Making waves: The sensitivity of lakes to brownification and issues of concern in ecological status assessment.
Brownification or increasing water colour is a common problem in aquatic ecosystems. It affects both physico-chemical properties and biotic communities of the impacted waters. A common view is that lakes having low background water colour are most sensitive to brownification. In this article, we show that although low-colour and high-colour lakes respond differently to brownification, the effects on biotic communities can be strong irrespective of water colour. For phytoplankton production, the effect of brownification can be positive at low colour and negative at high colour, the relative effect being strongest at high colour. For fish foraging, the disturbance per increasing unit of colour may also be highest at high-colour conditions. Additionally, the presently used classification systems mostly describe the effects of eutrophication and do not account for the effects of brownification. Studies on the whole colour range of lakes are needed and indicators used in the ecological status assessment of lakes must be developed to reveal the effects of brownification. Indicators distinguishing the effects of brownification from those of eutrophication are especially needed.


Isometric muscle training of the spine musculature in patients with spinal bony metastases under radiation therapy.
Osseous metastatic involvement of the spinal column affects many patients with a primary tumour disease of all entities. The consequences are pain both at rest and under exertion, impairments in going about day-to-day activities, diminished performance, the risk of pathological fractures, and neurological deficits. Palliative percutaneous radiotherapy is one of the therapeutical options available in this connection. The aim of this explorative study is to investigate the feasibility of muscle-training exercises and to evaluate the progression- and fracture-free survival time and the improvement of bone density, as well as to assess other clinical parameters such as pain, quality of life, and fatigue as secondary endpoints. This study is a prospective, randomized, monocentre, controlled explorative intervention study in the parallel-group design to determine the multidimensional effects of a course of exercises at first under physiotherapeutic instruction and subsequently performed by the patients independently for strengthening the paravertebral muscles of patients with metastases of the vertebral column parallel to their percutaneous radiotherapy. On the days of radiation treatment the patients in the control group shall be given physical treatment in the form of respiratory therapy and the so-called "hot roll". The patients will be randomized into one of the two groups: differentiated muscle training or physiotherapy with thirty patients in each group. The aim of the study is to evaluate the feasibility of the training programme described here. Progression-free and fracture-free survival, improved response to radiotherapy by means of bone density, and clinical parameters such as pain, quality of life, and fatigue constitute secondary study objectives. ClinicalTrials.gov: NCT01409720.


[Cosmetic results of posttraumatic eyeball subatrophy surgical treatment using "alloplant" biomaterials with subsequent use of prostheses].
A complex of surgical operations making use of Alloplant biomaterials, performed in 47 patients with initial posttraumatic subatrophy and 79 patients with well-developed and far advanced stages of this condition, helped preserve the eye as anatomical organ in 97.5% patients, with enlargement of the eyeball in two-thirds of patients and stabilization in one-third. Optic reconstructive operations were later performed and visual acuity improved in patients with the initial stage of subatrophy. Use of allotransplant for eyeball bandage in order to create a carcass for the sclera helped conceal the cicatricial deformation of the sclera and repair the shape and volume of the eyeball in patients with initial subatrophy, due to which a good cosmetic result was attained. In well-developed and far advanced subatrophy use of biomaterial for bandage created optimal conditions for thin-wall cosmetic prostheses, ruled out the irritating effect of the prosthesis in cases when corneal sensitivity was retained and/or there were coarse corneaoscleral cicatrices, and thus extended the indications for cosmetic prostheses of subatrophic eyes.


Glycerol 3-phosphate dehydrogenase of boar spermatozoa: inhibition by alpha-bromohydrin phosphate.
Boar spermatozoa incubated with glycerol 3-phosphate as substrate produced CO2 and an accumulation of dihydroxyacetone phosphate and fructose-1,6-bisphosphate. The rate of oxidation of glycerol 3-phosphate was decreased, as was the production of CO2 and the two glycolytic intermediates, in the presence of (R,S)-alpha-bromohydrin phosphate. In the presence of inhibitors of stage two of the glycolytic pathway, CO2 production was prevented, there was a marked increase in the concentration of the glycolytic intermediates but the rate of metabolism of the substrate was unaffected. Oxygen consumption by spermatoza incubated with glycerol 3-phosphate was unaffected in the presence of rotenone, whereas it was decreased when lactate was offered as the substrate. The results reported here confirm that in boar spermatozoa glycerol 3-phosphate dehydrogenase is an FAD-linked enzyme that is inhibited by (R,S)-alpha-bromohydrin phosphate in, possibly, a competitive manner.


Network analysis of associations between serum interferon-α activity, autoantibodies, and clinical features in systemic lupus erythematosus.
Interferon-α (IFNα) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFNα levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. This study was undertaken to detect associations between clinical and serologic disease manifestations and serum IFNα activity in a large diverse SLE cohort, using multivariate and network analyses. We studied 1,089 SLE patients (387 African American, 186 Hispanic American, and 516 European American patients). The presence or absence of individual American College of Rheumatology (ACR) clinical criteria for SLE, autoantibodies, and serum IFNα activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each ancestral background group separately to establish the network of associations between variables that were independently significant following Bonferroni correction. In all ancestral backgrounds, high IFNα activity was associated with anti-Ro and anti-double-stranded DNA antibodies (P = 4.6 × 10(-18) and P = 2.9 × 10(-16) , respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFNα activity (P ≤ 6.7 × 10(-4) ). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared among >1 ancestral background. Associations between clinical criteria were different for different ancestral backgrounds, while autoantibody-IFNα relationships were similar across backgrounds. IFNα activity and autoantibodies were not associated with ACR clinical features in multivariate models. Our findings indicate that serum IFNα activity is strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFNα may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations.


Lens changes and survival in a population-based study.
The Framingham Heart Study was begun in 1948 to study factors associated with cardiovascular disease. Participants have been reexamined approximately every two years. From 1973 to 1975, the Framingham Eye Study examined the eyes of available Heart Study participants. We used information about nearly 2000 persons from these population-based studies to investigate the relation of lens changes to survival. Follow-up ranged from five to eight years; 312 persons (16 per cent) died. Proportional-hazards regression analyses indicated an overall association of lens changes and decreased survival (P = 0.01), but detailed investigation showed (1) no association of lens changes and decreased survival among persons without diabetes (P = 0.29) and (2) a significant association of lens changes and decreased survival among persons with diabetes (P = 0.001). Diabetic persons with lens changes had an estimated death rate more than twice that of diabetics without lens changes. The duration of diabetes and degree of retinopathy were not associated with survival in this group, most of whom had adult-onset diabetes of short duration. We conclude that lens changes are earlier predictors of death in diabetics than these more traditional variables.


Intestinal microbiota influence the early postnatal development of the enteric nervous system.
Normal gastrointestinal function depends on an intact and coordinated enteric nervous system (ENS). While the ENS is formed during fetal life, plasticity persists in the postnatal period during which the gastrointestinal tract is colonized by bacteria. We tested the hypothesis that colonization of the bowel by intestinal microbiota influences the postnatal development of the ENS. The development of the ENS was studied in whole mount preparations of duodenum, jejunum, and ileum of specific pathogen-free (SPF), germ-free (GF), and altered Schaedler flora (ASF) NIH Swiss mice at postnatal day 3 (P3). The frequency and amplitude of circular muscle contractions were measured in intestinal segments using spatiotemporal mapping of video recorded spontaneous contractile activity with and without exposure to lidocaine and N-nitro-L-arginine (NOLA). Immunolabeling with antibodies to PGP9.5 revealed significant abnormalities in the myenteric plexi of GF jejunum and ileum, but not duodenum, characterized by a decrease in nerve density, a decrease in the number of neurons per ganglion, and an increase in the proportion of myenteric nitrergic neurons. Frequency of amplitude of muscle contractions were significantly decreased in the jejunum and ileum of GF mice and were unaffected by exposure to lidocaine, while NOLA enhanced contractile frequency in the GF jejunum and ileum. These findings suggest that early exposure to intestinal bacteria is essential for the postnatal development of the ENS in the mid to distal small intestine. Future studies are needed to investigate the mechanisms by which enteric microbiota interact with the developing ENS.


