Case studies illustrating the implementation of treatment strategies for acute and chronic asthma.
Considerations that enter into decisions about treatment strategies for acute and chronic asthma are illustrated in two case studies. A patient's signs, symptoms, vital signs, laboratory test results, recent history of illness or exposure to substances that can provoke asthma symptoms, and response to recently used asthma medications as well as efficacy, safety, and cost are important considerations in choosing drug therapy in the emergency department to treat an acute exacerbation. The need for a rapid onset of action and patient limitations may influence the choice of a dosage form, delivery device, and route of administration. Treatment strategies for patients with chronic asthma may require resolution of problems with adherence to the treatment plan or inhaler technique. Long-term control of asthma symptoms involves the use of preventive measures, including long-term-control medications, efforts to control asthma triggers, and self-monitoring of pulmonary function. Patient education and a written action plan are important elements of the treatment strategy. An individualized approach to treating patients with acute or chronic asthma that takes into consideration patient-specific factors as well as efficacy, safety, and cost of drug therapy is needed when devising and implementing a treatment strategy to optimize patient outcomes.


CRIP1 expression is correlated with a favorable outcome and less metastases in osteosarcoma patients.
Predicting the clinical course of osteosarcoma patients is a crucial prerequisite for a better treatment stratification in these highly aggressive neoplasms of bone. In search of new and reliable biomarkers we recently identified cysteine-rich intestinal protein 1 (CRIP1) to have significant prognostic impact in gastric cancer and therefore decided to investigate its role also in osteosarcoma. For this purpose we analyzed 223 pretherapeutic and well characterized osteosarcoma samples for their immunohistochemical expression of CRIP1 and correlated our findings with clinico-pathological parameters including follow‑up, systemic spread and response to chemotherapy. Interestingly and contrarily to gastric cancer, we found CRIP1 expression more frequently in patients with long‑term survival (10-year survival 73% in positive vs. 54% in negative cases, p = 0.0433) and without metastases (p = 0.0108) indicating a favorable prognostic effect. CRIP1 therefore seems to represent a promising new biomarker in osteosarcoma patients which should be considered for a prospective validation.


Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of colorectal cancer.
In this study, we used the ESTIMATE algorithm to analyze clinical data and transcriptome profiles of 1635 colorectal cancer (CRC) samples from the Gene Expression Omnibus and The Cancer Genome Atlas databases and identify prognostic immune-related genes (IRGs). We identified 941 differentially expressed (4 downregulated and 937 upregulated) genes by comparing samples with high and low immune, stromal scores and tumor purity. LASSO Cox regression analyses showed that the risk score based on a ten-IRG signature was an independent prognostic factor in CRC. The nomogram with pathological stages (TNM) and the ten-IRG signature showed a C-index of 0.769 (95% CI, 0.717-0.821), and area under ROC curve values of 0.788, 0.782 and 0.789 for 1-, 3-, and 5-year OS, respectively. TIMER database analysis showed positive correlation between the ten prognostic IRGs and the levels of tumor-infiltrated immune cells, including CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. These findings demonstrate that this novel ten-IRG signature correlates with the pathological stages and the levels of multiple tumor-infiltrated immune cell types. This makes the ten-IRG signature a potential prognostic factor for CRC patients.


Interactions between Parasitic Infections and the Human Gut Microbiome in Odisha, India.
Soil-transmitted helminth (STH) infections and malaria are parasitic diseases with enormous global health burdens. Research has demonstrated a relationship between each of these parasites and the gut microbiome, suggesting that the gut microbiota may be implicated in governing host susceptibility to diverse pathogens, and perhaps even coinfection by different pathogens, through similar microbiome-influenced pathways. Here, we have derived a first microbiome community profile associated with STH infections in Odisha, India, and tested the hypothesis that the gut microbiome can modulate host susceptibility to multiple parasite infections through the same pathways. This study revealed several bacterial taxa negatively associated with specific STH infections, including Lactobacillus and Lachnospiracaea. Our results also suggest that relative abundance of Lactobacillus is driven by the STH infection status more so than by the Plasmodium infection status. This study contributes to efforts to understand the effects of the microbiome on host susceptibility to parasitic infections in endemic communities.


[Surgical anatomy of the face lifting].
Contrast between an immutable anatomy and procedures which constantly evolve requires a dynamic vision and knowledge of the surgical anatomy. The surgeon, confronted with the reality of the anatomical risk must regularly re-examine his "basics" in anatomy and adapt them to techniques sometimes very invasive whose aesthetic benefit must be seriously counterbalanced by the operational risk. The authors endeavoured to present the surgical anatomy of the facelifts while insisting on the practical aspects and the concept of the evaluated surgical risk. Based on more than 15 years experience related on the one hand to more than 400 anatomical dissections of the face and the neck and on the other hand on more than 600 lifts of the face and the neck, the authors analyze the various successive plans from the skin toward the deep osseous plan as they are anatomically and as the surgeon meets them. Each one of these plans is presented according to the various anatomical areas while insisting on its anatomical characteristics and its specific surgical risks.


Adipose-derived stem cells promote human dermal fibroblast function and increase senescence-associated β‑galactosidase mRNA expression through paracrine effects.
Adipose‑derived stem cells (ADSCs) are known to secrete various cytokines, which affect fibroblast function through paracrine effects. In the present study, the paracrine effects of ADSCs on the function and senescence of young and aged human dermal fibroblasts (HDFs) were investigated in vitro. ADSCs and HDFs were isolated from healthy donors and flow cytometry was used for immunophenotype identification. ADSCs were co‑cultured with young or aged human dermal fibroblasts in Transwell plates, and control groups were established accordingly. Cellular proliferation was measured by an MTT assay. Type I collagen, matrix metalloproteinase‑1 (MMP‑1) and senescence-associated β‑galactosidase (SA‑β‑GAL) mRNA expression were measured by quantitative polymerase chain reaction. It was identified that ADSCs promoted proliferation of co‑cultured HDFs and induced increased expression of type I collagen and decreased expression of MMP‑1. The co‑cultured HDFs exhibited increased expression of SA‑β‑GAL. These results demonstrated that ADSCs improve fibroblast function through paracrine effects. The increased expression of SA‑β‑GAL indicated an accelerated aging process. It is proposed that ADSCs may improve fibroblast function, but not reverse the age status in vitro.


Implication of World Health Organization growth standards on estimation of malnutrition in young Chinese children: Two examples from rural western China and the Tibet region.
The aim of this study was to determine how malnutrition rates change in young Chinese children when 2006 World Health Organization (WHO) growth standards are used instead of 1978 WHO/National Center for Health Statistics reference. Cross-sectional survey data were used from rural western China and the Tibet region. The heights and weights of children of <36 months of age were measured. The nutritional status of the children was assessed by two references. Using 2006 reference instead of 1978 reference, the prevalence of stunting increased significantly (17.9% vs. 12.3% in rural western China and 37.5% vs. 28.1% in rural Tibet). The prevalence of underweight was lower in rural western China (7.7% vs. 11.7%) than rural Tibet (13.1% vs. 15.3%). For all ages, the prevalence of stunting increased and the greatest relative increase appeared in the first six months (102.9% in rural western China vs. 134.9% in rural Tibet). With respect to underweight, the relative increase occurred only during the first six months (314.3% in rural western China vs. 48.1% in rural Tibet); however, the reduction was observed in other age groups. For young Chinese Han and Tibetan children, the difference in estimation of malnutrition between two references differed in magnitude. The scale of change in the prevalence rates of stunting and underweight is much greater when 2006 reference was introduced.


Oxazole-bridged combretastatin A analogues with improved anticancer properties.
Three new oxazole-bridged combretastatin A analogues with additional functional groups at the B-ring [-SMe, -OH, p-quinone] were tested for antiproliferative activity and specificity on human HL-60 leukemia, 518A2 melanoma, and colon carcinomas HCT-116 (wt)/(p53(-/-)) and HT-29 cells. While all oxazoles, except quinone 8, were efficacious against HCT-116 cells at submicromolar IC(50) values (48 h incubation), only thioanisole 5 achieved this potency in combretastatin-refractory HT-29 cells by significant upregulation of p21(cip1/waf1) associated with an S/G(2) cell-cycle arrest.


Living the dream. Shared governance in the role of nurse executive.
After one year of jointly assuming the responsibility for the Vice President's position of a 415-bed regional medical center, the directors of nursing analyzed the reality of living the dream. The authors discuss the personal issues of power and the joys and sorrows of group problem solving and decision making through shared governance, and present reactions from various levels of hospital personnel to this innovative and unconventional approach to nursing management.


Activation of ribosomal protein S2 gene expression in a hamster model of chemically induced oral carcinogenesis.
7,12-Dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis of the hamster buccal pouch has been an excellent model for the study of squamous cell carcinogenesis in human head and neck cancer. Using a differential hybridization of cDNA cloning technique, we isolated a cDNA clone that is expressed in N-ras-transformed PA-1 cells but poorly expressed in non-tumorigenic PA-1 cells; the cDNA codes for the human ribosomal S2 gene product. To define the involvement of S2 gene expression during carcinogenesis in this animal model, we used in situ hybridization technique with non-radioactive digoxigenin-11-dUTP-labeled cDNA. S2 gene was expressed at low levels in basal and suprabasal cell layers of the epidermis in the control, but showed marked elevation throughout the epidermis other than the keratin layer in samples treated for 4 or 8 weeks; S2 was highly expressed in all malignant squamous cell carcinoma cells resulting from DMBA treatment for 16 weeks. As tumors progress from normal epithelium to squamous cell carcinomas, mRNA of the S2 gene was not only elevated sequentially, but also demonstrated the marked heterogeneity among transformed populations, particularly in dysplastic lesions and squamous cell carcinomas. The S2 gene was expressed in a stage-specific manner in the hamster tumor model; S2 could be useful as a neoplastic marker for the detection of certain epithelial origin of tumors and premalignant lesions as well.


