity of peritoneal macrophages and U-937 cells was measured as described above using Inhibitors,research,lifescience,medical a FXEX station 3 scanning fluorometer, and

values were expressed as fluorescent intensity/10000 cells. Next, we estimated the concentration of Hoechst 33342 to which the peritoneal macrophages had been exposed based on the control experiment. 3. Results and Discussion The initial pharmacokinetic study in DDS using PLGA was to investigate the tissue Venetoclax distribution of PLGA particles, which can be visualized by labeling with a fluorescent dye [3]. However, the essential aim of this investigation was not only to determine the localization of particles but also to analyze the kinetics Inhibitors,research,lifescience,medical of drug release and efficacy of cell targeting. In the present study we Inhibitors,research,lifescience,medical used Hoechst 33342 as an imitating drug and initially examined the effects of

Hoechst 33342 on cell viability. MTT assays demonstrated that Hoechst 33342 appeared to be nontoxic up to a concentration of 1μg/mL in two different cell types, epithelial and myeloid cells, at least within 4 days of exposure (Figures ​(Figures11 and ​and2).2). Hoechst 33342 was found to be highly toxic and induced cell death at a concentration of 5μg/mL (Figure 2(c)). When IEC-6 cells were cultured with 1μg/mL Hoechst 33342 for 7 or 12 days, bundle-like

Inhibitors,research,lifescience,medical structures were detected, suggesting that long-term culture in the presence of high concentrations of Hoechst 33342 may affect epithelial phenotype (Figures 2(e) and 2(f)). PLGA particles themselves were also nontoxic as shown in Figure 3. Figure 1 Effect of Hoechst 33342 concentration Inhibitors,research,lifescience,medical on the viability of IEC-6 (a) and U-937 cells (b). Both cell types were treated with different concentrations of Hoechst 33342 (0 to 5μg/mL) for up to 7 days. Cell viability was then determined by … Figure Oxalosuccinic acid 2 Phase contrast microscopy images of IEC-6 cells cultured with Hoechst 33342. (a), (b), and (c) show cultures grown in the absence of Hoechst 33342 (a), or in the presence of 1 (b), or 5μg/mL Hoechst 33342 (c) for 1 day. Note that many … Figure 3 Effect of PLGA particles on the viability of IEC-6 (a) and U-937 cells (b). PLGA particles were incorporated with PBS. Both cell types were treated with different concentrations of PLGA particles (0 to 250μg/mL) for up to 7 days. Cell … In the next step we measured fluorescence intensity of cells incubated in the presence of serial amounts of Hoechst 33352. Fluorescence intensity was clearly dose-dependent in both IEC and U-937 cells (Figures 4(a) and 4(b)).

There are still few studies in France concerning the prevalence of anxiety and somatoform disorders among outpatients. Lepine et al13 examined a general psychiatric outpatients sample (n=1271), gathered through a crossnational French survey. Anxiety and somatoform syndromes were assessed according to DSM-III and DSM-III-R criteria. Lifetime and 1 -month prevalence rates in this population were reported and a high level of comorbidity between anxiety syndromes was observed. Another epidemiological survey Inhibitors,research,lifescience,medical was conducted by Lepine and Lellouch14 in the

general population in an suburban development of the greater Paris area, and evaluated the prevalence of risk factor for anxiety Inhibitors,research,lifescience,medical and depressive disorders, based on the DSM-III-R criteria, using standardized interviews (DIS and CIDI). Data were obtained

for 1787 subjects randomly chosen from a telephone directory. One problem was the high rate of refusal to participate (35%). Furthermore, the study area greatly influenced the sociodemographic characteristics of the study population: young age Inhibitors,research,lifescience,medical (average: 36 years in women and 38 years in men), mostly married, working primarily in the tertiary sector, with 71% of the women aged 20 to 64 years being part of the active work force. The anxiety and depression Navitoclax price disorder prevalence data found in this study are consistent with those found in the international literature (Figure 1). They are, however, to be compared with the Inhibitors,research,lifescience,medical data found in the upper limit of this bracket. As was the case in the NCS, these data underline the high rate of comorbidity between anxiety and depressive disorders. Furthermore, in this study of French population, Lepine and Lellouch14 find the same cohort effect as that found

in other Western countries: Inhibitors,research,lifescience,medical an increase in the prevalence of depression in cohorts of subjects born after the end of the Second World War. Figure 1. Prevalence of Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) disorders in an outpatient sample (n=1 271). NA, not available. The epidemiology of anxiety disorders: focused studies Generalized anxiety disorder Diagnosis The DSM-III criteria for GAD require the presence of unrealistic or excessive anxiety and worry, accompanied by symptoms from three of the following categories: motor tension, autonomic hyperactivity, to vigilance and scanning, and apprehensive expectation. The anxious mood must continue for at least a month, and the diagnosis is not made if phobia, PD, or OCD is present, or if the disturbance is due to another physical or mental disorder, such as hyperthyroidism, major depression, or schizophrenia. By this definition, GAD is treated primarily as a residual category after exclusion of the other major anxiety disorders. DSM-III-R narrowed the definition further by requiring a minimum of six symptoms and a duration of 6 months.