Mechanical plethysmography and Doppler ultrasound. Diagnosis of deep-venous thrombosis.
Two hundred eighty-one patients were available for follow-up after undergoing bilateral lower-extremity venous laboratory evaluations for possible deep-venous thrombosis. Because of a recognized difficulty with such a clinical diagnosis, the use of Doppler ultrasound and mechanical plethysmography with air-filled cuffs was carefully studied. Eighty-three of the 281 patients had confirmatory results from venography or fibrinogen scan of the symptomatic or more-symptomatic leg, and these 83 patients were used to determine accuracy. The complete evaluation as performed was accurate in 70% of the patients with suspected deep-venous thrombosis. The Doppler examination alone was accurate in 71% of the patients, and the maximum venous outflow measurement was accurate in 67% of the patients. This study indicates a continuing need for venography or fibrinogen scanning for the diagnosis of deep-venous thrombosis.


Mediation of a preventive intervention's 6-year effects on health risk behaviors.
Using data from a 6-year longitudinal follow-up sample of 240 youth who participated in a randomized experimental trial of a preventive intervention for divorced families with children ages 9 to 12, the current study tested mechanisms by which the intervention reduced substance use and risky sexual behavior in mid to late adolescence (15-19 years old). Mechanisms tested included parental monitoring, adaptive coping, and negative errors. Parental monitoring at 6-year follow-up mediated program effects to reduce alcohol and marijuana use, polydrug use, and other drug use for those with high pretest risk for maladjustment. In the condition that included a program for mothers only, increases in youth adaptive coping at 6-year follow-up mediated program effects on risky sexual behavior for those with high pretest risk for maladjustment. Contrary to expectation, program participation increased negative errors and decreased adaptive coping among low-risk youth in some of the analyses. Ways in which this study furthers our understanding of pathways through which evidence-based preventive interventions affect health risk behaviors are discussed.


Delayed Bleeding Following Cold Snare Polypectomy for Small Colorectal Polyps in Patients Taking Antithrombotic Agents.
This study compared the incidence of delayed bleeding following 2 methods of cold snare polypectomy for colorectal polyps in patients taking antithrombotic agents. Patients undergoing cold snare polypectomy for colorectal polyps ≤10 mm without discontinuation of antithrombotic agents were enrolled. This was a retrospective study of a prospectively collected cohort based on a historical comparison of 2 time periods. A traditional cold snare was used between January 2012 and December 2013 and a dedicated cold snare was used between January 2014 and December 2015. Patients' and polyps' characteristics, antithrombotic agents used, the snare used, the number of clips used, and adverse events were documented from a hospital online database. Delayed bleeding was defined as bleeding that required endoscopic treatment within 2 weeks after polypectomy. The submucosal layer of the resected polyps (6 to 10 mm) was histologically examined for the presence of injured arteries. A total of 172 patients having 370 eligible polyps were enrolled; traditional cold snare group, N=100 (212 polyps) and dedicated cold snare group, N=72 (158 polyps). The patients' and polyps' characteristics were similar between the 2 groups. Hemostatic clips were used more often with the traditional than dedicated cold snares [33/100 (33%) vs. 13/72 (18%), P=0.044]. Delayed bleeding following cold snare polypectomy occurred in 1.2% (2/172); 0% (0/72) with dedicated snare versus 2% (2/100) with the traditional snare (P=0.63). The presence of histologically demonstrated injured submucosal arteries with the dedicated cold snare was significantly less than with the traditional cold snare [4.1% (4/98) vs. 16% (17/105), P=0.009]. Colorectal polyps ≤10 mm can be removed without an increase in delayed bleeding using dedicated cold snare polypectomy in patients taking antithrombotic agents.


Investigation of Auxetic Structural Deformation Behavior of PBAT Polymers Using Process and Finite Element Simulation.
The current work investigates the auxetic tensile deformation behavior of the inversehoneycomb structure with 5 × 5 cells made of biodegradable poly(butylene adipate-coterephthalate) (PBAT). Fused deposition modeling, an additive manufacturing method, was used to produce such specimens. Residual stress (RS) and warpage, more or less, always exist in such specimens due to their layer-by-layer fabrication, i.e., repeated heating and cooling. The RS influences the auxetic deformation behavior, but its measurement is challenging due to its very fine structure. Instead, the finite-element (FE)-based process simulation realized using an ABAQUS plug-in numerically predicts the RS and warpage. The predicted warpage shows a negligibly slight deviation compared to the design topology. This process simulation also provides the temperature evolution of a small-volume material, revealing the effects of local cyclic heating and cooling. The achieved RS serves as the initial condition for the FE model used to investigate the auxetic tensile behavior. With the outcomes from FE calculation without consideration of the RS, the effect of the RS on the deformation behavior is discussed for the global force-displacement curve, the structural Poisson's ratio evolution, the deformed structural status, the stress distribution, and the evolution, where the first three and the warpage are also compared with the experimental results. Furthermore, the FE simulation can easily provide the global stress-strain flow curve with the total stress calculated from the elemental stresses.


Imaging cardiac stem cell therapy: translations to human clinical studies.
Stem cell therapy promises to open exciting new options in the treatment of cardiovascular diseases. Although feasible and clinically safe, the in vivo behavior and integration of stem cell transplants still remain largely unknown. Thus, the development of innovative non-invasive imaging techniques capable of effectively tracking such therapy in vivo is vital for a more in-depth investigation into future clinical applications. Such imaging modalities will not only generate further insight into the mechanisms behind stem cell-based therapy, but also address some major concerns associated with translational cardiovascular stem cell therapy. In the present review, we summarize the principles underlying three major stem cell tracking methods: (1) radioactive labeling for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging, (2) iron particle labeling for magnetic resonance imaging (MRI), and (3) reporter gene labeling for bioluminescence, fluorescence, MRI, SPECT, and PET imaging. We then discuss recent clinical studies that have utilized these modalities to gain biological insights into stem cell fate.


RNA-seq analysis of lung adenocarcinomas reveals different gene expression profiles between smoking and nonsmoking patients.
Lung adenocarcinoma is caused by the combination of genetic and environmental effects, and smoking plays an important role in the disease development. Exploring the gene expression profile and identifying genes that are shared or vary between smokers and nonsmokers with lung adenocarcinoma will provide insights into the etiology of this complex cancer. We obtained RNA-seq data from paired normal and tumor tissues from 34 nonsmoking and 34 smoking patients with lung adenocarcinoma (GEO: GSE40419). R Bioconductor, edgeR, was adopted to conduct differential gene expression analysis between paired normal and tumor tissues. A generalized linear model was applied to identify genes that were differentially expressed in nonsmoker and smoker patients as well as genes that varied between these two groups. We identified 2273 genes that showed differential expression with FDR < 0.05 and |logFC| >1 in nonsmoker tumor versus normal tissues; 3030 genes in the smoking group; and 1967 genes were common to both groups. Sixty-eight and 70% of the identified genes were downregulated in nonsmoking and smoking groups, respectively. The 20 genes such as SPP1, SPINK1, and FAM83A with largest fold changes in smokers also showed similar large and highly significant fold changes in nonsmokers and vice versa, showing commonalities in expression changes for adenocarcinomas in both smokers and nonsmokers for these genes. We also identified 175 genes that were significantly differently expressed between tumor samples from nonsmoker and smoker patients. Gene expression profile varied substantially between smoker and nonsmoker patients with lung adenocarcinoma. Smoking patients overall showed far more complicated disease mechanism and have more dysregulation in their gene expression profiles. Our study reveals pathogenetic differences in smoking and nonsmoking patients with lung adenocarcinoma from transcriptome analysis. We provided a list of candidate genes for further study for disease detection and treatment in both smoking and nonsmoking patients with lung adenocarcinoma.


Patient and public involvement in patient-reported outcome measures: evolution not revolution.
This paper considers the potential for collaborative patient and public involvement in the development, application, evaluation, and interpretation of patient-reported outcome measures (PROMs). The development of PROMs has followed a well trodden methodological path, with patients contributing as research subjects to the content of many PROMs. This paper argues that the development of PROMs should embrace more collaborative forms of patient and public involvement with patients as research partners in the research process, not just as those individuals who are consulted or as subjects, from whom data are sourced, to ensure the acceptability, relevance, and quality of research. We consider the potential for patients to be involved in a much wider range of methodological activities in PROM development working in partnership with researchers, which we hope will promote paradigmal evolution rather than revolution.