[Cone Beam CT New tool in diagnostic imaging].
The goal of this article is to show the advantages of the Cone Beam Computerized Tomography (CBCT) compared to classical Computerized Tomography (CT) and to describe several clinical applications of interest with this rather new technology. Invented practically for dentistry, in particular in implantology, the CBCT found major indications in paranasal sinus imaging, in maxillofacial and oral surgery, in periodontology, endodontics and orthodontics. CBCT is very useful to characterize various lesions of jaws with a reserve concerning the study of soft tissues (in that case, an MRI or CT with contrast injection should be preferred). Recently, CBCT is more and more used for temporal bone imaging and studies of small peripheral articulations.


Identification and functional characterization of novel mutations in the melanocortin-4 receptor.
Melanocortin-4 receptor (MC4R) deficiency is the most common cause of monogenic obesity. In the present study, we screened the MC4R gene for mutations in a population of overweight and obese children and adolescents. Cross-sectional mutation analysis of 112 overweight/obese children and adolescents and 121 lean individuals. We identified 11 sequence variations, 5 of which were present in our control population or had been previously reported as polymorphisms. The remaining 6 variations are disease-causing mutations including 2 novel ones: a I186V mutation and a F280L mutation. The 4 previously described mutations (D90N, M200V, P260Q, Q307X) were identified in single probands. Using confocal imaging, we demonstrated that F280L and P260Q cause intracellular retention of the mutant receptor. No difference in cell surface expression could be detected for the I186V mutation. Using a cAMP responsive luciferase vector, we demonstrated that the receptor with I186V is unable to activate its intracellular signaling pathway while the P260Q mutation causes reduced activation of the receptor. We detected MC4R deficiency in 6 patients from our cohort, amounting to a prevalence of 5.3%. Two novel mutations were identified. We also confirmed that intracellular retention is a common pathogenic effect of MC4R mutations.


Cerebral blastomycosis: an immunodiagnostic study.
Cerebral blastomycosis may simulate a brain tumor. Its diagnosis is sometimes very difficult. The morphologic identification of the fungus may be misleading because it shares some common features with many other dimorphic fungi. Culturing and conversion of the organism from mycelial phase to yeast phase are not always successful. Immunofluorescent staining of the biopsy tissue is useful in confirming the diagnosis. However, a combination of double immunodiffusion (DID) test and complement fixation (CF) test makes the diagnosis more accurate and reliable. The direct role of macrophages in defending the host against blastomycosis is illustrated by electron microscopy.


Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger (Zingiber officinale): identification of curcuminoid synthase and hydroxycinnamoyl-CoA thioesterases.
Members of the Zingiberaceae such as turmeric (Curcuma longa L.) and ginger (Zingiber officinale Rosc.) accumulate at high levels in their rhizomes important pharmacologically active metabolites that appear to be derived from the phenylpropanoid pathway. In ginger, these compounds are the gingerols; in turmeric these are the curcuminoids. Despite their importance, little is known about the biosynthesis of these compounds. This investigation describes the identification of enzymes in the biosynthetic pathway leading to the production of these bioactive natural products. Assays for enzymes in the phenylpropanoid pathway identified the corresponding enzyme activities in protein crude extracts from leaf, shoot and rhizome tissues from ginger and turmeric. These enzymes included phenylalanine ammonia lyase, polyketide synthases, p-coumaroyl shikimate transferase, p-coumaroyl quinate transferase, caffeic acid O-methyltransferase, and caffeoyl-CoA O-methyltransferase, which were evaluated because of their potential roles in controlling production of certain classes of gingerols and curcuminoids. All crude extracts possessed activity for all of these enzymes, with the exception of polyketide synthases. The results of polyketide synthase assays showed detectable curcuminoid synthase activity in the extracts from turmeric with the highest activity found in extracts from leaves. However, no gingerol synthase activity could be identified. This result was explained by the identification of thioesterase activities that cleaved phenylpropanoid pathway CoA esters, and which were found to be present at high levels in all tissues, especially in ginger tissues. These activities may shunt phenylpropanoid pathway intermediates away from the production of curcuminoids and gingerols, thereby potentially playing a regulatory role in the biosynthesis of these compounds.


Nephrogenous cyclic AMP and plasma parathyroid hormone in hypercalcaemia: the influence of renal function.
Immunoreactive parathyroid hormone (PTH) levels and nephrogenous cyclic adenosine monophosphate (cAMP) have been reported to be useful parameters in the diagnosis of hyperparathyroidism. Measurements in hyperparathyroid patients usually give values above the normal range when PTH is measured with a carboxyterminal radioimmunoassay and when nephrogenous cAMP is related to glomerular filtration rate. We tested these two parameters in two groups of hypercalcaemic patients (twelve cases of primary hyperparathyroidism and fourteen cases of hypercalcaemia of non-parathyroid origin) and in two groups of normocalcaemic subjects (twenty-one young healthy volunteers and fourteen elderly subjects without parathyroid disease). Slight impairment of renal function caused elevated values of immunoreactive parathyroid hormone in a carboxyterminal radioimmunoassay and also of nephrogenous cAMP when related to glomerular filtration rate. We found that elevated nephrogenous cAMP without parathyroid disease could be attributed to renal insufficiency and to the mode of expression generally used for the nephrogenous cAMP.


Acute gouty sacroiliitis: a case report and review of the literature.
A 45-year-old black woman with an acute attack of severe unilateral sacroiliitis, negative microbiologic studies, is presented. An open biopsy specimen of the sacroiliac joint revealed evidence of tophaceous gout. The unique features of the case, differential diagnosis, and pertinent literature on gouty sacroiliitis are reviewed. Acute gouty sacroiliitis, although it is rare, does occur and should be included in the differential diagnosis of unilateral sacroiliitis in patients with a long-standing history of gout.


Laparoscopic liver resection for hepatocellular carcinoma: korean experiences.
The development of laparoscopic liver resection (LLR) has been slow due to technical difficulties. Therefore, LLR has been limited to easily accessible lesions. Recently, this procedure has been well applied to hepatocellular carcinoma. However, until now, the indications for LLR have been tumors in the peripheral portion of the anterolateral segments of the liver (segments II, III, V and VI and the inferior part of IV according to the classification of Couinaud). Due to the growing interest in LLR, there have been many attempts to apply this technique in difficult locations. The lesions in the posterior or superior part of the liver (segments I, VII, VIII and the superior part of IV), which are considered to be poor indications for LLR, have been reported to be successfully operated on by laparoscopic surgery. Accordingly, this laparoscopic approach has become similar to open surgery in many ways. One of the major advancements of LLR is anatomic liver resection including major and minor resection. Laparoscopic mono- and bisegmentectomies have also become possible with growing experience. There are a variety of monosegmentectomies and bisegmentectomies. The common representatives of bisegmentectomies are left lateral sectionectomy, right anterior sectionectomy and right posterior sectionectomy. The common operative types of monosegmentectomies are S4, S5, and S6 monosegmentectomies, etc. Central bi-sectionectomy will also be discussed. The Glissonian approach has been useful for these types of anatomic liver resection. The difficulty of controlling hemorrhage has been overcome by performing meticulous surgical techniques with newly developed instruments, and intraoperative sonography has been used to locate the lesions and guide the resection plane even for deep-seated or invisible lesions. Further accumulation of experience and technical refinements will make theses challenging procedures more reproducible and safer.


Characterization and radiosensitivity of fibroblasts derived from squamous cell carcinomas of the head and neck, and the surrounding oral mucosa.
Recently, extensive stromal fibroblast contamination has been reported in the modified Courtenay-Mills soft agar clonogenic assay for cellular in vitro radiosensitivity in tumour biopsies. The aim of the present study was to evaluate the hypothesis that an immunocytochemical analysis added to the modified Courtenay-Mills soft agar clonogenic assay provides a measure of both fibroblast and tumour cell radiosensitivity. Therefore, fibroblasts derived from squamous cell carcinomas of the head and neck, and from the surrounding oral mucosa were compared for immunocytochemistry, DNA ploidy, plating efficiency and surviving fraction of cells after a radiation dose of 2 Gy. The results of our study suggest that the stromal fibroblasts derived from tumour biopsies are representative of normal fibroblasts with respect to the characteristics examined using mucosal fibroblasts as normal controls.


Flexural Fatigue Properties of Ultra-High Performance Engineered Cementitious Composites (UHP-ECC) Reinforced by Polymer Fibers.
In recent years, the application of engineered cementitious composites (ECCs) in structures subjected to cyclic fatigue loading, such as highway bridges, has gained widespread attention. However, most existing ECCs do not have sufficient strength and ductility, which limits their applications, especially in highway bridge structures under high-stress. In this work, an ultra-high performance engineered cementitious composite (UHP-ECC) was configured, which had a compressive strength of approximately 120 MPa, a tensile strength of up to 12 MPa, and a tensile strain capacity of more than 8%. This paper presents a study of the fatigue performance of UHP-ECC at four different fatigue stress levels through the four-point bending test. The mid-span deflection of the specimen was monitored along with the crack opening displacement (COD) of the pure bending section at the bottom of the specimen, and the crack width. In addition, the dissipated energy was calculated at various stress levels. The progressive formation of cracks under static loading was monitored using the digital image correlation (DIC) technique. The fibers at the fractured surface of the specimens were observed and analyzed by environmental scanning electron microscopy, and the morphology of the fibers was obtained at different fatigue stress levels. Eventually, the fatigue life under different stress levels was obtained, and the relationship between the fatigue life and the stress level was established.


