Gestational Weight Gain: Historical Evolution of a Contested Health Outcome.
The history of research on gestational weight gain (GWG) in the United States and United Kingdom provides a context for current clinical practice. We trace the evolution of research on GWG in scientific literature from the 19th century to the present and examine its implications for contemporary clinical and public health practice. Obstetricians, beginning in the late 1800s, recommended dieting during pregnancy in order to limit GWG to 20 lb or less, driven by a belief that excessive weight gain was a cause of toxemia. Beginning in the 1930s, a burgeoning focus on nutrition and health allowed a better understanding of the effect of GWG on the health of the fetus and the newborn. Increased awareness of disparities in infant mortality in the 1960s, followed by systematic review of the literature, produced further refinements in GWG recommendations in the 1970s, which continue today. Current research focuses on epigenetic influences over the life course and has emphasized individualized recommendations. The complex historical perspective that this article provides serves as a reminder of both the interplay and the gaps between research and practice. These gaps result from the fact that clinical guidelines often reflect a specific point in a perpetually evolving state of knowledge that is influenced not only by advances in bench research, but also by refinements in statistical and epidemiologic methods, as well as by the political realities of the time in which they are drafted. Gestational weight gain and its relationship to maternal, fetal, and infant health are areas of active inquiry. We critically review evolution of scientific understanding of GWG from the 19th century to the present, and examine its implications for contemporary obstetric practice. We reviewed all English-language medical studies related to GWG published through 1930s as well as widely cited influential works from 1940s through present time. During the past century, recommendations for GWG have reversed from emphasizing dieting during pregnancy to the importance of proper nutrition during pregnancy. Obstetricians' focus has also evolved from being exclusively on the newborn to include the health of mothers. Contemporary obstetric practice seeks to achieve a balance between mothers' and infants' risk of adverse outcomes. Historical and social contexts of the United States and the United Kingdom led to distinct GWG policies in the 2 countries. Changes in GWG recommendations over the past century reflect developments in the allied fields, such as epidemiology and nutrition, as much as progress in obstetrics and gynecology. The complex historical perspective that this article provides serves as a reminder of both the interplay and the gaps between research and practice. These gaps result from the fact that clinical guidelines often reflect a specific point in a perpetually evolving state of knowledge that is influenced not only by advances in bench research, but also by refinements in statistical and epidemiologic methods, as well as by the political realities of the time in which they are drafted.


Artemisinin modulating effect on human breast cancer cell lines with different sensitivity to cytostatics.
To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin - Dox; cisplatin - DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment.


[Hemo-lymphangioma of the scrotum: a case report].
A 3-year-old boy was referred because of a painless mass in the left scrotum. On palpation, the mass was discriminated from the testis, epididymis and spermatic cord and showed transillumination. A part of the mass was dark purple in color. Total surgical excision of the mass was performed. The lesion was multicystic (2-15 mm), adherent to the scrotal skin, and easily dissectable from the testicle. Pathological examination revealed lymphangioma as a major component and hemangioma as a minor part. He has been free of recurrent disease for 2 years. This is the 7th case of hemo-lymphangioma of the scrotum in the Japanese literature.


Radial polarity in the first cranial neuromast of selected teleost fishes.
The neuromast is a sensory structure of the lateral line system in aquatic vertebrates, which consists of hair cells and supporting cells. Hair cells are mechanosensory cells, generally arranged with bidirectional polarity. Here, we describe a neuromast with hair cells arranged radially instead of bidirectionally in the first cranial neuromast of four teleost species: red seabream (Pagrus major), spotted halibut (Verasper variegatus), brown sole (Pseudopleuronectes herzensteini), and marbled sole (Pseudopleuronectes yokohamae). In these four species, this polarity was identified only in the first cranial neuromast, where it appeared at the rostral edge of the otic vesicle before hatching. We investigated the initial appearance and fate of this unique neuromast using scanning electron microscopy. We also assessed characteristics of radial neuromast pertaining to morphogenesis, development, and innervation using a vital fluorescent marker and immunohistochemistry in V. variegatus. The kinocilium initially appears at the center of each hair cell, then moves to its outer perimeter to form radial polarity by around 7 days postfertilization. However, hair cells arranged radially disappear about 15 days after hatching. This is followed by the appearance of bidirectionally arranged hair cells, indicating that polarity replacement from radial to bidirectional has occurred. In P. herzensteini, both afferent and efferent synapses between the nerve fibers and hair cells were observed by transmission electron microscopy, suggesting that radial neuromast is functional. Our discovery suggests that neuromasts with radial polarity could enable larval fish to assimilate multiaxial stimuli during this life stage, potentially assisting them in detecting small water vibrations or water pressure changes.


Identification of microorganisms isolated from jet fuel systems.
Seventy-two samples from jet aircraft fuel systems were examined for microbial contamination. Ten contaminated samples yielded 43 microorganisms which were classified into nine genera of bacteria and three genera of fungi. The predominant types, comprising about 37% of the isolated cultures, were identified as Bacillus spp. The remaining cultures were distributed among 11 genera, each of which represented 2 to 9% of the total isolates. Four cultures could not be assigned to a genus on the basis of the diagnostic criteria used. Only five isolates, in the genera Pseudomonas and Hormodendrum (Cladosporium), grew abundantly in a mineral salts solution with JP-4 fuel as the sole source of carbon. The presence of fuel utilizers in a fuel system may be a better index to potential problems that have been correlated with microbial contamination than the presence of aerobic sporeforming bacilli.


Dynamics and Transcriptomics of Skin Dendritic Cells and Macrophages in an Imiquimod-Induced, Biphasic Mouse Model of Psoriasis.
Psoriasis is a chronic inflammatory skin disease of unknown etiology. Previous studies showed that short-term, 5-7 d-long application of imiquimod (IMQ), a TLR7 agonist, to the skin of mice triggers a psoriasis-like inflammation. In the current study, by applying IMQ for 14 consecutive d, we established an improved mouse psoriasis-like model in that it recapitulated many of the clinical and cellular hallmarks observed in human patients during both the early-onset and the late-stable phase of psoriasis. Although macrophages and dendritic cells (DCs) have been proposed to drive the psoriatic cascade, their largely overlapping phenotype hampered studying their respective role. Based on our ability to discriminate Langerhans cells (LCs), conventional DCs, monocytes, monocyte-derived DCs, macrophages, and plasmacytoid DCs in the skin, we addressed their dynamics during both phases of our biphasic psoriasis-like model. Plasmacytoid DCs were not detectable during the whole course of IMQ treatment. During the early phase, neutrophils infiltrated the epidermis, whereas monocytes and monocyte-derived DCs were predominant in the dermis. During the late phase, LCs and macrophage numbers transiently increased in the epidermis and dermis, respectively. LC expansion resulted from local proliferation, a conclusion supported by global transcriptional analysis. Genetic depletion of LCs permitted to evaluate their function during both phases of the biphasic psoriasis-like model and demonstrated that their absence resulted in a late phase that is associated with enhanced neutrophil infiltration. Therefore, our data support an anti-inflammatory role of LCs during the course of psoriasis-like inflammation.


Bimodal signatures of germline methylation are linked with gene expression plasticity in the coral Acropora millepora.
In invertebrates, genes belonging to dynamically regulated functional categories appear to be less methylated than "housekeeping" genes, suggesting that DNA methylation may modulate gene expression plasticity. To date, however, experimental evidence to support this hypothesis across different natural habitats has been lacking. Gene expression profiles were generated from 30 pairs of genetically identical fragments of coral Acropora millepora reciprocally transplanted between distinct natural habitats for 3 months. Gene expression was analyzed in the context of normalized CpG content, a well-established signature of historical germline DNA methylation. Genes with weak methylation signatures were more likely to demonstrate differential expression based on both transplant environment and population of origin than genes with strong methylation signatures. Moreover, the magnitude of expression differences due to environment and population were greater for genes with weak methylation signatures. Our results support a connection between differential germline methylation and gene expression flexibility across environments and populations. Studies of phylogenetically basal invertebrates such as corals will further elucidate the fundamental functional aspects of gene body methylation in Metazoa.


[Surgical treatment of morbid obesity].
Morbid obesity is a multicausal disease with great importance because of the life threatening associated co-morbidities. Its treatment has many different aspects and needs multidisciplinary collaborations. The most powerful way of treatment is the surgical intervention which demands thorough preoperative investigations and patient selection. The bariatric surgical procedures went through significant development and many of them have only historical importance. Different interventions can be classified to malabsorptive, restrictive and combined subgroups. In Europe the laparoscopic adjustable gastric banding seems to be the most widely applied procedure which is purely a restrictive intervention. Apart from the low rate of complications it has many advantages which were not characteristic of the formerly used procedures. These include: minimal invasiveness, reversibility, preservation of the gastrointestinal anatomy, adjustability for demands of care.


Effect of Thyroxine on Transforming Growth Factor β1, Collagen I, and V Expression in Keratoconus Corneal Fibroblasts and Keratocytes, in Vitro.
Keratoconus (KC) is a corneal disorder, associated with oxidative stress, hypoxia and as several times discussed, potentially with thyroid gland dysfunction. We aimed to investigate the effect of thyroxine on transforming growth factor β1 (TGF-β1), collagen I and V (Col I and V) expression in human corneal fibroblasts (HCFs) and human keratocytes of KC corneas, in vitro. Primary human KC-keratocytes and normal keratocytes were isolated and cultured as corneal fibroblasts or keratocytes. The effect of 0.1 µg/ml and 1.0 µg/ml thyroxine on TGF-β1, Col I and Col V expression was investigated by qPCR, Western blot, and ELISA. Proliferation assay was performed using BrdU ELISA to observe the 24h effect of 1.0 µg/ml thyroxine on keratocytes, in vitro. TGFB1 mRNA expression of normal keratocytes increased following 1.0 µg/ml thyroxine stimulation for 24 h (p = .036), without changes in protein expression. Col I protein expression of KC-HCFs increased following 1.0 µg/ml thyroxine stimulation for 24 h (p = .0003). Proliferation of normal and KC keratocytes increased following a 7-day growth period and 24 hours thyroxine administration (p = .018; p = .024). Thyroxine may affect the Col I protein expression in KC-HCFs, but not in KC keratocytes, in vitro. Thyroxine administration has no effect on TGF-β1, collagen I and V expression of keratoconus keratocytes. Therefore, an increased thyroxine concentration alone seems not to be causally related to the development of keratoconus.