A prospective evaluation of the modified Alvarado score for acute appendicitis in children.
The accuracy of the modified Alvarado score was assessed prospectively in the preoperative diagnosis of acute appendicitis in children. A consecutive series of 118 patients (54 boys, 64 girls) with acute abdominal pain was studied prospectively over a 6 month period. Appendicitis was confirmed in 38 of 43 children undergoing appendicectomy, giving a false-positive appendicectomy rate of 11.6%. No child under active observation was subsequently found to have a perforated appendix. The overall sensitivity of a modified Alvarado score of > or = 7 was 76.3% and its specificity was 78.8%. Current clinical practice is more accurate than the modified Alvarado score in the diagnosis of acute appendicitis in children.


CLimate Impacts on Myocardial infarction deaths in the Athens TErritory: the CLIMATE study.
To evaluate the impact of meteorological variables on daily and monthly deaths caused by acute myocardial infarction (AMI). All death certificate data from the Athens territory were analysed for AMI deaths in 2001. Daily atmospheric temperature, pressure and relative humidity data were obtained from the National Meteorological Society for Athens for the same year. The total annual number of deaths caused by AMI was 3126 (1953 men) from a population of 2,664,776 (0.117%). Seasonal variation in deaths was significant, with the average daily AMI deaths in winter being 31.8% higher than in summer (9.89 v 7.35, p < 0.001). Monthly variation was more pronounced for older people (mean daily AMI deaths of people older than 70 years was 3.53 in June and 7.03 in December; p < 0.001) and of only marginal significance for younger people. The best predictor of daily AMI deaths was the average temperature of the previous seven days; the relation between daily AMI deaths and seven-day average temperature (R(2) = 0.109, p < 0.001) was U-shaped. Considering monthly AMI death rates, only mean monthly humidity was independently associated with total deaths from AMI (R(2) = 0.541, p = 0.004). Ambient temperature is an important predictor of AMI mortality even in the mild climate of a Mediterranean city like Athens, its effects being predominantly evident in the elderly. Mean monthly humidity is another meteorological factor that appears to affect monthly numbers of AMI deaths. These findings may be useful for healthcare and civil protection planning.


Humoral and cellular response to influenza vaccine in HIV-infected children with full viroimmunologic response to antiretroviral therapy.
It is unclear whether the ability to respond to vaccines is restored by antiretroviral therapy. We evaluated the influenza-specific immune responses elicited by a virosomal vaccine in HIV-infected children on long-term successful highly active antiretroviral therapy (HAART). This was an observational, prospective, open-label study enrolling 24 HIV-infected, HAART-treated (85 months' mean exposure), vaccine-naive children (median age=11.9 years) and 14 age- and gender-matched healthy controls. Mean CD4 T-cell counts (>900 cells/microL) and percentages (>37%) were comparable. The HIV RNA level was <50 copies/mL in all patients. Children received a single dose of trivalent virosome-adjuvanted influenza vaccine. A/H3N2-, A/H1N1-, and B-antigen-specific antibody (Ab) titers and subclasses and vaccine-specific interferon-gamma (IFNgamma)- and interleukin (IL)-2-producing T lymphocytes were analyzed at baseline and 1 and 6 months after immunization. Seroconversion (>or=4-fold Ab titer raise in >40% of patients) and seroprotection (Ab titer>or=1:40 in >70% of patients) was achieved at 1 month in both groups; however, fewer HIV-infected children fulfilled these criteria. The A/H3N2- and A/H1N1-specific Ab geometric mean titers were lower in HIV-infected children compared with healthy controls at 1 and 6 months; interestingly, a boost in vaccine-specific IgG3 T helper 1 type Ab was seen in healthy controls alone. Finally, vaccine specific-IFNgamma- and IL-2-producing T lymphocytes were reduced at both time points in HIV-infected children compared with healthy controls. One injection of virosomal-adjuvanted influenza vaccine stimulates good immune responses, although the humoral and cellular immune responses are reduced in HIV-infected children compared to healthy children. This indicates that immunologic function impairments may persist upon HIV infection even if HIV-positive viremia is suppressed and immune recovery seems to be achieved.


Efficacy and tolerance of a hydrocolloid dressing containing hyaluronic acid for the treatment of leg ulcers of venous or mixed origin.
This study was aimed at comparing efficacy and tolerance of a new hydrocolloid dressing containing hyaluronic acid (HC + HA) to a reference hydrocolloid not containing hyaluronic acid (HC) in the treatment of leg ulcers of venous or mixed origin. This was an open, prospective study, randomized in parallel groups, in which 125 patients were enrolled and treated for up to 42 days. The primary efficacy criterion was the reduction of the wound area; other efficacy criteria were the condition of the wound bed, and of the surrounding skin, and presence and severity of symptoms such as pain and itching. After 42 days of treatment the median reduction of ulcer area was -42.6% (95% confidence interval [CI]: -66.6; -5.7) and -31.0% (95% CI: -51.6; -8.8) in the HC + HA group and in the reference HC group, respectively. The difference between treatments was not statistically significant. A reduction > or = 90% of the initial ulcer area was seen in 15 patients in the HC + HA dressing group and in only seven patients in the HC dressing group. Changes in wound bed condition in the two groups were not significantly different, except for a more marked reduction of fibrinous tissue in the HC + HA dressing group (p = 0.04), at Day 28. Both treatments were well tolerated. The HC + HA dressing was equally well tolerated and with a trend to be more effective than the reference HC dressing in the treatment of leg ulcers of venous or mixed origin. Further research is needed to confirm these findings.


Silencing of p53 RNA through transarterial delivery ameliorates renal tubular injury and downregulates GSK-3β expression after ischemia-reperfusion injury.
p53, a pivotal protein in the apoptotic pathway, has been identified as a mediator of transcriptional responses to ischemia-reperfusion (IR) injury. The characteristics and functional significance of the p53 response in vivo are largely unknown in IR-induced kidney injury. Therapeutic opportunities of delivering small interfering RNA (siRNA) via venous injection have gained recognition; however, systemic adverse effects of siRNA therapy should be considered. To prevent IR-induced kidney injury, we tested the efficacy of transarterial administration of siRNA targeting p53 (p53 siRNA). Female C57BL/6 mice underwent unilateral renal artery ischemia for 30 min, followed by reperfusion. siRNA experiments utilized short hairpin (sh) RNA plasmid-based approaches. Transfection of shRNA was performed using cationic polymer transfection reagent. Injection of synthetic p53 shRNA into the left renal artery just after ischemia improved tubular injury, apoptosis, and the swelling of mitochondria in cells of the thick ascending limb of Henle (mTALH) at the outer medullary regions. Staining of upregulated p53 was colocalized with the inducible expression of glycogen synthase kinase-3β (GSK-3β) at mTALH after IR injury. p53 shRNA inhibited GSK-3β expression and restored β-catenin expression at mTALH. For IR-induced kidney injury, transarterial delivery of p53 siRNA is an effective pharmacological intervention. Targeting siRNA to p53 leads to an attenuation of apoptosis and mitochondrial damage through the downregulation of GSK-3β expression and upregulation of β-catenin. Local delivery of vectors such as p53 siRNA through a transaortic catheter is clinically useful in reducing the adverse effect of siRNA-related therapy.