[Morphologic changes in the coronary arteries in experimental coarctation of the aorta and following its correction].
In 33 puppies 2-4 months of age the model of a congenital heart disease was made as coarctation of the aorta. In 6-12 months 18 animals were taken to study, and in 15 animals the coarctation was removed. The latter animals were observed for other 6-12 months. The hearts of both groups were separately weighed, and the vessels of the coronary system were studied by means of a complex of histological and morphometric methods. Simultaneously, the number of smooth muscle cells, as well as the area and volume of their nuclei in media of small coronary arteries were estimated. At the experimental coarctation of the aorta certain hypertrophic-hyperplastic changes in coronary arteries at all branching levels take place. They are of a compensatory-adaptive character and reflect certain reactions of the vascular wall to an increased coronary hemodynamics under conditions of hyperfunction and hypertrophy of the cardiac muscle. Surgical removal of the coarctation is accompanied with a reduce of the hemodynamic loading of the heart, diminished degree of hypertrophy of the organ and a marked decrease of the hypertrophic-hyperplastic changes in its vessels. At the same time, the cardiac vascular system is adapting to the new conditions of circulation: rearrangement of some coronary arteries and arterioles according to the closed type and reduction of circulation in the vascular branches which have lost their importance in feeding the myocardium.


Anaphylaxis: an update on its understanding and management.
Anaphylaxis is the most concerning manifestation of hypersensitivity. Recent thorough investigations on the pathophysiology of anaphylaxis achieved important advances in its understanding, regarding in particular the emerging role of mediators such as platelet activating factor (PAF) and sphyngosine 1 phosphate (S1P) and the improved knowledge on the actors of the signaling cascade, from the contact between the specific allergen and the IgE fixed on the Fc-epsilon-RI receptor to the opening of calcium channels. These advances may provide new diagnostic and therapeutical tools. In particular, a role for PAF and S1P as laboratory markers of anaphylaxis is likely to be developed, and innovative preventive strategies able to induce a negative signaling are currently under evaluation. Also, using well known preventive treatments, such as allergen specific immunotherapy may offer new perspectives for the management of patients at risk of potentially fatal reaction to foods. In fact, controlled studies demonstrated that sublingual immunotherapy is able to significantly increase the tolerance to the causative foods, fulfilling the need and protecting the allergic subject from anaphylaxis caused by accidental ingestion of small food amounts. The article also presented some promising patents on anaphylaxis.


A Modified Ceramic-Coating Separator with High-Temperature Stability for Lithium-Ion Battery.
In this work, the ceramic coating separator (CCS-CS) prepared with polyethylene (PE) separator, Al₂O₃ inorganic particles, carboxymethyl cellulose sodium (CMC) and styrene-butadiene rubber (SBR) mix binders is further modified by coating with a thin polydopamine (PDA) layer through a simple chemical deposition method. Compared with the bare ceramic coating separator, the PDA-modified CCS-CS (CCS-CS-PDA) exhibits excellent thermal stability, which shows no thermal shrinkage after storing at 200 °C for 30 min. Compared with the PE separator, both the uptake and wettability with the electrolyte and water of CCS-CS-PDA are improved significantly. Meanwhile, when saturated with liquid electrolyte, the CCS-CS-PDA also shows enabled high ionic conductance. Furthermore, the test of the electrochemical impedances changing with the temperatures suggests that only the PE separator exhibits no thermal shutdown behaviors, and the CCS-CS separator only has a shutdown temperature range from 138 to 160 °C, while the CCS-CS-PDA shows a shutdown temperature range from 138 to more than 200 °C. The cells prepared with the CCS-CS-PDA also show stable repeated cycling performance and good rate capacity at room temperature.


Effects of cryoprotectants in combination on the survival of frozen sugarcane cells.
Cryoprotection of suspension cultures of sugarcane cells (Saccharum sp.) during freezing to various temperatures was tested using glucose, dimethylsulfoxide, and ethylene glycol at various concentrations, alone and in combinations. Viability of the thawed cells was assessed by triphenyltetrazolium chloride reduction, cell growth, and microscopic examination. Enhanced cryoprotection-as much as a doubling in viability value-was achieved by employing glucose and dimethylsulfoxide in mixtures, as compared with the lesser cryoprotective effect of either compound alone, at 1.9 molar total concentration in all cases; the mixture was most effective at a concentration of about 1.9 molar, with a molar ratio of the two components of about 1:3, respectively. Much of the increase in viability value arose from a decrease in toxic effect that came about through mixing the cryoprotective agents. Binary mixtures containing ethylene glycol and either glucose or dimethylsulfoxide were less effective and more toxic than comparable glucose-dimethylsulfoxide mixtures. Use of the optimized latter mixture allowed freezing of these tropical cells to -23 C with little decrease in survival, or to -40 C, still with the capability for delayed growth.


[Possible mechanism of the analgesic effect of interleukin-2 in central nervous system].
The monoclonal antibody against IL-2R (Tac) could not block the analgesic effect of IL-2, and IL-2 mutant that could not bind to beta subunit of IL-2 receptor still had capability of increasing the pain threshold of rats. All these facts suggest that the analgesic effect of IL-2 in CNS is not mediated through the IL-2 receptor, and that the immune and analgesic effects of IL-2 are mediated through different receptor mechanisms. It is suggested that there are common antigenic determinants and similar structure between IL-2 and endogenous opioid peptides (EOP). This implies that the analgesic effect of IL-2 might be mediated by interaction between IL-2 and opioid receptors in CNS. Using radioimmunoassay the contents of EOP of different nuclei were measured at different times after injecting IL-2 into the lateral ventricle of rats. The results suggested that the analgesic effect of IL-2 may be related to beta-EP and LEK in arcuate hypothalamic nucleus, paraventricular hypothalamic nucleus and locus ceruleus.


Rubisco rules fall; gene transfer triumphs.
The most common form of the CO2-fixing enzyme rubisco is a form I enzyme, heretofore found universally in oxygenic phototrophs (cyanobacteria and plastids) and widely in proteobacteria. Two groups, however (1-4), now report that in dinoflagellate plastids the usual form I rubisco has been replaced by the distantly related form II enzyme, known previously only from anaerobic proteobacteria. This raises the important question of how such an oxygen-sensitive rubisco could function in an aerobic organism. Moreover, the dinoflagellate rubisco has unusual molecular properties: it is encoded as a polyprotein, by nuclear (rather than plastid) genes, and these genes contain noncanonical spliceosomal introns. The nuclear location and alpha-proteobacterial affinity of dinoflagellate rubisco genes hint at a possible mitochondrial origin and highlight the extraordinary richness of lateral gene transfers, both between and within organisms, that have occurred during rubisco evolution.


Fractionated stereotactic radiotherapy for small-cell lung cancer patients with brain metastases.
Patients with small-cell lung cancer (SCLC) are at high risk of developing brain metastases (BM). Fractionated stereotactic radiotherapy (FSRT) alone or combined with whole brain radiation therapy can be used to treat intracranial metastases. This study was aimed to explore FSRT for BM from SCLC. We retrospectively analyzed 45 patients with BM from SCLC treated with fractionated linear accelerator FSRT. Multivariate analysis was used to determine independent risk factors of overall survival (OS). There were 35 patients treated with salvage FSRT and 10 patients treated with primary FSRT. The median OS was 10 months from the beginning of FSRT and 19 months from diagnosis of BM. The median OS of salvage FSRT group and primary FSRT group was 22 and 10 months from the diagnosis of BM, respectively (P = 0.011); 11 and 8 months from FSRT, respectively (P = 0.828). Recursive partitioning analysis class and the stage of the primary tumor were independent predictors of increased OS (relative risk [RR] = 2.634, P = 0.021 and RR = 2.324, P = 0.0210, respectively). Salvage and primary FSRT were both effective treatment options for BM from SCLC. Salvage and primary FSRT may have different OS from the time of diagnosis of BM.


Structural and Elastic Properties of Empty-Pore Metalattices Extracted via Nondestructive Coherent Extreme UV Scatterometry and Electron Tomography.
Semiconductor metalattices consisting of a linked network of three-dimensional nanostructures with periodicities on a length scale <100 nm can enable tailored functional properties due to their complex nanostructuring. For example, by controlling both the porosity and pore size, thermal transport in these phononic metalattices can be tuned, making them promising candidates for efficient thermoelectrics or thermal rectifiers. Thus, the ability to characterize the porosity, and other physical properties, of metalattices is critical but challenging, due to their nanoscale structure and thickness. To date, only metalattices with high porosities, close to the close-packing fraction of hard spheres, have been studied experimentally. Here, we characterize the porosity, thickness, and elastic properties of a low-porosity, empty-pore silicon metalattice film (∼500 nm thickness) with periodic spherical pores (∼tens of nanometers), for the first time. We use laser-driven nanoscale surface acoustic waves probed by extreme ultraviolet scatterometry to nondestructively measure the acoustic dispersion in these thin silicon metalattice layers. By comparing the data to finite element models of the metalattice sample, we can extract Young's modulus and porosity. Moreover, by controlling the acoustic wave penetration depth, we can also determine the metalattice layer thickness and verify the substrate properties. Additionally, we utilize electron tomography images of the metalattice to verify the geometry and validate the porosity extracted from scatterometry. These advanced characterization techniques are critical for informed and iterative fabrication of energy-efficient devices based on nanostructured metamaterials.


