Background. Tuberculosis is a huge global health problem. BCG is the only vaccine used for about 100 years against TB, but the reasons for protection variability in populations remain unclear. To improve BCG efficacy and develop a strategy for new vaccines, the underlying genetic differences among BCG subtypes should be understood urgently. Methods and Findings. Human B cell epitope data were collected from the Immune Epitope Database. Epitope sequences were mapped with those of 15 genomes, including 13 BCGs, M. bovis AF2122/97, and M. tuberculosis H37Rv, to identify epitopes distribution. Among 398 experimentally verified B cell epitopes, 321 (80.7%) were conserved, while the remaining 77 (19.3%) were lost to varying degrees in BCGs. The variable protective efficacy of BCGs may result from the degree of B cell epitopes deficiency. Conclusions. Here we firstly analyzed the genetic characteristics of BCGs based on B cell epitopes and found that B cell epitopes distribution may contribute to vaccine efficacy. Restoration of important antigens or effective B cell epitopes in BCG could be a useful strategy for vaccine development. Mycobacterium tuberculosis (M. tuberculosis), is an ancient scourge preceding the recorded human history [Tuberculosis (TB), mainly caused by history . Data re history , 3. Chin history . Mycobacterium bovis (M. bovis), which underwent 230 passages originally, has been the only permitted vaccine against TB for nearly a century worldwide. Despite debates focusing on its protective effects against TB [Bacille Calmette-Guérin (BCG), an attenuated derivative ofainst TB , 6, BCG It is widely accepted that protective immunity of humans against TB is mainly attributable to cell-mediated immunity, especially T lymphocytes. In addition, humoral immunity plays small role in the protective immunity to TB –9. HowevEven though BCG is the most widely used vaccine in human history, its mechanisms remain poorly understood. Additionally, there have been many daughter strains of BCG with varied protective efficacy , 14. Her M. tuberculosis H37Rv, and M. bovis AF2122/97 [http://dx.doi.org/10.1155/2016/3620141).The 15 genome sequences assessed in this study belonged to 13 BCG strains ,An online search in the Immune Epitope Database (IEDB) was performed, and peptidic epitopes were selected as targets in this study.The sequences of peptidic epitopes were compared to the H37Rv proteome, using BLAST to confirm which genes encoded the amino acid sequences of various B cell epitopes . If an e M. bovis AF2122/97 to determine B cell epitope distribution in different strains. All deletion regions of DNA encoding B cell epitopes were validated by PCR and DNA sequencing.The gene sequences encoding B cell epitopes were compared individually with the whole genomes of BCG strains andA total of 399 experimentally verified peptidic human B cell epitopes were obtained in the IEDB. Since 2 epitopes (epitope IDs 94762 and 94763) shared the same nucleic acid sequence with only a few modified amino acids, epitope 94763 was not included in this study. Finally, 398 B cell epitopes involved were analyzed. M. tuberculosis H37Rv and M. bovis AF2122/97 genomes, respectively; epitopes and genes are shown in Table S2. Although the gene homologous to Rv3347c was split into 2 genes in M. bovis AF2122/97 genome, there were finally 81 genes encoding B cell epitopes in M. bovis AF2122/97 because of the absence of a gene homologous to Rv2351c.All peptidic epitopes were included in 81 genes according to M. tuberculosis genes are classified into various categories based on function [Tuberculist  http://tuberculist.epfl.ch/). In this study, the 81 genes belonged to 9 categories ( Rv3874 (encoding CFP-10) [ Rv3875 (encoding ESAT-6) [ Rv1980c (encoding MPT-64) [ Rv0934 (encoding PstS1) [ Rv0350 (encoding HSP70) [ Rv0440 (encoding HSP65) [According to an analysis by Cole et al. in 1998, allfunction . And funtegories . The det CFP-10) , Rv3875  ESAT-6) , Rv1980c MPT-64) , Rv0934 g PstS1) , Rv0350 g HSP70) , and Rv0g HSP65) .DNA fragments encoding B cell epitopes, based on H37Rv gene sequence, were extracted from the 13 BCG genomes to assess the changes of B cell epitopes. A total of 398 B cell epitopes were analyzed. No SNP was identified in 321 epitopes of all BCGs (classified as Group 1); the remaining 77 epitopes varied in DNA levels among BCGs to different degrees. Of the 77 nucleic acid-altered epitopes, 15 presented the same nucleotide change in all BCGs (classified as Group 2). A total of 26 epitopes were lost in all BCGs because of gene deletion (classified as Group 3). There were 13 epitopes lost in 8 BCG strains, including BCG-Phipps, BCG-Danish, BCG-Prague, BCG-Tice, BCG-Glaxo, BCG-Mexico, BCG-Pasteur, and BCG-Frappier (classified as Group 4). The remaining 23 epitopes showed different SNPs or nucleotide deletions in different BCGs (classified as Group 5) . B cell  M. bovis AF2122/97 genome, only 2 of the 321 epitopes (epitope IDs 103022 and 103425) changed. The indicated changes likely derived from the original BCG, attenuated between 1908 and 1921 [Group 1 epitopes were present in all BCGs, with no SNP in these strains. In comparison withand 1921 . M. tuberculosis H37Rv. Interestingly, 9 epitopes  kept the same sequence in M. bovis AF2122/97 but differed in M. tuberculosis H37Rv; the remaining 6 epitopes  presented specific mutations in BCGs exclusively. We infer that mutations in the 9 epitopes are conserved in both BCGs and M. bovis, while the other 6 also likely resulted from the originally attenuated BCG strains.Group 2 included 15 epitopes showing the same SNPs in BCGs compared with M. tuberculosis H37Rv . The Rv1582c gene, located in Regions of Differences 3 (RD3), encodes the probable phage protein PhiRv1. The Rv2351c gene, located in RD7, encodes MTP40 antigen. The remaining 4 genes (Rv3874-3875 and Rv3878-3879c) were located in RD1 and encode CFP-10, ESAT-6, EspJ, and EspK, respectively [A total of 26 epitopes were classified as Group 3, involving 6 genes according toectively –30. Ther Rv1979c, Rv1980c, Rv1984c, and Rv1986. These genes were found in RD2 by comparative genomics of BCGs and lost in BCG-Danish, BCG-Prague, BCG-Glaxo, BCG-Frappier, BCG-Phipps, BCG-Tice, and BCG-Pasteur, between 1927 and 1931 [The epitopes in Group 4 were involved in 4 genes, includingand 1931 . We expeGroup 5 covered 23 epitopes with unique performances in different BCGs.In summary, the 398 epitopes could be divided into 2 categories, conserved and changed epitopes, based on nucleotide changes. The conserved epitopes contained 321 (80.7%) epitopes of Group 1. The changed ones included 77 (19.3%) epitopes of Groups 2, 3, 4, and 5. The epitopes encoding genes for “cell wall and cell processes” presented high variability .Here we compared B cell epitopes in 13 BCGs. All conserved and changed epitopes were analyzed according to BCG strain genomes. Finally, BCG-Tokyo 172 and BCG-China had the highest number of conserved epitopes (357 (89.7%)) .Tuberculosis, a horrible disease, had plagued humankind throughout the history. According to WHO data, 9.6 million new TB cases were estimated as well as 1.5 million TB related deaths in the world in 2014. BCG remains the only available and widely used vaccine against TB, although its protective effect against TB is not optimal, even with no protection for adults, because new TB vaccines are continually declared to be more effective in TB prevention. To date, at least 3 billion individuals have been immunized with BCG, and over 100 million doses of BCG are administered annually . HoweverThis is the first study analyzing the protective differences of BCGs based on B cell epitopes distribution. It has been acknowledged that BCG is not a single strain and has lots of descendants worldwide. After the original BCG was disseminated around the world, it likely to undergo various selective pressures. As a result, different daughter-BCGs were produced, with variable protective efficacy. The BCG ancestor was serially cultured for at least 230 passages from 1908 to 1921, losing some important epitopes ; meanwhile, some point-mutations occurred in the epitopes (Group 2). Therefore, all 13 BCGs contained epitopes of Groups 1 and 2, losing those of Group 3. Then, some BCGs successfully retained Group 4 epitopes, including BCG-Moreau, BCG-Sweden, BCG-China, BCG-Russia, and BCG-Tokyo 172. Of these strains, BCG-Moreau, BCG-Sweden, and BCG-Russia produced more changes in the next few years. In addition, other daughter-BCGs underwent a period of continuous change, losing Group 4 epitopes (coding with RD2), including BCG-Prague, BCG-Phipps, BCG-Glaxo, BCG-Frappier, BCG-Danish, BCG-Tice, BCG-Mexico, and BCG-Pasteur. Of these strains, 4 BCGs  produced more change in B cell epitopes (Group 5) when they were disseminated to various parts of the world. The currently available BCGs exhibited distinct process of attenuation after 1924 .Although the reasons for variable protective efficacy of BCGs are not fully understood, a key factor might be genetic differences in BCGs . BCG-Chi M. tuberculosis [B cell epitope is the region of a pathogen that interacts with the host immune system. As shown above, most epitopes identified from genes encoding antigens on the pathogen surface were recognized by the host. Generally, antigen epitopes tend to be hypervariable to evade immune detection by the host , 38. Accrculosis , 39 and rculosis . M. bovis, mimics M. tuberculosis to evoke immune protection in the host. If the BCG becomes too attenuated to imitate the natural pathogen, it would not produce sufficient protection. We showed that BCG-China and BCG-Tokyo 172, containing the most B cell epitopes also had 41 altered B cell epitopes compared with M. tuberculosis H37Rv. Some important antigens of M. tuberculosis are therefore lost in all BCGs, such as proteins encoded with RD1, RD3, and RD7. In other words the BCG which has all necessary epitopes compared with natural pathogen would be the best attenuated vaccine against TB. Thus, rebuilding the BCG to recover more lost epitopes and enhance innate properties could improve its protective efficacy [The BCG vaccine, an attenuated strain ofefficacy .In this study, a total of 398 experimentally verified human B cell epitopes were analyzed with 13 BCG genomes. Of these, 321 were conserved in all BCGs; the remaining 77 B cell epitopes, encoding Regions of Differences or other important genes, have been altered during the ongoing dissemination. Our analysis, based on B cell epitopes distribution, also revealed that BCG-China especially BCG-Tokyo 172 could be the most effective BCG vaccines used in the world. Restoration of important antigens in BCG or enhancing effective B cell epitopes in vaccines could be a useful strategy for vaccine development.Mycobacterium tuberculosis and 1 Mycobacterium bovis.Table S1: 15 genome sequences analyzed in this study. 15 strains used in this paper including 13 BCGs, 1 Mycobacterium tuberculosis H37Rv and Mycobacterium bovis AF2122/97, respectively.Table S2: 399 B cell epitopes and coding genes. 81 genes encoding 399 verified B cell epitopes according the genomes of Table S3: Functional classification of genes coding B cell epitope. 81 genes which encoded B cell epitopes could be classified into 9 categories.Table S4: B cell epitopes grouping in BCGs. All epitopes could be classified as 5 Groups based on distribution among BCGs.


