Microbe participation in aroma production during soy sauce fermentation.
Soy sauce is a traditional Japanese fermented seasoning that contains various constituents such as amino acids, organic acids, and volatiles that are produced during the long fermentation process. Although studies regarding the correlation between microbes and aroma constituents have been performed, there are no reports about the influences of the microbial products, such as lactic acid, acetic acid, and ethanol, during fermentation. Because it is known that these compounds contribute to microbial growth and to changes in the constituent profile by altering the moromi environment, understanding the influence of these compounds is important. Metabolomics, the comprehensive study of low molecular weight metabolites, is a promising strategy for the deep understanding of constituent contributions to food characteristics. Therefore, the influences of microbes and their products such as lactic acid, acetic acid, and ethanol on aroma profiles were investigated using gas chromatography/mass spectrometry (GC/MS)-based metabolic profiling. The presence of aroma constituents influenced by microbes and chemically influenced by lactic acid, acetic acid, and ethanol were proposed. Most of the aroma constituents were not produced by adding ethanol alone, confirming the participation of yeast in aroma production. It was suggested that lactic acid bacterium relates to a key aromatic compound, 2,5-dimethyl-4-hydroxy-3(2H)-furanone. However, most of the measured aroma constituents changed similarly in both samples with lactic acid bacterium and acids. Thus, it was clear that the effect of lactic acid and acetic acid on the aroma profile was significant.


[Infantile hemangiomas: differential diagnosis and associated anomalies].
Infantile hemangiomas are frequent benign vascular tumors that are often easily recognized. However, the diagnosis between infantile hemangiomas and other vascular tumors, whether benign or malignant, may be difficult. This chapter describes the different clinical presentations of hemangiomas and details the investigations that are needed to confirm the nature of the lesion and to diagnose the potentially associated anomalies. Knowledge on differential diagnosis enables clinicians to detect hemangiomas that can lead to complications and that necessitate a multidisciplinary approach.


A novel generation adversarial network framework with characteristics aggregation and diffusion for brain disease classification and feature selection.
Imaging genetics provides unique insights into the pathological studies of complex brain diseases by integrating the characteristics of multi-level medical data. However, most current imaging genetics research performs incomplete data fusion. Also, there is a lack of effective deep learning methods to analyze neuroimaging and genetic data jointly. Therefore, this paper first constructs the brain region-gene networks to intuitively represent the association pattern of pathogenetic factors. Second, a novel feature information aggregation model is constructed to accurately describe the information aggregation process among brain region nodes and gene nodes. Finally, a deep learning method called feature information aggregation and diffusion generative adversarial network (FIAD-GAN) is proposed to efficiently classify samples and select features. We focus on improving the generator with the proposed convolution and deconvolution operations, with which the interpretability of the deep learning framework has been dramatically improved. The experimental results indicate that FIAD-GAN can not only achieve superior results in various disease classification tasks but also extract brain regions and genes closely related to AD. This work provides a novel method for intelligent clinical decisions. The relevant biomedical discoveries provide a reliable reference and technical basis for the clinical diagnosis, treatment and pathological analysis of disease.


Neoadjuvant erlotinib and surgical resection of a stage iiia papillary adenocarcinoma of the lung with an L861Q activating EGFR mutation.
The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is evolving, as is an understanding of predictive biomarkers for tumour response in non-small-cell lung cancer (NSCLC). In this report, we describe a case of rapidly progressing, borderline-resectable, clinical stage IIIA (micro) papillary adenocarcinoma in a 78-year-old woman who experienced a profound response to neoadjuvant erlotinib without short-term toxicity. On EGFR mutation testing, this patient had an uncommon activating point mutation at L861Q in exon 21. Her response permitted successful surgical resection with negative margins and avoidance of chemoradiation, which she was deemed too frail to tolerate. Our case addresses unique management issues such as preoperative testing for EGFR mutation, utility of histology in predicting EGFR mutations, and use of EGFR-TKIs pre- and postoperatively for potentially resectable NSCLC.


Paraprofessional versus professional drug counselors: diverse routes to the same role.
The backgrounds and roles of ex-addict ( EXA ) and non-ex-addict (NEA) paraprofessional methadone maintenance and drug-free out-patient counselors were contrasted with those of degreed professional counselors (PRO). There was no evidence of differential assignment of clients to counselors based on drug use, drug treatment, criminal, educational, and employment histories. The three counselor groups were remarkably similar in their participation in 11 areas of job activities ranging from counseling duties per se through administrative support functions. The only reliable difference was the greater involvement of EXAs in counseling and community education activities which took them outside the program.


A public health approach to the needs of children affected by terrorism.
The devastating terrorist incidents of Pan Am Flight 103, the Oklahoma City bombing, the bombings of the embassies in Kenya and Tanzania, and the World Trade Center attack of September 11, 2001, have forever changed America. These terrorist acts have deeply shaken the sense of safety, security, and well-being of our surviving children and families. These terrorist acts may also have increased the public health risks of substance abuse and mental illness for our children. The Substance Abuse and Mental Health Services Administration is responsible for strengthening prevention and treatment of substance abuse and mental illness in children and families. America's children may exhibit a wide range of emotional, physical, and psychological reactions following natural and man-made disasters. Large-scale disasters witnessed by children all underscore the need for a broad mental health and substance abuse public health approach. This approach is critical for our children's well-being.


Evidence of Structure Sensitivity in the Fischer-Tropsch Reaction on Model Cobalt Nanoparticles by Time-Resolved Chemical Transient Kinetics.
The Fischer-Tropsch process, or the catalytic hydrogenation of carbon monoxide (CO), produces long chain hydrocarbons and offers an alternative to the use of crude oil for chemical feedstocks. The observed size dependence of cobalt (Co) catalysts for the Fischer-Tropsch reaction was studied with colloidally prepared Co nanoparticles and a chemical transient kinetics reactor capable of measurements under non-steady-state conditions. Co nanoparticles of 4.3 nm and 9.5 nm diameters were synthesized and tested under atmospheric pressure conditions and H2 /CO=2. Large differences in carbon coverage (ΘC ) were observed for the two catalysts: the 4.3 nm Co catalyst has a ΘC less than one while the 9.5 nm Co catalyst supports a ΘC greater than two. The monomer units present on the surface during reaction are identified as single carbon species for both sizes of Co nanoparticles, and the major CO dissociation site is identified as the B5 -B geometry. The difference in activity of Co nanoparticles was found to be a result of the structure sensitivity caused by the loss of these specific types of sites at smaller nanoparticle sizes.


Seven-week continuous-infusion paclitaxel concurrent with radiation therapy for locally advanced non-small cell lung and head and neck cancers.
The goal of these National Cancer Institute-sponsored phase I trials is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel combined with standard, curative-intent thoracic radiation therapy (XRT) for previously untreated, locally advanced non-small cell lung cancer and squamous cell cancer of the head and neck (HNSCC). Eligible patients have locally advanced (T4NXM0 or TXN2-3M0) non-small cell lung cancer ineligible for potentially curative surgical resection or locally advanced HNSCC with an expected 5-year survival rate of less than 25%, as well as a good performance status, adequate hematologic, hepatic, and renal function, and no distant metastases. Non-small cell lung cancer patients receive a total tumor dose of 64.8 Gy megavoltage XRT in 7 weeks at 1.8 Gy once daily, 5 d/wk. Patients with HNSCC receive 70 Gy megavoltage XRT in 7 weeks at 2 Gy once daily, 5 d/wk. Paclitaxel is delivered by continuous intravenous infusion starting 48 hours before XRT and continuing for its duration. The dose of paclitaxel is escalated in cohorts of three patients in a standard phase I design. To date, 49 patients have been entered on both studies and 43 are evaluable for toxicity. Paclitaxel dose is currently at the 17 mg/m2/d dose level, with no dose-limiting toxicity thus far. Clinical outcomes suggest significant activity for this combination. This therapy is feasible and has been well-tolerated through current dose levels. Dose escalation is ongoing.


Involvement of claudins in zebrafish brain ventricle morphogenesis.
Zebrafish brain ventricle morphogenesis involves an initial circulation-independent opening followed by a blood flow- and circulation-dependent expansion process. Zebrafish claudin-5a is required for the establishment of a neuroepithelial-ventricular barrier, which maintains the hydrostatic pressure within the ventricular cavity, thereby contributing to brain ventricle opening and expansion. In mammalia, several claudin family members, including claudin-3 and claudin-5, are expressed within microvessel endothelial cells of the blood-brain barrier. Whether zebrafish brain ventricle morphogenesis provides a model for studying these claudins during early embryonic development was unknown. This review focuses on the expression and function of these zebrafish claudins during brain ventricle morphogenesis.


Single nucleotide polymorphisms in toll-like receptor genes and case-control association studies with bovine tuberculosis.
Toll-like receptor 2 (TLR2) and TLR4 genes play critical roles in host recognition of Mycobacterium bovis infection and initiation of innate and adaptive immune response. The present study was aimed at exploring the association of seven single nucleotide polymorphisms (SNPs) in TLR2 and TLR4 genes with susceptibility/resistance against bovine tuberculosis (bTB) infection in cattle. A case-control resource population of 35 positive and 45 negative animals was developed after screening with single intradermal tuberculin test for bTB. Resource population was screened for SNPs in TLR2 and TLR4 genes using polymerase chain reaction-restriction fragment length polymorphism. The PROC LOGISTIC procedure of SAS 9.3 was used to find an association of allelic and genotypic frequencies with bTB. In TLR2 gene, two of SNPs under study (rs55617172 and rs68268253) revealed polymorphism while in the case of TLR4 gene all four SNPs under investigation (rs8193041, rs207836014, rs8193060, and rs8193069) were found to be polymorphic in case-control population. SNP locus rs55617172 in TLR2 gene was found significantly (p<0.01) associated with susceptibility/resistance to TB in cattle. These findings indicate the presence of SNPs in TLR2 and TLR4 genes in our resource population. Upon validation in independent, large resource population and following biological characterization, SNP rs55617172 can be incorporated in marker panel for selection of animals with greater resistance to bTB.