Under low nutrient conditions, cells usually engage in a multitude of cellular responses that allow their survival until growth resumes. Typically, the coordination of these cellular responses involves the global ABT-888 ic50 regulator guanosine-3′,5′-bis-pyrophosphate (ppGpp), a core molecule that primarily triggers the stringent response [3,4,5,6]. Although the synthesis

of ppGpp has been mainly associated with cellular responses to amino acid starvation, which in E. coli are mainly initiated by the activation of the ribosome-associated enzyme encoded by the relA gene catalyzing the conversion of cellular GDP into ppGpp Inhibitors,research,lifescience,medical [7], recent studies have indicated that this molecule also accumulates during carbon starvation [8,9,10]. A Inhibitors,research,lifescience,medical second ppGpp synthetase, i.e., the bifunctional enzyme SpoT that has both hydrolase and synthetase activities, has been described

to be involved in ppGpp accumulation during carbon starvation [11,12], but its activity was shown to be much weaker than the one of the RelA enzyme [13]. This suggests that RelA may be central in the response to carbon starvation. It was thus suggested that these two nutritional stress phenomena are strictly correlated, the exhaustion Inhibitors,research,lifescience,medical of carbon often resulting in a rapid decrease in amino acids availability, entangling the activity of both enzymes [8]. Therefore, it is expected that RelA, directly or indirectly, interferes in the cellular responses to carbon-limited conditions. These phenomena have been implicated in recombinant bioprocesses using E. coli as an expression host [14]. It was found that ppGpp-deficient strains can maintain Inhibitors,research,lifescience,medical a metabolically productive state longer than the parent strains [15]. Thus, reducing the intracellular ppGpp levels seems to attenuate the pleiotropic effects on the metabolism, which is beneficial for the synthesis of foreign

proteins. However, whether this is due to a less stress-responsive Inhibitors,research,lifescience,medical phenotype during recombinant production that eventually affects the metabolism, next or to changes in the metabolic basis of this strain is still unclear. Despite the effects on the synthesis of foreign proteins, the impact of this regulator on the cellular metabolism of host strains needs to be characterized. To investigate the metabolic state of E. coli cells and the role of the RelA enzyme (p)ppGpp synthetase in the E. coli responses to nutrient-limited growth conditions, a metabolomics approach was applied in this study. The intracellular metabolite profiles measured by gas chromatography–mass spectrometry (GC-MS) were used to assess the main metabolic changes resulting from different steady state growth conditions.

Intravenously administered AmB/ASCDP/DSPE-PEG

nanoparticles were detected at higher concentrations than Fungizone in HA-1077 solubility dmso plasma. Thus, the ASC-DP/DSPE-PEG nanoparticle system appears to be a promising delivery system for hydrophobic drugs. Figure 4 Particle size distribution patterns of ASC-DP/surfactant (1:1 molar ratio) suspensions. The surfactants Inhibitors,research,lifescience,medical included (a) SDS, (b) CTAB, (c) Brij78, and (d) DSPE-PEG. 2. Conclusions Formulation of hydrophilic and hydrophobic drugs using a nanosized carrier system is a promising way to achieve the desired therapeutic effect. Nanoparticle formation of ascorbic acid derivatives with or without drugs is practically applicable as transdermal and injectable formulations. The ascorbic acid derivatives shown in this paper can possibly be used as a model drug, a component

of the carrier, or both. Ascorbic acid derivatives have been Inhibitors,research,lifescience,medical widely used as antioxidative drugs, the activities of which are similar to that of ascorbic acid. When combined with other excipients, such as oil with lipids and chitosan derivatives, several kinds of ASC-P-incorporated nanoparticles were formulated. Ascorbic acid and its derivatives are also used as cytotoxic drugs against cancer Inhibitors,research,lifescience,medical cell lines. Ascorbic acid derivatives with an alkyl chain are preferred because of the interaction with and insertion into the hydrophobic part of the membrane. This combined use with anticancer drugs incorporated in the carrier system apparently increased the efficacy. A formulation design based on the chemical structure of the components is required not only to prepare stable drug nanoparticles but also to the broader application

of ascorbic acid derivatives in therapeutic uses. The intermolecular Inhibitors,research,lifescience,medical interaction between each component and ascorbic acid derivatives contributes to effective drug solubilization and stabilization to enable nanoparticle formulation. For example, aspasomes were formulated as vesicles composed of various components that interacted with each other [28]. Furthermore, Inhibitors,research,lifescience,medical the complex formation between the hydrophobic drug N-4472 and ascorbic acid and the subsequent self-association contributed to form the colloidal particles in aqueous solution (Figure 5) [33]. A novel drug delivery carrier system using ascorbic acid derivatives is going to be developed using this chemical structure-based design. Figure 5 Schematic representation for proposed unless structure of N-4472/ASA surface active complex formation and the subsequent self-association used to form the stable nanosuspension. Physicochemical characterization of the colloidal particles is important for understanding the drug absorption mechanism and therapeutic efficacy, although it is not easy. The molecular mobility measurement of a drug in aqueous media using NMR is useful to evaluate the molecular states of the drug in the formulation as well as in the dispersing media.