Background: Hyperlipidemia is a common problem after kidney transplantation.Objective: To uncover the real impact of post kidney transplantation hyperlipidemia on graft function and survival, and to determine whether it is just a biochemical phenomenon after using immunosuppressant or a part of disease pathology.e.g., hypertension, diabetes mellitus [DM], hyperlipidemia and coronary artery disease), rejection episodes, status of infection with cytomegalous virus [CMV], post-transplantation DM, hyperlipidemia, ischemic heart disease [IHD], and graft and patient survival were recorded. A serum creatinine level >2 mg/dL was considered as “graft deterioration,” and return to dialysis as “graft loss.” According to the presence or absence of post kidney transplantation hypercholesterolemia (>200 mg/dL) or hypertriglyceridemia (>200 mg/dL), the patients were classified into “hyperlipidemic” or “non-hyperlipidemic.” The presence of clinical or paraclinical coronary artery disease was also determined in both groups.Methods: 330 kidney transplants were managed in Sina Hospital Kidney Transplantation Unit affiliated to Tehran University of Medical Sciences, Tehran, Iran from September 1994 till February 2010. The demographic characteristics of the patients, causes of chronic kidney diseases, history of pretransplantation dialysis, pretransplantation comorbidities (Results: The incidence of hyperlipidemia elevated from 8% to 50% before and after transplantation. 2.7% developed clinical IHD. 13% of hyperlipidemics and 22% of non-hyperlipidemics developed graft deterioration. Among hyperlipidemics with deteriorated grafts 40% had premorbid diseases, 68% had CMV infection and 82% had hypertension. Only 22% had previous acute rejection and 27% received deceased kidney transplant.Conclusions: post kidney transplantation hyperlipidemia is just an associated phenomenon secondary to the use of immunosuppressant medications, which have no obvious impact on renal graft function and can be easily controlled by instituting dietary modifications and use of modern antilipid medications. Post kidney transplantation CMV infection and hypertension are considered as the main threatening risk for renal graft—even more dangerous than acute or chronic rejections. Innovative developments in immunosuppressant regimens have markedly improved patient and graft survival at one year. However, after the first year of transplantation, cardiovascular morbidity and mortality are the major causes of death with functioning graft. Among middle aged patients with a functioning graft, mortality rate due to coronary artery diseases is approximately 0.6% per year , which iper se adversely affect the patient and graft survival in recipients of organ transplants remains a matter of debate  uncovered the fact that modern immunosuppression is very effective in preventing and controlling of allogenic graft rejections, but none judged use of immunosuppression yield another mode of challenges like over immunosupression and undesirable side effects of immunosuppressive medications. However, the presence of post-transplantation hyperlipidemia without simultaneous clinical signs of IHD, made this association questionable.Although innovation of immunosupressive agents has improved the outcome of graft survival, association of these medications with various complications has caused challenges for patients and transplantation teams. Nowadays, the main bulk of chronic kidney diseases are systemic diseases that have serious chronic impacts on different vital organs (n period . We founIt seems that allograft rejection has a minor challenge in modern solid organ transplantation. The adverse effects of modern immunosuppressants have the main impact on longterm graft function. Post kidney transplantation hyperlipidemia is an associated biochemical phenomenon secondary to the use of immunosuppressive regimens, and has no obvious role in cardiovascular atherogenesis. The association between post kidney transplantation hyperlipidemia and hypertension or CMV infection makes the graft deterioration more likely.


The infection rapidly progressed and required extensive operative debridement. Her resulting full-thickness dorsal hand defect measured 120 cmDescribe the wound/defect seen and generate a differential diagnosis.What are the goals for reconstruction in this patient?What is Integra and what is it indicated for?What are some causes of graft failure?The wound seen in Treatment of paronychia is centered on drainage and antibiotic therapy.Integra  is a porous biological matrix composed of a cross-linked bovine tendon collagen and glycosaminoglycan scaffold that assimilates into wounds and stimulates vascularization and dermal regeneration. In the bilayer product, the matrix is covered with a layer of silicone that detaches as the matrix incorporates. Bilayer Integra is indicated for the management of partial- and full-thickness wounds and ulcers. Single-layer Integra is stripped of its silicone layer to allow for immediate thin skin autografting in a single-stage procedure.Risk factors for graft failure include poor vascularization, fluid accumulation in the form of a seroma or hematoma, shearing, and infection.In our patient, after adequate debridement and commencement of systemic antibiotic therapy, we applied a single-layer Integra matrix in combination with a split-thickness skin graft over the dorsal hand wound. Splinting the hand after application of Integra and a skin graft is essential to prevent shear and ensure successful integration of the graft. Although negative pressure therapy is not essential, it may improve graft survival, as it acts as a splint and prevents shearing or fluid accumulation  under thOur patient's complete wound healing allowed her to work with occupational therapy and achieve good hand function . Upper l