Appearance of dextrans and antidextran antibodies in human sera.
The serologically active moiety of an antigen detected occasionally in pathologic sera by double-diffusion gel precipitation tests, referred to in earlier studies as ubiquitous tissue antigen, was identified as a dextran composed predominantly, if not exclusively, of a(1 leads to 6)-linked glycopyranoses. By means of an enzyme immunoassay, dextran or dextran-like material, which inhibited the binding of antidextran serum to dextran, was detected in sera of several patients with various gastrointestinal (GI) diseases, especially GI ulcers (7/10), and also often in sera of aged people (9/21). However, 2 of 50 normal blood donor sera and a few sera from almost every disease group studied contained low quantities of dextran-like material. The levels of antidextran antibodies of the IgG class were also often elevated among patients with GI diseases and aged people as demonstrated by enzyme immunoassay with dextran T-500 as the solid phase antigen. OD values exceeding the mean plus 2.5 SD of 106 normal blood donor sera were recorded in ;69% of patients with gastric and duodenal ulcers, 40% with ulcerative colitis, 29% with Crohn's disease, 20% with colorectal carcinomas, and in 21% with rheumatoid arthritis. None of 23 children, but 9 of 23 aged people (35%) had elevated antibody levels. It is suggested that absorption of dextrans from food or their production by intestinal bacteria may be facilitated in various GI diseases.


EVIDENCE FOR SELECTION AGAINST HYBRIDS IN THE FAMILY CYPRINIDAE (GENUS NOTROPIS).
Notropis cornutus and N. chrysocephalus are two cyprinid fishes which hybridize extensively in the midwest. In this paper, statistical analysis was used to determine if the deficiency of Notropis cornutus × N. chrysocephalus hybrids can be attributed partly to selection against hybrids. Principal component analysis was used to construct a folded hybrid index (FHI) using morphological and electrophoretic characters which distinguish N. cornutus, N. chrysocephalus, and their hybrids. A Wilcoxon signed-rank test comparing mean FHI between successive age classes within cohorts and regression analysis of FHI on age supported the conclusion that hybrids are less fit than parentals in nature; however, this analysis did not include a test of selection at zygotic and larval life history stages or partial infertility of hybrids. Selection eliminated hybrids at a rate of 9.2% per year. Considering the intensity of selection and the age of hybridization, it is surprising that premating reproductive isolating mechanisms have not been perfected by selection against gametic wastage as predicted by classical speciation theory. It appears that the reinforcement of premating isolating mechanisms is an extremely slow process, if it occurs at all, despite apparently intense selection against hybrids.


Treatment of symptomatic middle cerebral artery stenosis with balloon-mounted stents: long-term follow-up at a single center.
Primary stenting is a well-established treatment for coronary artery disease and has been applied to symptomatic intracranial stenosis in selected patients. This study reports a large case series of middle cerebral artery revascularization using balloon-mounted coronary stents. The series consisted of 113 consecutive patients with symptomatic middle cerebral artery stenosis and more than 70% occlusion who underwent intracranial stenting at a single center from 2001 to 2006. Technical success, periprocedural complications, recurrent symptoms, and restenosis were retrospectively reviewed. Risk factors for restenosis were analyzed using logistic regression and the chi(2) test. The mean age of the patients was 48 +/- 11 years (range, 25-79 years). Seventy-three patients presented with transient ischemic attacks, and 40 patients were diagnosed with acute stroke. The technical success rate was 96.46%. The mean stenosis was reduced from 80.83 +/- 8.77% to 3.71 +/- 8.15%. The rate of stroke and death within 30 days was 4.42%. Eighty-nine patients were followed for an average period of 29 +/- 16 months (range, 9 months-5 years). Seventy-nine vessels were followed with transcranial Doppler and 36 vessels with angiography or computed tomographic angiography. Recurrent stroke or transient ischemic attacks occurred in 6 patients (6.74%). The restenosis rate was 20.25%. Restenosis was associated with diabetes and hyperlipidemia but not with age, sex, hypertension, or drug-eluting stent. Primary stenting of symptomatic middle cerebral artery stenosis can be performed with high success and low complication rates. Randomized clinical studies are warranted to compare the safety and efficacy of various endovascular revascularization techniques with maximal medical therapy in patients with symptomatic intracranial atherosclerosis.


Travel tips for a journey into academic administration.
A first-time administrator in a nursing academic setting can succeed in service to students and colleagues. To find the greatest personal contentment in this new role, the author suggests clarifying a personal purpose statement and becoming more self-aware. The author provides tips for finding exhilarating academic administration experiences in terms of association, action, and achievement.


Comparative Therapeutic Effects of Minocycline Treatment and Bone Marrow Mononuclear Cell Transplantation following Striatal Stroke.
We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated (N = 5), minocycline-treated (N = 5), and BMMC-transplanted (N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia. Animals were perfused at 7 days after ischemic induction. Coronal sections were stained with cresyl violet for gross histopathological analysis and immunolabeled for the identification of neuronal bodies (NeuN), activated microglia/macrophages (ED1), and apoptotic cells (active caspase-3). BMMC transplantation and minocycline reduced the number of ED1+ cells (p < 0.05, ANOVA-Tukey), but BMMC afforded better results. Both treatments afforded comparable levels of neuronal preservation compared to control (p > 0.05). BMMC transplantation induced a higher decrease in the number of apoptotic cells compared to control and minocycline treatment. Both therapeutic approaches improved functional recovery in ischemic animals. The results suggest that BMMC transplantation is more effective in modulating microglial activation and reducing apoptotic cell death than minocycline, although both treatments are equally efficacious on improving neuronal preservation.


Selective depletion of alloreactive T lymphocytes using patient-derived nonhematopoietic stimulator cells in allograft engineering.
Selective depletion of alloreactive T cells in vitro results in efficient graft-versus-host disease prophylaxis in allogeneic hematopoietic stem-cell transplantation, but it is accompanied by increased recurrence of leukemia. To spare donor T-cell-mediated graft-versus-leukemia immunity against hematopoiesis-restricted minor histocompatibility (minor-H) antigens, we explored the use of patient-derived nonhematopoietic antigen-presenting cells (APC) as allogeneic stimulators for selective allodepletion in leukemia-reactive donor T-cell lines. Primary keratinocytes, dermal fibroblasts, and bone marrow fibroblasts were generated from skin biopsies and diagnostic bone marrow aspirates of acute myeloid leukemia patients in vitro. Cell cultures were analyzed for expansion, phenotype, and immunostimulatory capacity in comparison with CD40-activated B cells as professional APC. In addition, nonhematopoietic APCs were used for selective allodepletion in vitro. Patient-derived fibroblasts could be reliably expanded to large cell numbers, whereas keratinocytes had limited growth potential. Interferon-gamma-pretreated fibroblasts showed increased expression of human leukocyte antigen (HLA)-class I and II molecules, CD40, and CD54. Fibroblasts and CD40-activated B cells comparably stimulated HLA-A*0301-specific CD8 T cells after transient expression of HLA-A*0301 as a model alloantigen. Finally, fibroblasts could be effectively applied to selectively deplete alloreactivity within leukemia-reactive donor CD8 T-cell lines by targeting the activation-induced antigen CD137. Primary fibroblasts can be efficiently used as allogeneic nonhematopoietic APC for selective depletion of donor T cells reactive to HLA and ubiquitously expressed minor-H antigen disparities in leukemia-stimulated CD8 T-cell lines. Therefore, harnessing alloreactivity to hematopoietic minor-H antigens in addition to leukemia-associated antigens might increase graft-versus-leukemia immunity of donor lymphocyte grafts in allogeneic hematopoietic stem-cell transplantation.


Human cathelicidin antimicrobial peptide is up-regulated in the eosinophilic mucus subgroup of chronic rhinosinusitis patients.
Eosinophilic mucus chronic rhinosinusitis (EMCRS) patients are a subgroup of CRS with a poorer prognosis due to frequent recurrences of disease. The cathelicidin antimicrobial peptide (CAMP) is an important innate defense peptide but its role in CRS is not well characterized. The purpose of this study was to investigate CAMP mRNA and protein expression from EMCRS, CRS, and normal control patients. Biopsy specimens of nasal mucosa and nasal polyps were taken from 59 CRS patients and 9 controls. CAMP mRNA and protein levels were analyzed by real-time quantitative reverse-transcriptase polymerase chain reaction, immunoassay, Western blot, and immunohistochemistry. The expression of CAMP mRNA was significantly increased in EMCRS patients compared with CRS patients (p = 0.0004). By immunohistochemistry, expression of CAMP was localized to nasal epithelial, submucosal glands, and inflammatory subepithelial cells. Western blotting confirmed the presence of CAMP in EMCRS, CRS, and control patients. However, we did not detect statistically significant differences in the protein levels in tissue homogenates between EMCRS, CRS, and control patients. This study shows expression of CAMP in nasal mucosa supporting its role in innate defenses against inhaled pathogens. Although CAMP mRNA was up-regulated in EMCRS patients, there were no statistically significant differences in protein levels in the nasal mucosa of EMCRS compared with CRS patients and controls.