Wound healing of the nasal and paranasal mucosa: a review.
Wound healing is a highly coordinated process involving clot formation, inflammatory reaction, immune response, and, finally, tissue remodeling and maturation. Only few data regarding the specific healing of the nasal or sinusal mucosa are available. After a short summary of the general principles of wound healing, the most important data regarding in vitro or in vivo models of wound healing of the nasal and paranasal mucosa are discussed. Attention is paid to clinical application. First observations regarding the specific regulation of epithelial regeneration by growth factors have underlined the complex relationship between extracellular matrix and epithelium during the repair process. However, only poor and aspecific correlations can be described between endoscopically and histomorphologically defined postoperative phases.


Efficacy of Cognitive Behavioral Therapy in Adherence to the Mediterranean Diet in Metabolic Syndrome Patients: A Randomized Controlled Trial.
Verify the efficacy of cognitive behavioral therapy (CBT) in adherence to the Mediterranean diet (MedDiet) in metabolic syndrome (MetS) patients. In the Multimodal Intervention Program for Patients with Metabolic Syndrome clinical trial, 79 MetS patients completed the intervention. Of those, 48 belonged to the experimental group and 31 to the control group. The intervention received by the experimental group was CBT; the control group followed usual care and attended a workshop on healthy lifestyle. Anthropometric, biochemical, psychological, and lifestyle measures were taken before and after the intervention at 3 and 6 months. Analyses included paired t tests, ANOVA, and ANCOVA. The ANOVA results showed a statistically significant interaction between the 2 groups in waist circumference (P = .009), triglycerides (P = .015), and adherence to the MedDiet (P = .026). The ANCOVA results indicated between-group difference in waist circumference (P = .026 and .062 at 3 and 6months, respectively), in triglycerides (P = .009 and .860 at 3 and 6 months, respectively), and in MedDiet (P = .024 and .273 at 3 and 6 months, respectively). In interventions in which CBT was applied, significant improvements were observed in MetS patients, especially in adherence to the MedDiet.


Wave reflections and the arterial pulse.
Studies of aortic dynamics have provided new information about the peripheral pulse. This brief review provides a summary of these findings and relates them to a number of clinical conditions.


Calmodulin colocalization with cold-stable and nocodazole-stable microtubules in living PtK1 cells.
To investigate the association of calmodulin (CaM) with microtubules (MTs) in the mitotic apparatus (MA), the distributions of both CaM and tubulin were examined in mitotic PtK1 cells in which MT subclasses had been selectively removed or altered by treatment with cold or with the MT inhibitor, nocodazole. A fluorescent CaM conjugate with tetramethylrhodamine isothiocyanate (CaM-TRITC) was microinjected into living cells, and the CaM distribution in the living cell was compared to the distribution of MTs indicated by tubulin immunofluorescence. In cells which had been treated for 2 h at 0 to 4 degrees C or with a low (0.03 micrograms/ml) dose of nocodazole, the only MTs remaining appeared to be kinetochore MTs (kMTs). The distribution of microinjected CaM-TRITC in these cells was indistinguishable from that found in untreated cells and appeared to be colocalized with the kMTs. In cells which were treated with a high (3.0 micrograms/ml) dose of nocodazole, only short MTs remained. When CaM-TRITC was injected into these cells, it formed a somewhat punctate distribution near the chromosomes and, after tubulin immunofluorescence processing, colocalized with what appeared to be remnants of kMTs. We believe that these observations support the hypothesis that CaM exists in the MA in a structural association with kMTs.


Biomimetic emulsions reveal the effect of mechanical forces on cell-cell adhesion.
Cell-cell contacts in tissues are continuously subject to mechanical forces due to homeostatic pressure and active cytoskeleton dynamics. In the process of cellular adhesion, the molecular pathways are well characterized but the role of mechanics is less well understood. To isolate the role of pressure we present a dense packing of functionalized emulsion droplets in which surface interactions are tuned to mimic those of real cells. By visualizing the microstructure in 3D we find that a threshold compression force is necessary to overcome electrostatic repulsion and surface elasticity and establish protein-mediated adhesion. Varying the droplet interaction potential maps out a phase diagram for adhesion as a function of force and salt concentration. Remarkably, fitting the data with our theoretical model predicts binder concentrations in the adhesion areas that are similar to those found in real cells. Moreover, we quantify the dependence of the area of adhesion on the applied force and thus reveal adhesion strengthening with increasing external pressure even in the absence of active cellular processes. This biomimetic approach reveals a physical origin of pressure-sensitive adhesion and its strength across cell-cell junctions.


Dialytic therapy for diabetic patients with terminal renal failure.
Diabetes mellitus is the leading cause of irreversible renal failure in the United States, Japan, and industrialized Europe. Of those diabetic patients begun on uremia therapy, 80% are treated with hemodialysis and 12% with peritoneal dialysis. Continuous ambulatory peritoneal dialysis is proposed by some as appropriate primary therapy for many diabetics with end-stage renal disease (ESRD), but peritonitis is common at one episode per 11 to 21 patient-months. Cardiovascular disease is accelerated in patients with diabetic ESRD and is the most common cause of death in diabetic dialysis patients. Although survival of diabetic ESRD patients is lower than that of nondiabetic patients (1- and 5-year patient survival is 74% and 19%, respectively, in diabetics and 78% and 40%, respectively, in all ESRD patients), morbidity and mortality figures have improved steadily over the past two decades. When possible, renal transplantation is advised as the treatment most likely to effect rehabilitation and long survival.


Sublethal and transgenerational effects of thiamethoxam applied to cotton seed on Chrysoperla externa and Harmonia axyridis.
Thiamethoxam, when applied as a seed treatment, can contaminate plant products, such as extrafloral nectar, and have non-target effects on beneficial arthropods. This study assessed the non-target effects of thiamethoxam applied to cotton seed on the life history parameters of the predators Chrysoperla externa (Neuroptera: Chrysopidae) and Harmonia axyridis (Coleoptera: Coccinellidae). Exposure of C. externa larvae to plants grown from thiamethoxam-treated seeds caused sublethal and transgenerational effects. Thiamethoxam treatment doubled the proportion of pharate adults and reduced egg fertility in C. externa F0 and F1 generations. In addition, the insecticide prolonged pupal developmental time in the C. externa F1 generation. Thiamethoxam treatment also had a transgenerational effect on exposed H. axyridis larvae, reducing pupal survival in the F1 generation. In the adult bioassay, thiamethoxam treatment reduced egg fertility of C. externa, prolonged the larval period, and reduced both fecundity and egg fertility of the F1 generation. Thiamethoxam also caused transgenerational effect on H. axyridis adults, reducing larval survival of the F1 generation. Thiamethoxam seed treatment was harmful for both predators, but C. externa was more affected by the insecticide than H. axyridis. © 2018 Society of Chemical Industry.


Cardiovascular impact of testosterone therapy for hypogonadism.
Since 2010 some evidence supporting the possible increased cardiovascular (CV) risk related to testosterone treatment (TTh) has created much debate in the scientific community. Based on these results, the US Food and Drug Administration agency has questioned TTh for aging men recognizing its value only for classical hypogonadism due to genetic or organic causes. To better clarify this topic, we scrutinized and summarized, also by using meta-analytic methods, the data generated during the last 7 years, as derived from the analysis of randomized controlled trials (RCTs) on TTh and CV risk. Areas covered: Analysis included 31 RCTs published between 2010 and 2018. Retrieved trials included 2675 and 2308 patients in TTh and placebo groups, respectively. The analysis documented that TTh was not associated with an increased CV mortality or morbidity either when overall or major adverse CV events were considered. Expert commentary: Despite present evidence it is important to recognize that the duration of the available trials is short (lower that 3 years) limiting final conclusions on this topic. In particular, the available information on possible long-term effects of TTh on CV risk is limited. Long-term safety studies are advisable to better clarify these points.


[The comparative characteristics of the antibacterial activity of new antiseptics and the prospects for their use in dental practice].
Antibacterial activities of modern antiseptics listerine, myramistine, cidipol, octenisept, tantum verde, matecide, and rautine drugs chlorhexidine and dioxidine are compared. The prospects of their use in dentistry for the treatment of inflammations associated with anaerobes are discussed. Metacide, listerine, chlorhexidine, and dioxidine are characterized by the widest spectrum of activity towards obligate anaerobic bacteria; moreover, these drugs inhibit bacterial growth when used in lower concentrations than other drugs.


[Sociohygienic monitoring in the Russian Federation: problems and tasks].
The State sociohygienic monitoring (SHM) system is one of the most important mechanisms of providing sanitary-and-epidemiological well-being in the population. The March 30, 1999 Federal Law on Sanitary-and-Epidemiological Well-being of the Population" refers SHM to as one of the mechanisms of state regulation in this field and defines as a state system for monitoring the population's health and the environment, for analyzing, evaluating, and predicting them, and for revealing cause-and-effect relations between the population's health status and the influence of environmental factors. Much work has been recently done to establish and manage a federal information fund (FIF) that is a database on the human health status and environment, based on long-term observations and an aggregate of normative legal acts and reference materials on the analysis of prediction and determination of cause-and-effect relations between the human health status and the influence of environmental factors. FIF obtains information from a great many sources, including databases of state executive authorities. This information is open and available to the institutions and organizations involved in the establishment of FIF. The elaboration and introduction of new, more informative indices for SHM management at the present stage are one of the urgent tasks. In accordance with the May 28, 2000 decision of the Board of the Ministry of Health of Russia, with the 2003-2004 regulatory documents of the Ministry of Health of Russia, much work to improve the list of SHM indices has been under way. The draft list of SHM indices is harmonized with the indices of the European SHN information system, with the list of social diseases, approved by the Russian Federation's Government Regulation No. 715 dated December 1, 2004, and the list of national security threat indices (A 21-2162 dated August 29, 2003). The draft list has been considered by the specialists of the Federal Service for Surveillance of Consumers' Rights Protection and Human Well-being; comments have been taken into account. The draft is under reconsideration and will require approval in the near future.