The structural and functional properties of non-gelatinized waxy rice starch were investigated after 1, 3, 7, and 10 freezing/thawing cycles. Freezing caused an increasing damaged starch from 1.36% in native waxy rice starch to 5.77% in 10 freezing/thawing-treated starch (FTS), as evidenced by the cracking surface on starch granules. More dry matter concentration was leached, which was characterized by high amylopectin concentration (4.34 mg/mL). The leaching was accompanied by a decrease in relative crystallinity from 35.19% in native starch to 31.34% in 10 FTS. Freezing treatment also led to significant deviations in the functional characteristics, for instance decreased gelatinization temperature range, enthalpy, and pasting viscosities. The resistant starch content of 10FTS significantly decreased from 58.9% to 19%, whereas the slowly digested starch content greatly increased from 23.8% in native starch to 50.3%. The increase in susceptibility to enzyme hydrolysis may be attributed to porous granular surface, amylopectin leaching, and the decrease in the relative crystallinity caused by freezing water. Freezing technology is a suitable method to retard some bread making measures and to produce fresh bread available in the retail stores after baking, or to make frozen goods available that the consumer can bake at home while required. However, freezing procedure provoked various physical and chemical damages to the product . ProteinGluten-free breads were instantly accessible in the market because of celiac disease and other allergic reactions/intolerances through gluten consumption. These breads were mainly formed by rice flour and hydrocolloids instead of gluten network . SeveralWaxy rice starch, which contained only amylopectin (AP), served as a simple model to determine the role of starch in deteriorating frozen products. Gelatinization properties, pasting behaviors, and in vitro digestibility of waxy rice starch were affiliated to amylopectin structure. A non-gelatinized system method was employed to elucidate the effects of freezing on the properties of waxy rice starch before cooking to control a better production process.Commercial waxy rice starch was provided by Suzhou Youi Foods Co., Ltd . Moisture contents were determined based on weight loss at 105°C to constant weight of 1.0 g of accurately weighed samples . All solAbout 30 g of waxy rice starch in excess water (45 mL) was stored at −20°C for 24h after pre-freezing at −30°C in a refrigerator to obtain an inner core temperature of −18°C. The sample was then thawed to equilibrate for 2h at an ambient temperature (25°C). This F/T cycle was repeated for different cycles  before removing the supernatants by centrifugation at 2200 × g for 20 min. The starch pellets were dried at 40°C for 2 days and passed through a 100 mesh sieve for the following analysis. The collected supernatant solutions after centrifugation were used for composition analyses.Freeze-dried starch pellets were mounted on a tray and coated with gold to detect micrographs. The morphology of native and F/T samples was observed under a Hitachi S-4800 field emission scanning electron microscope . The samples were viewed at an accelerating voltage of 10 kV, and representative micrographs from all the samples were selected for illustration.Aspergillusoryzae  was applied.The damaged starch content (%) were assessed by an fungal enzymatic standard method  and the The dry matter concentration of the starch supernatant was estimated using a vacuum oven keeping at 105°C for one night until their dry weights were recorded. Then it was measured using the following equation2-amylopectin were 551 and 761 nm, as determined using a spectrophotometer . The distilled water was selected as reference. The amylopectin concentration was calculated using the following formula. All analyses were performed in triplicate.About 10 mg of freeze—dried supernatant obtained by Labconco FreeZone  was dissolved in a 1 mL of 0.1 mL of ethanol and 0.9 mL of 1 M NaOH aqueous solution. Then the amylopectin concentration was determined by dual-wavelength spectrophotometry with iodine as the coloring agent . The optThe other coefficients were acquired from the regressive equation of amylopectin.The XRD patterns of starch powders were recorded in a scanning range of 4° to 40° at room temperature. A Bruker D8-Advance XRD instrument  was run in a scanning speed of 4°/min with radiation at a set voltage of 40 KV and current of 30 mA, respectively.o), peak (Tp), conclusion temperature (Tc), and enthalpy (ΔH) of gelatinization were obtained by TA Rheology System Software Muse, version 1.6 . Each sample was run in triplicate.Thermal properties were determined by a SIINT instrument . Prepared samples  were sealed into aluminum pans in blends of 6 μL of distilled water and equilibrated at 4°C for 24h. An empty pan was used as a reference; the sample pans were heated at a range of 20°C to 90°C with a constant rate of 10°C/min using nitrogen gas at a flow rate of 80 mL/min. The onset  was used to measure starch viscosity. An aqueous dispersion of starch suspension  was prepared in the viscosity measure cup. For the mixture with distilled water, the slurries were held at 30°C for 1 min, heated at a rate of 3.0°C/min to 95°C, maintained at that temperature for 30 min, cooled to 50°C at a rate of 3.0°C/min, and held at 50°C for 30 min. The average values for peak viscosity (PV) (BU), trough viscosity (TV) (BU), final viscosity (FV) (BU), pasting temperature (PT) (°C), breakdown (BV = PV-TV) (BU), and setback viscosity (SV = FV-TV) (BU) were obtained for each sample from triplicate Brabender viscosity measurements.Starch digestibility was determined by the procedure described by Englyst et al with modifications. Porcine pancreatic α-amylase  was dispersed in 0.1 M sodium acetate buffer (pH 5.2) and centrifuged at 1500 g for 10 min. Then 0.1 mL of amyloglucosidase  was added to the supernatant (8 mL). Starch (200 mg) and 4 mL of 0.1 M sodium acetate buffer (pH 5.2) were added to each test tube, followed by the prepared enzyme solution (1 mL). The mixture was incubated in a shaking water bath . Aliquots (0.1 mL) were taken at 20 min and 120 min and mixed with 0.9 mL of 95% ethanol. The hydrolyzed glucose content was measured by the 3, 5-dintrosalicylic acid  method. There were three starch fractions classified by the rate of hydrolysis: RDS (digested within 20 min), SDS (digested between 20 and 120 min), and RS (undigested starch after 120 min).All experiments were subjected to an analysis of variance (ANOVA) by Duncan’s test (p < 0.05) was conducted using the SPSS 16.0 software .Fig The pitted appearances were consistent with the altered damaged starch content, which was greatly increased from to 1.36% in NWS to 4.57% in 10 FTS . The dryThe XRD diffractograms were analyzed using Jade 5.0 software , and the relative crystallinity was calculated by dividing the area of the peaks by the total area of the diffractogram . No signo, Tp, and Tc, and the ΔH. The To, Tp, and Tc of the NWS were 72°C, 77°C, and 85°C, respectively. Freezing treatment (1 F/T) decreased the Tc, but did not greatly affect the To and Tp. The gelatinization temperature range (Tc–To) and ΔH significantly decreased from 12.76°C to 9.22°C, and from 15.43 J/g to 6.01 J/g, respectively, at the first F/T cycle. Slight changes were observed in To, Tp, and Tc, and ΔH between freezing/thawing-treated starches (FTS).c-To mirrored variations in the crystalline shape, size, degree of crystal perfection and the kind of starch chain intertwining that develop the double helical chains of starch crystallite [The differences in Tstallite . Therefostallite . Comparestallite . Gidley stallite  suggestestallite , who comWaxy starches have larger gelatinization enthalpy than normal starches because starch with greater amylopectin amount had increased crystalline and less amorphous regions . The entThe pasting outlines and characteristics of native and FTS were summarized in Waxy rice starch mainly consisted of amylopectin without amylose—lipid complexes. Thus, pasting properties were influenced by amylopectin content and the integrity of the swollen starch granules. Because starch swelling was mainly property of amylopectin , high amThe gel viscosity at the end of the test depended on the leached amylose concentration, occupied volume by the swollen granules, stiffness of the dispersed granules, and the attractive forces between granules and continuous phase . The finThe amount of waxy rice RDS, SDS, and RS nutritional fraction was presented in In vitro digestibility of starch comprised of enzyme diffusion into the substrate, enzyme adsorption to the substrate, and hydrolytic event ,29. ThisThis study showed that freezing/thawing (F/T) treatment had a substantial effect on the structural and functional characteristics of waxy rice starches. When waxy rice starch granule suspensions were frozen, a pressure chamber was developed because the internal or external ice crystals occupied more space than an equal amount of water. This pressure affected the structural and functional properties of waxy rice starch after multiple F/T cycles, causing the increased damaged appearance in the starch granules and amylopectin leaching of waxy rice starches. Moreover, freezing treatment prevented the increase in the relative crystallinity of starch. These substantial changes were accompanied by a decrease in gelatinized temperature range, enthalpy, and pasting viscosities with the F/T cycles. The removal of some materials may weaken the overall stability of starch granules, thereby leading to the significant changes to in vitro digestibility of freezing/thawing-treated starches. These experimental results provide useful information about the deteriorated qualities of frozen rice food.


International Journal for Organ Transplantation Medicine (IJOTM) has been incorporated in the respected Elsevier databases, Scopus and EMBASE/Excerpta Medica. The editorial staff of the IJOTM acknowledges this highly esteemed recognition to the sincere support of the Avicenna Transplantation Center and the continuous encouragement of Shiras University of Medical Sciences.It was a great pleasure to realize that the The Journal is the official publication of the Iranian Society of Organ Transplantation and also the Transplantation Division of the Avicenna Medical Institutions which boasts a brilliant record in patient throughput on international scale as well as a remarkable pace of growth in scientific advancement over the past decade.Thanks to the steady efforts of a large dedicated team of physicians and scientists, the center has recently launched on expansion of its infrastructure as well as the diversity of organs transplanted. It is anticipated that the organization will stand out as one of the leading centers of transplantation medicine in the near future.Shiraz, the city which harbors the Avicenna Institutes, enjoys an outstanding reputation as a medical center throughout the Persian history. Following the downfall of the renowned Medical Academy of Jundishapur, which was the first teaching center of medicine in the world, many of its erudites settled in nearby Shiraz to proceed with the advancement of science and medicine and thus create centers of their own. This led to the emergence of numerous scholars and polymaths who have influenced the development of medicine in the world. It is the aspiration of Avicenna Medical Institutions to be capable of reviving the past scientific glory of the country and pass its heritage of excellence on to the future generations.