Enhanced photocatalytic activity of zeolite-encapsulated TiO2 clusters by complexation with organic additives and N-doping.
In the literature it was found that titanium oxide clusters of a few metal atoms encapsulated inside the micropores of zeolite Y exhibit large blue shifts in the Ti-O ligand-to-metal charge-transfer band as compared to non-encapsulated bulk titanium dioxide particles. This blue shift of the Ti-O absorption band is believed to have a negative effect on the photocatalytic activity of zeolite-encapsulated TiO2. We report here on circumventing this problem and increasing visible-light absorption by means of a red shift of the absorption band caused by addition of some organic molecular modifiers containing acidic OH groups that can strongly bind with titanol groups TiOH. In the studied series of zeolite-encapsulated TiO2 samples, the red shift of the optical spectrum follows the order: catechol > 4-aminobenzoic acid > benzoic acid. Also N-doping of zeolite-encapsulated TiO2 clusters by thermal treatment with urea leads to a red shift of the TiO2 absorption band that depends on the annealing and hydration conditions. By comparison to the degradation of phenol in aqueous solution, we have demonstrated that these changes in the absorption spectrum on addition of the organic modifier are also reflected in the photocatalytic activity of the samples; a greater increase in photocatalytic activity (about 30%) was observed for the additive catechol.


Boundary slip from the immersed boundary lattice Boltzmann models.
We report an interesting and important observation of the velocity fields from immersed boundary lattice Boltzmann methods (IB-LBM). The computed velocity profiles can deviate from theoretical predictions greatly even for very simple flow situations, both in the immersed boundary layer and the bulk region. A rigorous analysis of the IB-LBM simulated velocity for a symmetric shear flow is carried out, and the analytical solutions indicate a strong dependence of velocity on the relaxation parameter (kinetic viscosity). Also our simulations demonstrate that simply increasing the immersed boundary layer thickness is not an efficient approach to reduce such velocity discrepancy. We hope this work will bring the awareness of this essential issue to people using IB-LBM for various flow situations.


Distribution of wild and stocked Japanese eels in the lower reaches of the Tone River catchment revealed by otolith stable-isotope ratios.
The natural occurrence of Japanese eels Anguilla japonica in Japan's highly altered catchments is a critical measure of habitat restoration and ecosystem health, yet this metric may be obscured by the incidence of co-occurring cultured eels. Distribution of wild and stocked A. japonica in the lower reaches of the Tone River cachment was investigated using otolith oxygen and carbon stable-isotope ratios (δ18 O and δ13 C). We developed a discrimination model to classify wild and cultured eels for 560 individuals and applied it to eels captured in the lower reaches of the Tone River catchment. Wild eels were found at all study sites of this part of the catchment, indicating natural recruitment of the species occurred from the estuary to third-order streams at least as far as Lake Imbanuma. The proportion of wild eels ranged from 86 to 100% at river and stream sites and was only 23% at upstream Lake Imbanuma sites. This difference probably depends on whether or not eels were released near the corresponding site. More than 50% of stocked eels occurred at sites proximate to release locations, indicating limited dispersal by cultured eels.


Using the Hepatitis C Virus RNA-Dependent RNA Polymerase as a Model to Understand Viral Polymerase Structure, Function and Dynamics.
Viral polymerases replicate and transcribe the genomes of several viruses of global health concern such as Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Ebola virus. For this reason they are key targets for therapies to treat viral infections. Although there is little sequence similarity across the different types of viral polymerases, all of them present a right-hand shape and certain structural motifs that are highly conserved. These features allow their functional properties to be compared, with the goal of broadly applying the knowledge acquired from studying specific viral polymerases to other viral polymerases about which less is known. Here we review the structural and functional properties of the HCV RNA-dependent RNA polymerase (NS5B) in order to understand the fundamental processes underlying the replication of viral genomes. We discuss recent insights into the process by which RNA replication occurs in NS5B as well as the role that conformational changes play in this process.


Introduction of a new hospital information system at the Innsbruck University Hospital.
The aim of the introduction of an advanced hospital information system at the Innsbruck University Hospital is mainly to support the care process and to improve quality and efficiency of care. These requirements entail changes in the clinical processes and many obstacles with respect to the organization have to be considered. The article gives an overview of the goals, organization and problems of the introduction which is still in the planning phase.


Bone Marrow Derived Mesenchymal Stromal Cells Ameliorate Ischemia/Reperfusion Injury-Induced Acute Kidney Injury in Rats via Secreting Tumor Necrosis Factor-Inducible Gene 6 Protein.
To investigate whether bone marrow derived mesenchymal stromal cells (BMSC) have ameliorated ischemia/reperfusion injury-induced acute kidney injury (IRI-AKI) via tumor necrosis factor-inducible gene 6 protein (TSG-6) and how TSG-6 exerted this effect. We used lentiviral vectors of short hairpin RNA (shRNA) targeting TSG-6 gene to silence TSG-6 in BMSC. And TSG-6-silenced BMSC were administrated into IRI-AKI rats. Then we analyzed serum creatinine (Scr) and renal histology of IRI-AKI rats treated with BMSC after different pretreatments. Furthermore, we explored the effect of TSG-6 on renal tubular epithelial cells proliferation in vivo and in vitro assays. The Scr levels of IRI-AKI rats treated with BMSC (73.5±7.8 μmol/L) significantly decreased compared to those of IRI-AKI rats treated without BMSC (392.5±24.8 μmol/L, P<0.05) or with DMEM (314.0±19.8 μmol/L, P<0.05). Meanwhile, the renal tissue injury in IRI-AKI rats treated with BMSC improved markedly. However, the Scr levels of IRI-AKI rats treated with TSG-6-silenced BMSC (265.1±21.2 μmol/L) significantly increased compared to those with BMSC (74.0±8.5 μmol/L, P<0.05). The proportion of Ki67-positive cells was reduced in IRI-AKI rats treated with TSG-6-silenced BMSC compared to that in IRI-AKI rats treated with BMSC (29.7±0.8% versus 43.4±3.0%, P<0.05). In vitro, the cell proliferation rate of TSG-6-stimulated NRK-52E cells under hypoxia (89.2±3.9%) increased significantly compared to that of NRK-52E cells alone under hypoxia (82.4±0.8%, P<0.05). Similarly, the proportion of Ki67-positive cells was significantly elevated in TSG-6-stimulated NRK-52E cells under hypoxia. Furthermore, TSG-6 could inhibit infiltration of neutrophils in kidney tissue of IRI-AKI. TSG-6 plays a key role in the treatment of IRI-AKI with BMSC, which may be due to its effect on promoting renal tubular epithelial cells proliferation by modulating inflammation.


Lack of an independent association between the human leukocyte antigen allele DQA1*0501 and Graves' disease.
The association between the human leukocyte antigen (HLA) serotype DR3 and Graves' disease (GD) in Caucasian populations is well known. However, an even stronger association has been reported recently, especially in the male population, between the closely linked HLA allele DQA1*0501 and GD. We postulated that the reported association between DQA1*0501 and GD may be a result of the linkage of this allele with DR3 and may not represent an independent association. Accordingly, we screened a population of North American Caucasians (n = 218), including patients with GD (n = 101, 32 males, 69 females) and individuals with documented normal thyroid function (n = 117, 51 males, 66 females), for the presence of the DQA1*0501 allele and those alleles corresponding to the DR3 serotype (DRB1*03). Screening was accomplished using sequence specific PCR. A significant association was documented in the total study population between DR3 positivity and GD (P = 0.0002), but not between DQA1*0501 positivity and GD (P = 0.06). After gender stratification, significant associations were found only in the female population (DR3, P = 0.0004; DQA1*0501, P = 0.012) and not in the male population (DR3, P = 1.0; DQA1*0501, P = 1.0). Additionally, in those DR3 negative female subjects (n = 100), there was no independent association between DQA1*0501 positivity (n = 26) and GD (p = 0.82). P-values were corrected, where appropriate, for gender stratification and/or the number of HLA alleles tested. In conclusion, our results demonstrate a lack of independent association between the presence of the HLA allele DQA1*0501 and GD. We suggest that the apparent association between this allele and GD in the female population may be the result of its' close linkage to DR3.


Frame localisation optical projection tomography.
We present a tomographic reconstruction algorithm (flOPT), which is applied to Optical Projection Tomography (OPT) images, that is robust to mechanical jitter and systematic angular and spatial drift. OPT relies on precise mechanical rotation and is less mechanically stable than large-scale computer tomography (CT) scanning systems, leading to reconstruction artefacts. The algorithm uses multiple (5+) tracked fiducial beads to recover the sample pose and the image rays are then back-projected at each orientation. The quality of the image reconstruction using the proposed algorithm shows an improvement when compared to the Radon transform. Moreover, when adding a systematic spatial and angular mechanical drift, the reconstruction shows a significant improvement over the Radon transform.


Correlation of mucocutaneous manifestations of HIV-infected patients in an ART center with CD4 counts.
As the search for reliable clinical indicators for management of human immunodeficiency virus/AIDS continues, mucocutaneous manifestations of HIV are considered among key clinical indicators for prediction of underlying degree of immunosuppression, systemic opportunistic infections, and disease progression. (1) To study the prevalence of mucocutaneous manifestations in HIV-seropositive patients attending the ART center of our hospital (2) To correlate mucocutaneous manifestations with CD4 cell counts. A total of 200 HIV-seropositive patients of adult age group visiting our hospital were included in the study. Information on demographics such as age, sex, transmission route, socioeconomic status, educational status, CD4 counts, and mucocutaneous findings was collected through interview administered survey and case records followed by oral and cutaneous examination. Mean CD4 cell count of asymptomatic HIV/AIDS patients was 580.96 cells/mm3. In comparison with the CD4 cell count of asymptomatic HIV-positive patients, (mean 580.96 cells/mm3) CD4 cell count of HIV-positive patients with various mucocutaneous manifestations (mean 409.65 cells/mm3) was correlated using student t-test and was statistically significant (P = 0.017). This study revealed maximum mucocutaneous lesions in the CD4 count range of 200-500. Nail changes accounted for the most common cutaneous manifestation with 53%, and pigmentation accounted for the most common oral manifestation with 39%. Mucocutaneous manifestations can arouse one to suspect the diagnosis of HIV infection in an otherwise healthy unwary patient. They can serve as a dependable marker of HIV disease.