[Total intravenous anesthesia (TIVA) in geriatric surgery. S-(+)-ketamine versus alfentanil].
In this prospective, randomized study, two regimens of total intravenous anaesthesia (TIVA), with propofol and S(+)-ketamine (S-ketamine) and with propofol and alfentanil, were compared with reference to endocrine stress response, circulatory effects and recovery. METHODS. The investigation was conducted in two groups of 20 ASA I-III patients over 60 years of age who were scheduled for endoprothetic orthopaedic surgery. After oral premedication with midazolam, patients received a TIVA with body-weight-adjusted doses of propofol, and S-ketamine or alfentanil as the analgesic component. For CPPV (PEEP 5 mbar), air and oxygen (FiO2 33%) were used. For muscle relaxation, patients of both groups received vecuronium in body-weight-adjusted doses. Blood samples were taken through a central venous line at seven time points before induction of anaesthesia and on the first morning after the operation also for analysis of epinephrine, norepinephrine (by HPLC/ECD), and ADH, ACTH and cortisol (by RIA). In addition, SAP, HR, arterial oxygen saturation, recovery from anaesthesia and side effects were observed. RESULTS. The two groups had comparable group mean values for age (S-ketamine group 71 years, alfentanil-group 70 years), other biometric data, and duration of anaesthesia and operation (Table 1). Plasma levels of epinephrine, norepinephrine (Table 2, Fig. 1), ADH (Table 2, Fig. 2) ACTH and cortisol (Table 2, Fig. 3) were higher in the S-ketamine-group (P < 0.05) owing to the intraoperative course of these endocrine parameters. Before induction, and on the first morning after the operation, levels were comparable between the groups. 5 min after the induction of anaesthesia, SAP and HR (Table 3) were significantly lower in the alfentanilgroup (P = 0.001). Recovery from anaesthesia (orientation with respect to person and location) was faster in the alfentanilgroup (16 vs 39 min, P = 0.001). An arterial oxygen saturation below 90% was observed in 7 patients in the S-ketamine- and 13 patients in the alfentanilgroup (P = 0.03). Four patients with S-ketamine reported dreams, and 1 dream was judged negative. Postoperative emesis was found in 6 patients in the S-ketaminegroup and 12 patients in the alfentanilgroup (P = 0.03). All patients said they would agree to undergo the same anaesthetic technique again. CONCLUSIONS. Considerable differences were found in the endocrine stress response of the two groups. With respect to endocrine response and circulation, TIVA with propofol and S-ketamine had sympathomimetic properties with positive circulatory effects and led to moderate endocrine stimulation. This should be kept in mind in patients with hypotension, hypothyrosis, or adrenocortical insufficiency; because "eustress" might be beneficial in this group of patients. On the other hand, TIVA with propofol and alfentanil showed sympatholytic properties, with negative circulatory effects and a remarkable reduction of endocrine stress response. This might be beneficial in patients with hypertension and states of endocrine hyperfunction. Both regimens were accompanied by such typical side effects as dreams, delayed recovery, reduced ventilation, and emesis, which should also be considered.


Characterization of two highly metastatic variants of Lewis lung carcinoma with different organ specificities.
The biological properties and metastasis of two sublines of the Lewis lung carcinoma (3LL) which have maintained a stable pattern of organ-selective metastasis have been studied. Subline M-3LL, a lung-specific variant which originated from a lung metastasis of the parent line, metastasized only to the lung following injection of 10(4)-10(6) tumor cells i.v. or s.c. Lymphatic metastases of this tumor were rarely detected. Subline H-3LL which was developed from a rare, spontaneous hepatic metastasis of the parent line metastasized primarily to the liver, but pulmonary metastases have also been observed. While it grew at local s.c. sites, this tumor metastasized to the regional lymph nodes draining the tumor site, as determined by histology and by bioassay of the lymph nodes following their grafting into new recipient animals. Histologically, the two lines were indistinguishable with the exception of a higher incidence of giant cells detected in tissue sections and culture monolayers of the liver-colonizing variant H-3LL. Ten clones derived from each of the variant lines were expanded in vitro and inoculated i.v. While none of the ten clones derived from line M-3LL gave rise to extrapulmonary metastasis, nine of ten clones derived from Tumor H-3LL gave rise to hepatic metastasis. Highly metastatic clones selected from each tumor were subsequently used to study the patterns of distribution and arrest of radiolabeled tumor cells following their inoculation i.v. No correlation could be found between the initial distribution of the radiolabeled tumor cells and the organ selectivity eventually noted in the site of the metastases.


Estrogen level monitoring in artificial frozen-thawed embryo transfer cycles using step-up regime without pituitary suppression: is it necessary?
To discuss the meaning of serum oestradiol monitoring in frozen embryo transfer cycle using hormone replacement without pretreatment with gonadotropin hormone (GnRH) agonist. The data from two hundred twelve women undergoing two hundred seventy-four frozen-thawed embryo transfer (FET) cycles was included in this retrospective cohort study. They were detected of serum oestradiol levels and endometrium thicknesses during hormone supplement FET cycles and compared their pregnancy outcomes according to their oestradiol level on progesterone initiation day. Patients with different levels of serum oestradiol (percentile 0-25th, 25th-75th and 75th-100th) on progesterone initiation day yielded the endometrium thickness of 9.3 +/- 0.12, 8.9 +/- 0.07 and 9.1 +/- 0.11 mm(P > 0.05) and the pregnancy rate of 32.2%, 38.4% and 36.3% (P > 0.05) respectively. The serum estradiol level did not predict pregnancy success in hormone replacement FET cycles, suggesting that oestradiol monitoring in this method of endometrial preparation is unnecessary.


Nedocromil sodium vs. sodium cromoglycate for preventing exercise-induced bronchoconstriction in asthmatics.
Nedocromil sodium and sodium cromoglycate inhaled shortly before exercise appear to reduce the severity of exercise-induced bronchoconstriction. There is some debate over which drug may be more effective. The objective of this review was to compare the effects on post-exercise lung function between prophylactic doses of nedocromil sodium (NSG) and sodium cromoglycate (SCG) in persons diagnosed with exercise-induced bronchoconstriction. Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register which compiles searches of CINAHL, EMBASE, MEDLINE and CENTRAL, plus hand searches for trials in 20 journals. Bibliographies of relevant studies and review articles were searched and primary authors, content experts and manufacturers of drugs were contacted for additional relevant studies. No language restrictions were applied. Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were included if: the participants, aged 6 or over, had a confirmed diagnosis of asthma with exercise-induced bronchoconstriction, were subjected to an exercise challenge sufficient to trigger bronchoconstriction, and the measures of lung function were reported as either changes in forced expiratory volume in one second or peak expiratory flow rate. Data extraction and methodological quality assessments were conducted independently by two reviewers using standard forms and validated assessment criteria. In some cases results were extrapolated from graphs. Results from similar studies were pooled and reported as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CI) using the random effects model. Of the 92 citations retrieved from the original search, a total of 8 studies were included in this review (117 participants). No significant difference was noted between NCS and SCG with respect to the maximum percent decrease in FEV1 (WMD = -0.88; 95% CI: -4.50, 2.74), complete protection (i.e. maximum % fall FEV1 still =>10%); OR = 0.95; 95% CI: 0.50 to 1.8, clinical protection (i.e. < 50% improvement over placebo); OR = 0.71; 95% CI: 0.36 to 1.39; unpleasant taste (OR = 6.85; 95% CI: 0.77, 60.73), or sore throat (OR = 3.46; 95% CI: 0.32, 37.48). For these pooled comparisons, no statistically significant heterogeneity was identified. Subgroup analyses based on age, dosage of medications and timing of exercise post-inhalation were consistent with the overall pooled analyses. No significant differences were evident between the effect of NCS and SCG during the immediate post-exercise period in adults and children with EIB with regards to pulmonary function - specifically maximum percent decrease in FEV1, complete protection, clinical protection, or side effects.


Interaction between carotid baroreflex and exercise pressor reflex depends on baroreceptor afferent input.
Because arterial baroreceptor and skeletal muscle receptor afferents project to cardiovascular regions in the lower brain stem such as the nucleus tractus solitarii (NTS), it is likely that the level of baroreceptor afferent input will modify the excitatory cardiovascular responses evoked by contraction-sensitive skeletal muscle afferents. The purpose of this study was to determine the effect of carotid sinus baroreceptor afferent input (CSA) on reflex heart rate (HR) and mean arterial pressure (MAP) responses evoked by activation of skeletal muscle receptor afferents (SMA). CSA input was servo controlled at three levels of carotid sinus pressure using the isolated carotid sinus preparation, and SMA input was varied by induced muscle contraction (L7-S1 ventral root stimulation) or passive muscle stretch. Experiments were performed in alpha-chloralose-anesthetized and vagotomized dogs (n = 9). When CSA input was low (106 +/- 35 mmHg), electrically induced muscle contraction increased HR and MAP (30 +/- 8 beats/min and 42 +/- 12 mmHg, respectively, P < 0.05). However, when CSA input was high (221 +/- 9 mmHg), the reflex changes in HR and MAP during muscle contraction were attenuated (6 +/- 4 beats/min and 18 +/- 4 mmHg, respectively, P < 0.05). Similarly, the sympathoexcitatory responses evoked by passive muscle stretch were attenuated in a baroreceptor-dependent manner. These results suggest that changing CSA input from low (106 mmHg) to high (221 mmHg) shifts the interaction from facilitation to inhibition. Therefore, it is concluded that the nature of the interaction (i.e., facilitation or inhibition) between the baroreflex and the exercise pressor reflex is dependent on the level of baroreceptor input. Moreover, our findings substantiate early studies showing that the level of afferent input from arterial baroreceptors is a powerful modulator of sympatho-excitation evoked by mechanically and metabolically sensitive skeletal muscle receptors.