Adipocyte fatty acid binding protein (A-FABP) is a novel fat-derived circulating protein, which is independently and positively associated with atherosclerosis. The present study evaluated the relationship between fasting serum A-FABP and central arterial stiffness in geriatric adults.Fasting blood samples were obtained from 87 geriatric patients and the serum A-FABP levels were measured using an enzyme immunoassay. Carotid-femoral pulse wave velocity (cfPWV) was determined using the SphygmoCor system. cfPWV values of >10 m/s represented the high arterial stiffness group, while values ≤10 m/s defined the low arterial stiffness group.P = 0.044) and hypertension (P = 0.043). Body weight (P = 0.027), waist circumference (P = 0.035), body mass index (P = 0.001), systolic blood pressure (P = 0.005), diastolic blood pressure (P = 0.045), pulse pressure (P = 0.038), and serum A-FABP level (P < 0.001) were also higher in the high arterial stiffness group than in the low arterial stiffness group. Multivariate logistic regression analysis of the factors significantly associated with arterial stiffness revealed that A-FABP  was an independent predictor of arterial stiffness in geriatric adults.High arterial stiffness group comprised of 42 geriatric adults (48.3 %). When compared to those in the low arterial stiffness group, the high arterial stiffness group had a higher rate of diabetes mellitus (Serum A-FABP levels constitute a major risk factor in the development of central arterial stiffness in the geriatric population. Vessel stiffness is one of the multiple characteristics of cardiovascular (CV) disease, including abnormalities like, the thickening of the vessel wall, formation of fatty streaks, atherosclerotic plaques, and coronary artery calcification . ArteriaAberrant production of the adipokines, due to adiposopathy (fat dysfunction), is an important risk factor for the development of obesity-related CV diseases. Adipocyte fatty acid binding protein (A-FABP), a polypeptide with 132 amino acids and a molecular mass of 14.6 kDa, is one of the most abundant proteins in mature adipocytes, accounting for about 6 % of their total cellular protein content . A-FABP Previously, we had reported that A-FABP was associated with metabolic syndrome in patients with coronary artery disease and in hemodialysis patients , 10. In Eighty seven elderly volunteers, aged 65 years or older, were enrolled into this study between January and December 2012, at a medical center in Hualien, eastern Taiwan. Trained staff measured blood pressure (BP) in the morning for all participants, using standard mercury sphygmomanometers with appropriate cuff sizes, after the participants had been sitting for at least 10 min. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken at points of appearance and disappearance of the Korotkoff sounds, respectively. SBP and DBP were taken three times at 5-min intervals and were averaged for analysis. Pulse pressure was calculated by subtracting DBP from SBP. In the prevalence survey, hypertension (HTN) was defined as SBP ≥140 mmHg, and/or DBP ≥90 mmHg, or prescription of antihypertensive medication in the past 2 weeks. A person was regarded as having diabetes mellitus (DM), if the fasting plasma glucose was either 126 mg/dL or more, or if he/she was using diabetes medication  ), and HTN (n = 42 [48.3 %]). The medications prescribed to the geriatric adults included angiotensin-converting enzyme inhibitors , angiotensin receptor blockers , β-blockers (n = 24 [27.6 %]), calcium channel blockers , statins (n = 28 [32.2 %]), and fibrate (n = 10 [11.5 %]). Forty-two geriatric adults (48.3 %) belonged to the high arterial stiffness group, and when compared to the geriatric adults in the low arterial stiffness group, they had a higher incidence of DM  or HTN . There was no statistically significant difference between the high and low arterial stiffness groups, based on, gender, ACEi, ARB, β-blocker, CCB, statins, or fibrate use.Demographic, biochemical, and clinical characteristics of the 87 geriatric adults are shown in Tables P = 0.027), waist circumference , BMI , SBP , DBP , pulse pressure  were higher in the high arterial stiffness group, as compared to the low arterial stiffness group. Moreover, serum A-FABP was also elevated in the high arterial stiffness group than in the low arterial stiffness group  was an independent predictor of arterial stiffness in geriatric adults  revealed that A-FABP : 1.123–2.993, ts Table .Table 4CThe current results reveal that the fasting A-FABP levels were higher in the high arterial stiffness group than in the low arterial stiffness group, and A-FABP is an independent predictor for the development of arterial stiffness in the geriatric population.A systematic review had shown that BP was independently associated with PWV in approximately 90 % of the studies . CeceljaStudies had shown that there is a crosstalk between CV diseases and adipokines, such as, adiponectin, leptin, and A-FABP –23. MakoClinical reports reveal a significant correlation of baseline serum A-FABP with BMI, homeostasis model of insulin resistance, and cardio-ankle vascular index, which is a marker of arterial stiffness , 26. In Classic CV risk factors, including DM, hyperlipidemia, elevated BMI and smoking, had been implicated in accelerating arterial stiffness. However, Cecelja et al. have indicated that the prognostic value of cfPWV may be related to a process of arterial ageing, and probably unrelated to the classic risk factors, other than HTN . AdditioSeveral types of medications had been demonstrated to affect arterial stiffness. Studies of β-blockers on arterial stiffness showed less impact on central BP decline compared with the peripheral BP , 30. OldThe major limitation of this study is that, this was a cross-sectional study with a limited number of geriatric adults. Therefore, the findings of this study must be confirmed by long-term prospective studies before a causal relationship between the serum A-FABP and arterial stiffness can be established in the geriatric patient population. However, to the best of our knowledge, this is the first study to examine the relationship between serum A-FABP and arterial stiffness in the geriatric population.In conclusion, we found that serum A-FABP levels were higher in geriatric population having high arterial stiffness. More importantly, A-FABP may serve as an independent predictor for the development of arterial stiffness in geriatric adults. Whether serum A-FABP directly contributes to the development of arterial stiffness or not, needs to be further validated in larger cohorts.


Journal clubs provide an informal way of discussing research and how it applies to practice. We established a journal club within the Edinburgh Clinical Trials Unit to stimulate discussion of research around trial conduct and methodology and how research applied to staff within the unit. Our aims were to:• Support professional development• Keep up-to-date with the literature around clinical trial methodology• Disseminate information on and build up debate about good practice• Ensure that professional practice is evidence-based• Learn and practice critical appraisal skills• Develop ideas for research, descriptions of good practice within the unit that could be presented at meetings and/or submitted for publication• Provide an enjoyable educational and social occasionThe journal club is led by two trial managers and all staff are invited. Meetings are held monthly with a mix of discussions on published papers and presentations from the team.We conducted an online survey to get feedback on our first year, and received 21 responses (18 completed and 3 not completed). The feedback was positive and there was general agreement that we had achieved our aims, in particular that journal club was an enjoyable educational and social occasion (100%) and helped disseminate information on and build up debate about good practice (94%).In summary, journal club has been a positive initiative and has led to more discussion within the group on published research and how this applies to our practice.