Rating of Eating Disorder Severity Interview for Children: psychometric properties and comparison with EDI-2 symptom index.
This study aimed to evaluate the psychometrics of the Rating of Eating Disorder Severity Interview for Children (REDS-C) and compare it with the Eating Disorder Inventory-2 symptom index. The psychometrics of the REDS-C were analyzed utilizing data from 336 patients, of ages 8 to 18 years. Receiver operator curve analyses were performed to evaluate the ability of the REDS-C and the Eating Disorder Inventory-2 symptom index to discriminate severity of eating disorder symptoms in relationship to an objective standard, defined as hospitalisation for medical stabilisation beyond 1 week. Three factors were identified using 14 of the 16 original REDS-C items. Resulting subscales demonstrated acceptable reliability and validity. The receiver operator curve results demonstrated the usefulness of the 14-item version of the REDS-C in predicting hospitalisation greater than 7 days as an indicator of symptom severity. The 14-item REDS-C is a reliable tool to assist clinicians in evaluating the severity of eating disorder symptoms in children and adolescents.


Endocrinological status of postmenopausal osteoporosis.
The knowledge of the endocrinological status of postmenopausal osteoporosis has considerably progressed in recent years, although many issues remain to be settled. Better knowledge will foster better understanding of the pathogenesis of this disabling condition, and will be of help in designing more effective ways of preventive therapy in a disease where a recent survey showed that 34% of the physicians were unsure as to whether or not it is preventable. Other approaches dealing with exercise, fitness, nutrition, environment, genetic and racial background, or the quality of bone, should not be neglected. Many of these other factors may also be related, at least partially, to the hormonal status.


Micromechanical Characterization of Polysilicon Films through On-Chip Tests.
When the dimensions of polycrystalline structures become comparable to the average grain size, some reliability issues can be reported for the moving parts of inertial microelectromechanical systems (MEMS). Not only the overall behavior of the device turns out to be affected by a large scattering, but also the sensitivity to imperfections gets enhanced. In this work, through on-chip tests, we experimentally investigate the behavior of thin polysilicon samples using standard electrostatic actuation/sensing. The discrepancy between the target and actual responses of each sample has then been exploited to identify: (i) the overall stiffness of the film and, according to standard continuum elasticity, a morphology-based value of its Young's modulus; (ii) the relevant over-etch induced by the fabrication process. To properly account for the aforementioned stochastic features at the micro-scale, the identification procedure has been based on particle filtering. A simple analytical reduced-order model of the moving structure has been also developed to account for the nonlinearities in the electrical field, up to pull-in. Results are reported for a set of ten film samples of constant slenderness, and the effects of different actuation mechanisms on the identified micromechanical features are thoroughly discussed.


Correlation between the Variability of Glycosylated Hemoglobin and Cardiovascular Risk in New-Onset T2DM Patients.
To investigate the relationship between glycosylated hemoglobin variant index and cardiovascular disease in patients with type 2 diabetes. A total of 120 patients with type 2 diabetes who were admitted to the Department of Endocrinology in Chun'an Branch of Zhejiang Provincial People's Hospital from January 2014 to January 2017 were enrolled. The clinical data, fasting blood glucose, and glycosylated hemoglobin levels of the patients were collected, and HGI was obtained by calculating the FPG level into the formula. Follow-up for three years was performed to observe the cardiovascular disease (including coronary heart disease and ischemic stroke) in patients. The occurrence of CVD was analyzed in patients with different levels of HGI. Multivariate logistics regression analysis was used to analyze the risk factors of CVD in patients with T2DM. After three years of follow-up, 8 cases of 120 patients were lost to follow-up. In the end, 24 cases of CVD occurred in 112 patients, with an incidence rate of 21.43%. Comparing the clinical data of CVD patients and non-CVD patients, it was found that the proportion of age, FPG, HbA1c, HGI, and insulin control in the CVD group was higher than that of the non-CVD group, and the difference was statistically significant (P < 0.05). After grouping according to different HGI levels, it was found that with the increase of HGI level, the proportion of HbA1c, FPG, TC, CVD, and insulin use showed an upward trend (P < 0.05). Multivariate logistic regression analysis showed that high HGI level (OR = 4.660), older age (OR = 4.815), and higher FPG level (OR = 1.717) are independent risk factors that affect T2DM patients with cardiovascular disease (P < 0.05). High HGI is independently associated with CVD events in patients with type 2 diabetes. HGI testing is helpful for clinical assessment of personalized assessment and prediction of cardiovascular risk in patients with diabetes.


Peptide-Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide.
The tripeptide H-dPro-Pro-Asn-NH2 is presented as a catalyst for asymmetric conjugate addition reactions of aldehydes to maleimide. The peptidic catalyst promotes the reaction between various aldehydes and unprotected maleimide with high stereoselectivities and yields. The obtained products were readily derivatized to the corresponding pyrrolidines, lactams, lactones, and peptide-like compounds. (1) H NMR spectroscopic, crystallographic, and computational investigations provided insight into the conformational properties of H-dPro-Pro-Asn-NH2 and revealed the importance of hydrogen bonding between the peptide and maleimide for catalyzing the stereoselective C-C bond formation.


System analysis and improvement in the process of transplant patient care.
Clinical information concerning transplant patients is voluminous and difficult to manage using paper records. A system analysis was performed to assess information system needs of the liver, kidney, and pancreas transplant program at LDS Hospital in Salt Lake City, Utah. After evaluating workflow, decision support needs, and requirements, we designed and implemented an extendable information system to support care following liver transplantation. We developed and implemented a standardized operative note, forms to enter external laboratory results and transplant-related information into the electronic health record, and computerized alerts to notify the transplant nurses when liver transplant patients had new, abnormal, or overdue laboratory results. The information system has improved the quality of clinical data available in the EHR, clinician satisfaction, and efficiency with management of laboratory results. The components developed for this project can be extended to meet other transplant program needs.


Immunoprotective activity of capsular polysaccharide in Klebsiella pneumoniae ribosomal preparations does not involve ribonucleic acid.
Two peaks were obtained by cesium chloride density gradient ultracentrifugation of Klebsiella pneumoniae ribosomal preparations. Peak I contained capsular polysaccharide, lipopolysaccharide, protein, and less than 0.5% ribonucleic acid. Peak II consisted mainly of ribonucleic acid, with low amounts of protein and capsular polysaccharide. Expressed as capsular polysaccharide content, the 50% protective dose of peak I and of nonfractionated ribosomal preparations was nearly constant (2.6 and 1.2 ng, respectively). Since peak I contained less than 0.5% ribonucleic acid, these results provide evidence that ribosomal ribonucleic acid is not required for protection of mice by K. pneumoniae capsular polysaccharide which contaminates ribosomal preparations.


X-ray, structural assignment and molecular docking study of dihydrogeodin from Aspergillus Terreus TM8.
A re-cultivation of the thermophilic fungus Aspergillus terreus TM8, and working up of its extract afforded the dichloro-benzophenone derivative, dihydrogeodin (1) in addition to the butyrolactones I (2), V (3) and VI (4). A literature surveying revealed one recent structural assignment trial for dihydrogeodin (1), however, with some inaccuracies. We report herein a full assignment of dihydrogeodin (1) using extensive study of 1D, 2D NMR and ESI HR mass data. For the first time as well, we report the planar structure of 1 using X-ray crystallography. Docking and molecular dynamic simulation of dihydrogeodin (1) on the isomerase cyclophilin A has revealed its significant potential activity as an antiviral and immunosuppressive agent.


Alpha-factor inhibition of the rate of cell passage through the "start" step of cell division in Saccharomyces cerevisiae yeast: estimation of the division delay per alpha-factor.receptor complex.
A highly sensitive, kinetically unambiguous assay for alpha-factor-induced delay of cell passage through the "start" step of cell division in yeast is presented. The assay employs perfusion with periodic microscopy to monitor the bud emergence kinetics on the 20% of cells within an exponentially growing population which exist prior to the alpha-factor execution point of start. The t1/2 for cell passage through start by this population of cells is 31 min in the absence of alpha-factor. The inhibition constant, KI, represents the alpha-factor concentration which produces a 50% inhibition of this rate and is equal to 2 X 10(-10) M. A second assay for maximal cell division arrest by alpha-factor on whole populations of cells is presented. This assay shows a maximum cell division arrest time of 125 +/- 5 h at saturating alpha-factor, and a K50 (that is, an alpha-factor concentration which produces a half-maximal response) of 2.5 X 10(-8) M. Both assays were performed in the effective absence of alpha-factor inactivation. Values of the dissociation constant KD and total number of receptors per cell which specifically mediate cell division arrest or delay were estimated to be 2.5 X 10(-8) M and 10(4), respectively. These estimates, along with the quantitative dose-response data for division arrest which are presented here, are consistent with each receptor.alpha-factor complex which is present on the cell at equilibrium producing a 43 +/- 10 s delay of cell passage through start. Surprisingly, this number is constant within twofold over the entire range of cellular division arrest responses to alpha-factor, that is, from a 1.9-fold inhibition of the rate of cell passage through start at 0.17 nM alpha-factor to a 125 +/- 5 h maximum arrest at saturating alpha-factor concentrations of greater than 170 nM. The possible significance of this observation toward the mechanism of alpha-factor-induced cell division arrest is discussed.