[Combined surgical treatment for bullous keratopathy with concomitant uncompensated glaucoma].
The article discusses a clinical case of combined surgical treatment for painful bullous keratopathy in an eye with uncompensated far-advanced glaucoma. Ex-PRESS Glaucoma Filtration Device was used for anterior chamber drainage. The procedure was supplemented by amniotic membrane implantation under the scleral flap, microdiathermocoagulation of large corneal epithelial bullae, and epikeratoplasty.


A comparison of several regression models for analysing cost of CABG surgery.
Investigators in clinical research are often interested in determining the association between patient characteristics and cost of medical or surgical treatment. However, there is no uniformly agreed upon regression model with which to analyse cost data. The objective of the current study was to compare the performance of linear regression, linear regression with log-transformed cost, generalized linear models with Poisson, negative binomial and gamma distributions, median regression, and proportional hazards models for analysing costs in a cohort of patients undergoing CABG surgery. The study was performed on data comprising 1959 patients who underwent CABG surgery in Calgary, Alberta, between June 1994 and March 1998. Ten of 21 patient characteristics were significantly associated with cost of surgery in all seven models. Eight variables were not significantly associated with cost of surgery in all seven models. Using mean squared prediction error as a loss function, proportional hazards regression and the three generalized linear models were best able to predict cost in independent validation data. Using mean absolute error, linear regression with log-transformed cost, proportional hazards regression, and median regression to predict median cost, were best able to predict cost in independent validation data. Since the models demonstrated good consistency in identifying factors associated with increased cost of CABG surgery, any of the seven models can be used for identifying factors associated with increased cost of surgery. However, the magnitude of, and the interpretation of, the coefficients vary across models. Researchers are encouraged to consider a variety of candidate models, including those better known in the econometrics literature, rather than begin data analysis with one regression model selected a priori. The final choice of regression model should be made after a careful assessment of how best to assess predictive ability and should be tailored to the particular data in question.


KIR3DL1/S1 Allotypes Contribute Differentially to the Development of Behçet Disease.
Behçet disease is a chronic, relapsing-remitting autoinflammatory syndrome with a strong HLA-B*51 association. In this paper, we describe a human cohort of 267 individuals with Behçet disease and 445 matched controls from a tertiary referral center in the U.K. HLA-B*51 was confirmed as a genetic risk factor in this group (p = 0.0006, Bonferroni-Dunn correction for multiple testing [Pc] = 0.0192, odds ratio [OR] 1.92, 95% confidence interval [CI] 1.33-2.76). KIR3DL1/S1 allele-level analysis indicated that low-expressing KIR3DL1/S1 alleles in combination with KIR3DS1 increased the risk of developing Behçet disease (KIR3DL1LOW/KIR3DS1: p = 0.0004, Pc = 0.0040, OR 2.47, 95% CI 1.43-4.25), whereas high-expressing KIR3DL1/S1 alleles in combination with a null-expressing KIR3DL1 reduced the risk of disease (KIR3DL1HIGH/KIR3DL1NULL: p = 0.0035, Pc = 0.0350, OR 0.53, 95% CI 0.33-0.87). Behçet disease can manifest as a purely mucocutaneous disease or can involve other organ systems such as the eyes. In the U.K. cohort studied in this study, KIR3DL1LOW/KIR3DS1 increased the risk of ophthalmic disease (p = 1.2 × 10-5, OR 3.92, 95% CI 2.06-7.47), whereas KIR3DL1HIGH/KIR3DL1NULL reduced the risk of having purely mucocutaneous disease (p = 0.0048, OR 0.45, 95% CI 0.25-0.81). To our knowledge, this is the first analysis of KIR3DL1/S1 allelic variation in Behçet disease and may provide insight into the pathogenic role of HLA-B*51 and its interaction with KIR3DL1/S1.


Radical surgery of left-sided klatskin tumors.
Left-sided cholangiocarcinoma includes hilar cholangiocarcinoma (HC), predominantly involving the left hepatic duct, and intrahepatic cholangiocarcinoma (ICC) in the left liver. Left hepatectomy, or left hepatic trisectionectomy, is indicated as radical surgery of left-sided HC or ICC with or without hilar bile duct invasion. Left lateral sectionectomy, or left medial sectionectomy, is performed for the small mass-forming type ICC. Left hepatic trisectionectomy is indicated for left-sided HC with further cancer progress along the right anterior sectional duct or left-sided ICC involving the right anterior section over the middle hepatic vein and/or the right anterior pedicle. Combined caudate lobe and extrahepatic bile duct resection are mandatory in cases of HC or ICC involving the hepatic confluence. Preoperative biliary drainage should be performed not only for jaundiced patients but also for non-icteric patients with right-sided biliary dilatation of the future remnant liver. Preoperative left trisegment portal vein embolization after biliary drainage of the right posterior section should be carried out prior to left hepatic trisectionectomy. Left hepatectomy has been used as a radical and safer surgical procedure, but in European countries has still been associated with higher morbidity and about 10% operative mortality. Japanese surgeons have had no hospital deaths after carrying out left hepatic trisectionectomy done after preoperative biliary drainage followed by left trisegment portal vein embolization to increase safety and to prolong postoperative survival for patients with locally advanced left-sided cholangiocarcinoma.


Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones.
Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).


Mosquito (Diptera: Culicidae) fauna in an area endemic for West Nile virus.
Mosquito collections with CDC light traps using dry ice and pigeon-baited traps were carried out in south Moravia (Czech Republic) from April to October in 2007 and 2008 at two study sites. In 2007, 11 two-day captures were carried out in two-week intervals, and 1,490 female mosquitoes of nine species were caught. In 2008, 15 two-day trappings of mosquitoes were carried out: 6,778 females of 22 species of mosquitoes were trapped. The results showed marked differences in abundance and species composition of mosquitoes between both study sites and between the trapping methods. In the floodplain forest ecosystem of the Soutok study area, Aedes vexans predominated. The species composition in the Nesyt study site was more varied and the most common species was Culex pipiens. At the latter study site, Anopheles hyrcanus (var. pseudopictus) and Uranotaenia unguiculata, mosquito species with largely southern Eurasian distribution, were repeatedly demonstrated. The largest capture of mosquitoes was in traps with CO2 placed at a height 1 m above the ground. The capture of mosquitoes in the pigeon-baited traps as well as in the traps with CO2 placed in the canopy of trees was markedly lower in both study sites, with the predominant species being Culex pipiens.


Tele-Interpersonal Psychotherapy Acutely Reduces Depressive Symptoms in Depressed HIV-Infected Rural Persons: A Randomized Clinical Trial.
Human immunodeficiency virus (HIV)-positive rural individuals carry a 1.3-times greater risk of a depressive diagnosis than their urban counterparts. This randomized clinical trial tested whether telephone-administered interpersonal psychotherapy (tele-IPT) acutely relieved depressive symptoms in 132 HIV-infected rural persons from 28 states diagnosed with Diagnostic and Statistical Manual of Mental Disorders-IV major depressive disorder (MDD), partially remitted MDD, or dysthymic disorder. Patients were randomized to either 9 sessions of one-on-one tele-IPT (n = 70) or standard care (SC; n = 62). A series of intent-to-treat (ITT), therapy completer, and sensitivity analyses assessed changes in depressive symptoms, interpersonal problems, and social support from pre- to postintervention. Across all analyses, tele-IPT patients reported significantly lower depressive symptoms and interpersonal problems than SC controls; 22% of tele-IPT patients were categorized as a priori "responders" who reported 50% or higher reductions in depressive symptoms compared to only 4% of SC controls in ITT analyses. Brief tele-IPT acutely decreased depressive symptoms and interpersonal problems in depressed rural people living with HIV.