[X-ray morphology of osseous changes in pigmented villonodular synovitis of the joints].
Pigmented villonodular synovitis (PVNS) of the joints is a rare, benign and generally monoarticular tumour-like soft tissue lesion of the synovium. The secondary bone changes, seen in plain films of 25 patients with PVNS are described. The main radiological features were paraarticular erosions, often with a thin sclerotic border. As a late manifestation these erosions tended to coalesce and to form large multicystic areas. These defects were observed particularly in the more tightly encapsulated joints, such as the hip, wrist, finger and toe. In 3 cases with involvement of the knee the lesions were monostotic. PVNS may be mistaken radiologically for other lesions such as malignant tumours or inflammatory disorders. The differential diagnosis is discussed.


Attitudes Toward Bile Extraction From Living Bears: Survey of Citizens and Students in Beijing.
Bear bile is a traditional Chinese medicine that has been used for millennia. Several arguments support and oppose the use of bear farming in terms of conservation and nonhuman animal welfare. This study involved designing a questionnaire and surveying a random sample of general citizens and college students in Beijing to elicit their attitudes on bile extraction from living bears. Older people and people with lower education levels used more bear bile medicines. In total, 29.47% (n = 204) of citizens and 23.14% (n = 81) of students surveyed used bear bile medicine since 1990. Students were less willing to use bear bile medicines than citizens (p < .05). The level the respondents agreed with the blue side (against the extraction of bile from living bears; anti for short) was significantly higher than that for the red side (support the extraction of bile from living bears; pro for short; p < .05). Additionally, college students had a more distinct attitude toward the opposing views, which indicates they were more inclined to oppose bile extraction from living bears.


The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan.
Background and objective Allogeneic hematopoietic stem cell transplantation (alloHSCT) provides curative treatment for several hematological illnesses. In this study, we evaluated the impact of ABO compatibility and incompatibility on outcomes and complications related to hematopoietic stem cell transplantation (HSCT) performed for various hematological disorders at our center. Methodology This was a retrospective, single-center, cohort study in which patients were categorized according to the ABO match and mismatch status. The mismatch group was further subcategorized into major, minor, and bidirectional groups. Results A total of 117 patients underwent alloHSCT, out of which 82 (70.1%) were male and 35 (30%) were female. The median age of the patients was 9.5 years (range: 46 years). The most common indications for stem cell transplant were beta-thalassemia major (BTM; n=58, 49%) and aplastic anemia (AA; n=42, 35.8%). However, the outcomes in match and mismatch groups showed significant results for positive direct Coombs test (DCT), indicating the occurrence of hemolysis. Despite the increased need for blood transfusions, ABO blood group incompatibility (ABOi) had no negative impact on the clinical results. Conclusion Based on our findings, ABO incompatibility does not affect the outcomes in patients undergoing alloHSCT. Patient monitoring can aid in early detection and treatment, thereby minimizing the frequency of fatal events.


Association Between Blood Lead Levels and Hypertension in a South Indian Population: A Case-Control Study.
Background Exposure to lead and its accumulation in the body can lead to progressive adverse effects, including increased blood pressure which is associated with the onset of cardiovascular diseases. In this study, we aimed to determine the relationship between blood lead levels and blood pressure. In addition, we compared blood lead levels between hypertensives and normotensives to determine relationships, if any, between lead exposure and high blood pressure. Methodology This was a hospital-based, case-control study. In total, 102 individuals (hypertensives = 51, normotensives = 51) were included in this study. Hypertensive patients (defined as systolic blood pressure (SBP) of ≥140 mmHg, diastolic blood pressure (DBP) of ≥90 mmHg, or taking antihypertensive medication for regulating blood pressure) were considered to be study cases and normotensive individuals were considered to be study controls. Blood lead levels were compared between the two groups, and the effects of blood lead levels on SBP and DBP were estimated. The blood lead levels were measured using optical emission spectrometry. Results The mean blood lead level among hypertensive individuals (5.5743 ± 1.77 µg/dL) was significantly higher compared to normotensive individuals (4.5029 ± 1.3213 µg/dL, P = 0.001). A positive correlation was detected between blood lead levels and SBP (r = 0.304, P = 0.002). However, no significant correlation was found between blood lead levels and DBP. Conclusions Blood lead levels were significantly higher in hypertensive patients compared to normotensive individuals. A significant positive correlation was observed between blood lead levels and SBP.


Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable breast cancer: preliminary data of a prospective randomized trial.
Paclitaxel has significant antitumor activity in patients with metastaticbreast cancer who have been previously treated with or exposed to anthracycline-containing chemotherapy. In this prospective randomized trial, the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer. Five hundred twenty-four patients were randomized to be treated either with 4 cycles of paclitaxel followed by 4 cycles of combination therapy with 5-fluorouracil, Adriamycin, and cyclophosphamide (Pac/FAC) or with 8 cycles of FAC alone. Patients with intact primary breast cancer received the initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting. Planned duration of therapy was the same in all patients. After completion of 8 cycles of chemotherapy, those patients who were > or =50 years and whose tumors were positive for estrogen receptors received tamoxifen for 5 years. Ninety-two patients have had a recurrence after a median follow-up of 60 months with a range of 5-89 months. Estimated disease-free survival at 48 months was 0.83 for FAC and 0.86 for Pac/FAC group. The difference between the two groups was not statistically significant (P = 0.09). The overall estimated hazard ratio for Pac/FAC compared with FAC derived by fitting the Cox regression model and incorporating terms for prognostic factors was 0.66. Preliminary results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or neoadjuvant therapy may further reduce the risk of disease recurrence; however, differences were not statistically significant. At the time of this analysis, there have been 47 deaths. The survival data are too preliminary to permit meaningful evaluation of the impact of paclitaxel on mortality.


Usefulness of various lactate dehydrogenase isoenzyme 1 profiles after myocardial infarction.
Isoenzyme profiles of lactate dehydrogenase (percent LD-1 of total LD, LD-1/LD-2 ratio, and absolute LD-1) have all been studied as late markers for myocardial infarction. It is known, however, that elevations of LD-5 frequently occur in this period as a result of liver congestion. Elevations of LD-5 may also occur as a result of complicating conditions. Such elevations could result in a reduced percent LD-1 of total LD, giving rise to false negatives. Receiver operating characteristic (ROC) curves were constructed for LD-1, LD-1/LD-2 and percent LD-1 of total LD from 285 specimens (124 patients) with suspected myocardial infarction. There was little difference in overall diagnostic power among the three assays. Using cutoffs determined from the ROC curves, 6 patients (18 specimens) were evaluated who appeared to be in the late period or who exhibited complicating conditions which could increase LD-5. In 14/18 specimens, increases in LD-5 resulted in false negatives by percent LD-1 of total LD. Only 5/18 specimens were false negatives by LD-1 or LD-1/LD-2. It is concluded that the percent LD-1 of total LD was affected by an increase in LD-5, and caution is recommended when using it.


Downregulation of long non-coding RNA ANRIL suppresses lymphangiogenesis and lymphatic metastasis in colorectal cancer.
This study aimed to investigate the effect of ANRIL on the lymphangiogenesis and lymphatic metastasis in colorectal cancer. Using RT-PCT and Northern blot, we detected ANRIL expression in tissues (cancer vs. normal) and cell lines (HCoEpic, SW480, HT29, LoVo and HCT116), finding that ANRIL was overexpressed in colorectal cancer. By statistical analysis, increased ANRIL was found to be in close association with TNM staging, Duke staging and lymphatic metastasis and poor prognosis. We down-regulated the high ANRIL expression in LoVo and HCT116 with lentivirus transfection, and found that the activity of cell mobility and invasion was remarkably reduced. And also we also identified that ANRIL down-regulation could suppress in-vitro tube formation HLECs invasion. In addition, we built a mouse model of colorectal cancer. In the mouse model, we recorded, after ANRIL downregulation, decreased tumor growth rates and tumor size and reduced lymphatic metastasis rate and frequency of transferred lymph nodes, LMVD and expressions of VEFG-C, VEGFR-3 and LYVE-1. Based on these findings, we concluded that increased ANRIL is promoter in the development of colorectal cancer. Through down-regulation of the overexpressed ANRIL, lymphangiogenesis may be suppressed and therefore lymphatic metastasis may be inhibited. On this ground, we suggest that ANRIL may be a therapeutic target for colorectal cancer.


The Korean American woman's face: anthropometric measurements and quantitative analysis of facial aesthetics.
To assess the differences in facial proportions between Korean American (KA) women and North American white (NAW) women and to quantitatively describe aesthetic facial features in the KA women. Anthropometric survey and facial aesthetic evaluation. Volunteer sample of KA women (n = 72) who served as models for part 1 of the study and a different sample of KA women (n = 5) and men (n = 5) who served as judges for part 2 of the study. All subjects were between ages 18 and 35 years and had Korean parents and no previous facial surgery or trauma. Intervention For part 1 of the study, standardized and referenced frontal and lateral photographs were taken of the models, and 26 standard anthropometric measurements were determined. Results were compared with published NAW standards. For part 2 of the study, 10 judges evaluated frontal views of the models for facial aesthetics using a visual analog scale. Quantitative analysis was done of the faces of attractive KA women (>90th percentile in aesthetic scores) and comparisons were made with the faces of NAW women and average KA women. The KA woman's face did not fit the neoclassical facial canons. Compared with NAW women, 24 of the 26 facial measurements in KA women were significantly different. Only 9 of the 26 facial measurements were significantly different when the attractive KA women were compared with the NAW women. Nine of the 17 nonsignificant facial measurements were very similar to those of the NAW women; many of these facial features centered around the midface. Although the average KA woman's facial anthropometric measurements were very different from those of the NAW woman, attractive KA women reflected many of the facial features of NAW women. These findings support the need for ethnically sensitive facial canons and further research into transcultural aesthetics.