Selection of bacterial mutants from Salmonella specifically recognizing determinants on the cell surface of activated T lymphocytes. A novel system to define cell surface structures.
The isolation of bacterial mutants from Salmonella is described with specific binding capacities to allogeneically or concanavalin A-activated T lymphocytes. The enrichment of these mutants was achieved by separation of T cell blasts with adhering mutants from nonresponsive lymphocytes and nonadhering bacteria through 1 x g sedimentation. Binding of the mutants was specific for T cells early after antigen or mitogen stimulation. No adherence was observed with unstimulated T or B lymphocytes and with B cell blasts. Further results suggested that the binding of Salmonella mutants was mediated by the heteropolysaccharide moiety of lipopolysaccharides with a specificity for protein receptor sites on activated T lymphocytes. Significantly, these heteropolysaccharides also inhibited the differentiation of prekiller to killer cells from allogeneic mixed lymphocyte cultures but did not depress the proliferative response or the activity of cytotoxic effector cells. Bacterial adherence, as well as polysaccharide activity in functional tests, showed strain specificity since reactivity could only be obtained with activated T cells from AKR, C57BL/6, C3H but not with BALB/c and A/J strain mice. It is discussed whether the heteropolysaccharides mimic the structure of naturally occurring molecules and thus compete for their receptor sites. Selection of bacterial mutants with adherence properties may become a general procedure for detecting cell surface molecules on lymphoid and nonlymphoid cells.


Interleukin-10 gene -1082 G/A polymorphism in cervical cancer and cervical intraepithelial neoplasia: meta-analysis.
To assess the association between polymorphism in the interleukin (IL)-10 promoter region of 1082 G/A and the risk of cervical cancer and/or cervical intraepithelial neoplasia (CIN), using meta-analysis. The electronic literature databases PubMed®, Embase®, Web of Science, CBMdisc and CNKI were searched for relevant studies. The strength of association between IL-10 gene -1082 G/A polymorphism and cervical cancer and/or CIN was measured using pooled odds ratios with 95% confidence intervals in four genetic models: allelic model (A allele versus G allele); additive model (A/A versus G/G); recessive model (A/A versus G/A+G/G); dominant model (A/A+G/A versus G/G). Eight studies involving 1983 cases and 1618 controls were identified and included in the meta-analysis. No significant associations were found between IL-10 gene -1082 G/A polymorphism and cervical cancer and/or CIN in any of the genetic models. IL-10 gene -1082 G/A polymorphism does not appear to be associated with the risk of cervical cancer and/or CIN.


Renin-angiotensin-aldosterone system and COVID-19 infection.
With the multiplication of COVID-19 severe acute respiratory syndrome cases due to SARS-COV2, some concerns about angiotensin-converting enzyme 1 (ACE1) inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARB) have emerged. Since the ACE2 (angiotensin-converting enzyme 2) enzyme is the receptor that allows SARS COV2 entry into cells, the fear was that pre-existing treatment with ACEi or ARB might increase the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection. The present article discusses these concerns. ACE2 is a membrane-bound enzyme (carboxypeptidase) that contributes to the inactivation of angiotensin II and therefore physiologically counters angiotensin II effects. ACEis do not inhibit ACE2. Although ARBs have been shown to up-regulate ACE2 tissue expression in experimental animals, evidence was not always consistent in human studies. Moreover, to date there is no evidence that ACEi or ARB administration facilitates SARS-COV2 cell entry by increasing ACE2 tissue expression in either animal or human studies. Finally, some studies support the hypothesis that elevated ACE2 membrane expression and tissue activity by administration of ARB and/or infusion of soluble ACE2 could confer protective properties against inflammatory tissue damage in COVID-19 infection. In summary, based on the currently available evidence and as advocated by many medical societies, ACEi or ARB should not be discontinued because of concerns with COVID-19 infection, except when the hemodynamic situation is precarious and case-by-case adjustment is required.


Clarifying the role of C-reactive protein as a bacterial infection predictor in decompensated cirrhosis.
Bacterial infections are frequent in cirrhosis and may induce other deleterious complications. Ultrasensitive C-reactive protein (US-CRP), like other acute-phase proteins, is often considered useful in predicting bacterial infection in decompensated cirrhosis. However, US-CRP's reliability remains inconclusive, as inflammation in cirrhosis causes US-CRP synthesis independently of infection. The aim of this study was to clarify US-CRP's role as an infection predictor in decompensated cirrhosis. This was a prospective single-center study with systematic inclusion of cirrhotic patients admitted because of decompensation. A total of 118 patients were enrolled, of whom 47 (39.8%) had an overt infection, defined by clinical and laboratory/imaging criteria. Within those, 17 had infection confirmed by culture bacterial identification. Escherichia coli was the most frequent isolated bacteria. Seventeen patients had spontaneous bacterial peritonitis, but only four (23.5%) had positive ascitic fluid cultures. US-CRP levels were significantly higher in cases of overt infection and positive culture groups than the no infection group (median: 4.14 and 6.40 vs. 1.11 mg/dl, P<0.0001 for both). When considering both overt infection and positive culture groups, the US-CRP values of area under the curve as an infection predictor were, respectively, 0.824 and 0.870, P<0.0001 for both, with associated cutoff values of 2.40 and 3.92 mg/dl, and sensitivity and specificity of 78.7/74.6 and 82.4/79.2%, respectively. The ideal US-CRP infection confirmatory cutoff is probably situated between 2.40 and 3.92 mg/dl. However, as infection is somewhat concealed and hazardous in cirrhotic patients, if not considered with lower US-CRP levels according to specific clinic scenarios, it should be carefully considered, at least, if US-CRP is greater than 2.40 mg/dl (0.5 mg/dl normal upper cutoff).


Metabolite profiling of germinating rice seeds.
A metabolite profiling approach based on gas chromatography-mass spectrometry (GC-MS) was used to investigate time-dependent metabolic changes in the course of the germination of rice. Brown rice kernels were soaked and incubated for a total of 96 h under ambient conditions. Samples taken during the germination process were subjected to an extraction and fractionation procedure covering a broad spectrum of lipophilic (e.g., fatty acid methyl esters, hydrocarbons, fatty alcohols, sterols) and hydrophilic (e.g., sugars, acids, amino acids, amines) low molecular weight rice constituents. Investigation of the obtained fractions by GC resulted in the detection of 615 distinct peaks, of which 174 were identified by means of MS. Statistical assessment of the data via principal component analysis demonstrated that the metabolic changes during the germination process are reflected by time-dependent shifts of the scores, which were similar for the three rice materials investigated. Analysis of the corresponding loadings showed that polar metabolites were major contributors to the separation along the first principal component. Relative quantifications based on standardized peak heights revealed dynamic changes of the metabolites in the course of the germination.


In vitro and in vivo Experimental Investigation of Anti-Inflammatory Effects of Peucedanum japonicum Aqueous Extract by Suppressing the LPS-Induced NF-[Formula: see text]B/MAPK JNK Pathways.
Peucedanum japonicum Thunberg has been used to treat cold, cough, and inflammatory diseases in Southern and Eastern Asia. The effects of P. japonicum root aqueous extract (PJ) on lipopolysaccharide (LPS)-induced inflammation were investigated in RAW264.7 macrophages and an animal model of septic shock. Lipopolysaccharides are endotoxins that trigger excessive inflammatory responses, similar to those elicited by gram-negative bacteria. Inflammation is characterized by a primary defense system against pathogens and the onset of sundry diseases or illnesses, and macrophages are important components of the phagocytic system during inflammatory processes. The present study evaluated the effects of PJ on the production of pro-inflammatory mediators, such as nitric oxide and prostaglandin E2, and assessed the expression of enzymes that induce the production of pro-inflammatory mediators using western blotting. We also evaluated the production and mRNA expression of pro-inflammatory cytokines using enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. Using western blotting, we determined whether nuclear factor-kappa B (NF-[Formula: see text]B) and c-Jun N-terminal kinase (JNK) are involved in the molecular mechanisms induced by PJ that suppressed LPS-induced inflammatory responses. We also found that PJ inhibited NF-[Formula: see text]B and JNK pathways in macrophages and reduced LPS-induced mortality in the mouse model of septic shock by inhibiting the activation of NF-[Formula: see text]B and JNK pathways that downregulated the expression of inflammatory mediators. These results indicated that PJ is an effective inflammatory suppressor.


The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study.
Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.


An Overview of Developmental Dysplasia of the Hip and Its Management Timing and Approaches.
Developmental dysplasia of the hip (DDH), if uncorrected, can result in several chronic abnormalities, including chronic hip pain, degenerative arthritis, and gait abnormalities. The outcome of DDH generally depends on the age of presentation; a worse prognosis is linked to a higher age of presentation. Although treatment continues to be a challenge, recent advancements in the field have improved our understanding of the disease, which has resulted in advancements in DDH surveillance during infancy and the reduction of complications with early intervention. The databases used for this overview include Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, MEDLINE, and EMBASE. These databases were used to search for ongoing trials related to the management and diagnosis of DDH.


Effects of Unconventional Work and Shift Work on the Human Gut Microbiota and the Potential of Probiotics to Restore Dysbiosis.
The work environment is a factor that can significantly influence the composition and functionality of the gut microbiota of workers, in many cases leading to gut dysbiosis that will result in serious health problems. The aim of this paper was to provide a compilation of the different studies that have examined the influence of jobs with unconventional work schedules and environments on the gut microbiota of workers performing such work. As a possible solution, probiotic supplements, via modulation of the gut microbiota, can moderate the effects of sleep disturbance on the immune system, as well as restore the dysbiosis produced. Rotating shift work has been found to be associated with an increase in the risk of various metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes. Sleep disturbance or lack of sleep due to night work is also associated with metabolic diseases. In addition, sleep disturbance induces a stress response, both physiologically and psychologically, and disrupts the healthy functioning of the gut microbiota, thus triggering an inflammatory state. Other workers, including military, healthcare, or metallurgy workers, as well as livestock farmers or long-travel seamen, work in environments and schedules that can significantly affect their gut microbiota.