This prospect of controlling the orientation of fibers is a pre-requirement for biomimicking natural tissues. Altering the concentration/viscosity

of the polymer solution affects fiber diameter: the higher the concentration, the larger the diameter of the fibers. Its simplicity allows electrospinning to be used in a laboratory setting and used successfully in scale-up and mass production. Stem cells grown on fibrous scaffolds have also shown differentiation-dependent behavior in terms of the fiber chemistry, size, and alignment. For example, MSCs grown on electrospun-aligned PCL scaffolds showed preferential differentiation to a chondrogenic lineage on Inhibitors,research,lifescience,medical nanoscale versus microscale fibers. While cells aligned in the direction of the fibers for both nano- and microscale scaffolds, the nanofibers (<500 nm diameter) promoted higher levels of glycosaminoglycan production and mRNA expression of collagen II and aggrecan. Electrospun nanofiber matrices show morphological similarities to the natural Inhibitors,research,lifescience,medical ECM, characterized by ultrafine continuous fibers with a high surface-to-volume ratio. Hosseinkhani et al. demonstrated that PGA/collagen nanofibers fabricated through electrospinning significantly enhanced cell adhesion compared with PGA/collagen microfibers.50

Furthermore, different scaffold architectures Inhibitors,research,lifescience,medical may have varying influence on cell function. Generally, electrospinning produces a 3D Inhibitors,research,lifescience,medical mesh of nonwoven nano/micro fibers. Influencing cellular function using electrospun scaffolds remains a challenge, as the scaffold must mimic some of the components that make up the natural ECM while providing the appropriate biochemical and mechanical

inputs for the cellular microenvironment. Chemical cues in the form of various biomolecules (nanometer scale), such as adhesive protein or growth factors, also significantly Inhibitors,research,lifescience,medical influence cell behavior.45 49 51 Self-assembly involves the spontaneous organization of individual components into an ordered and stable structure with noncovalent bonds.52 The most common particles used in self-assembly for medical purposes are amphiphilic particles that interact in solution, driven by shielding of hydrophobic regions, out hydrogen bonding, and electrostatic repulsing forces. Self-assembly is a rather complex laboratory procedure that is limited to only a select few polymer configurations. This technique generally creates nanofibers that are 5 nm to 8 nm in diameter and 1 μm in Selleck Gemcitabine length. In a rat model of myocardial infarction, Guo et al. demonstrated that survival was improved when stem cells were delivered with a self-assembling peptide nanoscaffold.53 The differentiation of bone marrow-derived MSCs on nanofibrous membranes or hydrogels could be another area of research that might accelerate the cardiac regeneration process.

If, however, we assume that Muslims do not adhere to fatawa, then our conclusion is that the religious prohibition

expressed by the fatawa in their fatawa is not strong enough to resist the financial need of the poor. In this case, penal and social state legislations should be put into action. Footnotes Conflict of interest: No potential conflict of interest relevant to this article was reported.
Organ transplantation has a key role in medicine worldwide and has become an essential treatment modality in saving and prolonging lives in a wide variety of clinical conditions. Kidney, heart, liver, lung, and pancreas are among the vital organs that are routinely used for transplantation, #find more keyword# but many other organs that draw less public attention such as small bowel, skin, ligaments, bones, and cornea are used in various clinical conditions to provide temporary or permanent relief for various clinical conditions. In general, organ transplantation Inhibitors,research,lifescience,medical saves lives, prolongs survival, and increases the quality of life. Kidney transplantation has been proven to have a survival advantage over hemodialysis, accompanied by a marked increase Inhibitors,research,lifescience,medical in the quality of life. In general, organ implantation is co-ordinated

via regional or national allocation programs, which set up the priorities for organ allocation and provide the essential logistics and laboratory support for the transplantation process.1,2 These organs can be preserved for a relatively short period of time, and therefore mechanisms for immediate organ allocation, once a donor is identified, are critical. Organ transplantation is one of the most complex procedures in medicine Inhibitors,research,lifescience,medical for several reasons. First and foremost, it involves dealing with the

medical aspects of the recipient patient in parallel to Inhibitors,research,lifescience,medical dealing with a matched donor in case of a living donor or his family for a deceased donor. Whether involving a deceased or a living donor, the ethical rules that wrap the process of organ transplantation are complex and often convoluted by ethical and religious nuances. Ethical issues Adenylyl cyclase with the timely and unequivocal definition of death are among the most debatable and complex dilemmas in medicine,3–5 and the public opinion is often skewed by religious and cultural influences and ethical standards that vary between different cultures and religions. On top of that, the field of transplantations is faced with a worldwide shortage of organs,6,7 and this mandates the need to guard the ethical standard of medical priorities for those patients that depend on the transplantation to save their lives. In this review, I will discuss the major dilemmas that we face in Israel and worldwide regarding organ transplantation. SHORTAGE OF ORGANS The shortage of organs is a major problem worldwide.6,7 There are many more patients awaiting transplantation than there are organ donors.