Parental attitudes and expectations towards receiving genomic test results in healthy children.
Little evidence is available to guide returning genomic results in children without medical indication for sequencing. Professional guidelines for returning information on adult-onset conditions are conflicting. The goal of this study was to provide preliminary information on parental attitudes and expectations about returning medically actionable genomic results in children who have been sequenced as part of a population biobank.Four focus groups of parents with a child enrolled in a population biobank were conducted. A deliberative engagement format included education about professional guidelines and ethical issues around returning results to children. Parents were presented two scenarios where their healthy child has a pathogenic variant for: (a) a medically actionable childhood condition; (b) a hereditary cancer syndrome with no medical management until adulthood. Thematic analysis was conducted on verbatim transcripts. Regardless of the scenario, parents stated that the genomic information was important, was like other unexpected medical information, and disclosure should be tailored to the child's age and result. Parents wanted the results in their child's medical record. Reasons for learning adult-onset results in their healthy children included to prepare their child for necessary medical action in adulthood. Parents also provided suggestions for program design. This preliminary evidence suggests that parents desire genomic results and expect to use this information to protect their child's health. More empirical research on psychosocial adjustment to such information with continued engagement of parents and children is needed to further inform how to best support families in the communication and use of genomic information.


Radioarsenic from a portable (72)Se/(72)As generator: a current perspective.
Positron emission tomography (PET) of slower biological processes calls for the use of longer lived positron emitting radioisotopes. Beyond radionuclide production considerations, practicality and rapidity of subsequent labeling chemistry further limits the selection of radioisotopes with potentially favorable nuclear properties. One additional limitation is the availability of PET radiotracers at the point-of-care with appropriate on-site production methodologies or robust radionuclide generator systems. The positron emitter (72)As (half-life 26 h) is generated via decay of (72)Se (half-life 8.5 d); this pair comprises and excellent generator system for clinical availability of a longer lived PET isotope. Many (72)Se/As generator systems have been introduced utilizing the rich interplay of Se(IV)/Se(VI) and As(III) /As(V) chemical behavior. This paper describes available generator concepts, and briefly outlines some current arsenic labeling methodologies for the introduction of radioarsenic into biomolecules.


Biological activity and binding of estradiol to SK-Mel 23 human melanoma cells.
Patients expressing estradiol receptors in melanoma cells have been reported to have a better prognosis. We therefore decided to investigate the in vitro effects of beta-estradiol and tamoxifen on the growth and tyrosinase activity of SK-Mel 23 human melanoma cells. Twenty-four-hour treatment with 0.4 nM beta-estradiol inhibited cell proliferation in 30% (0.70 +/- 0.03 x 10(5) cells) and increased tyrosinase activity in 50% (7130.5 +/- 376.5 cpm/10(5) cells), as compared to untreated cells (1.0 +/- 0.05 x 10(5) cells and 4769 +/- 25.5 cpm/10(5) cells, respectively). Both responses were completely (100%) blocked by 1 microM tamoxifen. Higher concentrations (up to 1.6 nM) or longer treatments (up to 72 h) did not result in a larger effect of the hormone on proliferation or tyrosinase activity. Competition binding assays demonstrated the presence of binding sites to [2,4,6,7-3H]-beta-estradiol, and that the tritiated analogue was displaced by the unlabeled hormone (1 nM to 100 microM, Kd = 0.14 microM, maximal displacement of 93%) or by 10 microM tamoxifen (displacement of 60%). Beta-estradiol also increased the phosphorylated state of two proteins of 16 and 46 kDa, after 4-h treatment, as determined by Western blot. The absorbance of each band was 1.9- and 4-fold the controls, respectively, as determined with Image-Pro Plus software. Shorter incubation periods with beta-estradiol did not enhance phosphorylation; after 6-h treatment with the hormone, the two proteins returned to the control phosphorylation levels. The growth inhibition promoted by estradiol may explain the better prognosis of melanoma-bearing women as compared to men, and open new perspectives for drug therapy.


Follow-up of children who received complex invasive therapies early in life.
The present article reviews existing literature and outcome assessment processes used in programs that provide various complex paediatric therapies. The published literature is summarized, and enrolment and assessment details used in the Complex Paediatric Therapies Registry in the province of Alberta are discussed. Several studies have reported the outcomes of infants and children who received various complex invasive therapies. Four hundred eighty-three infants and children who received specific complex therapies in Alberta and survived to discharge were enrolled in neonatal follow-up programs in their home provinces. Compliance rates are 96% or higher at baseline, 18 months and four years of age. In general, cerebral palsy, blindness and deafness are very rare, but developmental delay and borderline cognitive function are more frequent. Analysis of the predictors of the adverse outcomes of such infants has permitted optimal parent counselling and initiation of efforts to improve outcomes.


The association of periodontal disease parameters with systemic medical conditions and tobacco use.
The objective of this study was to determine if an association existed between periodontal disease and various systemic medical conditions and tobacco use. The study design was a case-controlled, retrospective chart review. Patient charts (n=2006) were selected from more than 13,000 active patients attending the University of Minnesota dental clinics. These charts were examined to determine patient's self-reported systemic condition and smoking history. In addition, the number of missing teeth and bone loss were recorded. Two examiners collected the data. One examiner abstracted patient's medical history from the standard clinic medical questionnaire. The second examiner assessed the radiographs and dental charts to determine bone loss and number of missing teeth. Each examiner was blind to the findings of the other. After adjusting for age, sex, diabetes and smoking (yes/no) status, seven conditions were significantly (p=0.0003-0.04) related to bone loss or number of missing teeth (vascular disease, heart surgery, vascular surgery, heart attack, thyroid problems, arthritis, stomach ulcers). From these conditions, thyroid problems and arthritis had a negative association with bone loss. These findings support the results from previous investigators that a number of systemic conditions and smoking are closely associated with missing teeth or bone loss.


Circulating antibodies and antigens in Presbytis monkeys infected with the filarial parasite Wuchereria bancrofti.
Levels of circulating filarial antigen, and humoral antibody to other defined antigenic targets, were measured over the course of experimental infection of three Presbytis cristatus monkeys with Wuchereria bancrofti. Circulating antigen levels, measured with an anti-phosphorylcholine monoclonal antibody, varied widely although all animals were positive for some period of the infection. Circulating antigen levels tended to be inversely related to the titre of anti-phosphorylcholine antibody, and this trend was maintained even following acid dissociation and inactivation of immune complexed host antibody. Other antibody specificities were measured by Western blotting against somatic proteins and immunoprecipitation of surface antigens. Amongst somatic antigens, targets between 14,000 and 200,000 daltons were recognised by monkey antibodies, but no correlation with infection status could be discerned. Likewise when measuring the response to the 29,000 dalton major adult surface glycoprotein, one animal produced a rapid response but the others did not recognise it until late in infection. In general, the experimental findings are characterised by wide variability between individuals, as may perhaps be expected in a primate host for a human spectral disease.


Number needed to treat in cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists: A systematic review with temporal analysis.
Cardiovascular outcome trials (CVOTs) investigating the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have highlighted some important differences among these medications. The recent American Diabetes Association and European Association for the Study of Diabetes consensus underlines that each trial constitutes a single experiment; therefore, it remains unclear if, and to what extent, the observed differences reflect the heterogeneous pharmacological properties of each compound. To help clarify the evidence, in this systematic review we investigated differences in trial characteristics which may have had an impact on the primary and secondary trial results, including baseline control of risk factors, prevalence of cardiovascular diseases, absolute rates of events, duration of the study, and definitions of the inclusion criteria and outcomes. Aiming at enhancing the clinical interpretation of these CVOTs, we quantified the absolute treatment effect over time in terms of the number needed to treat to avoid one major adverse cardiovascular event, showing variations among GLP-1RAs.


PSORS1C1 Hypomethylation Is Associated with Allopurinol-Induced Severe Cutaneous Adverse Reactions during Disease Onset Period: A Multicenter Retrospective Case-Control Clinical Study in Han Chinese.
Background: Allopurinol-induced severe cutaneous adverse reactions (SCARs), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), are life-threatening autoimmune reactions. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmune diseases. However, the potential role of aberrant DNA methylation in allopurinol-SCARs is largely unknown. Objective: To address the knowledge gap between allopurinol-SCARs and DNA methylation, we studied the DNA methylation profiles in peripheral blood cells from allopurinol-SCARs and allopurinol-tolerant subjects. Methods: A genome-scale DNA methylation profiling was conducted using the Illumina Infinium HumanMethylation450 (HM450) platform on 15 patients with allopurinol-SCARs (3 TEN, 2 SJS/TEN overlap and 10 SJS) and 20 age- and gender-matched allopurinol-tolerant controls at disease onset. Pyrosequencing was used to validate the candidate CpG (cytosine-guanine dinucleotide) sites in an independent cohort of 40 allopurinol-SCARs and 48 allopurinol-tolerants. Results: After bioinformatics analysis of methylation data obtained from HM450 BeadChip, we identified 41 differentially methylated CpG loci (P < 0.05) annotated to 26 genes showing altered DNA methylation between allopurinol-SCARs and allopurinol-tolerants. Among these genes, significant hypomethylation of PSORS1C1 (cg24926791) was further validated in a larger sample cohort, showing significant difference between DRESS and controls (P = 0.00127), ST (SJS and TEN) and controls (P = 3.75 × 10-13), and SCARs and controls (P = 5.93 × 10-15). Conclusions: Our data identified differentially methylated genes between allopurinol-SCARs and allopurinol-tolerant controls and showed that PSORS1C1 hypomethylation was associated with allopurinol-SCARs (OR = 30.22, 95%CI = 4.73-192.96) during disease onset, suggesting that aberrant DNA methylation may be a mechanism of allopurinol-SCARs. Limitations: Firstly, the data come from whole blood samples known to possess epigenetic heterogeneity, i. e., blood samples comprise a heterogeneous cell population with varying proportions of distinct cell-types with different DNA methylation patterns. Consequently, the interpretation of DNA methylation results should be performed with great caution due to the heterogeneous nature of the sample. Secondly, whether the identified disease-associated changes of epigenome precede disease onset, or result from the disease progression, needs further investigation. Comparing the methylation status before patients develop allopurinol-SCARs and after may help examine methylation levels from disease onset to disease progression.


Chlorambucil versus observation after anti-Helicobacter therapy in gastric MALT lymphomas: results of the international randomised LY03 trial.
Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty-one patients were registered. Ninety-seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow-up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = -9% to 29%, P = 0.15. No difference was detected in recurrence/progression-free survival [Hazard Ratio (HR) = 0.96, 95% CI = 0.41-2.2, P = 0.91] or overall survival (HR = 1.93, 95% CI = 0.39-9.58, P = 0.42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti-H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas.