New insights into redox homeostasis as a therapeutic target in B-cell malignancies.
The goal of this review is to summarize recent advances in our understanding of the regulation of redox homeostasis and the subtype-specific role of antioxidant enzymes in B-cell-derived malignancies. Furthermore, it presents selected prooxidative therapeutic strategies against B-cell neoplasms. Recent reports have shown that the disturbed redox homeostasis in B-cell malignancies is regulated by cancer-specific signaling pathways and therefore varies between the individual subtypes. For instance, in a subtype of diffuse large B-cell lymphoma with increased oxidative phosphorylation, elevated reactive oxygen species are accompanied by higher levels of thioredoxin and glutathione and inhibition of either of these systems is selectively toxic to this subtype. In addition, growing number of small molecule inhibitors targeting antioxidant enzymes, such as auranofin, SK053, adenanthin, or decreasing glutathione level, such as imexon, buthionine sulfoximine, and L-cysteinase, trigger specific cytotoxic effects against B-cell malignancies. Lastly, attention is drawn to recent reports of effective treatment modalities involving prooxidative agents and interfering with redox homeostasis provided by stromal cells. Recent findings reveal important differences in redox homeostasis within the distinct subsets of B-cell-derived malignancies that can be therapeutically exploited to improve existing treatment and to overcome drug resistance.


Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy.
To assess the profile, utilization patterns, satisfaction and perceived effects among users of electronic cigarettes ('e-cigarettes'). Internet survey in English and French in 2010. Online questionnaire. Visitors of websites and online discussion forums dedicated to e-cigarettes and to smoking cessation. There were 3587 participants (70% former tobacco smokers, 61% men, mean age 41 years). The median duration of electronic cigarette use was 3 months, users drew 120 puffs/day and used five refills/day. Almost all (97%) used e-cigarettes containing nicotine. Daily users spent $33 per month on these products. Most (96%) said the e-cigarette helped them to quit smoking or reduce their smoking (92%). Reasons for using the e-cigarette included the perception that it was less toxic than tobacco (84%), to deal with craving for tobacco (79%) and withdrawal symptoms (67%), to quit smoking or avoid relapsing (77%), because it was cheaper than smoking (57%) and to deal with situations where smoking was prohibited (39%). Most ex-smokers (79%) feared they might relapse to smoking if they stopped using the e-cigarette. Users of nicotine-containing e-cigarettes reported better relief of withdrawal and a greater effect on smoking cessation than those using non-nicotine e-cigarettes. E-cigarettes were used much as people would use nicotine replacement medications: by former smokers to avoid relapse or as an aid to cut down or quit smoking. Further research should evaluate the safety and efficacy of e-cigarettes for administration of nicotine and other substances, and for quitting and relapse prevention.


Accuracy of non-invasive and minimally invasive hemodynamic monitoring: where do we stand?
One of the most important variables in assessing hemodynamic status in the intensive care unit (ICU) is the cardiac function and blood pressure. Invasive methods such as pulmonary artery catheter and arterial line allow monitoring of blood pressure and cardiac function accurately and reliably. However, their use is not without drawbacks, especially when the invasive nature of these procedures and complications associated with them are considered. There are several newer methods of noninvasive and minimally invasive hemodynamic monitoring available. In this manuscript, we will review these different methods of minimally invasive and non-invasive hemodynamic monitoring and will discuss their advantages, drawbacks and limitations.


Organization of visual mossy fiber projections and zebrin expression in the pigeon vestibulocerebellum.
Extensive research has revealed a fundamental organization of the cerebellum consisting of functional parasagittal zones. This compartmentalization has been well documented with respect to physiology, biochemical markers, and climbing fiber afferents. Less is known about the organization of mossy fiber afferents in general, and more specifically in relation to molecular markers such as zebrin. Zebrin is expressed by Purkinje cells that are distributed as a parasagittal array of immunopositive and immunonegative stripes. We examined the concordance of zebrin expression with visual mossy fiber afferents in the vestibulocerebellum (folium IXcd) of pigeons. Visual afferents project directly to folium IXcd as mossy fibers and indirectly as climbing fibers via the inferior olive. These projections arise from two retinal recipient nuclei: the lentiformis mesencephali (LM) and the nucleus of the basal optic root (nBOR). Although it has been shown that these two nuclei project to folium IXcd, the detailed organization of these projections has not been reported. We injected anterograde tracers into LM and nBOR to investigate the organization of mossy fiber terminals and subsequently related this organization to the zebrin antigenic map. We found a parasagittal organization of mossy fiber terminals in folium IXcd and observed a consistent relationship between mossy fiber organization and zebrin stripes: parasagittal clusters of mossy fiber terminals were concentrated in zebrin-immunopositive regions. We also describe the topography of projections from LM and nBOR to the inferior olive and relate these results to previous studies on the organization of climbing fibers and zebrin expression.


The Effects of Chronic Naltrexone on Reinstatement of Opioid-Induced Drug-Seeking Behavior and Antinociception.
Opioid addiction is a chronic relapsing disorder in which drug-seeking behavior during abstinence can be provoked by exposure to a µ-opioid receptor (MOR) agonist or opioid-associated cues. Opioid self-administration behavior in laboratory subjects can be reinstated by priming with MOR agonists or agonist-related stimuli, providing a procedure comparable to relapse. The opioid antagonist naltrexone has been forwarded as a pharmacologically effective approach to forestalling relapse and, in an extended-release formulation, has demonstrated some treatment success. However, chronic naltrexone treatment has not been extensively investigated in nonhuman subjects and aspects of its pharmacology remain uncertain. For example, the relative effectiveness of naltrexone in reducing the priming strength of opioid agonists differing in efficacy is not well understood. Here, using i.v self-administration and warm-water tail withdrawal procedures, we investigated changes in the direct reinforcing effects of oxycodone and in the priming strength and antinociceptive effects of opioid agonists in squirrel monkeys (n=4) during chronic treatment with naltrexone (0.2mg/kg/day). Results show that naltrexone produced: 1) a ten-fold rightward shift in the dose-response function for the reinforcing effects of oxycodone, and 2) in reinstatement and antinociception experiments, comparable rightward shifts in the dose-response functions for higher-efficacy MOR agonists (methadone, heroin, oxycodone) but rightward and downward shifts in the dose-response functions for lower-efficacy MOR agonists (buprenorphine, nalbuphine, butorphanol). These results suggest that, while chronic naltrexone should be effective in forestalling relapse following exposure to lower- and higher-efficacy agonists, the inability of lower-efficacy agonists to surmount naltrexone antagonism may complicate the prescription of opioids for pain. Significance Statement Though naltrexone is used in the treatment of OUD, its ability to reduce the priming strength of opioid agonists has not been extensively investigated. Here we show that chronic naltrexone treatment induces rightward shifts in the reinstatement and antinociceptive properties of higher efficacy opioid agonists, but rightward and downward shifts for lower efficacy opioid agonists, suggesting lower efficacy agonists may not surmount naltrexone-induced antagonism of these two effects and that perhaps naltrexone offers greater protection against lower efficacy agonists.


Variable restriction endonuclease sites of herpes simplex virus type 1 isolates from encephalitic, facial and genital lesions and ganglia.
The distribution of restriction endonuclease (RE) sites was compared for 84 herpes simplex virus type 1 (HSV-1) isolates obtained from the ganglia, facial lesions, genital lesions and from brain tissue from herpes encephalitis cases. The isolates came from Canada, the U.K., the U.S.A. and Japan. Out of a total of 224 sites identified, 87 were variable. Three of the 30 most variable sites were at significantly (P less than 0.05) different frequencies in groups of isolates from distinct anatomical sites of isolation; one of these, and a further two sites, were at significantly different frequencies in groups from distinct geographical origins. There are at least two inter-related linkage groups. However, most of the site combinations appear to be random. The variability of RE sites in contiguous genome segments, which include both non-coding and coding sequences, show a marked heterogeneity, indicating that some viral gene sequences are more variable than others. The three RE sites at different frequencies in viral groups from distinct anatomical sites of isolation are in two genome segments: map units 27 to 35 and 50 to 57. We infer from the observed associations with anatomical site of viral isolation that part of at least one of these segments may modulate viral virulence in man following infection.


Pathogenicity of a quail (Coturnix coturnix japonica)-derived Marek's disease virus rescued from the QT35 cell line.
The QT35 cell line was established in 1977 from methylcholanthrene-induced tumors in Japanese quail. It was later shown that at least some of the QT35 cell lines were latently infected with Marek's disease (MD) virus (MDV). An MDV-like herpesvirus, named quail MDV (QMDV), was isolated from QT35 cells in 2000 by Yamaguchi et al. To determine the pathogenicity of QMDV, we inoculated 10-day-old specific-pathogen-free chickens with QMDV JM (virulent), RB-1B (very virulent), or 584A (very virulent plus). In addition, we inoculated 5-day-old Japanese quail with QMDV, JM, or RB-1B. QMDV is pathogenic in chickens with a tumor incidence comparable to JM. QMDV also caused MD in three out of 18 infected Japanese quail. In conclusion, QMDV is a virulent MDV, and its presence in QT35 cells has implications for the use of QT35 cells for vaccine production.