4-aminopyridine does not enhance flocculus function in tottering, a mouse model of vestibulocerebellar dysfunction and ataxia.
The potassium channel antagonist 4-aminopyridine (4-AP) improves a variety of motor abnormalities associated with disorders of the cerebellum. The most rigorous quantitative data relate to 4-AP's ability to improve eye movement deficits in humans referable to dysfunction of the cerebellar flocculus. Largely based on work in the ataxic mouse mutant tottering (which carries a mutation of the Cacna1a gene of the P/Q voltage-activated calcium channel), 4-AP is hypothesized to function by enhancing excitability or rhythmicity of floccular Purkinje cells. We tested this hypothesis by determining whether systemic or intrafloccular administration of 4-AP would ameliorate the eye movement deficits in tottering that are attributable to flocculus dysfunction, including the reductions in amplitude of the yaw-axis vestibulo-ocular reflex (VOR) and vision-enhanced vestibulo-ocular reflex (VVOR), and the optokinetic reflex (OKR) about yaw and roll axes. Because tottering's deficits increase with age, both young and elderly mutants were tested to detect any age-dependent 4-AP effects. 4-AP failed to improve VOR, VVOR, and OKR gains during sinusoidal stimuli, although it may have reduced the tendency of the mutants' responses to VOR and VVOR to decline over the course of a one-hour recording session. For constant-velocity optokinetic stimuli, 4-AP generated some enhancement of yaw OKR and upward-directed roll OKR, but the effects were also seen in normal C57BL/6 controls, and thus do not represent a specific reversal of the electrophysiological consequences of the tottering mutation. Data support a possible extra-floccular locus for the effects of 4-AP on habituation and roll OKR. Unilateral intrafloccular 4-AP injections did not affect ocular motility, except to generate mild eye elevations, consistent with reduced floccular output. Because 4-AP did not produce the effects expected if it normalized outputs of floccular Purkinje cells, there is a need for further studies to elucidate the drug's mechanism of action on cerebellar motor dysfunction.


Regulatory B Cells in Pregnancy: Lessons from Autoimmunity, Graft Tolerance, and Cancer.
The success of pregnancy is contingent on the maternal immune system recognizing and accommodating a growing semi-allogeneic fetus. Specialized subsets of lymphocytes capable of negative regulation are fundamental in this process, and include the regulatory T cells (Tregs) and potentially, regulatory B cells (Bregs). Most of our current understanding of the immune regulatory role of Bregs comes from studies in the fields of autoimmunity, transplantation tolerance, and cancer biology. Bregs control autoimmune diseases and can elicit graft tolerance by inhibiting the differentiation of effector T cells and dendritic cells (DCs), and activating Tregs. Furthermore, in cancer, Bregs are hijacked by neoplastic cells to promote tumorigenesis. Pregnancy therefore represents a condition that reconciles these fields-mechanisms must be in place to ensure maternal immunological tolerance throughout gravidity to allow the semi-allogeneic fetus to grow within. Thus, the mechanisms underlying Breg activities in autoimmune diseases, transplantation tolerance, and cancer may take place during pregnancy as well. In this review, we discuss the potential role of Bregs as guardians of pregnancy and propose an endocrine-modulated feedback loop highlighting the Breg-Treg-tolerogenic DC interface essential for the induction of maternal immune tolerance.


Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice.
The early phase lipid accumulation is essential for liver regeneration. However, whether this acute lipid accumulation can serve as signals to direct liver regeneration rather than simply providing building blocks for cell proliferation remains unclear. Through in vivo CRISPR screening, we identify MIER1 (mesoderm induction early response 1) as a key epigenetic regulator that bridges the acute lipid accumulation and cell cycle gene expression during liver regeneration in male animals. Physiologically, liver acute lipid accumulation induces the phosphorylation of EIF2S1(eukaryotic translation initiation factor 2), which consequently attenuated Mier1 translation. MIER1 downregulation in turn promotes cell cycle gene expression and regeneration through chromatin remodeling. Importantly, the lipids-EIF2S1-MIER1 pathway is impaired in animals with chronic liver steatosis; whereas MIER1 depletion significantly improves regeneration in these animals. Taken together, our studies identify an epigenetic mechanism by which the early phase lipid redistribution from adipose tissue to liver during regeneration impacts hepatocyte proliferation, and suggest a potential strategy to boost liver regeneration.


Primary renal lymphoma: a case report and literature review.
Primary renal lymphoma (PRL) is a rare disease which is often mistaken for renal cell carcinoma. In the present study, a 56-year-old man visited a clinic complaining of an intermittent fever and right flank pain. A computerized tomography examination revealed a hypoenhancing mass in his right kidney. Radical nephrectomy was conducted, and a diagnosis of diffuse large B-cell lymphoma was confirmed. The present case was determined to be a true PRL according to the results of a positron emission tomography examination and a bone marrow biopsy to rule out any lymphoma invasions apart from the right kidney.


Synthesis of biofuel precursors from benzaldehyde and cyclopentanone via aldehyde-ketone condensation in a deep eutectic solvent system.
Production of biofuel precursors from biomass-derived platform compounds (BDPC) has a profound influence on biofuel industries. Herein, an efficient catalytic system composed of the deep eutectic solvent (DES, i.e., ChCl/Fa) and SnCl4 (ChCl/Fa-SnCl4) was developed to produce biofuel precursors (C12 and C19) through aldehyde-ketone (A-K) condensation of benzaldehyde (BD) and cyclopentanone (CPO). ChCl/Fa-SnCl4 exhibited the prospective catalytic performance and given the high selectivity (SC12 = 49.20%, SC19 = 15.20%) and total yield (YC12+C19 = 64.37%) of C12 and C19, as well as 99.96% BD conversion under the optimized conditions (BD : CPO molar ratio of 1 : 6, ChCl : Fa molar ratio of 1 : 12, 4 mmol SnCl4, 80 °C for 120 min). Subsequently, the C12 and C19 precursors were successfully applied to generate cyclic alkanes (C12H14 and C19H18) by hydrodeoxygenation with selectivity of 37.61% and 24.10%, respectively. Finally, the potential catalytic mechanism was explored by density functional theory (DFT) calculations. The results unveiled that the formation of a stable structure for the ChCl/Fa-SnCl4 system was ascribed to the viable interactions among ChCl, Fa and SnCl4 by coordination bonds, electrostatic interactions and H-bonds, which decreased reaction energy barriers and drove the condensation of BD and CPO. In this case, the catalytic reactions between BD and CPO were enhanced to promote the synthesis of C12 and C19. This work provides a novel strategy for the applicability of different BDPC to synthesize fuel precursors for the development of liquid biofuels.


From customer satisfaction survey to corrective actions in laboratory services in a university hospital.
To find out the satisfaction of clinical units with laboratory services in a university hospital, to point out the most important problems and defects in services, to carry out corrective actions, and thereafter to identify the possible changes in satisfaction. and Senior physicians and nurses-in-charge of the clinical units at Oulu University Hospital, Finland. Customer satisfaction survey using a questionnaire was carried out in 2001, indicating the essential aspects of laboratory services. Customer-specific problems were clarified, corrective actions were performed, and the survey was repeated in 2004. In 2001, the highest dissatisfaction rates were recorded for computerized test requesting and reporting, turnaround times of tests, and the schedule of phlebotomy rounds. The old laboratory information system was not amenable to major improvements, and it was renewed in 2004-05. Several clinical units perceived turnaround times to be long, because the tests were ordered as routine despite emergency needs. Instructions about stat requesting were given to these units. However, no changes were evident in the satisfaction level in the 2004 survey. Following negotiations with the clinics, phlebotomy rounds were re-scheduled. This resulted in a distinct increase in satisfaction in 2004. Satisfaction survey is a screening tool that identifies topics of dissatisfaction. Without further clarifications, it is not possible to find out the specific problems of customers and to undertake targeted corrective actions. Customer-specific corrections are rarely seen as improvements in overall satisfaction rates.


Role of Apis cerana cerana N-terminal asparagine amidohydrolase (AccNtan1) in oxidative stress.
N-Terminal asparagine amidohydrolase is a component of the ubiquitin-dependent N-end rule pathway of protein degradation that has been implicated in a variety of physiological functions, including the sensing of heme, oxygen, nitric oxide, selective elimination of misfolded proteins and the repair of DNA. We identified the Apis cerana cerana N-terminal asparagine amidohydrolase (AccNtan1) gene from A. cerana cerana and investigated its role in oxidation resistance. Multiple sequence alignments and phylogenetic analysis revealed that N-terminal asparagine amidohydrolase is highly conserved in insect species. Quantitative real-time polymerase chain reaction analysis indicated that the expression levels of AccNtan1 were significantly lower in the wing, honey sac and abdomen than in other tissues and were significantly higher in early stages of development, including the larva, prepupa and pink-eyed pupa stages, than in later stages. We further observed that AccNtan1 expression was induced by several environmental stressors, including aberrant temperature, H2O2, UV, heavy metals and pesticides. Moreover, a bacteriostatic assay suggested that overexpression of AccNtan1 enhances the resistance of bacteria to oxidative stress. In addition, knockdown of AccNtan1 using RNA interference significantly affected the expression levels of most antioxidant genes and the activity levels of several antioxidant enzymes. Thus, we hypothesize that AccNtan1 plays important roles in environmental stress responses and antioxidative processes.