Effects of running experience on coordination and its variability in runners.
The purpose of this study was to examine the differences in coordination variability in running gait between trained runners and non-runners using continuous relative phase (CRP) analysis. Lower extremity kinematic data were collected for 22 participants during the stance phase. The participants were assigned to either a runner or non-runner group based on running volume training. Segment coordination and coordination variability were calculated for selected hip-knee and knee-ankle couplings. Independent t-tests and magnitude-based inferences were used to compare the 2 groups. There were limited differences in the CRP and its variability among runners and non-runner groups. The runners group achieved moderately lower coordination compared with non-runners group in the phase angle for hip abduction/adduction and knee flexion/extension. The runners tended to show moderately lower coordination variability in the phase angle for knee flexion/extension and subtalar inversion/eversion in comparison to non-runners group. These results suggested that levels of experience as estimated from weekly training volume had little influence on coordination and its variability.


Ontogenetic difference in ethanol reinforcing properties: the role of the opioid system.
Previous data indicate that ethanol intoxication (3 g/kg, intragastric) on postnatal day (PD) 7 and 8 increases ethanol acceptance, but on PD 10 and 11 generates an aversion in infant rats. We investigated the participation of the opioid system in these effects. Subcutaneous administration of naloxone (1 or 10 mg/kg) followed by ethanol intoxication on PD 7 and 8 prevented the increased ethanol intake effect observed in the younger pups, but when ethanol intoxication occurred on PD 10 and 11, naloxone treatment did not affect the aversion observed at this age. An aversion to ethanol was evidenced in the younger pups administered ethanol and naloxone, but only when exposed to ethanol odor during ethanol intoxication. Results indicate that the increased ethanol acceptance induced by ethanol intoxication in the younger pups is mediated by the opioid system, and that ethanol may also induce conditioned aversions at this early age.


Air travel and children's health issues.
With more children travelling by air, health care professionals should become more familiar with some of the unique health issues associated with air travel. A thorough literature search involving a number of databases (1966 to 2006) revealed very few evidence-based papers on air travel and children. Many of the existing recommendations are based on descriptive evidence and expert opinion. The present statement will help physicians to inform families about the health-related issues concerning air travel and children, including otitis media, cardiopulmonary disorders, allergies, diabetes, infection and injury prevention. An accompanying document (Information for Parents and Caregivers) is also available in this issue of Paediatrics & Child Health (pages 51-52) to help answer common questions from parents.


2,2'-Anhydro-1-(3',5'-di-O-acetyl-β-D-arabinofuranosyl)uracil, a cyclouridine nucleoside with a C4'-endo furanosyl conformation.
2,2'-Anhydro-1-(3',5'-di-O-acetyl-β-D-arabinofuranosyl)uracil, C13H14N2O7, was obtained by refluxing 2',3'-O-(methoxymethylene)uridine in acetic anhydride. The structure exhibits a nearly perfect C4'-endo ((4)E) conformation. The best four-atom plane of the five-membered furanose ring is O-C-C-C, involving the C atoms of the fused five-membered oxazolidine ring, and the torsion angle is only -0.4 (2)°. The oxazolidine ring is essentially coplanar with the six-membered uracil ring [r.m.s. deviation = 0.012 (5) Å and dihedral angle = -3.2 (3)°]. The conformation at the exocyclic C-C bond is gauche-trans which is stabilized by various C-H...π and C-O...π interactions.


Enzymatic release of folate activity from the red cells in megaloblastic anaemia of pregnancy.
The content of folate activity precursors in washed red cells and the enzymatic plasma factor activity, necessary for the release of folate from the precursors, were studied in normal subjects and in patients with megaloblastic anaemia of pregnancy. Subjects with megaloblastic anaemia of pregnancy had a significantly reduced folate activity precursor content, and 14 subjects (58%) had significantly low plasma factor activity, which in at least four subjects may have been due to the presence of inhibitors. This study indicates that impaired activity of the plasma factor may play a part in the aetiology of megaloblastic anaemia of pregnancy.


Coronary response to diadenosine pentaphosphate after ischaemia-reperfusion in the isolated rat heart.
Diadenosine polyphosphates are vasoactive mediators that may be released from platelet granules and which may be present at higher concentrations during coronary ischaemia-reperfusion. The objective of this study was to analyse their effects in such conditions. Rat hearts were perfused in a Langendorff preparation and the response to diadenosine pentaphosphate (Ap5A, 10(-7)-10(-5) M) was recorded. In control hearts, Ap5A produced a small, transient coronary vasoconstriction followed by marked vasodilatation, as well as a reduction in the left ventricular developed pressure dP/dt and heart rate, both at the basal coronary resting tone or after pre-contracting coronary arteries with 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F2alpha (U46619). After ischaemia-reperfusion, the vasoconstriction in response to Ap5A was augmented and vasodilatation diminished, both in hearts with basal or increased vascular tone. The pyridoxal derivative P(2) purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 3 x 10(-6) M), inhibited this vasoconstriction, while the antagonist of purinergic P(2Y) receptors, Reactive Blue 2 (2 x 10(-6) M), inhibited the vasodilatation, both before and after ischaemia-reperfusion. The antagonist of nitric oxide synthesis N-omega-nitro-L- arginine methyl ester (L-NAME, 10(-4) M) did not modify the response to Ap5A, whereas the cyclooxygenase inhibitor, meclofenamate (2 x 10(-6) M), reduced contraction and increased the relaxation in response to Ap5A after ischaemia-reperfusion but not under control conditions. Ischaemia-reperfusion reduces the vasodilatory response to Ap5A and increases the vasoconstriction provoked due to a reduced influence of purinergic P(2Y) receptors and/or to the production of vasoconstrictor prostanoids.


Design of Copper-Based Bimetallic Nanoparticles for Carbon Dioxide Adsorption and Activation.
Cu-based nanoparticles (NPs) are promising candidates for the catalytic hydrogenation of CO2 to useful chemicals because of their low cost. However, CO2 adsorption and activation on Cu is not feasible. In this work we demonstrate a computational framework that identifies Cu-based bimetallic NPs able to adsorb and activate CO2 based on DFT calculations. We screen a series of heteroatoms on Cu-based NPs based on their preference to occupy a surface site on the NP and to adsorb and activate CO2 . We revealed two descriptors for CO2 adsorption on the bimetallic NPs, the heteroatom (i) local d-band center and (ii) electropositivity, which both drive an effective charge transfer from the NP to CO2 . We identified the CuZr bimetallic NP as a candidate nanostructure for CO2 adsorption and showed that although the Zr sites can be oxidized because of their high oxophilicity, they are still able to adsorb and activate CO2 strongly. Importantly, our computational results are verified by targeted synthesis, characterization, and CO2 adsorption experiments that demonstrate that i) Zr segregates on the surface of Cu, ii) Zr is oxidized to form a bimetallic mixed CuZr oxide catalyst, which iii) can strongly adsorb CO2 , whereas Cu NPs cannot. Overall our work highlights the importance of the generation of binding sites on a NP surface based on (catalyst) stability and electronic structure properties, which can lead to the design of more effective CO2 reduction catalysts.


Cystic lung disease in adult Indigenous Australians in the Northern Territory of Australia.
Indigenous Australians have a high prevalence of chronic lung diseases. However, no previous studies have reported on cystic lung disease in an Indigenous patient cohort. This report describes 20 adult Indigenous patients noted to have incidental lung cysts on chest computed tomography (CT) while being referred to undergo lung function tests in the Northern Territory of Australia. Of the total 20 Indigenous patients demonstrating presence of pulmonary cysts on chest CT scan, 13/20 (65%) were males with a mean age of 49.9 years (range 24-74 years), with no significant difference in age between males and females. The majority reported a smoking history and spirometry demonstrated moderate reduction in lung function parameters. While there was no pattern in the size or location of cysts, most demonstrated multiple cysts (55% had ≥5 cysts) with bilateral involvement (65%), alongside a range of concurrent pulmonary radiological abnormalities. The aetiology for lung cysts was largely unknown. This is the first report to illustrate cystic lung disease within an Indigenous population. Further radiology studies are required to investigate the causes and prognostications of cystic lung disease in Indigenous patients.


From disease modelling to personalised therapy in patients with CEP290 mutations.
Mutations that give rise to premature termination codons are a common cause of inherited genetic diseases. When transcripts containing these changes are generated, they are usually rapidly removed by the cell through the process of nonsense-mediated decay. Here we discuss observed changes in transcripts of the centrosomal protein CEP290 resulting not from degradation, but from changes in exon usage. We also comment on a landmark paper (Drivas et al. Sci Transl Med. 2015) where modelling this process of exon usage may be used to predict disease severity in CEP290 ciliopathies, and how understanding this process may potentially be used for therapeutic benefit in the future.


Identification of ICE2, a gene involved in cold acclimation which determines freezing tolerance in Arabidopsis thaliana.
Several transcription factors are presently known to regulate the response to cold stress. Here we describe a new positive regulator, ICE2, which is a transcription factor of the bHLH family that participates in the response to deep freezing through the cold acclimation-dependent pathway in Arabidopsis thaliana plants. An overexpression of ICE2 (as we named the At1g12860 locus) in transgenic Arabidopsis plants results in increased tolerance to deep freezing stress after cold acclimation. The seeds of transgenic lines that overexpressed ICE2 were characterized by decreased levels of carbohydrate and increased levels of lipids. The analysis of expression of CBF1 gene (also known as DREB1B), which have been shown to be required for the complete development of cold acclimation response in Arabidopsis indicated a difference between expression of the CBF1 gene in transgenic plants and the wild-type control plants, Col-0. These results suggested that the CBF1 transcription factor, known as one of the regulators of the cold stress response, has a dominant role in providing freezing tolerance in transgenic plants characterized by overexpression of ICE2.