Defining popular iconic metaphor.
Popular Iconic Metaphor is added to the cognitive linguistic lexicon of figurative language. Popular Iconic Metaphors employ real or fictional celebrities of popular culture as source domains in figurative discourse. Some borders of Popular Iconic Metaphor are identified, and Elvis Presley is offered as a prototype example of a popular iconic source domain, due to his ubiquity in American popular culture, which affords his figurative usage in ways consistent with decision heuristics in everyday life. Further study of Popular Iconic Metaphors may serve to illuminate how figurative expressions emerge in their localized contexts, structure conduct and experience, and affect mediation of cultural and personal meanings.


Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment.
There is increasing evidence that age-associated chronic low-grade inflammation promotes the development of both large-vessel disease (myocardial infarction, stroke, peripheral arterial disease) and small-vessel pathologies (including vascular cognitive impairment) in older persons. However, the source of age-related chronic vascular inflammation remains unclear. To test the hypothesis that cell-autonomous mechanisms contribute to the proinflammatory changes in vascular phenotype that accompanies advancing age, we analyzed the cytokine secretion profile of primary vascular smooth muscle cells (VSMCs) derived from young (∼13 years old) and aged (∼21 years old) Macaca mulatta. Aged VSMCs cultured in the absence of systemic factors exhibited significantly increased secretion of interleukin-1β, MCP-1, and tumor necrosis factorα compared with young control cells. Secretion of interleukin-6 also tended to increase in aged VSMCs. This age-associated proinflammatory shift in the cellular secretory phenotype was associated with an increased mitochondrial O(2)(-) production and nuclear factor κ-light-chain-enhancer of activated B cells activation. Treatment of aged VSMCs with a physiologically relevant concentration of resveratrol (1 μM) exerted significant anti-inflammatory effects, reversing aging-induced alterations in the cellular cytokine secretion profile and inhibiting nuclear factor κ-light-chain-enhancer of activated B cells. Resveratrol also attenuated mitochondrial O(2)(-) production and upregulated the transcriptional activity of Nrf2 in aged VSMCs. Thus, in non-human primates, cell-autonomous activation of nuclear factor κ-light-chain-enhancer of activated B cells and expression of an inflammatory secretome likely contribute to vascular inflammation in aging. Resveratrol treatment prevents the proinflammatory properties of the aged VSMC secretome, an effect that likely contributes to the demonstrated vasoprotective action of resveratrol in animal models of aging.


Generation of a Maximally Entangled State Using Collective Optical Pumping.
We propose and implement a novel scheme for dissipatively pumping two qubits into a singlet Bell state. The method relies on a process of collective optical pumping to an excited level, to which all states apart from the singlet are coupled. We apply the method to deterministically entangle two trapped ^{40}Ca^{+} ions. Within 16 pumping cycles, an initially separable state is transformed into one with 83(1)% singlet fidelity, and states with initial fidelity of ⪆70% converge onto a fidelity of 93(1)%. We theoretically analyze the performance and error susceptibility of the scheme and find it to be insensitive to a large class of experimentally relevant noise sources.


Outcomes of septoplasty in young adults: the Nasal Obstruction Septoplasty Effectiveness study.
The goal of this study was to compare the outcome of septoplasty in our patients with previous reports. We found some different outcomes of septoplasty at our center compared with the reports in the literature. One of the major differences between this and previous studies is in the mean age of patients undergoing surgery, 22.44 years in our study vs more than 40 years in most studies. In this study, 86 patients with septal deviation were asked using an outcomes instrument (the Nasal Obstruction Symptom Evaluation scale) before and 3 and 6 months after septoplasty. Seventy-seven patients (89.5%) reported a subjective improvement in their nasal obstruction, which is more than the experience of most authors. There was a significant improvement in mean Nasal Obstruction Symptom Evaluation score at 3 months after septoplasty, and some symptom improvement continued to 6 months. We conclude that younger patients who have nasal obstruction with septal deviation benefit more from septoplasty.


Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models.
Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Because carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K(+)](o), 4-aminopyridine, or bicuculline, and in vivo against seizures evoked by 6 Hz stimulation in mice, audiogenic stimulation in Fring's mice, and maximal electroshock and subcutaneous pentylenetetrazol (Metrazol) in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. 2DG (10mM) reduced interictal epileptiform bursts induced by 7.5mM [K(+)](o), 4-aminopyridine, and bicuculline, and electrographic seizures induced by high [K(+)](o) in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation in mice (effective dose [ED]50 = 79.7 mg/kg) and audiogenic stimulation in Fring's mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a twofold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions, and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis.


Early Clinical Features of Pseudoexfoliation Syndrome in Anterior Segment and Gonioscopy Examination.
To determine the early signs of pseudoexfoliation (PEX) in fellow eyes of cases with unilateral PEX. Fellow eyes of 34 cases with unilateral PEX were evaluated by slit-lamp and gonioscopy. Findings associated with PEX were recorded. Mean age was 67.8±8.1 years (range 55-86 years). Twenty-five patients (73.5%) had pigmentation in the inferior angle and 23 patients (67.6%) had Sampaolesi's line located on the inferior angle in fellow eyes. The other most common findings were loss of peripupillary ruff in 10 patients (29.4%) and pigment dispersion following pupil dilation in 14 patients (41.1%). Pigmentation in the inferior angle and Sampaolesi's line on the inferior angle seem to be the most common early findings associated with PEX. Special attention should be paid to these findings in cases with ocular hypertension for proper management.


Frequency of ovarian endometriosis in epithelial ovarian cancer patients.
The aim of this study was to determine the frequency of endometriosis in epithelial ovarian cancer patients. Patients who had undergone epithelial ovarian cancer surgery between 2000 and 2004 were subjected to a retrospective analysis. The analysis focused on the presence of ovarian endometriosis, histological types and stages of ovarian cancer, treatment types and five-year survival rate. Out of the 210 operated ovarian cancer patients, 23 had coexisting ovarian endometriosis. Ovarian endometriosis was detected in 3.5% (4 of 113 patients) of cases with serous ovarian cancer, in 31.6% (12 of 38 patients) of cases with endometrioid, and in 36.8% (7 of 19 patients) of cases with clear cell ovarian cancer. The treatment of ovarian cancer patients was a combination of surgery and chemotherapy. Endometriosis was most frequently present in patients with clear cell (36.8%) and endometrioid ovarian cancers (31.6%). The five-year survival rate for ovarian cancer patients in all stages was 39.1%.


Primary melanoma of testis.
Primary melanoma of testis is extremely rare and even the existence of such an entity is questioned. We present the case of a 60-year-old man with primary malignant melanoma in the testis. We report this case to emphasize the need for awareness of the possibility of the testis being the primary site in the patient with a melanoma and to underline the necessity of meticulous investigation of suspicious lesions of the testis in patients with or without a past history of malignant melanoma.


Adenylate Levels, Energy Charge, and Phosphorylation Potential during Dark-Light and Light-Dark Transition in Chloroplasts, Mitochondria, and Cytosol of Mesophyll Protoplasts from Avena sativa L.
The compartmentation of cellular energy relations during dark-light and light-dark transitions was studied by means of a newly developed technique to fractionate oat (Avena sativa L., var. Arnold) mesophyll protoplasts. Using an improved microgradient system with hydrophobic and hydrophilic layers of increasing density, a pure plastid pellet (up to 90% of total chloroplasts) could be separated from an interphase of only slightly contaminated mitochondria (70 to 80% of total mitochondria), and a cytoplasmic supernatant could be obtained within 60 seconds. Appropriate controls indicate that, under the conditions employed, metabolic interconversions of adenylates can be kept to a minimum and, thus, be determined and corrected for. Cross contamination of the fractions, as well as liberation of organelles to the supernatant, was assessed by specific markers, and the metabolite levels recorded were corrected accordingly. Using this technique, we found that, during dark-light transition, the chloroplastic and cytosolic ATP exhibits a rapid increase, while the mitochondrial ATP level decreases. In all compartments, ADP levels mirror alterations of the ATP pool in the opposite way, at least to some extent. To compensate fully for the rise in ATP, chloroplastic and mitochondrial AMP levels change accordingly, indicating that, due to the more or less unchanged level of total adenylates, there is no net flux of adenylates between the compartments. In contrast to the organelles, no AMP could be detected within the cytosol. When the light is turned off, a decrease of ATP coincides between chloroplast stroma and the cytosol for only about 30 seconds. Under prolonged dark treatment, cytosolic ATP rises again, while stroma ATP levels exhibit a further decrease. After about 60 seconds of darkness, the cytosolic ATP level is back to its initial value. This obviously is due to the immediate rise in mitochondrial ATP upon darkening, which cumulates after about 60 seconds; then, caused by an ATP/ADP exchange with the cytosol, it levels off again at the state before changing the conditions, as soon as the cytosolic ATP is also back to its original level. All of these events are closely mirrored by the change in the ATP/ADP ratio and the energy charge within the compartments. While the values for chloroplasts exhibit considerable differences between dark and light, those calculated for mitochondria and the cytosol exhibit only transient changes. These are limited to about 60 seconds of undershoot or overshoot, with respect to the cytosol, and then return to nearly the levels observed before changing the conditions. Adenylate kinase was found to be exclusively associated with chloroplasts (90% of total activity level) and mitochondria. Isotonic liberation of vacuoles did not point toward a significant association of adenylates with this compartment.The results are discussed with respect to an effective collaboration between photosynthetic and oxidative phosphorylation in order to keep the cytosolic energy state at a constant, preset value.