The semiology of tilt-induced psychogenic pseudosyncope.
To provide a detailed semiology to aid the clinical recognition of psychogenic pseudosyncope (PPS), which concerns episodes of apparent transient loss of consciousness (TLOC) that mimic syncope. We analyzed all consecutive tilt-table tests from 2006 to 2012 showing proven PPS, i.e., apparent TLOC had occurred without EEG changes or a decrease in heart rate (HR) or blood pressure (BP). We analyzed baseline characteristics, video data, EEG, ECG, and continuous BP measurements on a 1-second time scale. Data were compared with those of 69 cases of tilt-induced vasovagal syncope (VVS). Of 800 tilt-table tests, 43 (5.4%) resulted in PPS. The majority (74%) were women. The median duration of apparent TLOC was longer in PPS (44 seconds) than in VVS (20 seconds, p < 0.05). During the event, the eyes were closed in 97% in PPS but in only 7% in VVS (p < 0.0001). A sudden head drop or moving down the tilt table was more common in PPS than in VVS (p < 0.01), but jerking movements occurred more frequently in VVS (p < 0.0001). In PPS, both HR and BP increased before and during apparent TLOC (p < 0.0001). PPS is clinically distinct from VVS and can be diagnosed accurately with tilt-table testing and simultaneous EEG monitoring. Compared with VVS, eye closure during the event, long periods of apparent TLOC, and high HR and BP are highly specific for PPS. Improved understanding of the semiology of PPS as a clinical entity is vital to ensure accurate diagnosis.


Laser-induced retinal damage threshold for repetitive-pulse exposure to 100-μs pulses.
The laser-induced retinal injury thresholds for repetitive-pulse exposures to 100-μs-duration pulses at a wavelength of 532 nm have been determined for exposures of up to 1000 pulses in an in vivo model. The ED50 was measured for pulse repetition frequencies of 50 and 1000 Hz. Exposures to collimated beams producing a minimal retinal beam spot and to divergent beams producing a 100-μm-diameter retinal beam spot were considered. The ED50 for a 100-μs exposure was measured to be 12.8 μJ total intraocular energy for a minimal retinal beam spot exposure and 18.1 μJ total intraocular energy for a 100-μm-diameter retinal beam spot. The threshold for exposures to N > 1 pulse was found to be the same for both pulse repetition frequencies. The variation of the ED50 with the number of pulses is described well by the probability summation model, in which each pulse is considered an independent event. This is consistent with a threshold-level damage mechanism of microcavitation for single-pulse 100-μs-duration exposures. The data support the maximum permissible exposure levels for repetitive-pulse exposure promulgated in the most recent laser safety guidelines.


A northern glacial refugium for bank voles (Clethrionomys glareolus).
There is controversy and uncertainty on how far north there were glacial refugia for temperate species during the Pleistocene glaciations and in the extent of the contribution of such refugia to present-day populations. We examined these issues using phylogeographic analysis of a European woodland mammal, the bank vole (Clethrionomys glareolus). A Bayesian coalescence analysis indicates that a bank vole population survived the height of the last glaciation (approximately 25,000-10,000 years B.P.) in the vicinity of the Carpathians, a major central European mountain chain well north of the Mediterranean areas typically regarded as glacial refugia for temperate species. Parameter estimates from the fitted isolation with migration model show that the divergence of the Carpathian population started at least 22,000 years ago, and it was likely followed by only negligible immigration from adjacent regions, suggesting the persistence of bank voles in the Carpathians through the height of the last glaciation. On the contrary, there is clear evidence for gene flow out of the Carpathians, demonstrating the contribution of the Carpathian population to the colonization of Europe after the Pleistocene. These findings are consistent with data from animal and plant fossils recovered in the Carpathians and provide the clearest phylogeographic evidence to date of a northern glacial refugium for temperate species in Europe.


The entropic nature of protein thermal stabilization.
We performed thermodynamic analysis of temperature-induced unfolding of mesophilic and thermophilic proteins. It was shown that the variability in protein thermostability associated with pH-dependent unfolding or linked to the substitution of amino acid residues on the protein surface is evidence of the governing role of the entropy factor. Numerical values of conformational components in enthalpy, entropy and free energy which characterize protein unfolding in the "gas phase" were obtained. Based on the calculated absolute values of entropy and free energy, a model of protein unfolding is proposed in which the driving force is the conformational entropy of native protein, as an energy of the heat motion (T·S(NC)) increasing with temperature and acting as an factor devaluating the energy of intramolecular weak bonds in the transition state.


Outcomes of Simulation-Based Education for Vascular Access: A Systematic Review and Meta-Analysis.
Simulation training is key to developing skills for vascular access. However, the efficacy of simulation-based education remains unclear. We conducted a well-designed and updated systematic review to investigate the efficacy of these programs. Randomized controlled trials (RCTs) were researched using the following databases from inception until July 26, 2020: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Education Resources Information Center (ERIC), Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, and International Clinical Trials Registry Platform (ICTRP). RCTs included patients undergoing insertion of central venous catheters (CVCs), peripherally inserted central catheters (PICCs), and radial arterial catheters. We compared the group that received simulation training with the group that received traditional training. We also assessed the success rate, adverse events, and first-attempt success using a random-effects meta-analysis. The protocol was registered at Protocols.io (dx.doi.org/10.17504/protocols.io.biu6keze). Seven RCTs (n=866) were evaluated. The meta-analysis showed that simulation-based education increased the overall success rate compared with traditional education (risk ratio: 1.08, 95% CI: 1.03 to 1.13; six RCTs; 840 participants; I2=0%; moderate certainty of evidence). However, it was unclear whether or not simulation-based education had an effect on reducing adverse events when compared with traditional education (risk ratio: 1.00, 95% CI: 0.63 to 1.58; five studies; 750 participants; I2=37%; very low certainty of evidence) or on raising first-attempt success rates (risk ratio: 1.34, 95% CI: 0.93 to 1.94; three studies; 244 participants; I2=59%; very low certainty of evidence). Simulation-based education may help develop skills for successful vascular access. However, it is unclear whether simulation-based education actually reduces the incidence of adverse events. Fine control of the needle tip is probably necessary to prevent adverse events. Simulation-based education might be required in the future for outcome-based task training.


Doppler echocardiography as a modern tool to diagnose and monitor non-cardiac surgical patients: does it improve outcome?
Echocardiography and Doppler provide intraoperative and immediate insight when a haemodynamic deterioration occurs. Both morphological and haemodynamic features can be diagnosed instantly. Furthermore, this tool is used as a functional haemodynamic monitoring device offering on line information on systolic function, preload and afterload. No clear data exist on improvement of outcome in noncardiac surgery, but analogy to cardiac patients suggest strongly outcome can be advanced with echo-Doppler.


A matrix-based algorithm for estimating multiple coherence of a periodic signal and its application to the multichannel EEG during sensory stimulation.
The coherence between the stimulation signal and the electroencephalogram (EEG) has been used in the detection of evoked responses. The detector's performance, however, depends on both the signal-to-noise ratio (SNR) of the responses and the number of data segments (M) used in coherence estimation. In practical situations, when a given SNR occurs, detection can only be improved by increasing M and hence the total data length. This is particularly relevant when monitoring is the objective. In the present study, we propose a matrix-based algorithm for estimating the multiple coherence of the stimulation signal taking into account a set of N EEG channels as a way of increasing the detection rate for a fixed value of M. Monte Carlo simulations suggest that thresholds for such multivariate detector are the same as those for multiple coherence of Gaussian signals and that using more than six signals is not advisable for improving the detection rate with M = 10. The results with EEG from 12 normal subjects during photic stimulation at 10 Hz showed a maximum detection for N greater than 2 in 58% of the subjects with M = 10, and hence suggest that the proposed multivariate detector is valuable in evoked responses applications.


An unusual case of pulmonary-renal syndrome associated with defects in type IV collagen composition and anti-glomerular basement membrane autoantibodies.
Commercial serological assays for the presence of anti-glomerular basement membrane (GBM) antibodies are thought to be indicative of Goodpasture's syndrome. We report a case in which commercial tests inaccurately suggested that a patient with a pulmonary-renal syndrome had Goodpasture's disease. Additional laboratory testing using recombinant type IV collagen NC1 domain proteins showed that the autoantibodies in question were not directed against the Goodpasture antigen (the alpha3NC1 domain), but against the alpha2NC1 domain of type IV collagen. Our findings represent the first known case of human autoantibodies to the alpha2NC1 domain. Further investigation showed that this patient has decreased alpha3 and alpha5 chain expression in the GBM and defects in type IV collagen, resembling abnormalities in patients with Alport's syndrome.


The logic of contrition.
A highly successful strategy for the Repeated Prisoner's Dilemma is Contrite Tit For Tat, which bases its decisions on the "standings" of the two players. This strategy is as good as Tit For Tat at invading populations of defectors, and much better at overcoming errors in implementation against players who are also using it. However, it is vulnerable to errors in perception. In this paper, we discuss the merits of Contrite Tit For Tat and compare it with other strategies, like Pavlov and the newly-introduced Remorse. We embed these strategies into an eight-dimensional space of stochastic strategies which we investigate by analytical means and numerical simulations. Finally, we show that if one replaces the conventions concerning the "standing" by other, even simpler conventions, one obtains an evolutionarily stable strategy (called Prudent Pavlov) which is immune against both mis-perception and mis-implementation.