Effects of HgCl2 on the expression of autoimmune responses and disease in diabetes-prone (DP) BB rats.
Repeated exposure of Brown Norway (BN) rats to relatively low doses of HgCl2 induces autoantibodies to renal antigens (e.g., laminin) and a membranous glomerulonephropathy characterized by proteinuria. In contrast, Lewis (LEW) rats are "resistant" to the autoimmune effects of mercury and, when exposed to this metal, are protected against experimental autoimmune encephalomyelitis (EAE) and Heymann's nephritis. To date, there is no information on "suppressive" effects of mercury in naturally occurring (so-called "spontaneous") rat models of autoimmune disease. Therefore, we have administered HgCl2 to diabetes-prone (DP) BB rats, animals that spontaneously develop both insulin-dependent diabetes mellitus (IDDM) and thyroiditis. We found that DP rats treated with mercury or water for a period of 40-125 days developed autoantibodies to thyroglobulin, with a higher incidence in HgCl2-injected animals (92% vs. 56% in H2O-injected controls). A novel finding of our study was the detection of autoantibodies to laminin in the same rats, again with an increased incidence after HgCl2 treatment (83% vs. 44%). IgG2a was the most frequently detected isotype of antibodies to laminin, followed by IgG1, IgG2b and IgG2c. The IgG isotype profile suggests that treatment with HgCl2 may activate both Th1 and Th2 lymphocytes in BB rats. In spite of these stimulatory effects on autoantibody responses, we found that there was no difference in the incidence of IDDM and thyroiditis between HgCl2-treated and control animals. We conclude that the suppressive effects of mercury previously observed in EAE and Heymann's nephritis of LEW rats do not occur in "spontaneous" autoimmune IDDM and thyroiditis of BB rats. Therefore, immune suppression caused by HgCl2 cannot be considered a common phenomenon, but may be a genetically determined characteristic of LEW rats, possibly related to a specific or unique cytokine profile of this particular rat strain. In contrast, while mercury does not seem to recruit, induce or rescue regulatory T cell function in DP rats, it does stimulate autoantibody responses in these animals.


Influence of interleukin-1alpha on androgen receptor expression and cytokine secretion by cultured human dermal papilla cells.
Dermal papilla cells (DPC) control the growth character of the hair follicle through their elaboration of mitogenic factors and extracellular matrix components. Further, the dermal papilla is a primary site of androgen action in the hair follicle. Interleukin-1alpha (IL-1alpha) is prominent in skin wounding and inflammatory responses although regarded as a negative hair growth regulator. We studied the effect of IL-1alpha and the potent androgen 5alpha-dihydrotestosterone (DHT) on the expression of the androgen receptor (AR) and various factors secreted by cultured human temporal scalp DPC. IL-1alpha triggered cellular changes consistent with nuclear factor-kappaB pathway activation as well as reduced AR mRNA and protein expression levels for DHT-stimulated DPC. This cytokine also increased DPC supernatant keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. IL-1alpha did not influence DPC supernatant levels of transforming growth factor-beta1, a negative hair growth regulator. The stimulatory effect of IL-1alpha on DPC VEGF, GM-CSF, KGF, and IL-8 expression was also evident at the mRNA level for these cytokines. IL-1alpha also increased mRNA transcript levels of protease-nexin-1, a secreted serine protease inhibitor expressed in the dermal papilla of anagen-stage hair follicles. Although DHT did not affect supernatant cytokine concentrations, the androgen altered mRNA transcript levels of several factors for DPC co-stimulated with IL-1alpha. In consideration of its in vitro activity profile, IL-1alpha may be an important modifier of dermal papilla activity as well as potentially influence androgen-regulated gene expression in DPC.


Effect of cocaine self-administration on striatal PKA-regulated signaling in male and female rats.
Chronic cocaine produces changes in the dopamine (DA)/D1/cAMP/protein kinase A (PKA)-regulated signaling pathway that may underlie the development of addiction. Given sex differences in the progression to cocaine addiction, we examined the possibility that the PKA pathway is differentially activated by cocaine in male and female rats. Rats were given 24-h access to cocaine (1.5 mg/kg) or saline for 7 days under a discrete trial procedure (four trials per hour). Rats were then retested on responding for cocaine under a progressive-ratio schedule after either 0 (no-delay retest) or 10 (10-day-delay retest) days of abstinence. Markers of PKA-regulated signaling in the striatum and nucleus accumbens were evaluated by Western blotting, including phosphorylation of DA and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at Thr 34 and glutamate receptor 1 (GluR1) at Ser 845. Compared to males, females had higher levels of DARPP-32 phosphorylated at the PKA site in the striatum. Increased phosphorylation of DARPP-32 at the PKA site was also seen in the nucleus accumbens of females compared to males, particularly among controls and rats tested after a 10-day abstinence period. DARPP-32 phosphorylation was also increased as a consequence of cocaine when tested after a 0-day abstinence period in male rats but not female rats. These findings indicate sex differences in PKA-regulated signaling in drug-naïve controls. Furthermore, these data suggest that regulation of PKA signaling by cocaine is differentially influenced in male and female rats as a consequence of cocaine exposure and cocaine abstinence period.


Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study.
To evaluate the efficacy and toxicity of combination gemcitabine plus cisplatin (GC) chemotherapy in metastatic or recurrent nasopharyngeal carcinoma (NPC). Forty-four patients of Chinese ethnicity with metastatic or recurrent NPC received ambulatory GC chemotherapy every 28 days (gemcitabine 1000 mg/m(2) days 1, 8 and 15; cisplatin 50 mg/m(2) days 1 and 8). There were 40 male and four female patients with a mean age of 47.4 years. More than half (54.5%) of the patients had received either prior platinum-based chemotherapy and/or radiotherapy to target lesions. There were nine complete responses and 23 partial responses in the 44 patients, achieving an overall response rate of 73% (78% for the 41 assessable patients). The mean duration of response was 5.3 months. Improved subjective symptom-control scores were found in 78% of patients with pre-existing symptoms, while 64% of patients experienced improved general well-being scores. Toxicity was mainly hematological: grade III/IV anemia, granulocytopenia and thrombocytopenia were found in 11, 37 and 16% of cycles, respectively. With a median follow-up of 17.2 months, 62% survived 1 year while 36% were alive and progression free. Gemcitabine plus cisplatin chemotherapy offers a satisfactory overall response rate, subjective patient improvement and safety profile for metastatic and recurrent NPC.


Prolonged inhibition of a spinal reflex after intense stimulation of distant peripheral nerves in the decerebrated rabbit.
1. In decerebrated rabbits, repetitive stimulation of the high-threshold afferents of the left common peroneal (CP) nerve evokes prolonged depression of the sural-gastrocnemius medialis (GM) reflex recorded in the same limb. This inhibition is antagonized by co-administration of the opioid antagonist naloxone with the alpha 2-adrenoceptor antagonist idazoxan. The present study was designed to investigate whether such inhibition could be elicited from the contralateral hindlimb or the forelimbs. 2. The sural-GM reflex of decerebrated rabbits was depressed for more than 15 min after stimulation of either ipsilateral or contralateral common peroneal (CP) or median nerves with 500 pulses of 20 V, 1 ms given at 5 Hz. The order of efficacy for generating this inhibition was ipsilateral CP greater than contralateral CP greater than or equal to ipsilateral median = contralateral median. In three of thirty-nine rabbits, stimulation of the median nerves caused facilitation of the sural-GM reflex. 3. Idazoxan (1-2 mg/kg I.V.) did not significantly alter the depressant effect of ipsilateral CP stimulation but reduced that evoked by either median nerve and almost abolished the inhibition evoked from the contralateral CP nerve. 4. Naloxone (0.25 mg/kg I.V.) reduced the effects of ipsilateral CP stimulation, did not alter the inhibition evoked from contralateral CP, and had equivocal actions on the responses to median nerve stimulation. 5. When given together, the two antagonists almost abolished the effects of stimulating the median nerves and the contralateral CP nerve, and markedly reduced the inhibition evoked from the ipsilateral CP nerve. 6. These data show that prolonged inhibition of the sural-GM reflex can be evoked by stimulation of nerves in all four limbs and that in each case the inhibition can be blocked or reduced by co-administration of antagonists to opioid and alpha 2-adrenergic receptors. Such persistent inhibition of reflexes may serve to inhibit withdrawal reflexes in situations where interruptions to normal movement would be disadvantageous.


SNORD116 deletions cause Prader-Willi syndrome with a mild phenotype and macrocephaly.
Prader-Willi syndrome is a complex condition caused by lack of expression of imprinted genes in the paternally derived region of chromosome 15 (15q11q13). A small number of patients with Prader-Willi phenotype have been discovered to have narrow deletions, not encompassing the whole critical region, but only the SNORD116 cluster, which includes genes codifying for small nucleolar RNAs. This kind of deletion usually is not detected by the classic DNA methylation analysis test. We present the case of a male patient with a mild Prader-Willi phenotype and a small deletion including SNORD116, diagnosed by methylation-sensitive multiplex ligation-dependent probe amplification (MLPA. The patient showed neonatal hypotonia, hyperphagia, obesity, central hypogonadism, hypothyroidism, strabismus. Stature and intellectual development are within the normal range. The presence of macrocephaly, observed in other cases of SNORD116 deletions as well, is uncommon for the classic phenotype of the syndrome.


[Fluorescence spectroscopy studies of interactions of leucyl-tRNA-synthetase with substrates].
Interactions of leucyl-tRNA synthetase with substrates were studied by fluorescence spectroscopy. The formation of enzyme-substrate complexes results in the quenching of protein fluorescence. The equilibrium binding constants were determined for L-leucine, ATP, tRNAleu and leucyladenylate. It is shown that the interaction of the enzyme with ATP or tRNAleu leads to 10-30-fold increase in the binding constants for subsequent interaction of the second substrate. The data obtained indicate to the cooperative interaction between ATP and tRNA binding sites.