Socio-economic and Demographic Determinants of Antenatal Care Services Utilization in Central Nepal.
The importance of maternal health services in lessening maternal mortality and morbidity as well as neonatal deaths has received substantial recognition in the past decade. The lack of antenatal care has been identified as a risk factor for maternal mortality and other adverse pregnancy outcomes. The purpose of this study was to determine the factors affecting attendance of antenatal care services in Nepal. This is a cross-sectional descriptive study carried out in Central Nepal. Using semi-structured questionnaire, interviews were conducted with married women aged between 15-49 years, who had delivered their babies within one year. Systematic random sampling method was used to select the sample. Results were obtained by frequency distribution and cross-tabulation of the variables. More than half of the women were not aware of the consequences of lack of antenatal care. Age, education, income, type of family were strongly associated with the attendance at antenatal care service. In Nepal and in other developing countries, maternal mortality and morbidity continue to pose challenges to the health care delivery system. Variety of factors including socio-demographic, socio-economic, cultural and service availability as well as accessibility influences the use of maternal health services.


ctDNA Analysis for Cancer? Not So Fast.
An expert panel has concluded that more research is needed before circulating tumor DNA analyses are adopted in clinical care. This finding may slow the use of such testing among oncologists, some of whom are already basing treatment decisions on the results of these assays.


Etomidate and mortality in cirrhotic patients with septic shock.
Clinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone. This is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome. Sixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality. In this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.


The Impact of miRNAs in Health and Disease of Retinal Pigment Epithelium.
MicroRNAs (miRNAs), a class of non-coding RNAs, are essential key players in the control of biological processes in both physiological and pathological conditions. miRNAs play important roles in fine tuning the expression of many genes, which often have roles in common molecular networks. miRNA dysregulation thus renders cells vulnerable to aberrant fluctuations in genes, resulting in degenerative diseases. The retinal pigment epithelium (RPE) is a monolayer of polarized pigmented epithelial cells that resides between the light-sensitive photoreceptors (PR) and the choriocapillaris. The demanding physiological functions of RPE cells require precise gene regulation for the maintenance of retinal homeostasis under stress conditions and the preservation of vision. Thus far, our understanding of how miRNAs function in the homeostasis and maintenance of the RPE has been poorly addressed, and advancing our knowledge is central to harnessing their potential as therapeutic agents to counteract visual impairment. This review focuses on the emerging roles of miRNAs in the function and health of the RPE and on the future exploration of miRNA-based therapeutic approaches to counteract blinding diseases.


Development of a magnetic particle-based enzyme immunoassay for the determination of penoxsulam in water.
A competitive enzyme-linked immunoassay (ELISA) for the quantitation of Penoxsulam [2-(2,2-difluoroethoxy)-6-(trifluoromethyl-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl))benzenesulfonamide] in ground and surface waters was developed. This immunoassay utilizes magnetic particles as the solid phase to which polyclonal rabbit anti-Penoxsulam antibodies are attached. The ELISA has an estimated detection limit of 0.17 ppb (microg/mL) of Penoxsulam in water. Specificity studies indicate that the antibody can distinguish Penoxsulam from its major metabolites and structurally similar pesticides. Interference studies indicate that the ELISA has a wide tolerance of sample pH and salinity and for compounds commonly found in surface and ground waters. The ELISA was shown to compare favorably to LC-MS/MS on ground and surface water samples (r(2) = 0.957). The various studies performed demonstrate the usefulness of the ELISA technique as a rapid and high-throughput analytical method for the cost-effective monitoring of water samples.


Timing of parenchymal enhancement on dual-phase dynamic helical CT of the liver: how long does the hepatic arterial phase predominate?
Dual-phase dynamic helical CT is now being used to detect and characterize benign and malignant hypervascular lesions in the liver. The purpose of this study is to define the timing and degree of parenchymal enhancement of normal liver during the hepatic arterial phase. This prospective study included 102 patients with known or suspected hypervascular hepatic lesions who underwent dual-phase helical CT. After unenhanced CT scanning, we injected iopamidol (Isovue 300; Bracco Diagnostics, Princeton, NJ) at 3 ml/sec for 120 ml, then at 2 ml/sec for 55-60 ml. Scan delay for the hepatic arterial phase was 25 sec and for the portal venous phase was 76 sec. Section thickness was 7 mm and pitch was 1:1. Operator-defined regions of interest were obtained from all three phases. Mean unenhanced attenuation of the liver was 51 +/- 12 H. The liver revealed progressive enhancement during the hepatic arterial phase as follows: an increase of 10 H occurred at a mean time of 33 +/- 4 sec, 20 H at 39 +/- 6 sec, 30 H at 44 +/- 8 sec, 40 H at 46 +/- 6 sec, and 50 H at 48 +/- 5 sec. At 20 H and 30 H of enhancement, we found a statistically significant difference (p < .01) for the mean times of men and women. Mean peak enhancement during the portal venous phase was 89 +/- 23 H. Because the hepatic arterial contribution to liver perfusion is approximately 30%, parenchymal enhancement greater than approximately 30% of peak might indicate portal venous predominance. In our study, this percentage corresponded to an increase of approximately 30 H. Therefore, detection of hypervascular lesions in the hepatic arterial phase may be compromised when imaging lasts longer than approximately 44 sec after the initiation of contrast material injection because 44 sec was the mean time for 30 H of enhancement in our series. However, variability between patients was marked, particularly between men and women. Furthermore, the data suggests that the hepatic arterial phase may be relatively brief and that it may be difficult to image properly using current helical CT technology.


Apples before the fall: Does shape stability coincide with maturity?
Fruit shape is the result of the interaction between genetic, epigenetic, environmental factors and stochastic processes. As a core biological descriptor both for taxonomy and horticulture, the point at which shape stability is reached becomes paramount in apple cultivar identification, and authentication in commerce. Twelve apple cultivars were sampled at regular intervals from anthesis to harvest over two growing seasons. Linear and geometric morphometrics were analysed to establish if and when shape stabilised and whether fruit asymmetry influenced this. Shape stability was detected in seven cultivars, four asymmetric and three symmetric. The remaining five did not stabilise. Shape stability, as defined here, is cultivar-dependent, and when it occurs, it is late in the growing season. Geometric morphometrics detected stability more readily than linear, especially in symmetric cultivars. Key shape features are important in apple marketing, giving the distinctness and apparent uniformity between cultivars expected at point of sale.


Childhood abuse as a risk for partner abuse among women in methadone maintenance.
This study examines the relationship between childhood abuse and partner abuse among a sample of predominantly African-American and Hispanic women, who were patients in methadone clinics in Harlem and the South Bronx. A structured questionnaire addressing demographics, psychosocial and physical health characteristics, depression, childhood abuse, and domestic violence was administered to 151 women. Over half of the women (60%, n = 98) reported lifetime physical, life-threatening, or sexual abuse by a spouse or boyfriend. Multiple logistic regression analysis was used to assess the associations between childhood physical abuse and abuse by a spouse or boyfriend and between childhood sexual abuse and abuse by a spouse or boyfriend. After controlling for potential confounders, women who reported childhood physical abuse were almost nine times more likely to report having been abused by a spouse or boyfriend (OR = 8.74, CI, = 3.25 to 23.57). Women who reported childhood sexual abuse were almost four times more likely to report having been abused by a spouse or boyfriend (OR = 3.93, CI = 1.46 to 10.59). Depression and need for social support were significantly associated with partner abuse, while current heroin use was inversely associated with partner abuse. The high rate of domestic violence and the strong association between childhood and partner abuse found in this study suggest areas for intervention in chemical dependency among women.


Spectral broadening and compression of femtosecond light pulses that pass through dye amplifiers.
The amplification of femtosecond light pulses in multistage as well as in traveling-wave dye amplifiers is studied numerically, taking into account group velocity dispersion, self-phase modulation that is due to Kerr-type nonlinearity, and gain depletion. The combined action of these processes results in a spectral broadening that can be utilized for pulse compression. The results are compared with experimental findings.


Surgical process re-engineering: carpal tunnel decompression--a model.
Surgical process re-engineering is a methodology where the entire surgical process is systematically analysed and re-designed. The process starts with mapping of the current process followed by in-depth analysis of the existing process. A new process is drafted with the aim of making the whole procedure more efficient. The new process is then discussed with all the staff involved in the operating room. Following implementation of the process, surgical process re-engineering should ideally be routinely carried out to continuously improve the procedure. We present an example of surgical process re-engineering which we carried out on the procedure of carpal tunnel release. We used carpal tunnel release as a model as it is a very common operation, with predictable intra-operative findings, and the patient is likely to benefit directly from procedure time reduction. A preliminary mapping of three procedures was done followed by a detailed timed mapping of five routine carpal tunnel decompression procedures. The mapped process was analysed in detail and a number of changes were made in the process. After implementing the new process, a further five procedures were mapped and timed again. In comparison to the original process, we achieved a reduction of 20% in the mean procedure time and a reduction of 42% in the number of steps from 66 to 37.


Purinergic Signalling: Therapeutic Developments.
Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson's disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.


Localised dissection in the convexity of the aortic arch.
We present images of a chest CT scan of an 89-year-old man, showing an area of localised dissection in the convexity of the aortic arch. The ascending and descending aorta were not involved in the disease. The patient suffered a stroke, with severe neurological impairment. Differential diagnosis was undertaken.