Change in tinnitus handicap after translabyrinthine vestibular schwannoma excision.
To evaluate the change in tinnitus handicap after translabyrinthine vestibular schwannoma excision. Prospective administration of the Tinnitus Handicap Inventory (THI) preoperatively and at 3 and 12 months postoperatively. : A tertiary referral neuro-otology clinic. A total of 149 patients from a series of 170 consecutive patients who had vestibular schwannomas excised between May 1998 and July 2002 and who had completed THIs preoperatively and at 3 and 12 months postoperatively. Translabyrinthine excision of a unilateral sporadic vestibular schwannoma. THI scores. The number of patients with moderate or severe handicap was 21 (14%) in the preoperative group and 21 (14%) in the 12-month postoperative group. No significant differences in group data were found comparing (by Wilcoxon signed rank test) preoperative data with 3 months postoperative data (p = 0.09), preoperative data with 12 months postoperative data (p = 0.09), and 3 months postoperative data with 12 months postoperative data (p = 0.33). Considering group data, tinnitus handicap is neither alleviated nor exacerbated by translabyrinthine surgery. The application of the validated 20-point criteria for significant change in the status of an individual patient indicates that tinnitus handicap was worse in 10 (6.5%), unchanged in 129 (87%), and better in 10 (6.5%). The findings of the current study can be used during preoperative patient counseling. In particular, the clinician is now able to take an informed and positive stance about the tinnitus handicap to be expected postoperatively.


A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo.
We used a screening procedure to identify protein domains from phage-displayed cDNA libraries that bind both to bone marrow endothelial progenitor cells and tumor vasculature. Screening phage for binding of progenitor cell-enriched bone marrow cells in vitro, and for homing to HL-60 human leukemia cell xenograft tumors in vivo, yielded a cDNA fragment that encodes an N-terminal fragment of human high mobility group protein 2 (HMGN2, formerly HMG-17). Upon i.v. injection, phage displaying this HMGN2 fragment homed to HL-60 and MDA-MB-435 tumors. Testing of subfragments localized the full binding activity to a 31-aa peptide (F3) in the HMGN2 sequence. Fluorescein-labeled F3 peptide bound to and was internalized by HL-60 cells and human MDA-MB-435 breast cancer cells, appearing initially in the cytoplasm and then in the nuclei of these cells. Fluorescent F3 accumulated in HL-60 and MDA-MB-435 tumors after an i.v. injection, appearing in the nuclei of tumor endothelial cells and tumor cells. Thus, F3 can carry a payload (phage, fluorescein) to a tumor and into the cell nuclei in the tumor. This peptide may be suitable for targeting cytotoxic drugs and gene therapy vectors into tumors.


Gene correction in patient-specific iPSCs for therapy development and disease modeling.
The discovery that mature cells can be reprogrammed to become pluripotent and the development of engineered endonucleases for enhancing genome editing are two of the most exciting and impactful technology advances in modern medicine and science. Human pluripotent stem cells have the potential to establish new model systems for studying human developmental biology and disease mechanisms. Gene correction in patient-specific iPSCs can also provide a novel source for autologous cell therapy. Although historically challenging, precise genome editing in human iPSCs is becoming more feasible with the development of new genome-editing tools, including ZFNs, TALENs, and CRISPR. iPSCs derived from patients of a variety of diseases have been edited to correct disease-associated mutations and to generate isogenic cell lines. After directed differentiation, many of the corrected iPSCs showed restored functionality and demonstrated their potential in cell replacement therapy. Genome-wide analyses of gene-corrected iPSCs have collectively demonstrated a high fidelity of the engineered endonucleases. Remaining challenges in clinical translation of these technologies include maintaining genome integrity of the iPSC clones and the differentiated cells. Given the rapid advances in genome-editing technologies, gene correction is no longer the bottleneck in developing iPSC-based gene and cell therapies; generating functional and transplantable cell types from iPSCs remains the biggest challenge needing to be addressed by the research field.


[Continuous subcutaneous morphine--treatment of pain in patients with terminal cancer].
Nine patients with terminal cancer were treated for pain with continuous subcutaneous injection of morphine via a portable battery-driven injection pump. Treatment was instituted on account of failure of other forms of treatment with oral or epidural morphine derivatives or on account of severe nausea and vomiting which necessitated parenteral administration. Treatment proved reasonably effective and no side effects of significance occurred. Two of the patients could be treated in their homes. The method is thus considered as suitable for treatment of pain in patients with terminal cancer.


[Clinical trial with a preparation based on propolis "propolisina" in human giardiasis].
The results of a clinic assay with an extract made out of propolis (bee glue) or "Propolisina" were showed with the aim of showing its effectivity against giardiasis. One hundred and thirty eight patients were studied 48 children and 90 adults, in 2 groups and they selected aleatorily to be treated with "Propolosina" or an imidazole derivate (tinidazole). The method for an exact diagnosis in children was duodenal aspiration and in adults duodenal mucosa frotis by means of duodenoscopy. Similar studies were carried out as a cure criterium in a 5-day term after being through with the treatment. Propolisina was used with different concentrations: in children (concentration at 10%) results showed a 52% cure. In 40 adults (concentration at 20%) it was obtained a similar result to that of tinidazole; and when propolisina concentration was elevated at 30% in the remaining 50 patients there was a higher effectivity (60 of cure Vs 40% with tinidazole). This work shows the success of this natural product, which is very easy to obtain in Cuba and with no side effects in the treatment of this intestinal parasitism, what is of great economical importance for our countries.


Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.
Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.


Gallium-67 imaging to localize urinary-tract infections.
To differeniate upper from lower-tract urinary infections, 73 patients were imaged with 67Ga citrate. Renal uptake of the radioisotope occurred in pyelonephritis (documented in 47 patients by ureteral cathieterization, bladder washout, or histology) with an accuracy of 86%. There were 15% false-positives and 13% false-negatives. 67Ga may prove to be a clinically valuable test in the diagnosis of pyelonephritis. Results are promptly available 24 hours after injection, and it is non-invasive test that can safely be repeated to follow recurrent infections.


Donor/Acceptor-Stabilized 1-Silaketene: Reversible [2+2] Cycloaddition with Pyridine and Evolution by an Olefin Metathesis Reaction.
The reaction of silacyclopropylidene 1 with benzaldehyde generates a 1-silaketene complex 2 by a formal atomic silicon insertion into the C=O bond of the aldehyde. The highly reactive 1-silaketene 2 undergoes a reversible [2+2] cycloaddition with pyridine to give sila-β-lactam 3. Of particular interest, in the presence of 4-dimethylaminopyridine (DMAP), 1-silaketene complex 2 evolves through an intramolecular olefin metathesis reaction, generating a new 1-silaketene complex 8 and cis-stilbene. Theoretical studies suggest that the reaction proceeds through the formation of a transient silacyclobutanone, a four-membered-ring intermediate, similar to that proposed by Chauvin and co-workers for the transition-metal-based olefin metathesis.


Flow cytometry in cytopathology. Overview and perspectives.
The future applications of flow cytometry (FCM) are briefly discussed. Whereas the early goals of its clinical applications were cancer diagnosis and classification, it has now become apparent that FCM can more successfully provide information on a variety of cell constituents of crucial importance in the evaluation of tumor prognosis and treatment sensitivity. It is suggested that (1) the data being provided by FCM will probably lead to a more clinically relevant classification of tumors, based more on the biochemical/molecular markers of individual cells and an assessment of tumor heterogeneity and less on classical cell morphology and tumor progression, and (2) FCM seems likely to become established as a routine methodology in cytopathology.


Stability of traffic breakup patterns in urban networks.
We investigate the behavior of extended urban traffic networks within the framework of percolation theory by using real and synthetic traffic data. Our main focus shifts from the statistical properties of the cluster size distribution studied recently, to the spatial analysis of the clusters at criticality and to the definition of a similarity measure between whole urban configurations. We discover that the breakup patterns of the complete network, formed by the connected functional road clusters at criticality, show remarkable stability from one hour to the next, and predictability for different days at the same time. We prove this by showing how the average spatial distributions of the highest-rank clusters evolve over time, and by building a taxonomy of traffic states via dimensionality reduction of the distance matrix, obtained via a clustering similarity score. Finally, we show that a simple random percolation model can approximate the breakup patterns of heavy real traffic when long-ranged spatial correlations are imposed.


The PyRosetta Toolkit: a graphical user interface for the Rosetta software suite.
The Rosetta Molecular Modeling suite is a command-line-only collection of applications that enable high-resolution modeling and design of proteins and other molecules. Although extremely useful, Rosetta can be difficult to learn for scientists with little computational or programming experience. To that end, we have created a Graphical User Interface (GUI) for Rosetta, called the PyRosetta Toolkit, for creating and running protocols in Rosetta for common molecular modeling and protein design tasks and for analyzing the results of Rosetta calculations. The program is highly extensible so that developers can add new protocols and analysis tools to the PyRosetta Toolkit GUI.


Common cancers in Khuzestan province, south west of Iran, during 2005-2011.
Cancer is the third highest cause of premature mortality in Iran. We aimed to determine trend of common cancers in Khuzestan province, Iran. It was a hospital based survey on 4065 subjects from their hospital files, those had registered as cancer case in Shafa hospital which has known as a biggest center of cancer in Khuzestan province, Iran during 2005-2011.All data has entered by SPSS (version 19), descriptive statistic and adjusted odds ratio of common cancers for age and sex were calculated from multiple logistic regression model. From all subjects; (51% and 49%) were male and female respectively. The most frequent age group was 60-50 years and common cancers were breast 16%, colorectal 6.3%, blood 2%, lung 8% and stomach 8%. Prevalence of cancers has increased markedly with age in Khuzestan Providence. Therefore, it is essential to prevent through early prevention, using screening and identifying cases in initial stages.


Assessment of Parkinson's disease.
The quantitative assessment of clinical deficits in Parkinson's disease has become more difficult due to such factors as the introduction of therapy that induces involuntary movements, the recognition of marked fluctuations in response to treatment, and an increasing of memory disturbance in patients. An attempt to take these problems into account using a brief and simple scale of evaluation is presented.