Prevalence of enteric infections among hospitalized patients in two referral hospitals in Ghana.
Diarrhea is an important cause of morbidity and mortality worldwide. In Africa and Ghana in particular, it is estimated to contribute directly to 19 and 25% of pediatric mortality among children under 5 years, respectively. Surveillance for hospitalized acute diarrheal illness was initiated in November 2010 through October 2012 in a referral hospital in southern Ghana, and a teaching hospital in northern Ghana. Consenting hospitalized patients who met a standardized case definition for acute diarrheal illness provided demographic and epidemiologic data. Stool samples were collected and tested by culture for bacteria and by enzyme immunoassays for a panel of viruses and parasites. A total of 429 patients were enrolled; 216 (50.3%) were under 5 years, and 221 (51.5%) were females. Stool samples were received from 153 patients. Culture isolates included Shigella sp., Salmonella spp., Plesiomonas sp. and Vibrio cholerae. Of 147 samples tested for viruses, 41 (27.9%) were positive for rotaviruses, 11 (7.5%) for astroviruses, 10 (6.8%) for noroviruses, and 8 (5.4%) for adenoviruses. Of 116 samples tested for parasitic infections; 4 (3.4%) were positive for Cryptosporidium sp. and 3 (2.6%) for Giardia lamblia. Of the enrolled patients, 78.8% had taken antibiotics prior to sample collection. Diarrheal pathogens were identified across all ages, however, predominantly (81%) in the children under 5 years of age. This study also detected high antibiotic use which has the potential of increasing antibiotic resistance. The most common enteric pathogen detected (49.4%) was rotavirus.


How human activities in commercial areas contribute to phthalate ester pollution in street dust of Taiwan.
Exposure to phthalate esters (PAEs) poses health risks to humans. Much research has been performed evaluating PAE levels in foodstuffs, river sediment and drinking water, but little attention has been paid to their presence in urban outdoor environments where human activities are highly intense. Here we evaluated PAE presence and distribution in street dust in Kaohsiung, the most industrialized city in Taiwan. Our results showed that PAEs were ubiquitous in fifty-two street-dust samples (levels of total PAEs 5.4-989.2 mg kg-1). Di-(2-ethylhexyl) phthalate was the most abundant congener observed and made up 85.0%, 79.7%, and 97.2% of the total PAEs found in industrial, residential and commercial areas, respectively. PAE levels in street dust in commercial areas (night markets) were significantly higher, suggesting a higher risk of contamination on people present in these areas (H value > χU2). In residential and commercial areas, the higher the intensity of human activity, the higher the PAE content observed. PAE content decreased progressively from the center to the outskirts of the Houjing night market, suggesting that the increased human and consumer activities inside this commercial hotspot were the main PAE source in street dust. Children had higher estimated daily intakes (DIs) than adults and dermal absorption contributed more to these levels than oral ingestion. Although all calculated DIs were below referenced danger thresholds, street dust PAEs in the area should remain an environmental concern especially since night markets play an important role in Taiwanese/Asian culture and economy. Contrary to other studies, PAEs in this study were found less related to industrial manufacturing activities but highly linked to commercial activities. These findings are relevant for future pollution prevention efforts dedicated to mitigating public exposure to PAEs. PAE levels in street dust are related to commercial activities. Night markets, an important commercial activity in Taiwan, were found to contribute considerably to PAE contamination in street dust.


Organized dentistry and the pursuit of entry control.
Organized dentistry spent nearly a century laboring to obtain control over entry into the profession. The first attempt, the American Society of Dental Surgeons, failed because the issue of using amalgam so split the Society that collective action became impossible. The second attempt, state licensing during 1870-1900, gave preferential treatment (automatic licensing) to dental school graduates and appeared at first to be the solution to the entry problem, given the small number of schools in operation. However, dental school entrepreneurs recognized a profitable opportunity, and the supply of dental schools expanded rapidly. Thus, in the third and final attempt at obtaining entry control, organized dentistry attacked the for-profit schools. The dental practice acts were amended to require all candidates to pass a licensing examination, provided first that they were graduates of a school considered "reputable" by the state board of dental examiners. Moreover, rising costs generated by increased school standards took the profit out of for-profit operation, and by 1930 such schools ceased to exist. However, the competitive nature of the 1930s made altogether clear that entry control was a necessary, but not sufficient, condition for the maximization of dentist profits, and thus organized dentistry began its turn inward, focusing on the competitive behavior of existing dentists.


Endovascular repair of ruptured saccular aneurysms of the descending thoracic aorta.
Open repair of ruptured aneurysms of the descending thoracic aorta (DTA) is associated with early mortality rates of 20%-60% and severe morbidity rates exceeding 40%. The present report describes three octogenarian patients and one sexagenarian patient at poor surgical risk admitted with acutely ruptured saccular DTA aneurysms (two of four were anastomotic) unrelated to trauma or infection who underwent successful endovascular therapy, which involved the use of aortic endovascular cuffs in three cases. Mean intensive care unit and total hospital stay durations were 1.75 days (range, 1-4 d) and 6 days (range, 3-13 d), respectively. At 30 days, all patients were alive and free of repeat intervention, with aneurysm exclusion achieved in all cases but one, which featured a marginal type II endoleak. These data support endovascular therapy for ruptured saccular DTA aneurysms enabling short-term outcomes that otherwise would have been unrealistic.


Ligand and loop variations at type 1 copper sites: influence on structure and reactivity.
Type 1 (T1) copper sites promote biological electron transfer and are found in the cupredoxins and a number of copper-containing enzymes including the multi-copper oxidases. A T1 copper site usually has a distorted tetrahedral geometry with strong ligands provided by the thiolate sulfur of a Cys and the imidazole nitrogens of two His residues. The active site structure is typically completed by a weak axial Met ligand (a second weak axial interaction is found in azurin resulting in a trigonal bipyramidal geometry). The axial Met is not conserved and Gln, Phe, Leu and Val are also found in this position. Three of the four ligands at a T1 copper site are situated on a single C-terminal loop whose length and structure varies. Studies are discussed which investigate both the influence of physiologically relevant axial ligand alterations, and also of mutations to the length and structure of the ligand-containing loop, on the properties of T1 copper sites.


Do probiotics have a therapeutic role in gastroenterology?
Several hundred species of bacteria inhabit the gut, and affect its cell biology, morphology and homeostasis. Many bacteria are however potential pathogens, especially if the integrity of the epithelial barrier is physically or functionally breached. Conversely, the interaction between host and commensal microbes can confer important health benefits. This has led to commercial and public interest in "probiotics", live microbes principally taken as food supplements. Might probiotics also be used in disease therapy? Experimental evidence that probiotics modulate gut physiology, particularly barrier integrity and immunological function, underpins exciting new gastroenterological research. We discuss below the scientific basis for probiotic effects and present a critical perspective for their use in relation to gastrointestinal disease.


Evaluation of endothelial function in postkeratoplasty eyes.
To evaluate corneal endothelium function in postkeratoplasty eyes. Endothelial function was assessed in 23 clear corneal grafts. After a measurable corneal edema was induced by soft contact lens wear, serial pachometric readings were taken for 3 hours to arrive at the percentage recovery per hour (PRPH) index. The assessed PRPH values of the clear corneal grafts ranged from 24.6% to 73.0%, with a mean value of 51.8% +/- 12.2%. Of the six corneal grafts that demonstrated an initial PRPH value of less than 47.5%, four became edematous within 6 months of follow-up. Assessed PRPH, as an in vivo-measured index of endothelial function, is a valuable method for monitoring endothelial function in postkeratoplasty eyes. The low PRPH index identifies eyes at risk of spontaneous nonimmunologic failures.


Post-infectious ARDS: mechanisms of lung injury and repair.
Lung infections are considered the most common causes of ARDS. Additionally, superimposed secondary lung infections may occur in the setting of ARDS and further aggravate lung damage. Substances released by neutrophils are the major mediators of lung injury, although other factors, such as endotoxin, exotoxins, macrophages, and immune mechanisms, are significant contributors. Neutrophil-induced lung injury results from the production of oxygen radicals, the release of products of arachidonate metabolism, and the activation of lysosomal enzymes. The development of ARDS is associated with high mortality. Although a large proportion of survivors eventually recover adequate lung function, some patients progress to severe fibrosis. Experimental evidence suggests that the development of fibrosis results from increased synthesis of ECM components by lung fibroblasts. Fibroblast synthesis of ECM components is normally influenced by alveolar cells, by circulating growth factors, by the external milieu, and by the extent of gene expression of the specific ECM components. These factors undergo significant alterations during the evolution of experimental lung fibrosis. Growth factors are more abundant, alveolar cells are activated, and gene expression is enhanced. These factors, which play a crucial role in promoting experimental lung fibrosis, are likely to be involved in the pathogenesis of fibrosis in post-infectious ARDS.


Sterility and Stability of Diluted Carprofen in a Multidose Vial in the Laboratory Animal Setting.
Using compounded multidose vials (cMDV) is a common practice in the laboratory animal setting, where medications often are diluted to provide appropriate doses to rodents. However, bacterial contamination of MDV has been well established in both the human and veterinary medical literature. For this study, we created 14 cMDV by diluting carprofen into sterile water (dilution, 1:10) and stored 6 cMDV each at 5 and 24 °C. The stoppers of the cMDV were not cleaned with alcohol, and all were punctured twice daily for 28 d. The sterility of the diluted carprofen was evaluated by assessing bacterial growth on days 0, 7, 14, 21, and 28 and by testing for bacterial endotoxin on days 0 and 28. We used liquid chromatography-tandem mass spectrometry to assess the stability of 2 cMDV, with each cMDV being divided into the 2 storage-temperature subsets for days 0, 7, 14, 21, and 28. Neither bacterial contamination nor endotoxin was detected, and drug stability was stable over the 28 d. We suggest that with pragmatic techniques, such as secondary containment and consistent use of new needles, the contents of cMDV can remain sterile and stable for 28 d.


Gastrotoxic activity and inhibitory effects on gastric mucosal PGE2 production with different non-steroidal anti-inflammatory drugs: modifications induced by pretreatment with zinc acexamate.
Gastrotoxic activities of different non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac, indomethacin, ketoprofen, naproxen and piroxicam) administered per os were compared with their ability to inhibit gastric prostaglandin E2 (PGE2) synthesis in the rat. In a parallel study, effects of pretreatment with zinc acexamate (ZAC) were also assessed. NSAIDs invariably caused gastric mucosal damage and a decrease of PGE2 levels. A good correlation between the decrease of PGE2 levels and the index of gastric lesion (r = 0.41; p < 0.021) was observed when results obtained with the different NSAIDs were pooled. ZAC pretreatment significantly decreased the overall severity of lesions induced by NSAIDs. However, no correlation between gastric lesion index and depletion of PGE2 gastric levels was observed after treatment with ZAC (r = 0.012; p < 0.948). These data corroborate the hypothesis that preservation of the capability to synthesize endogenous PGs is of critical importance in the maintenance of gastric mucosal integrity. The gastroprotective action observed with ZAC involves alternative mechanisms other than modification of PGE2 levels.