Effect of the Self-Assembled Structures of Hydrated Polyzwitterionic and Polyanionic Brushes on Their Self-Cleaning Capabilities.
The capability of polyelectrolyte brushes to spontaneously clean oil fouling via water is determined by factors including water wettability and the self-assembled structures of hydrated polyelectrolytes. Although the charged groups of polyelectrolytes provide the original source of water wettability, the self-assembled structures play a significant role in the self-cleaning performances. Here, we employ coarse-grained molecular dynamics simulations to study the general self-cleaning characteristics of two types of surface-grafted polyelectrolyte brushes (i.e., zwitterionic and anionic polyelectrolytes). It has been found that the high grafting density is favorable to fouling reduction for both polyzwitterions and polyanions. To be specific, the hydrated polyzwitterions form an intermolecular cross-linked network via zwitterionic complexes, resulting in better self-cleaning capabilities than the polyanions at lower grafting densities. However, polyanions form bundles with each consisting of several chains via hydrophobic interactions and electrostatic repulsions presenting better self-cleaning performances than the polyzwitterions at higher grafting densities.


The application of physico-chemical procedures in the analysis of urinary calculi.
All physico-chemical techniques used in the analysis of urinary calculi have inherent advantages and limitations. Although x-ray powder diffraction can identify constituents unambiguously, certain minor components can be missed. Infrared spectroscopy is more sensitive but band assignment at low concentrations is difficult. Scanning electron microscopy together with energy dispersive x-ray analysis permits the simultaneous investigation of morphology and chemical microstructure. However, microanalysis of elements lighter than sodium is not possible and constituents are prone to irradiation damage. With the electron microprobe, minor constituents can be detected but tedious sample preparation procedures are required. Transmission electron microscopy is extremely useful in determining constituent inter-relationships and ultrastructure but ultramicrotomy is very difficult. Thermal gravimetric analysis gives quantitative information easily but does not satisfactorily distinguish between struvite and brushite. In an attempt to assess the accuracy of chemical analyses, 62 calculi were investigated applying several chemical tests. Those for Mg2+, PO4(3-), NH4+ and uric acid proved highly reliable while that for Ca2+ often yielded an incorrect result. The test for oxalate was totally unsatisfactory. Investigators of stone composition and structure should include x-ray diffraction (or infrared spectroscopy) and scanning electron microscopy as their methods of first choice. In addition, chemical or thermogravimetric analyses should be utilized in an auxiliary capacity.


Low-density array PCR analysis of reperfusion biopsies: an adjunct to histological analysis.
Histologic evaluation of baseline kidney biopsies is an inconsistent tool to predict graft outcomes, which might be assisted by gene expression analysis. We evaluated 49 consecutive kidney graft biopsies obtained post-reperfusion in 18 deceased donors (DD) and 31 living donors (LD) at our center. Biopsies were evaluated and scored using Banff criteria. Low-density real-time polymerase chain reaction arrays were used to measure intragraft expression of 95 genes associated with programmed cell death, fibrosis, innate and adaptive immunity and oxidative stress signaling. A pool of 25 normal kidney biopsies was used as control. We applied a stepwise forward selection procedure to build a multiple regression model predicting estimated glomerular filtration rate (eGFR) at 1 year after transplant using baseline clinical characteristics and gene expression levels. DD grafts displayed a pattern of gene expression remarkably different from LD, including an increased expression of complement protein C3, and chemokines, CXCL1 and CXCL2, consistent with the proinflammatory setting of ischaemia-reperfusion injury. There was no association between any of the reperfusion biopsy histological features and either renal function at 1 year post-transplant or risk of acute rejection. Conversely, older donor age (R(2) = 0.17, P < 0.001) and higher integrin β2 gene expression levels (incremental R(2) versus Donor Age-only model = 0.23, P < 0.001) jointly predicted lower eGFR at 1 year after transplant (multiple regression R(2) = 0.40). Patients with higher ITGβ2 expression levels in baseline biopsies showed lower eGFR, higher levels of proteinuria and more transplant glomerulopathy on the 1-year per-protocol biopsies. ITGβ2 gene expression in reperfusion biopsies may represent a prognostic marker for kidney transplant recipients, potentially helpful in shaping patients' treatment. Further studies are needed to confirm our findings.


Structural restoration of nematodes and acanthocephalans fixed in high percentage alcohol using DESS solution and rehydration.
Ninety-five percent ethanol is the most widely used field and laboratory preservative for nematodes and other helminth specimens intended for use in molecular systematics. Preservation of nematodes in high-concentration alcohols results in structural dehydration artifacts, including shrinkage and body surface distortions sufficient to obscure features required for morphological identification and analysis, thereby compromising precise morphometrics. However, treating dehydrated nematodes using a solution of DMSO, disodium EDTA, and NaCl, followed by rehydration in water produces marked improvements in specimen shape and surface features, resulting from diffusion of water into the tissues and pseudocoelom as the internal salt concentration is reduced. Following rehydration, tissue samples can be obtained for molecular research and individuals can be fixed for morphological examination. This treatment method is demonstrated for species of 3 nematode genera that vary substantially in body size ( Baylisascaris , Uncinaria , and Bidigiticauda ). The method also works on nematodes that have been cut in half, provided the individuals are large enough to be folded and clamped during treatment. This method appears promising for other helminths, although for an acanthocephalan, the treatment restored the body surface but failed to reverse the retracted proboscis.


[Dangerous marine animals].
Sea-biological basic knowledge for divers is offered only in special lessons for advanced scuba divers. According to statistics, however, five per cent of the deadly diving accidents are caused by underwater organisms. This number could be reduced to a fraction, by correct behaviour during the dive and after an accident. The most frequent accidents with sea animals during water sports are not by unprovoked shark attacks, which cause six deaths world-wide per year on the average, but turn out with usually well camouflaged sea inhabitants, that do not attack humans, rather by their inadvertence coincidentally get in contact with it. The various defense instruments of the often small, inconspicuous organisms reach from teeth over poison stings, pricks, spines, scalpelles, nettle injections and chemical weapons up to poison arrows. Due to that variety of the maritime life, the most important representatives of its type are explained including severity level of the caused injury or contamination. Both, diagnostic position and therapy possibility are described as follows: 1. Porifera (sponge), 2. Hydrozoa (white weed, yellow flower head), Actinaria (sea anemones), 3. Conidae (cone shells), Tridocna (giant clam), octopoda (octopus), 4. Acanthaster planci (crown of thorns), Echinodea (sea urchins), Holothurioidea (sea cucumber), 5. Selachoidei (shark), Batoidei (Ray), Muraenidae (moray), Plotosidae (barbel eels), Synanciidae (stonefish), Scorpaenidae (scorpionfish), Pterois (lion fish), Sphyraena Spec. (barracuda), Balistidae (triggerfish), Ostracionidae (puffer).


Differentiation of newly described antarctic bacterial isolates related to Roseobacter species based on 16S-23S rDNA internal transcribed spacer sequences.
The 16S-23S rDNA internal transcribed spacer (ITS) of Roseobacter denitrificans, Roseobacter litoralis, Ruegeria algicola and strains of the recently described species Antarctobacter heliothermus and Roseovarius tolerans were analysed in order to examine DNA sequence variations and to draw conclusions about inter- and intraspecific relationships. A. heliothermus included four strains with an ITS fragment length of 1092 bp. Roseovarius tolerans was described on the basis of eight strains. Five of these harboured two ITS fragments of different lengths (959 and about 1100 bp), while the others had one fragment of either 1083 bp (two strains) or 1165 bp (one strain). ITS lengths of the related species Roseobacter denitrificans, Roseobacter litoralis and Ruegeria algicola were found to be 980, 984 and 1158 bp, respectively. Phylogenetic analyses of the DNA sequences allowed species affiliation of strains with sequence length differences of > 200 bp and recognition of relationships based on a well-supported ITS tree. The strains of A. heliothermus and Roseovarius tolerans each formed a monophyletic branch and they were separated from each other by Ruegeria algicola. This species was now clearly separated from Roseobacter denitrificans and Roseobacter litoralis, which corresponded to the new genus affiliation of Ruegeria algicola. These data were additionally supported by analyses of the structure, relative position and order of genes for tRNA(Ile) and tRNA(Ala) found within the ITS of each strain. Comparative DNA sequence analyses of ITS and 16S rDNA revealed limitations, on species and strain levels, with respect to the phylogenetic resolution of the 16S rDNA due to the limited number of informative (variable) sites, while ITS sequence analyses provided more variable and sufficiently conserved positions to discriminate between strains and to reconstruct their taxonomic relationships.