To explore patients’ concepts of stiffness in polymyalgia rheumatica (PMR), and how they think stiffness should be measured.Eight focus groups were held at three centres involving 50 patients with current/previous PMR. Each group had at least one facilitator and one rapporteur making field notes. An interview schedule was used to stimulate discussion. Interviews were recorded, transcribed and analysed using an inductive thematic approach.Major themes identified were: symptoms: pain, stiffness and fatigue; functional impact; impact on daily schedule; and approaches to measurement. The common subtheme for the experience of stiffness was “difficulty in moving”, and usually considered as distinct from the experience of pain, albeit with a variable overlap. Some participants felt stiffness was the “overwhelming” symptom, in that it prevented them carrying out “fundamental activities” and “generally living life”. Diurnal variation in stiffness was generally described in relation to the daily schedule but was not the same as stiffness severity. Some participants suggested measuring stiffness using a numeric rating scale or a Likert scale, while others felt that it was more relevant and straightforward to measure difficulty in performing everyday activities rather than about stiffness itself.A conceptual model of stiffness in PMR is presented where stiffness is an important part of the patient experience and impacts on their ability to live their lives. Stiffness is closely related to function and often regarded as interchangeable with pain. From the patients’ perspective, visual analogue scales measuring pain and stiffness were not the most useful method for reporting stiffness; participants preferred numerical rating scales, or assessments of function to reflect how stiffness impacts on their daily lives. Assessing function may be a pragmatic solution to difficulties in quantifying stiffness. Polymyalgia rheumatica (PMR) is an inflammatory musculoskeletal disease that affects older people. Core clinical features for the diagnosis of PMR include bilateral shoulder and/or hip pain, morning stiffness, and abnormal inflammatory markers such as the erythrocyte sedimentation rate . “MorninCurrent clinical guidelines recommend that patients treated for PMR should be monitored on the basis of symptoms , since conventional inflammatory markers can be misleading in PMR . Factor In preliminary informal discussions with groups of patients with PMR ,7, patieFocus group methodology allows discussion between participants  and the Ethical approval was received from NRES Committee London-City and East ; and governance approval was received from hospital research and development committees at Ashford and St Peter’s Hospital NHS Trust, Leeds Teaching Hospitals NHS Trust, and University Hospitals Bristol NHS Trust. Patients with a rheumatologist-confirmed diagnosis of PMR who were receiving treatment either currently or within the previous three years were invited to participate in focus groups. Prior to data collection all participants were provided with an information sheet and written informed consent was provided in advance, in line with the Declaration of Helsinki.At all stages of the project, from planning the protocol to analysis and writing the results, advice and input was received from co-authors MN and JD, patient research partners with personal experience of PMR in accordance with the European League Against Rheumatism (EULAR) recommendations for patient research involvement .Participants  were purposively selected from secondary care (rheumatology) clinics at three geographically distinct UK NHS trusts aiming for diversity of age, gender and disease duration. .Each focus group had one facilitator managing the contributions of each group member, and one rapporteur who made field notes to aid transcription accuracy. A common interview schedule was used . The schIf your PMR was an animal what would it be?’ This question has been used in previous research to help patients describe their inflammatory arthritis and how this impacted upon them I never had anything like it, nothing like. I’ve never had anything like it ever.” [B/1/M/265-6]“Stiffness was defined as a restriction of movement, and was a different experience from pain, even if sometimes both were experienced together. Participants kept returning to the idea that it was easiest to describe stiffness in terms of what it stopped them doing, which included many everyday or “fundamental” activities.Er I had a very sore shoulder, and that was pain there. But then one morning I woke up and I can only say I felt I was in a coffin, in that restricted place, absolutely solidly stiff.”[L/2/F/609-11]“Yeah well about hard to define it, it’s hard to get up out of a chair, I know that.” [B/1/M/1849-50]“loss of control), or their body moving through a viscous substance or being weighed down by something very heavy (which could in itself be painful). These quotes illustrate the close relationship of the idea of stiffness to the idea of movement.Asked to elaborate further, participants explained stiffness using mechanical ideas: for example, a machine that was not working  and was seen as more than simply an effect of insufficient sleep; it was described as a significant symptom of PMR with its own diurnal rhythm:Fatigue, often called “tiredness”, seemed to be pervasive .With stiffness present, everyday activities became “For many participants, pain did not stop them doing their valued activities but stiffness did.And it—it was really the impediment of movement that I was er suffering, rather than pain in itself. In other words, I do get quite a lot of—of pain er with it. But the pain doesn’t actually stop me doing things. The stiffness does, it’s a much greater impediment, I think, to um er—to generally living life.” [L/1/M/177-181]“Sorry—on the days that I can’t get up the stairs say easily, I’m not sure whether I’m stiff or I’m in pain, to be honest. Because I go up on all fours, that’s the only way I can get up there.” [SPH/1/F/579-82].“the small hours” of the morning or on waking, although for some participants, pain predominated at night and stiffness during the day.PMR symptoms had a 24-hour cycle of severity; usually all symptoms were worst in “think nights were pain, really painful … And through the day was more stiffness.” [B/1/F/1586-90]“I You dread the morning to come. You don’t want to wake up” [B/1/F/143]“The diurnal variation in symptoms was dramatic, and prompted several participants to reorganise their activities to the afternoon.“Now I can guarantee that in a morning I can hardly get up, but by 2 o’clock it’s gone.” [L/3/F/44-45]“1 to 5” or “1 to 10”) and some preferred words ; no patient suggested visual analogue scales, a common patient outcome measure. However, rating scales were generally felt to need more context than simply a grading of the symptoms, for example assessment of the ability to perform everyday activities.When asked what and how they would measure stiffness and pain, some participants suggested a numerical rating scale “After prompting from the facilitator, some agreed that duration of morning stiffness was an aspect that could be measured, since this related to the diurnal variation in symptom severity. However this was reflected back more in terms of function rather than using the word stiffness itself.You know, you know, er it’s just—there’s no um—but I think the sort of morning one would be quite a good one for me, how long it takes you to get—get going really.” [L/1/F/1230-3]“However, duration of morning stiffness was rarely volunteered spontaneously as a suggestion for how stiffness might be measured, possibly due to stiffness being difficult to quantify due to daily variation.“Um I find that very difficult to quantify. Um because it’s not the same every day.” [L/1/M/1230-1]Another participant suggested measuring the change in severity of stiffness over the day, rather than duration of stiffness itself:“I would measure it, in my mind, I would measure it from 1–10, how you feel when you get up in the morning, and grade it in numbers, as 10 being the worst, and grade it down to 1, throughout the day, so you know where you are on a level. Because during the day you do feel differently.” [SPH/1/F/274-9]but very much reduced”, suggesting that it would be valid to measure them in the same way before and after treatment. “What about measuring it every time you go down a notch on your steroids? So then you measure for a week.” [SPH/1/F/1892-3]Participants reported that the symptoms in treated PMR were the same as in untreated PMR “Four major points emerge from these results. First, patients’ experience of stiffness in PMR can be characterised under eight themes. These fall under overarching headings of bodily symptoms, impact on function, impact on daily schedule and measuring stiffness. Second, many patients found it difficult to distinguish between pain and stiffness, and often used the words interchangeably. Others were able to distinguish them and reported that they had different consequences. Third, the measurement of the impact of stiffness might be best undertaken by the assessment of function. Fourth, the consequences of the symptoms of PMR permeated everything to do with patients’ daily routine. A further observation is that it may prove difficult to discover the attribution of symptoms which may persist or recur after successful treatment with glucocorticoids.This aim of this study was to explore the patient’s concept of “stiffness” in PMR to ensure that it is measured in a way that is relevant to this. The relationship between stiffness and pain appeared more complex than we had anticipated; furthermore many patients reported fatigue as a significant problem in PMR. Stiffness was defined as inability to move; this loss of control of the body had a devastating impact on ability to perform everyday activities, and participants felt that assessing changes in functional ability would be a valid, though indirect, way to assess changes in stiffness itself.Participants told us that pain/ache responded well to medication, particularly glucocorticoids, but stiffness responded more variably, and fatigue even less well. Indeed, in most previous studies, not all patients with PMR have a complete response to glucocorticoids , 17–18. Assessment of stiffness does not appear to be straightforward. Rating scales for stiffness itself were suggested by some, but were felt to lack context. Some patients found the difference between pain and stiffness difficult to characterise, but nevertheless it appears important to measure the symptom of stiffness specifically. There was significant diurnal variation in symptom severity, but the worst time of day was not the same for everybody. The most straightforward way to assess the impact of stiffness was felt to be by assessing ability to do everyday activities. In previous studies the Stanford Health Assessment Questionnaire, or the shorter Modified Health Assessment Questionnaire, have been used; function correlates with other measures of disease activity in PMR and is responsive to change , 21. OneMorning stiffness duration was felt to be a separate matter to stiffness severity, but duration of morning stiffness was reported to vary from day to day; this raises the question of whether the observed poor test-retest reliability of morning stiffness duration  may be dLimitations of this study include the restriction to the UK and those with English as a first language. We did not require fulfilment of classification criteria for PMR, but all patients had to be diagnosed by a rheumatologist. We did not take a quantitative approach, and as for any qualitative study, generalizability outside this setting remains to be established. However, this study sampled for a range of age, disease durations and disability; and recruited from three different hospitals in the UK, thereby accessing a range of disease experiences and care pathways. At two of the centres the focus groups were co-facilitated by rheumatologists . The clinicians’ own experience and understanding of PMR would inevitably have influenced the research process, but some clinical input was deemed important for an understanding of the clinical trial context to which these findings would be ultimately applied. At these two centres focus groups were co-facilitated by a non-clinical researcher (MW), and critical self-reflection of facilitators’ prior knowledge, background and assumptions was encouraged. At the third centre, the focus groups were facilitated entirely by rheumatology nurse researchers trained in qualitative methods. Facilitators were all aware of the importance of focus group methodology whereby the inquiry should come to surround the participants’ agenda and a breadth of opinion is achieved . AnalysiBasing the study around a genuine problem (How do we measure stiffness in PMR?) helped to focus the research question, and we used theoretical concepts in outcomes research to develop our conceptual model. This conceptual model, based on the eight themes identified during the analysis, will inform the future development of a core outcome set in PMR.


Laurentiu M. Popescu, a world renowned expert in the field of molecular medicine, Professor of Cellular and Molecular Medicine at Carol Davila University of Medicine and Pharmacy, Bucharest (Romania) and General Director of the National Institute of Pathology of Romania, passed away on August 3, 2015, at the age of 71.Born on April 15, 1944, in Campulung, Romania, he devoted 48 years to research and teaching activities starting soon after graduation  of ‘Carol Davila’ University of Medicine and Pharmacy. Backed by a constant progression in his academic career he became the Rector, between 1992 and 2004, of the ‘Carol Davila’ University , considered an example of progress and innovation in the 150 years of history of the University.Professor Laurentiu Popescu was a very special and extraordinary scientist who gave a unique point of view to the international scientific community of medical and cellular sciences. He was awarded for his scientific achievements multiple prestigious prizes and was selected as member of many international scientific organizations. He was also the President of the Medical Science Section of the Romanian Academy of Sciences, President of the Romanian Academy of Medical Sciences, President of the Federation of the European Academies of Medicine, President of the International Society for Adaptive Medicine, and more.In 2000 he founded the Journal of Cellular and Molecular Medicine. As Editor-in-Chief, he grew this journal very rapidly, transforming it, from a non-indexed journal into a world-class scientific journal (2014 Impact Factor 4.014).While his academic career was pivoted around ‘Carol Davila’ University of Medicine and Pharmacy, a great part of the scientific achievements were centered on ‘Victor Babes’ National Institute of Pathology. Known as a visionary, he had a strong ability to inspire the people who worked with him. We will remember him for a myriad of virtues as wisdom, confidence, empathy and honesty, as well as outstanding motivation and communication skills. For us he has been a wonderful mentor, being extremely creative, and a really hard working person, endowed with great organizational skills. He was also a scientific advisor for numerous PhD and postdoctoral students sharing his outstanding experience and knowledge with all his disciples. Besides his impressive scientific knowledge he was also widely cultured, recognizing in one of his interviews “The idea to call the newly discovered cells telocytes came to me during a break at the Vienna State Opera”.Professor Laurentiu M. Popescu’s vast scientific activity could be approximatively split in two main periods. The major scientific results of the first period were crystallized around the ideas of caveolae involvement in calcium regulation in smooth muscle, or around the relation between cGMP and vasodilation. The most fruitful and the most impressive one is the later part of Professor Laurentiu M. Popescu’s scientific activity dedicated to the discovery of a new type of interstitial cell in living organisms—Telocytes —and development of this top research field. This marvelous ‘scientific adventure’ started in 2005 as a typical case of serendipity when looking in pancreas interstitium for Interstitial Cells of Cajal, Professor Laurentiu M. Popescu attested and described the presence of a new type of interstitial cell, totally distinct from that one which intended to look for—Telocytes. Progressively, subsequent research conducted either by Professor Popescu’s group, or by other individual groups worldwide, documented the presence of telocytes within interstitium of many human and mammals cavitary and non-cavitary organs. He was an author of more than 300 scientific papers which have been published in international journals.In 2009, his accomplishments were acknowledged with the highest honors by the government of Romania—The National Order “Star of Romania”.The sudden disappearance of such a great personality creates a void in our hearts, and also strengthens the desire to continue the encouraging research developed together with him. As close co-workers, we will miss Professor Laurentiu M. Popescu’s great ideas and the capacity to assemble and organize a team and for bringing concepts to life. The keen productive working atmosphere surrounding him, was abundant of creativity and trust. He gave us values and rules and those were the pillars to construct that space of work and progress. The quintessence of his personality resides in the spirit of integrity, inherited by the team he exemplary lead. His tireless and motivational activity projected in perspective, thus permanently creating new aims for research.Once the existence of Telocytes was attested, the saga of looking for their roles started, naturally. It appears that Telocytes are involved in tissue regeneration. If this will be confirmed, it could have a tremendous potential in cellular regeneration therapies. Perhaps this pursuit of telocytes roles will change the way we think physiology and/or pathology.Instead of epilogue …Francois Rabelais’ last words “I am heading to find-out the Biggest Perhaps” are best describing our Professor’s state of mind and his last majestic lesson for us.