Initiation and management of adult veno-arterial extracorporeal life support.
Extracorporeal life support (ECLS) for patients suffering from acute cardiopulmonary collapse is the penultimate therapy to provide hemodynamic stability. Although it can be a life sustaining as well as life-saving therapy, there are important factors that contribute to its success. In this review, we will describe the indications, management, pitfalls and limitations of ECLS.


Developmental changes in rat cardiac DNA, RNA and protein tissue base: implications for the interpretation of changes in gene expression.
During cardiac development the expression levels of many genes change as determined by Northern blot, dot blot, RNase protection, quantitative RT-PCR. Western blot or immunoprecipitation analyses. It is not always realized that the total amount of RNA or protein per gram of heart, dubbed tissue base, may change significantly during development as well. If this would be the case, this has to be taken into account. So far, the (changing) tissue base has not been established during cardiac development. To this end developmental profiles of cardiac DNA, RNA and protein concentration were determined in rats ranging in age from embryonic day 13 until neonatal day 121. The profiles show significant development changes in each parameter, that closely match the distinct growth phases of the developing heart and provide the parameters that are essential for an adequate interpretation of changes in the amount of a distinct mRNA and/or protein. In a comparison between in situ hybridization and Northern blot analysis it is demonstrated that the same developmental profile leads to an almost opposite conclusion depending on whether or not the changing tissue base is taken into account. These findings are of great interest for studies aimed at unravelling the molecular mechanisms underlying the regulation of gene expression during cardiac development.


Time-course changes of hippocalcin expression in the mouse hippocampus following pilocarpine-induced status epilepticus.
Hippocalcin participates in the maintenance of neuronal calcium homeostasis. In the present study, we examined the time-course changes of neuronal degeneration and hippocalcin protein level in the mouse hippocampus following pilocarpine-induced status epilepticus (SE). Marked neuronal degeneration was observed in the hippocampus after SE in a time-dependent manner, although neuronal degeneration differed according to the hippocampal subregions. Almost no hippocalcin immunoreactivity was detected in the pyramidal neurons of the cornu ammonis 1 (CA1) region from 6 h after SE. However, many pyramidal neurons in the CA2 region showed hippocalcin immunoreactivity until 24 h after SE. In the CA3 region, only a few hippocalcin immunoreactive cells were observed at 12 h after SE, and almost no hippocalcin immunoreactivity was observed in the pyramidal neurons from 24 h after SE. Hippocalcin immunoreactivity in the polymorphic cells of the dentate gyrus was markedly decreased from 6 h after SE. In addition, hippocalcin protein level in the hippocampus began to decrease from 6 h after SE, and was significantly decreased at 24 h and 48 h after pilocarpine-induced SE. These results indicate that marked reduction of hippocalcin level may be closely related to neuronal degeneration in the hippocampus following pilocarpine-induced SE.


Acute appendicitis on abdominal MR images: training readers to improve diagnostic accuracy.
To determine if training with direct feedback helps to improve the diagnostic performance of inexperienced readers in the detection of appendicitis on magnetic resonance (MR) images. The institutional review board approved this retrospective study and waived the requirement for informed consent. Nine radiologists and eight residents without experience in evaluating MR images for acute abdominal conditions evaluated a training set of images from 100 MR imaging examinations of patients suspected of having appendicitis and received direct feedback after each evaluation. An expert panel made a diagnosis of appendicitis in 45 patients and an alternative diagnosis in 55 patients on the basis of histopathologic examination and follow-up. Readers recorded two diagnoses: the first after viewing images from conventional MR sequences (half-Fourier rapid acquisition with relaxation enhancement and true fast imaging with steady-state precession) and the second after viewing diffusion-weighted (DW) MR images. Reader sensitivity and specificity were calculated per set of 25 cases. The average reader sensitivity for detecting appendicitis improved significantly after training (0.82 vs 0.92, P = .003); the average specificity improved nonsignificantly (0.82 vs 0.88, P = .10). Sensitivity for radiologists increased from 0.81 in the first set of 25 cases to 0.91 in the last set, and specificity improved from 0.82 to 0.85. For residents, sensitivity increased from 0.82 to 0.94, and specificity increased from 0.82 to 0.91. Sensitivity improved from 0.80 to 0.87 (P < .001) in all readings combined when DW images were read in addition to conventional MR images. Diagnostic accuracy of inexperienced readers in the evaluation of abdominal MR images for acute appendicitis improved after training with direct feedback, and the addition of DW images improved reader sensitivity.


Parallel Specification of Visuomotor Feedback Gains during Bimanual Reaching to Independent Goals.
During goal-directed reaching, rapid visuomotor feedback processes enable the human motor system to quickly correct for errors in the trajectory of the hand that arise from motor noise and, in some cases, external perturbations. To date, these visuomotor responses, the gain of which is sensitive to features of the task and environment, have primarily been examined in the context of unimanual reaching movements toward a single target. However, many natural tasks involve moving both hands together, often to separate targets, such that errors can occur in parallel and at different spatial locations. Here, we examined the resource capacity of automatic visuomotor corrective mechanisms by comparing feedback gains during bimanual reaches, toward two targets, to feedback gains during unimanual reaches toward single targets. To investigate the sensitivity of the feedback gains and their relation to visual-spatial processing, we manipulated the widths of the targets and participants' gaze location. We found that the gain of corrective responses to cursor displacements, while strongly modulated by target width and gaze position, were only slightly reduced during bimanual control. Our results show that automatic visuomotor corrective mechanisms can efficiently operate in parallel across multiple spatial locations.


Thanatophobia (Death Anxiety) in the Elderly: The Problem of the Child's Inability to Assess Their Own Parent's Death Anxiety State.
Thanatophobia is omnipresent in our lives. Research has shown separate but connected constructs: fear of death or fear of the dying process. The influences on death anxiety are varied including religiosity, gender, psychological state, and age. It is often assumed by the children of the elderly that the fear of death is prevalent in their parents. Daily the medical staff encounters the presence of death anxiety: from family members or the staff itself. In order to understand this phenomenon, a three-tier study was conducted on non-terminal elderly inpatients in an acute geriatric care ward. The study showed that the elderly had low levels of anxiety (scoring 4/15 on Templer's Death Anxiety Scale) but their children scored higher for themselves (6.9/15) and for their parents (8.9/15). A regression model showed that only the presence of generalized anxiety and religiosity of parent had an effect explaining 33.6% of the variance. Death anxiety of death is usually absent in the elderly but rather they fear the dying process. On the other hand, their children do fear death, which they extrapolate onto their parents. This causes conflicts since the children prevent disclosure of relevant medical information to their parents. This has to be addressed by the staff when dealing with family members, to allow open and honest communication with their patients. The staff need to explain to the family that the elderly are not afraid of death but of the suffering from the dying process.


[Spondyloarthropathies in childhood].
In this paper the author presents the own and other authors' current opinions about the classification, pathophysiology, clinical picture, differential diagnosis, treatment and prognostic problems in the course of juvenile spondyloarthropathies.


TECHNOLOGY ASSESSMENT IN HOSPITALS: LESSONS LEARNED FROM AN EMPIRICAL EXPERIMENT.
Hospital Based Health Technology Assessment (HBHTA) practices, to inform decision making at the hospital level, emerged as urgent priority for policy makers, hospital managers, and professionals. The present study crystallized the results achieved by the testing of an original framework for HBHTA, developed within Lombardy Region: the IMPlementation of A Quick hospital-based HTA (IMPAQHTA). The study tested: (i) the HBHTA framework efficiency, (ii) feasibility, (iii) the tool utility and completeness, considering dimensions and sub-dimensions. The IMPAQHTA framework deployed the Regional HTA program, activated in 2008 in Lombardy, at the hospital level. The relevance and feasibility of the framework were tested over a 3-year period through a large-scale empirical experiment, involving seventy-four healthcare professionals organized in different HBHTA teams for assessing thirty-two different technologies within twenty-two different hospitals. Semi-structured interviews and self-reported questionnaires were used to collect data regarding the relevance and feasibility of the IMPAQHTA framework. The proposed HBHTA framework proved to be suitable for application at the hospital level, in the Italian context, permitting a quick assessment (11 working days) and providing hospital decision makers with relevant and quantitative information. Performances in terms of feasibility, utility, completeness, and easiness proved to be satisfactory. The IMPAQHTA was considered to be a complete and feasible HBHTA framework, as well as being replicable to different technologies within any hospital settings, thus demonstrating the capability of a hospital to develop a complete HTA, if supported by adequate and well defined tools and quantitative metrics.


Contemporary update on neoadjuvant therapy for bladder cancer.
Administration of neoadjuvant chemotherapy preceding radical cystectomy in patients with bladder cancer remains a matter of debate. Results of prospective, randomized studies have demonstrated an overall absolute survival benefit of 5% at 5 years, provided cisplatin-based combination regimens are used. Owing to the perception of a modest survival benefit, the medical community has been slow to adopt the use of neoadjuvant chemotherapy. Other reasons for the underuse of neoadjuvant chemotherapy range from patient ineligibility to fear of delaying potentially curative surgery in nonresponders. Instead, several institutions have adopted an individualized, risk-adapted approach, in which the decision to administer chemotherapy is based on clinical stage and patient comorbidity profile. The development of new cytotoxic and targeted therapies, in particular immune checkpoint inhibitors, warrants well-designed prospective studies to test their efficacy alone or in combination in the neoadjuvant setting. Moving forward, genomic characterization of muscle-invasive bladder cancer could offer information that aids clinicians in selecting the appropriate chemotherapy regimen. Following neoadjuvant therapy, every effort should be made to ensure optimal surgery, as surgical margins and the number of removed lymph nodes are prognostic factors; thus, radical cystectomy and a meticulous extended pelvic lymph node dissection should be performed by expert surgeons.