Developmental changes in the functional characteristics and expression of voltage-gated K+ channel currents in rat aortic myocytes.
Active control of the arterial diameter by vascular smooth muscle is one of the principle mechanisms by which vessels adapt to a significant rise in blood pressure after birth. Although voltage-gated K+ (Kv) channels play an important role in the regulation of excitation-contraction coupling in arteries, very little is known about postnatal modification of Kv channels. We therefore investigated changes in the functional characteristics and expression of Kv channels in rat aortic myocytes (RAMs) during early postnatal development. Kv currents (I(Kv)) were investigated in single smooth muscle cells freshly dispersed from neonatal (1-3 days) and adult Wistar rat thoracic aorta using the whole-cell patch clamp technique. I(Kv) in neonates had significantly faster activation kinetics and was inactivated at more positive voltages than I(Kv) in adults (half-inactivation potential -24+/-2 and -40+/-3 mV and slope factor 4.2+/-0.4 and 11.1+/-0.5 mV, respectively). No difference in the steady state activation was found. I(Kv) in neonates was insensitive to a high concentration of tetraethylammonium (TEA, 10 mM) but blocked 4-aminopyridine (4-AP, IC(50)=0.5+/-0.1 mM), whereas I(Kv) in adult RAMs was almost completely abolished by 10 mM TEA and was relatively insensitive to low concentrations of 4-AP. I(Kv) in both age groups was insensitive to charybdotoxin (300 nM) or alpha-dendrotoxin (200 nM). Immunoblot analysis showed that the expression of Kv1.2 alpha-protein decreased and Kv2.1 increased with development. Significant changes in functional characteristics of the native I(Kv) and the expression of particular Kv channel proteins occurred during postnatal vascular development. These changes could play an important role in adaptation to extrauterine life.


Necrotizing stomatitis in the developed world.
We present a case of a malnourished 68-year old man with occult hypothyroidism who presented with malaise, pyrexia, tongue swelling, oral ulceration and dysphagia after a 6-month period of increasing lethargy and failing self-care. Severe necrotic oral ulcerative lesions were accompanied by cutaneous purpura, blood-filled blisters and bedsores. It was concluded that the patient's clinical condition reflected necrotizing stomatitis on a background of malnutrition with scorbutic skin lesions and hypothyroidism. The patient made a good recovery with scrupulous oral hygiene, debridement, intravenous metronidazole and nutritional support. Healing occurred with marked fibrosis and trismus, which has slowly improved with mouth-opening exercises. Necrotizing stomatitis is more commonly encountered in malnourished children in developing countries, and may subsequently result in devastating facial defects and death. Patients in the developed world with poor oral hygiene, malnourishment and immunosuppression are also at risk, but early diagnosis and treatment is life-saving and reduces subsequent disability.


m6A: An Emerging Role in Programmed Cell Death.
Programmed cell death is an active extinction process, including autophagy, ferroptosis, pyroptosis, apoptosis, and necroptosis. m6A is a reversible RNA modification which undergoes methylation under the action of methylases (writers), and is demethylated under the action of demethylases (erasers). The RNA base site at which m6A is modified is recognized by specialized enzymes (readers) which regulate downstream RNA translation, decay, and stability. m6A affects many aspects of mRNA metabolism, and also plays an important role in promoting the maturation of miRNA, the translation and degradation of circRNA, and the stability of lncRNA. The regulatory factors including writers, erasers and readers promote or inhibit programmed cell death via up-regulating or down-regulating downstream targets in a m6A-dependent manner to participate in the process of disease. In this review, we summarize the functions of m6A with particular reference to its role in programmed cell death.


Functionalization of cellulose acetate fibers with engineered cutinases.
In the present work, we describe for the first time the specific role of cutinase on surface modification of cellulose acetate fibers. Cutinase exhibits acetyl esterase activity on diacetate and triacetate of 0.010 U and 0.007 U, respectively. An increase on the hydroxyl groups at the fiber surface of 25% for diacetate and 317% for triacetate, after a 24 h treatment, is estimated by an indirect assay. Aiming at further improvement of cutinase affinity toward cellulose acetate, chimeric cutinases are genetically engineered by fusing the 3'-end coding sequence with a bacterial or a fungal carbohydrate-binding module and varying the linker DNA sequence. A comparative analysis of these genetic constructions is presented showing that, the superficial regeneration of cellulose hydrophilicity and reactivity on highly substituted cellulose acetates is achieved by chimeric cutinases.


Impact of Schistosoma mansoni co-infection on serum profile of interferon-gamma, interleukin-4 and interleukin-10 in patients with chronic hepatitis C virus infection.
T cell immunoregulatory cytokines may play a crucial role in the host response to hepatitis C virus infection. While T-helper type 1 (Th1) cytokines are required for host antiviral immune responses, T-helper type 2 (Th2) cytokines can inhibit the development of these effector mechanisms. The aim of this study was to investigate the serum levels of IFN-gamma, IL-4 and IL-10 and their roles in the pathogenesis of chronic HCV infection. Also, to explore the influence of Schistosoma mansoni co-infection on that profile of cytokines. Serum levels of IFN- gamma, IL-4 and IL-10 were measured by ELISA in 15 healthy control subjects (group 1), 18 patients with chronic HCV infection (group II) and 17 patients with chronic HCV co-infected with S. mansoni (group III). Routine liver function tests were performed for all groups. All patients had positive HCV RNA by reverse transcription polymerase chain reaction and elevated alanine amino transferase (ALT) levels for more than 6 months. Diagnosis of S. mansoni infection was based on detection of the parasite in the stools and/or rectal snips and seropositivity for schistosomal antibodies by ELISA. Hematoxylin and eosin stained liver biopsy sections were available and were examined for 25 patients (12 of group II and 13 of group III). There was no statistical difference in serum IFN- gamma levels between patients with chronic HCV infection and healthy controls. IL-4 and IL-10 serum levels were significantly elevated in chronic HCV patients compared to controls (P < 0.05). Chronic HCV patients co-infected with S. mansoni had significantly lower IFN-gamma and significantly higher IL-4 and IL-10 serum levels compared to the other groups (P < 0.05). Serum levels of IL-4 and IL-10 did not correlate to each others in both groups of patients (r = 0.29, P > 0.05 for group II, r = 0.30, P > 0.05 for group III). Patients co-infected with HCV and S. mansoni had necro-inflammatory scores significantly higher in comparison to patients infected with HCV alone (P < 0.05). Serum levels of IFN-gamma, IL-4 and IL-10 did not correlate with the different laboratory parameters, histological activity index or HCV-RNA viral load for all patients population (P > 0.05 for all comparisons). In Conclusions, Th1/Th2 cytokines imbalance is probably involved in the pathogenesis of chronic HCV infection. S. mansoni co-infection induces more alteration in the cytokine milieu, along with more-severe liver disease.


A Comparison of the Efficacies of OK-432 and Talc Slurry for Pleurodesis in Patients with Prolonged Air Leak after Pulmonary Resection.
A prolonged air leak (PAL) is one of the common postoperative complications of pulmonary resection. The aim of this study was to evaluate the efficacy and safety of pleurodesis with sterile talc or OK-432 for postoperative air leak. Patients with postoperative air leak who received chemical pleurodesis using sterile talc or OK-432 were retrospectively identified from medical records data. For pleurodesis with either agent, prior assessment and approval by the hospital safety department were carried out for each case, in addition to individual consent. Between February 2016 and June 2022, 39 patients had PALs and underwent chemical pleurodesis. Among them, 24 patients received pleurodesis with talc (Talc group) and 15 with OK-432 (OK-432 group). The leak resolved after less than two pleurodesis treatments in 22 patients (91.7%) in the Talc group compared with 14 patients (93.3%) in the OK-432 group. Pleurodesis significantly increased white blood cell counts, C-reactive protein concentration, and body temperature in the OK-432 group compared with that in the Talc group (p <0.001, p = 0.003, and p <0.001, respectively). Pleurodesis with talc may be an effective treatment option for postoperative air leak. Our findings suggest that talc was as effective as OK-432 and resulted in a milder systemic inflammatory response.


Legal issues for pathologists.
For better or for worse, the practice of pathology has evolved rapidly in the last decade, particularly the last several years. The dominance of certain national and regional pathology providers and the in-sourcing of pathology services as a revenue stream by nonpathology specialists have transformed pathology services into a commodity in many market, rather than a professional medical service. Despite significant health care reform and a myriad of compliance laws and regulations, it is unlikely that pathology practice will return to "the good old days." As a result, it is important for pathologists to become familiar with the trends in their specialty and have familiarity with the legal issues presented by these trends.


[Chemotherapy-resistant germ cell cancer of the testis treated by salvage surgery: a case report].
A 38-year-old patient who had a non-seminomatous testicular cancer was treated by resection of the retroperitoneal metastatic mass that had proven refractory to bleomycin, etoposide and cisplatin (BEP) and paclitaxel, ifosfamide and cisplatin (TIP) chemotherapies. Although salvage chemotherapy was given against the chemorefractory metastatic lesions in the retroperitoneum, the serum alpha-fetoprotein level elevated to 3,252 ng/ml. Retroperitoneal lymph node dissection was performed, and viable cells were identified histopathologically in the resected tissues. The serum AFP level normalized after surgery. No recurrence has been observed for 22 months postoperatively. This experience indicates that salvage surgery even under high serum marker levels may have a beneficial outcome for selected cases of chemotherapy-resistant germ cell tumors.


Local anaesthesia in cosmetic surgery.
The author reports on his experience with a new form of local anaesthesia in cosmetic surgery, namely a cream for local application produced by the Swedish firm ASTRA under the name of EMLA. It is a mixture of prilocaine and lidocaine. The effect sets in 45 min after application. The technique and indication range in cosmetic surgery are described.


Use of mapping and spatial and space-time modeling approaches in operational control of Aedes aegypti and dengue.
The aims of this review paper are to 1) provide an overview of how mapping and spatial and space-time modeling approaches have been used to date to visualize and analyze mosquito vector and epidemiologic data for dengue; and 2) discuss the potential for these approaches to be included as routine activities in operational vector and dengue control programs. Geographical information system (GIS) software are becoming more user-friendly and now are complemented by free mapping software that provide access to satellite imagery and basic feature-making tools and have the capacity to generate static maps as well as dynamic time-series maps. Our challenge is now to move beyond the research arena by transferring mapping and GIS technologies and spatial statistical analysis techniques in user-friendly packages to operational vector and dengue control programs. This will enable control programs to, for example, generate risk maps for exposure to dengue virus, develop Priority Area Classifications for vector control, and explore socioeconomic associations with dengue risk.