Despite major advances in the treatment of hematological diseases over the last decades, allogeneic hematopoietic stem cell transplantation  still remains the only curative option for many of them. According to the recent survey of the European Society of Blood and Marrow Transplantation (EBMT), nearly 15 000 alloHSCT are currently performed each year across Europe and EBMT-affiliated countries (Approximately 50% of these patients will develop a major late complication – chronic graft-vs-host disease (cGVHD), a multi-organ allo- and auto-immune disorder affecting the skin, lungs, mouth, liver, eyes, joints, and gastrointestinal and genital tracts -4. As a Chronic GVHD can last for many years causing severe medical, social, and quality of life problems, as well as significantly impacting health-related costs and health care management. A recently published report from the Center for International Blood and Marrow Transplant Research has identified a clear increase in the incidence of cGVHD from 1995 to 2007 due to the more frequent use of peripheral blood graft instead of bone marrow, unrelated donors, and older recipients  Consensus classification was developed in 2005 and prospectively validated ,6-10. HoThe German-Austrian-Swiss cGVHD consortium assessed the usefulness of the NIH criteria in routine clinical practice and reported high rates of acceptance for definitions of cGVHD, as well as overall and organ-specific NIH cGVHD severity scoring among the vast majority of participants . An inteTherefore, there has been significant research activity and renewed interest in cGVHD in the world over the last decade. It is likely that the current better characterization of cGVHD, standardization of research tools, and numerous new treatment opportunities will lead to improved clinical outcomes, such as clinical symptoms, function status, quality of life, morbidity, and survival.However, not a single agent has yet been approved for cGVHD prevention or treatment, neither by the US Food and Drug Administration (FDA) nor by the European Medicines Agency (EMA). The current standard front-line steroid therapy has a 50% failure rate with significant toxicity, and there are no standards for second-line (and beyond) therapeutic options.Croatian Medical Journal presents several excellent articles that are a product of these enhanced international collaborations and efforts by teams across Europe to address cGVHD.The focus now in this field is on further in-depth study of the biology of cGVHD, developing and validating new biomarkers, and pursuing clinical trials of new agents that would eventually develop pathways to their FDA and EMA regulatory approvals. The aim is to develop more effective, less toxic, and more targeted treatments that will not interfere with the beneficial graft-vs-tumor effects. To advance this field and break the 30-year-old suboptimal treatment paradigms, the goal is that each cGVHD patient should be either treated in a clinical trial or at least should be documented within a registry capturing essential clinical data on the course of cGVHD. The tools and opportunities to harness cGVHD and create better and safer alloHSCT are in our hands right now. This issue of the Acknowledgment This work is supported by the Unity Through Knowledge Fund project entitled “Clinical and Biological Factors Determining Severity and Activity of Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.” The opinions expressed here are those of the authors and do not represent the official position of the National Institutes of Health or the US Government.


People often take either the role of an actor or that of recipient in positive and negative interpersonal events when they interact with others. The present study investigated how the actor-recipient role affected the neural responses to self in emotional situations. Twenty-five participants were scanned while they were presented with positive and negative interpersonal events and were asked to rate the degree to which the actor/the recipient was that kind of person who caused the interpersonal event. Half of the trials were self-relevant events and the other half were other-relevant events. Results showed that people were more likely to isolate self from negative events when they played the role of actor relative to recipient. Pregenual anterior cingulate cortex (pgACC) and posterior dorsal anterior cingulate cortex (pdACC) were more active for self than other only in negative events. More importantly, also in negative interpersonal events, dorsal medial prefrontal cortex (dmPFC) showed greater self-related activations (self-other) when participants played the role of recipient relative to actor, while activities in orbitofrontal cortex (OFC) were greater for self than other only when the evaluation target played the role of recipient. These results showed that the actor-recipient role affected neural responses to self in emotional situations, especially when a recipient role was played in negative situations. In the other half of the trials, other-relevant events were presented  and “other” was the evaluation target. We predicted greater self-serving evaluations for actor than for recipient and this effect was stronger for negative relative to positive information based on the abundant evidence for negativity bias . The twenty-five participants included in the data analysis consisted of 5 undergraduate students  and 20 graduate students . None of the participants reported a significant abnormal neurological history. All the participants gave informed consent before scanning and were paid RMB50 for their participation. This study was approved by the Ethical Committee of East China Normal University.Twenty-nine right-handed volunteers from the university community with normal or corrected-to-normal vision participated in this experiment. Four participants had to be excluded due to excessive head movements, leaving 25 subjects for analyses  but equated for arousal, familiarity and frequency.Verbs with mean valence ratings of larger than 6 (positively) and smaller than 3 (negatively) based on 9-point pleasant-unpleasant ratings were selected from Chinese Affective Words System  and Role (Actor vs. Recipient). An example of a verb with positive valence  is given below with four respective sentences and their judgment questions.For self-relevant events, “self” was randomly assigned as the actor  or recipient  and self was the target of evaluation. For other-relevant events, both the actor  and the recipient  would become the targets of evaluation separately. Similarly, the negatively valenced verbs were also used to construct four different types of conditions.Participants were asked to complete 160 trials in the scanner with 20 trials in each condition. In each trial, participants were presented with a one-sentence interpersonal event, a question and a 4-point scale . For functional images, 35 slices were acquired using a gradient-echo echo-planar imaging (EPI) sequence . Before the functional run, a high-resolution structural image was acquired using a T1-weighted, multiplanar reconstruction (MPR) sequence .3 voxels), and spatial smoothing . A high-pass filter with a cutoff period of 128 s was applied.Data preprocessing and statistical analyses were performed with Statistical Parametric Mapping . Preprocessing included discarding the first five functional images to allow for scanner equilibrium effects, rigid-body motion correction, spatial normalization into the MNI space , Role (Actor vs. Recipient) and Valence (Positive vs. Negative). They were modeled using a canonical hemodynamic response function with a temporal derivative. We have chosen the onset of the stimulus as the onset time point and the RT from the stimulus onset to button press as the duration (epoch with variable time length). Six regressors modeling movement-related variance and one modeling the overall mean were also employed in the design matrix. A general linear model analysis created 8 contrast images for each participant summarizing differences of interest. The eight first-level contrast images from each participant were then analyzed at the second level employing a random-effects model .F-contrast to analyze the Target × Valence interaction effect across roles. Then, in order to examine the effect of the actor-recipient role on self-processing in emotional situations, F-contrast was further used to examine the Target × Valence × Role interaction. Areas of activation were identified as significant only if they passed the threshold of p < 0.05 family-wise error (FWE) corrected for multiple comparisons at the cluster level with an underlying voxel level of p < 0.0001 uncorrected, unless otherwise indicated. Marsbar toolbox  = 31.79, p < 0.001)  = 103.01, p < 0.001). Paired-sample t test revealed that participants’ attribution ratings of self were significantly higher than those of other in positive events (t(24) = 2.68, p = 0.01), and participants’ attribution ratings were significant lower to self than other in negative events (t(24) = 9.68, p < 0.001). When the evaluation target played the role of recipient, repeated measures ANOVA revealed that the interaction between target and valence was also significant  = 42.84, p < 0.001). Paired-sample t test revealed that participants’ attribution ratings were significantly lower to self than other in negative events (t(24) = 7.68, p < 0.001), whereas there was no significant difference between self and other in positive events (t(24) = 0.83, p = 0.42).A 2(Target: Self vs. Other) × 2 × 2(Role: Actor vs. Recipient) repeated measures ANOVA revealed that participants’ attribution ratings were characterized by a significant Target × Valence × Role interaction  when participants played the role of actor relative to recipient in positive (t(24) = 3.06, p = 0.005) and negative (t(24) = 4.85, p < 0.001) interpersonal events. These results indicated that participants were more likely to endorse positive events to self and isolate self from negative events, and this attribution bias was greater when participants played the role of actor relative to recipient.Moreover, paired-sample F = 26.93, p < 0.001), Valence  = 10.05, p = 0.004) and Role  = 36.11, p < 0.001)  were made significantly faster than those in the other condition . Judgments in the positive condition  were made significantly faster than those in the negative condition . Judgments in the actor condition  were also made significantly faster than those in the recipient condition .Repeated measures ANOVA revealed that participants’ RT was characterized by main effects of Target  × Valence (Positive vs. Negative) interaction across roles revealed significant activations in pregenual ACC (pgACC)  and posterior dACC (pdACC)   Figure . Additiot test revealed similar pattern of activations in pgACC and pdACC, that is, in both the actor and recipient conditions, the activities in these two regions were greater for self than other only in negative events (actor: t(24) = 3.41, p = 0.002, and recipient: t(24) = 4.95, p < 0.001 for pgACC; actor: t(24) = 2.47, p = 0.02, and recipient: t(24) = 5.16, p < 0.001 for pdACC) but not in positive events (actor: t(24) = 1.04, p = 0.31, and recipient: t(24) = 1.76, p = 0.10 for pgACC; actor: t(24) = 0.36, p = 0.72, and recipient: t(24) = 1.23, p = 0.23 for pdACC).Parameter estimates across pgACC and pdACC were extracted. Paired-sample F-contrast of Target × Valence × Role interaction revealed significant activations in dmPFC  and OFC   = 3.74, p = 0.001; negative: t(24) = 2.08, p = 0.05) and recipient conditions (positive: t(24) = 3.57, p = 0.002; negative: t(24) = 6.93, p < 0.001). Interestingly, paired-sample t-test revealed greater self-related dmPFC activations (self-other) for the recipient relative to actor in negative interpersonal events (t(24) = 4.61, p < 0.001) but not in positive events (t(24) = 1.77, p = 0.09). The dmPFC has been argued to be associated with self-evaluation processes . A significant cluster of activation was detected in dmPFC , indicating greater self-related dmPFC activations were associated with longer RT for self relative to other for the recipient in negative events. We then overlapped activations from correlation analyses with activations from the F-contrast of Target × Valence × Role interaction. Clusters in dmPFC overlapped  = 1.89, p = 0.07) and recipient (t(24) = 1.38, p = 0.18) conditions. In negative events, the brain activity in OFC was greater for self than other only in the recipient condition (t(24) = 5.98, p < 0.001) but not in the actor condition (t(24) = 0.65, p = 0.52). Moreover, paired-sample t test revealed that OFC showed greater self-related activations when participants played the role of recipient relative to actor in negative interpersonal events (t(24) = 3.69, p = 0.001) but not in positive events (t(24) = 0.84, p = 0.41).Paired-sample The present study explored the impact of the actor-recipient role on neural responses to self in emotional situations. Results of attribution ratings revealed that people tended to endorse positive events as self-relevant only when they performed the role of actor, whereas they were more likely to isolate self from negative events when they played the role of actor relative to recipient, indicating greater self-serving evaluations when actor role was played in negative situations. Activities in pgACC and pdACC were greater for self than other only when the interpersonal events were negative. Moreover, activities in dmPFC were greater for self than other when the actor or recipient role was played in both positive and negative events, whereas activities in OFC were greater while responding to self than to other only when the evaluation target played the role of recipient in negative interpersonal events. Importantly, OFC and dmPFC showed greater self-related activations when participants played the role of recipient relative to actor in negative interpersonal events. These results showed that the actor-recipient role affected neural responses to self in emotional situations, especially when a recipient role was played in negative situations.Previous research had claimed that people had the tendency to make claims that cast the self in a favorable light (Sedikides et al., It has been suggested that the dmPFC is engaged in self-evaluation and self-related reappraisal (Northoff and Bermpohl, The current study also showed that activities in OFC were greater while responding to self than to other only when the evaluation target played the role of recipient in negative interpersonal events. That is, OFC was modulated by the actor-recipient role in negative interpersonal events. Previous studies had shown that OFC was associated with accurate self-view (Beer et al., Previous studies had revealed the engagement of mTG in attribution decisions (Blackwood et al., In conclusion, the current study further illustrated neural models of social cognition by examining the impact of the actor-recipient role on self-processing in emotional situations. The pgACC, pdACC, OFC, and dmPFC were involved in emotional self-processing. Self-related pgACC and pdACC activations in negative events indicated its association with monitoring conflict in negative self-related processing. More importantly, dmPFC and OFC were modulated differently by the actor-recipient role in emotional self-processing, with dmPFC associated with self-evaluation processes and OFC engaged in accurate self-view. Taken together, these results demonstrated that the actor-recipient role affected neural responses to self in emotional situations.All authors were involved in the design and implementation of the study and the writing of the manuscript. Authors Xiaoyan Wang, Li Zheng, Xuemei Cheng, Lin Li and Xiuyan Guo devised the concept and supervised the study. Authors Xuemei Cheng and Qianfeng Wang collected the imaging data. Authors Xiaoyan Wang, Li Zheng carried out the analysis. Authors Li Zheng, Xuemei Cheng, Lin Li and Xiuyan Guo joined in the interpretation of data. Authors Lining Sun joined in the writing of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