Altered vocalization rate during the estrous cycle in dairy cattle.
Correct detection of estrus is a problem in dairy herds. In practice, several procedures exist for detection of estrus besides conventional visual observation by humans. These procedures deliver very different results regarding detection of estrus. It is known that the calls of female mammals can contain information about reproductive status. It is also suspected that the vocalizations of cattle contain information about age, sex, dominance status, and stage in the estrous cycle. In the present study, a methodology for the continuous automatic recording of vocalization of heifers during the periestrous period is presented. It was shown in 10 tethered heifers that the estrous climax results in an increase in vocalization rate. Vocalization rate of heifers increased approximately 84% from d -2 to 0 (related to observed estrus) and approximately 59% from d -1 to d 0. After d 0, vocalization rate decreased about 79%. Increased vocalization was correlated with the visual observation of estrus by humans. We also found 2 different structures in the vocalization of heifers. The harmonic structure showed regular frequency bands, whereas the nonharmonic structure was noisy. The hypothesis that the disharmonic structure increases near the estrous climax was confirmed. Hence, it seems possible to get information about stage of the estrous cycle of dairy cattle by means of monitoring vocalization. The presented method of automatically detecting the rate of cattle vocalization (patent pending) could be used solely or in combination with other automated systems for detecting estrus and could considerably increase current estrus detection rates once its applicability can be demonstrated in nontethered cattle.


Two-dimensional crystals of Escherichia coli RNA polymerase holoenzyme on positively charged lipid layers.
Escherichia coli RNA polymerase holoenzyme forms two-dimensional crystals when adsorbed to positively charged lipid layers at the air/water interface. Adsorption of the protein is driven by electrostatic interactions between the positively charged lipid surface and the polymerase molecule, which has a net negative charge. Crystallization is dependent on the adsorption and concentration of RNA polymerase on fluid lipid surfaces. Image analysis of electron micrographs of crystals in negative stain, which diffract to 30 A resolution, shows irregularly shaped protein densities about 100 x 160 A, consistent with the dimensions of single polymerase molecules.


Lutein protects against severe traumatic brain injury through anti‑inflammation and antioxidative effects via ICAM‑1/Nrf‑2.
Many studies have reported that lutein may exert its biological activities, including anti‑inflammation, anti‑oxidase and anti‑apoptosis, through effects on reactive oxygen species (ROS). Thus, lutein may prevent the damaging activities of ROS in cells. The current study investigated the effect of lutein against severe traumatic brain injury (STBI) and examined the mechanism of this protective effect. Sprague‑Dawley rats were randomly divided into 5 groups: Control group, STBI model group, 40 mg/kg lutein‑treated group, 80 mg/kg lutein‑treated group and 160 mg/kg lutein‑treated group. In this study, lutein protects against STBI, suppressed, interleukin (IL)‑1β, IL‑6 and monocyte chemoattractant protein‑1 expression, reduced serum ROS levels, and reduced superoxide dismutase and glutathione peroxidase activities in STBI rats. Treatment with lutein effectively downregulated the expression of NF‑κB p65 and cyclooxygenase‑2, intercellular adhesion molecule (ICAM)‑1 protein, and upregulated nuclear factor erythroid 2 like 2 (Nrf‑2) and endothelin‑1 protein levels in STBI rats. These findings demonstrated that lutein protects against STBI, has anti‑inflammation and antioxidative effects and alters ICAM‑1/Nrf‑2 expression, which may be a novel therapeutic for STBI the clinic.


Sclerosing foam in the treatment of varicose veins and telangiectases: history and analysis of safety and complications.
To review the use of sclerosing foam in the treatment of varicose veins, to describe the different techniques of foam preparation, and to report the complications of our 3-year experience with this treatment. From November 1997 to the end of October 2000, 453 patients were treated with a sclerosing foam for large, medium, and minor varicosities with sodium tetradecylsulfate (STS) or polidocanol (POL). A first group of 257 patients (90 for minor varicosities and 167 for medium to large veins) received a sclerosing foam according to the Monfreux technique. From December 1999 to October 2000, 196 patients were treated with a sclerosing foam prepared according to Tessari's method (36 for minor size veins or teleangectasias and 170 for medium-large veins). Every patient was studied with (color-flow) duplex scanning before and after the treatment and large vein injections were administered under duplex guide. The immediate success rate was 88.1% in the first group for the medium-large veins. In the same districts we registered an early success rate in 93.3% for the patients treated with the Tessari's method. The complication rate (mostly minor complications) was 8.5% in the first group and 7.1% in the second group. The use of sclerosing foam may become an established therapy in the treatment of varicose veins with a high success rate, low cost, and low major complication rate. According to our actual experience and knowledge, the safe amount of foam should not exceed the 3-ml limit, but further advancements could come from standardization of the foam preparation technique.


[Composition and antioxidant capacity of the guava (Psidium guajava L.) fruit, pulp and jam].
Guava (Psidium guajava L.) is a tropical fruit widely relished in the tropics, consumed fresh and processed. In this work, free acidity, pH, ash, nitrogen and water contents were measured, besides the total polyphenol content and the antioxidant capacity of the peel, the shell and the pulp of the fresh fruit and the processed guava pulp and jam. The highest phenolic content was found in the guava skin la (10.36 g/100 g skin) and the lowest in the jam (1.47 g/ 100 g jam), in dry weight. The antioxidant capacity of the skin was 10 times higher than that of the pulp, and the jam was twice that of the shell.


Retest reliability of the Halstead Impairment Index in a normal, a schizophrenic, and two samples of organic patients.
In a 1974 study Matarazzo, et al. reported the test-retest reliability of the Halstead-Reitan Neuropsychological Battery for a sample of normal young men and a comparison group of older Ss with cerebrovascular disease. The present study extended this earlier one by addition of comparable test-retest findings from two additional comparison groups: a sample of chronic schizophrenic Ss and a sample of organic patients who underwent endarterectomy. Despite the lack of comparability across the four samples on many dimensions, including age and test-retest interval, the results again reveal a high degree of clinical as well as purely psychometric reliability for most of the tests in the neuropsychological battery and the additional suggestion for further research that the test-retest instability found for some of the Ss in the schizophrenic sample may, itself, hold promise of differential clinical significance in the diagnosis of a "schizophrenic" vs. "organic" process.


Novel insights into genetic characteristics of blaGES-encoding plasmids from hospital sewage.
The prevalence of Guiana extended-spectrum (GES)-type carbapenemase producers is increasing worldwide, and hospital water environments are considered as potential reservoirs. However, the genetic features underlying this resistance are not yet fully understood. This study aimed to characterize blaGES-encoding plasmids from a single-hospital sewage sample in Japan. Carbapenemase producers were screened using carbapenemase-selective agar and polymerase chain reaction. Whole-genome sequencing analyzes were performed on the carbapenemase-producing isolates. Eleven gram-negative bacteria (four Enterobacter spp., three Klebsiella spp., three Aeromonas spp., and one Serratia spp.) with blaGES-24 (n = 6), blaGES-6 (n = 4), and blaGES-5 (n = 1) were isolated from the sewage sample. Five blaGES-24 and a blaGES-5 were localized in IncP-6 plasmids, whereas three blaGES-6 plasmids were localized in IncC plasmids with IncF-like regions. The remaining blaGES-6 and blaGES-24 were, respectively, localized on IncFIB-containing plasmids with IncF-like regions and a plasmid with an IncW-like replication protein. The IncP-6 and IncW-like plasmids had a close genetic relationship with plasmids from Japan, whereas the IncC/IncF-like and IncFIB/IncF-like plasmids were closely related to those from the United States and Europe. All blaGES genes were located on the class 1 integron cassette of the Tn3 transposon-related region, and the IncC/IncF-like plasmid carried two copies of the integron cassette. Eight of the eleven blaGES-encoding plasmids contained toxin-antitoxin system genes. The findings on the plasmids and the novel genetic content from a single wastewater sample extend our understanding regarding the diversity of resistance and the associated spread of blaGES, suggesting their high adaptability to hospital effluents. These findings highlight the need for the continuous monitoring of environmental GES-type carbapenemase producers to control their dissemination.


Mental health and wellbeing outcomes of youth participation: A scoping review protocol.
There is growing recognition that young people should be given opportunities to participate in the decisions that affect their lives, such as advisory groups, representative councils, advocacy or activism. Positive youth development theory and sociopolitical development theory propose pathways through which youth participation can influence mental health and wellbeing outcomes. However, there is limited empirical research synthesising the impact of participation on youth mental health and/or wellbeing, or the characteristics of activities that are associated with better or worse mental health and/or wellbeing outcomes. This scoping review seeks to address this gap by investigating the scope and nature of evidence detailing how youth participation initiatives can influence mental health and/or wellbeing outcomes for participants. To be eligible, literature must describe youth (aged 15-24) in participation activities and the impact of this engagement on participant mental health and/or wellbeing outcomes. A systematic scoping review of peer-reviewed and grey literature will be conducted using Scopus, PsycINFO, Embase, Medline and grey literature databases. The scoping review will apply established methodology by Arksey and O'Malley, Levac and colleagues and the Joanna Briggs Institute. Title, abstract, and full text screening will be completed by two reviewers, data will be extracted by one reviewer. Findings will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), including a qualitative summary of the characteristics of youth participation and their influence on youth mental health outcomes. Youth advisory group members will be invited to deliver governance on the project from the outset; participate in, and contribute to, all stages of the review process; reflect on their own experiences of participation; and co-author the resulting publication. This scoping review will provide essential knowledge on how participation activities can be better designed to maximise beneficial psychosocial outcomes for involved youth.