Cost-Effectiveness of Intraoperative CT Scanning in Cochlear Implantation in Fee-for-Service and Bundled Payment Models.
Electrode array tip fold-over is a complication of cochlear implant surgery that results in poor hearing outcomes and often leads to revision surgery. However, tip fold-over can be corrected immediately if identified through intraoperative computed tomography, which also potentially provides information about final intracochlear positioning. Our objective was to provide the first economic analysis of intraoperative computed tomography by generating models in fee-for-service and bundled payment reimbursement structures of payer and institutional cost-effectiveness of this technology used in cochlear implantation over 1, 5, and 10-year time periods. Cost data specific to a commerically available intraoperative computed tomography machine was obtained from the manufacturer, Xoran Technologies. Institutional tip fold-over rate was obtained from already published data. Medicare reimbursement rate for cochlear implantation was obtained from institutional accountants. Private payer reimbursement for and cost of revision cochlear implantation were estimated based on available data. At large volume centers, cost-effectiveness of this technology is possible in both fee-for-service and bundled payment reimbursement structures at various time points dependent on payer mix. Even low volume cochlear implantation centers (<150 per year) can financially benefit from intraoperative computed tomography in bundled payment models at 5- and 10-year periods regardless of payer mix. This model demonstrates key factors at play in determining cost-effectiveness of this technology including institutional factors and payer type and suggests this technology can align incentives both to improve patient care and outcomes with institutional and payer financial well-being.


Is Hyperbaric Oxygen Therapy Effective for Traumatic Brain Injury? A Rapid Evidence Assessment of the Literature and Recommendations for the Field.
This systematic review examines the efficacy of hyperbaric oxygen (HBO2) for traumatic brain injury (TBI) to make evidence-based recommendations for its application and future research. A comprehensive search was conducted to identify studies through 2014. Methodological quality was assessed and synthesis and interpretation of relevant data was performed. Twelve randomized trials were included. All mild TBI studies demonstrated minimal bias and no statistically significant differences between HBO2 and sham arms. Statistically significant improvement occurred over time within both groups. Moderate-to-severe TBI studies were of mixed quality, with majority of results favoring HBO2 compared with "standard care." The placebo analysis conducted was limited by lack of details. For mild TBI, results indicate HBO2 is no better than sham treatment. Improvements within both HBO2 and sham groups cannot be ignored. For acute treatment of moderate-to-severe TBI, although methodology appears flawed across some studies, because of the complexity of brain injury, HBO2 may be beneficial as a relatively safe adjunctive therapy if feasible. Further research should be considered to resolve the controversy surrounding this field, but only if methodological flaws are avoided and bias minimized.


[Transplantation-associated infections].
Transplantation-associated infections are caused by an infected transplanted organ or the endogenic or exogenic environment of the recipient in a state of induced immunodeficiency. The best therapy would be to reconstitute the immunodeficiency, but this is usually impossible as it endangers the transplanted organ. Thus, a specific, standardised anti-infectious therapy is needed even in the absence of clearly identified micro-organisms [bacteria (in two thirds gram-positive rods), parasites (in central Europe predominantly Toxoplasma), fungi (especially Candida spp. or Aspergillus spp.) or viruses (such as Parvovirus B19 and Cytomegalovirus)]. Origins of infection (e.g., hygiene), types of infection (e.g., reactivation), typical localisations, diagnostic tools (e.g., blood cultures, antigenic tests, PCR, CT, advantages and disadvantages of antibody assays) and possible therapies are briefly discussed. The take home messages are to avoid economy measures in microbial diagnostics and to use CMV-seronegative donors whenever possible.


Untapped capacity for resilience in environmental law.
Over the past several decades, environmental governance has made substantial progress in addressing environmental change, but emerging environmental problems require new innovations in law, policy, and governance. While expansive legal reform is unlikely to occur soon, there is untapped potential in existing laws to address environmental change, both by leveraging adaptive and transformative capacities within the law itself to enhance social-ecological resilience and by using those laws to allow social-ecological systems to adapt and transform. Legal and policy research to date has largely overlooked this potential, even though it offers a more expedient approach to addressing environmental change than waiting for full-scale environmental law reform. We highlight examples from the United States and the European Union of untapped capacity in existing laws for fostering resilience in social-ecological systems. We show that governments and other governance agents can make substantial advances in addressing environmental change in the short term-without major legal reform-by exploiting those untapped capacities, and we offer principles and strategies to guide such initiatives.


Pharmacological targeting of cGAS/STING-YAP axis suppresses pathological angiogenesis and ameliorates organ fibrosis.
Organ fibrosis is accompanied by pathological angiogenesis. Discovering new ways to ameliorate pathological angiogenesis may bypass organ fibrosis. The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been implicated in organ injuries and its activation inhibits endothelial proliferation. Currently, a controversy exists as to whether cGAS/STING activation exacerbates inflammation and tissue injury or mitigates damage, and whether one of these effects predominates under specific context. This study unveiled a new antifibrotic cGAS/STING signaling pathway that suppresses pathological angiogenesis in liver and kidney fibrosis. We showed that cGAS expression was induced in fibrotic liver and kidney, but suppressed in endothelial cells. cGAS genetic deletion promoted liver and kidney fibrosis and pathological angiogenesis, including occurrence of endothelial-to-mesenchymal transition. Meanwhile, cGAS deletion upregulated profibrotic Yes-associated protein (YAP) signaling in endothelial cells, which was evidenced by the attenuation of organ fibrosis in mice specifically lacking endothelial YAP. Pharmacological targeting of cGAS/STING-YAP signaling by both a small-molecule STING agonist, SR-717, and a G protein-coupled receptor (GPCR)-based antagonist that blocks the profibrotic activity of endothelial YAP, attenuated liver and kidney fibrosis. Together, our data support that activation of cGAS/STING signaling mitigates organ fibrosis and suppresses pathological angiogenesis. Further, pharmacological targeting of cGAS/STING-YAP axis exhibits the potential to alleviate liver and kidney fibrosis.


Cloning of complementary DNAs encoding structurally related homeoproteins from preimplantation mouse embryos: their involvement in the differentiation of embryonic stem cells.
During the preimplantation development of mouse embryos between the 4-cell to 8-cell stage and the morula stage, when the first irreversible segregation of cell fates proceeds into the pluripotent inner cell mass (progenitor cells to form the fetus) and the trophectoderm (to form the placenta) of blastocysts, pluripotency-maintaining and differentiation-inducing genes are expressed to coordinately regulate cell fates. Three structurally related cDNAs (Crxos1, Crxos1 sv2, and Crxos1 tv3) that exhibited concomitant elevated expression during this critical period were identified by subtractive cDNA cloning. CRXOS1 contains two homeodomains, while CRXOS1 sv2 and CRXOS1 tv3 each contain one of the homeodomains included in CRXOS1. Crxos1, Crxos1 sv2, and Crxos1 tv3 were expressed differentially during in vitro embryonic stem (ES) cell differentiation. Even under differentiation-inducing conditions, forced expression of Crxos1 sv2 inhibited the differentiation of ES cells. In contrast, under conditions that promote self-renewal of ES cells, forced expression of Crxos1 induced differentiation. Forced expression of Crxos1 resulted in induction of Gata4 but in repression of T, probably indicating that Crxos1 promotes the differentiation of ES cells into primitive endoderm, while inhibiting differentiation into mesoderm. On the other hand, no apparent effects of forced expression of Crxos1 tv3 were observed. Taken together, it was concluded that these transcripts encoding homeoproteins are capable of regulating the maintenance and/or differentiation of mouse ES cells and likely regulate that of preimplantation embryos.


Sjögren Syndrome in Systemic Lupus Erythematosus: A Subset Characterized by a Systemic Inflammatory State.
An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLE patients without SS (SLE-nonsSS) and controls. We included 504 consecutive patients with SLE, fulfilling the 1982 revised American College of Rheumatology criteria, and 319 controls from the general population, matched for age and sex to the first 319 patients. SLE-sSS was defined according to the American-European Consensus Criteria (AECC). A thorough clinical examination, including subjective and objective quantifications of sicca symptoms, was performed in all participants. Autoantibodies and 20 selected cytokines were measured by luminex and multiplex analysis, respectively. SLE-sSS, as defined by AECC, occurred in 23% of the patients with SLE. In comparison to SLE-nonsSS, the SLE-sSS group was older and more frequently female. Leukopenia and peripheral neuropathy were more frequent and nephritis less frequent. Circulating levels of 6/20 investigated proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 6, monocyte chemoattractant protein 4, macrophage inflammatory protein 1β, IL-12/IL-23p40, and interferon γ-induced protein 10], total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA) were higher in the SLE-sSS group (p < 0.05 for all comparisons). The frequency of SLE-sSS increased with age and affected roughly one-quarter of all patients with SLE. Despite less internal organ involvement, a systemic inflammatory state with high levels of proinflammatory cytokines is present in the SLE-sSS subgroup. This is a novel observation that may affect future understanding and treatment of the SLE-sSS subset.


Bilateral orbital involvement in Erdheim-Chester disease.
Erdheim-Chester disease is an idiopathic condition characterized by a xanthogranulomatous process infiltrating the bones, lungs, heart, retroperitoneum and other tissues. This condition is often fatal. Ocular findings are rare. The authors report a case of bilateral xanthelasmas and bilateral massive orbital infiltration in a 61-year-old man with severe retroperitoneal fibrosis, renal and cardiovascular problems. The ophthalmic manifestations and differential diagnosis of this peculiar pathologic condition are discussed.