That Journal of Neonatal Surgery (JNS) has completed its three years of existence is a source of the highest gratification to its founding patrons and editors; is a matter of unbiased congratulation to all those concerned in its inception, interested in its progress, or imbued with a sense of the purposes for which it was established. That it has succeeded beyond the most sanguine expectations of its promoters, no one can gainsay; that it has accomplished the objects that it had in view, i.e., the upholding of publication ethics, the advancement of professional knowledge, and the promotion of good fellowship and good feeling between the members of the fraternity across the borders, no one can controvert; that it will succeed and overcome triumphant all opposing force; that its compulsive course, without retiring ebb, will keep due on the issues published over the past three years most abundantly testify.We shall continue the same general plan of bringing out the journal issue quarterly, but shall deviate somewhat in detail, as we plan to instantly add on the journal website the accepted manuscripts under the section “Ahead of Publication” without assigning pagination in a sense to disperse latest advances in the specialty without even a minute delay. The coming year 2015 looks promising as we see the light at the end of the tunnel as to the much-awaited indexation with PubMed Central. We look forward to get every manuscript archived on PubMed Central that we have published since the inception of JNS.Source of Support: NilConflict of Interest: None


To the Editor: Mayaro virus (MAYV), a mosquitoborne alphavirus endemic to South America, causes a self-limiting febrile arthralgia syndrome closely resembling Chikungunya fever . Two of the cases occurred during 2014; 4 occurred during 2011–2013 (The 6 travelers comprised 2 men and 4 women who were 20–54 (median 36) years of age  Table. TThe student had traveled for 3 weeks in Ecuador, visiting rainforest villages and hiking in the jungle. During her stay, she had experienced myalgia of the forearms, arthralgia of fingers and toes, subfebrile but elevated body temperatures, and maculopapular exanthema. On examination in Germany, the student had no clinical signs of disease, but she reported arthralgia of the ankles and hands. Laboratory test results showed a slightly increased C-reactive protein level ; liver and kidney values and blood count were within reference ranges. MAYV indirect immunofluorescence assay showed positive IgM and IgG titers   bilateral foot pain. Laboratory test results showed C-reactive protein levels, and liver and kidney function values, and full blood count within reference ranges. MAYV indirect immunofluorescence assay was negative for IgM but positive for IgG . Postacute MAYV infection was diagnosed. Two months later, follow-up serologic testing showed unchanged titers. Arthralgia with pronounced morning stiffness lasted for 6 months.<30 days after symptom onset, n = 3) or postacute . Twenty serum samples from healthy blood donors were run in parallel. During the acute phase of MF, interleukin (IL) 10, IL-12p70, RANTES , and vascular endothelial growth factor concentrations for patients were significantly elevated compared with those for healthy controls . Blood was drawn at different times after symptom onset (15–117 days). Serum samples were classified as acute (controls . Furthercontrols . No signThe most striking clinical feature of MF is long-lasting arthralgia, similar to that seen in chikungunya fever, which develops in the acute phase and persists thereafter. In the travel-associated cases, arthralgia lasted for 2 to >12 months. In the examined patients, the prolonged arthralgia recovery phase was paralleled by significantly increased proinflammatory cytokine levels, indicating ongoing inflammation, probably related to arthritis. Elevated levels of RANTES and IP-10 suggest T-cell recruitment, possibly reflecting virus persistence and replication, as described for the related Chikungunya virus (International travelers who were recently diagnosed with Mayaro fever and were included in this study.


The following information is missing from the Funding section: David Harder was supported by a Clement J. Zablocki VA Medical Center Career Research Scientist Award.


Staphylococcus aureus. We present the first reported case of neonatal mastitis caused by Acinetobacter baumannii, an unusual organism for this type of infection.Neonatal mastitis is a rare infection. When it does occur, infants younger than 2 months of age are typically affected and the majority of cases are caused by S. aureus. Drainage culture identified pan-susceptible Acinetobacter baumannii/haemolyticus and antibiotic therapy was changed to ceftazidime. He was discharged after 5 days of ceftazidime with complete resolution of his symptoms.A 15-day-old full-term Caucasian male neonate presented to our emergency room following fever at home and was admitted for routine neonatal sepsis evaluation. After admission, he developed purulent drainage from his right nipple, was diagnosed with mastitis, and was started on empiric therapy with clindamycin and cefotaxime with presumed coverage for S. aureus causing infection. Acinetobacter baumannii is considered part of the normal human flora and is associated with serious infections in intensive care units. This is the first case report describing Acinetobacter baumannii as an etiologic agent of neonatal mastitis and highlights the importance of including unusual organisms in the differential for infectious etiologies for general practitioners.This case illustrates the importance of obtaining drainage cultures in mastitis cases because of the possibility of organisms besides  Staphylococcus aureus and, less commonly, group B Streptococcus, group A Streptococcus, Escherichia coli, Bacteroides species, Klebsiella pneumoniae, and Enterococcus[S. aureus (38%), methicillin-susceptible S. aureus (35%), coagulase-negative Staphylococcus (15%), group B Streptococcus (4%) and Enterobacter aerogenes (2%)[S. aureus, tailored for either methicillin-resistant or methicillin-sensitive strains based on the local community prevalence, should be initiated upon diagnosis of mastitis[Acinetobacter baumannii as an etiologic agent of mastitis.The most common etiologic agents of neonatal mastitis are erococcus,2. A rec. aureus 8%, methi. aureus 8%, methiA 15-day-old full-term Caucasian infant presented to our emergency room with fever , decreased urine output, decreased feeding, lethargy and irritability for 1 day. He was born vaginally at 41 weeks and 6 days with no complications. On physical examination, his rectal temperature was 37.6°C and he appeared well. His umbilical stump was not erythematous and had no purulent drainage. He had no rashes or vesicles. His laboratory examination in our emergency department demonstrated an elevated white blood cell count of 15,500, with 76% neutrophils and 13% lymphocytes on the differential. A urine analysis and chest X-ray were reassuring. Blood and urine cultures were obtained. A lumbar puncture was attempted twice, but was unsuccessful. He was admitted to our general pediatrics service on no antibiotics, but with the plan to obtain cerebrospinal fluid (CSF) with another lumbar puncture and initiate antibiotics if he became febrile.S. aureus, which is prevalent in the area.Within a few hours of admission, he developed right breast induration, erythema around his nipple (4cm diameter), and purulent drainage. The wound drainage was cultured. He was empirically treated with clindamycin and cefotaxime, with coverage for methicillin-resistant Acinetobacter baumannii/haemolyticus. His isolate was susceptible to all the antibiotics tested, including amikacin, cefepime, ceftazidime, ciprofloxacin, gentamicin, levofloxacin, meropenem and tobramycin.His right nipple continued to drain 2 to 3mL of purulent material over the next 24 hours. Because he remained afebrile, was otherwise healthy appearing, and had a source of infection to explain the presenting fever, no lumbar puncture was performed. His blood and urine cultures were negative after 5 days. The right breast drainage, erythema and induration improved significantly within 24 to 36 hours, and completely resolved by day 4 of admission. His right breast wound culture initially revealed Gram-negative rods on Gram stain, and ultimately grew Acinetobacter baumannii/haemolyticus infection. He tolerated this antibiotic regimen with no appreciated adverse effects and continued to breastfeed well during his admission. At discharge, he showed no clinical signs of mastitis, and was not prescribed any oral antibiotics.Our pediatric infectious diseases consultant recommended 5 days of treatment with intravenous ceftazidime for mastitis secondary to Acinetobacter species infections have been previously documented, so this finding was unexpected. A. baumannii is an aerobic, Gram-negative coccobacillus that is considered part of the normal human flora of the skin and mucous membranes of the pharynx, human respiratory secretions, urine and rectum[Acinetobacter species are the only Gram-negative bacteria that are considered part of the normal flora on human skin, and up to 42.5% of healthy individuals are colonized with Acinetobacter species[Acinetobacter species infection in this case of a previously healthy full-term neonate remains unknown, although possible sources include the local environment or contact through the patient’s father’s employment in a veterinary office.No cases of neonatal mastitis secondary to d rectum. Of inteAcinetobacter species are most commonly associated with opportunistic infections in war veterans, serious nosocomial infections in intensive care units, and increased resistance to multiple classes of antibiotics. In the pediatric population, most (89%) Acinetobacter outbreaks occur in neonatal intensive care units, and bacteremia and meningitis are the most common clinical presentations of infection[Acinetobacter infections from community settings can also occur, although mainly in warm humid climates[Acinetobacter species[nfection. Howeverclimates. In a ca species.Acinetobacter have been reported in only two case reports. One described an abscess in the antecubital fossa at the site of a previous intravenous cannula in a neonate born at 26 weeks who previously grew A. baumannii from endotracheal tube secretions. This infant appeared well during the initial presentation of the abscess; however, almost 1 week after abscess development, the neonate developed sepsis and blood cultures grew A. baumannii and Enterococcus. He recovered with antibiotic treatment with amoxicillin-clavulanate and gentamicin[Acinetobacter was also described in a 24-day-old female infant admitted for birth asphyxia at 2 days of life who subsequently developed an abscess at the site of intravenous scalp vein cannulation. Wound cultures from the abscess grew Acinetobacter calcoaceticus var. anitratus. This infant developed meningitis and CSF cultures grew the same organisms with the same susceptibilities. She recovered with antibiotic treatment with trimethoprim-sulfamethoxazole[Skin abscesses in pediatric patients due to ntamicin. A seconhoxazole.Our patient had negative blood and urine cultures, but we were initially unable to obtain CSF, so no CSF culture was performed. Whether all well-appearing infants with mastitis should receive a lumbar puncture as part of a complete sepsis evaluation is debatable,9,10. MuS. aureus and empiric antibiotic coverage should include this organism, less common infections also need to be considered. This case highlights the importance of obtaining cultures from breast abscesses because of the possibility of an uncommon infecting organism and provides a brief introduction to Acinetobacter species infections in the pediatric population.In conclusion, although most breast abscesses are caused by Written informed consent was obtained from the patient’s parent for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.CSF: Cerebrospinal fluid.The authors declare that they have no competing interests.EM, AB, JZ and PS participated in conception and design of this report and were involved in drafting and revising the manuscript. EM participated in final revisions of the manuscript. All authors read and approved the final manuscript.


The mission of AmSECT, since its charter, has remained the same, “… The Journal of ExtraCorporeal Technology has been one of the principle avenues used by AmSECT in pursuit of its mission through the publication and dissemination of scholarly work since 1967.A milestone for the Journal was when it became indexed in MEDLINE through PubMed and the Cumulative Index of Nursing and Allied Health Literature in 1990. Since then nearly 1,000 scholarly articles have been indexed and abstracted in the National Library of Medicine’s PubMed database.The Journal of ExtraCorporeal Technology became the Official Journal of the ANZCP. ANZCP members now receive electronic access to the journal, including all archived volumes going back to 1974. This partnership has fostered improved patient care and safety by expanding and disseminating the published knowledge related to extracorporeal technology.Over the last several years AmSECT has strived to form partnerships with other perfusion societies to more broadly disseminate new knowledge and to provide tangible benefits to their members. In 2013, the Australian and New Zealand College of Perfusion (ANZCP) partnered with AmSECT where by Three years ago, the Journal Editorial Board began deliberate discussion about what could be done to further share our content and it became clear that “open access” was a highly effective avenue to share more. According to Peter Suber, Director of the Harvard Office for Scholarly Communication, open access is compatible with copyright, peer review, revenue (even profit), print, preservation, prestige, quality, career advancement, indexing, and other features associated with conventional scholarly literature . FurtherThe Journal of ExtraCorporeal Technology’s content, beginning from December 2011, is now archived in PMC. Content published in The Journal of ExtraCorporeal Technology is now available free to the world six months after it is first published in the Journal.Opening access to the Journal’s content to the world was the right thing to do, and we determined that PubMed Central® (PMC) was the best vehicle to accomplish this objective. PMC is a free archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health’s National Library of Medicine. Participating journals continue to hold copyright of the content, but grant free distribution rights to digital copies of articles from PMC. providing for the continuing education and professional needs of the extracorporeal circulation technology community.”Congratulations to the Journal’s Editorial Board for their vision to pursue this avenue to further disseminate new knowledge, and to the AmSECT Board of Directors for approval of this important bold step, an important stride forward in the mission, “


Cardiac magnetic resonance elastography (CMRE) is a novel imaging technique to noninvasively quantify myocardial stiffness. Previous studies have demonstrated that excess interstitial fluid or fibrosis causes increased myocardial stiffness and also alter T1, T2 relaxation times, and myocardial extracellular volume fraction (ECV). Nonetheless, T1, T2 and ECV have not yet been correlated with either invasive or noninvasive measures of myocardial stiffness. The aim of our study was to demonstrate the feasibility of quantifying right ventricular free wall (RVFW) stiffness using CMRE and correlate it with intrinsic myocardial relaxation times and ECV in dogs with severe congenital pulmonary valve stenosis causing RV hypertrophy.In-vivo CMRE was performed on six dogs using a 1.5T scanner . A basal RV short-axis slice was acquired using GRE-MRE, T1-Molli and T2 prepared B-SSFP sequences. Wave images were processed using MRE Lab  to obtain end-systolic and end-diastolic stiffness maps. Regions of interest (ROIs) were drawn to determine RVFW effective stiffness, T1 and T2 values. Blood pool T1 values were obtained by placing ROIs in the center of the RV. Pre-contrast T1 values were corrected for varying heart rate. ECV was calculated using the formula: (ΔR1 myocardium/ΔR1 blood) × (1-hematocrit). Least squares linear regression was performed to determine the correlation between end-systolic and end-diastolic RVFW stiffness against ECV, T1 and T2 relaxation times.RVFW myocardial effective stiffness in all animals was higher at end-systole (5.9 to 13.5 kPa) compared to end-diastole (3.3 to 6.8 kPa). RVFW native T1, T2 and ECV values ranged from 811 to 883 ms, 36 to 53 ms and 15% to 34%, respectively. Positive correlations were found between effective stiffness versus T1 and ECV  in four dogs Figures . T2 relaThis study demonstrates the feasibility of measuring effective RVFW stiffness using CMRE in the setting of RV hypertrophy. The correlation between T1, ECV and RVFW stiffness, may potentially suggest interdependence between changes in extracellular matrix and the mechanical properties of the heart. The absence of correlation between effective stiffness and T2 can be attributed to an absence of acute myocardial injury with edema in this specific cohort of dogs presenting chronic pressure overload.Department of Radiology, The Ohio State University College of Medicine.