Risk perceptions, condom use, and sexually transmitted diseases among adolescent females according to social network position.
Adolescent females are frequently treated as a homogenous group but could differ on their sexually transmitted disease (STD) risk because of individual attitudes and exposure through sexual networks. The goal of this study was to determine if risk perceptions, condom use, and STD prevalence differs within sexual networks. Three hundred three adolescent females participating in a longitudinal study of adolescent STD risk perceptions and condom use were categorized as "core," "bridge," and "periphery" in a sexual network according to their and their main sex partner's risk information. Regression analysis determined differences in risk perceptions by network location. We demonstrated an inverse relationship between STD risk perceptions and network location. Adolescents with higher risk perceptions were more likely to use condoms, irrespective of network location. Female adolescents are a heterogeneous group exhibiting different risk perceptions. Different intervention strategies for adolescents at higher risk could be necessary. Interventions designed to raise risk perceptions could be associated with condom use, even for those adolescents at greatest risk.


Tracing the Sources of Atmospheric Phosphorus Deposition to a Tropical Rain Forest in Panama Using Stable Oxygen Isotopes.
Atmospheric dust deposition can be a significant source of phosphorus (P) in some tropical forests, so information on the origins and solubility of atmospheric P is needed to understand and predict patterns of forest productivity under future climate scenarios. We characterized atmospheric dust P across a seasonal cycle in a tropical lowland rain forest on Barro Colorado Nature Monument (BCNM), Republic of Panama. We traced P sources by combining remote sensing imagery with the first measurements of stable oxygen isotopes in soluble inorganic phosphate (δ(18)OP) in dust. In addition, we measured soluble inorganic and organic P concentrations in fine (<1 μm) and coarse (>1 μm) aerosol fractions and used this data to estimate the contribution of P inputs from dust deposition to the forest P budget. Aerosol dry mass was greater in the dry season (December to April, 5.6-15.7 μg m(-3)) than the wet season (May to November, 3.1-7.1 μg m(-3)). In contrast, soluble P concentrations in the aerosols were lower in the dry season (980-1880 μg P g(-1)) than the wet season (1170-3380 μg P g(-1)). The δ(18)OP of dry-season aerosols resembled that of nearby forest soils (∼19.5‰), suggesting a local origin. In the wet season, when the Trans-Atlantic Saharan dust belt moves north close to Panama, the δ(18)OP of aerosols was considerably lower (∼15.5‰), suggesting a significant contribution of long-distance dust P transport. Using satellite retrieved aerosol optical depth (AOD) and the P concentrations in aerosols we sampled in periods when Saharan dust was evident we estimate that the monthly P input from long distance dust transport during the period with highest Saharan dust deposition is 88 ± 31 g P ha(-1) month(-1), equivalent to between 10 and 29% of the P in monthly litter fall in nearby forests. These findings have important implications for our understanding of modern nutrient budgets and the productivity of tropical forests in the region under future climate scenarios.


Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover.
Loss of NEDD8-activating enzyme (NAE) function by siRNA knockdown or inhibition by the small molecule NAE inhibitor MLN4924 leads to increased steady-state levels of direct Cullin-RING ligase (CRL) substrates by preventing their ubiquitination and proteasome-dependent degradation. Many of these CRL substrates are involved in cell cycle progression, including a critical DNA replication licensing factor CDT1. Cell cycle analysis of asynchronous and synchronous cultures after NAE inhibition revealed effects on cell cycle distribution and activation of DNA break repair signaling pathways similar to that reported for CDT1 overexpression. The siRNA knockdown of cullins critical for the turnover of CDT1 recapitulated the aberrant rereplication phenotype while CDT1 knockdown was suppressing. Although NAE inhibition leads to deregulation of many CRL substrates, these data demonstrate that CDT1 accumulation mediates the DNA rereplication phenotype resulting from loss of NAE function. DNA rereplication is an unrecoverable cellular insult and the small molecule inhibitor MLN4924, currently in phase I trials, represents an unprecedented opportunity to explore this mechanism of cytotoxicity for the treatment of cancer.


H2O2 production downstream of FLT3 is mediated by p22phox in the endoplasmic reticulum and is required for STAT5 signalling.
The internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor has been associated with increased reactive oxygen species (ROS) generation in acute myeloid leukemia (AML). How this elevated level of ROS contributes to the leukemic phenotype, however, remains poorly understood. In this work we show that ROS in the FLT3-ITD expressing AML cell line MV4-11 is reduced by treatment with PKC412, an inhibitor of FLT3, DPI, a flavoprotein inhibitor, and VAS2870, a Nox specific inhibitor, suggesting that ROS production is both FLT3 and NADPH oxidase dependent. The majority of these ROS co-localize to the endoplasmic reticulum (ER), as determined with the H(2)O(2)-specific aryl-boronate dye Peroxyorange 1, which also corresponds to co-localization of p22phox. Moreover, knocking down p22phox dramatically reduces H(2)O(2) after 24 hours in the ER, without affecting mitochondrial ROS. Significantly, the FLT3 inhibitor PKC412 reduces H(2)O(2) in FLT3-ITD expressing cell lines (MV4-11, MOLM-13) through reduction of p22phox over 24 hours. Reduced p22phox is achieved by proteasomal degradation and is prevented upon GSK3-β inhibition. Knockdown of p22phox resulted in reduced STAT5 signalling and reduced Pim-1 levels in the cells after 24 hours. Thus, we have shown that FLT3 driven H(2)O(2) production in AML cells is mediated by p22phox and is critical for STAT5 signalling.


Phase II study of CGP 69846A (ISIS 5132) in recurrent epithelial ovarian cancer: an NCIC clinical trials group study (NCIC IND.116).
ISIS 5132 is a 20-base phosphorothioate DNA oligonucleotide against human c-raf kinase, a downstream effector of ras oncogene function. C-raf kinase is a molecule in the MAP kinase signaling cascade which is essential for cellular proliferation, the overexpression of which leads to malignant expression. Activity of this compound was documented in a woman with ovarian cancer in a Phase I study. We evaluated ISIS 5132 at a dose of 4 mg/kg/day by continuous venous infusion, administered for 21 days q 4 weeks in 22 patients with recurrent ovarian cancer in a standard two-stage Phase II design. Three patients were ineligible; 19 patients are evaluable for toxicity and 16 for response. All patients had previously received systemic therapy for ovarian cancer (6 had one and 13 had two prior regimens). Patients were treated with a median of two cycles and 79% of the patients received >90% planned dose intensity. ISIS 5132 was well tolerated with no episodes of Grade 3 or 4 hematologic or biochemical (creatinine, AST, bilirubin) toxicity. There were six episodes of grade 3 nonhematologic toxicity in 4 patients thought to be treatment related (lethargy 2; anorexia 1; abdominal pain 2; shortness of breath 1). No responses were seen in the 16 patients who are evaluable for response; 4 had stable disease for a median of 3.8 months and 12 patients had documented progressive disease. ISIS 5132 at 4 mg/kg/day as a single agent did not show activity in recurrent ovarian cancer.


Development of the EQ-5D-Y: a child-friendly version of the EQ-5D.
To develop a self-report version of the EQ-5D for younger respondents, named the EQ-5D-Y (Youth); to test its comprehensibility for children and adolescents and to compare results obtained using the standard adult EQ-5D and the EQ-5D-Y. An international task force revised the content of EQ-5D and wording to ensure relevance and clarity for young respondents. Children's and adolescents' understanding of the EQ-5D-Y was tested in cognitive interviews after the instrument was translated into German, Italian, Spanish and Swedish. Differences between the EQ-5D and the EQ-5D-Y regarding frequencies of reported problems were investigated in Germany, Spain and South Africa. The content of the EQ-5D dimensions proved to be appropriate for the measurement of HRQOL in young respondents. The wording of the questionnaire had to be adapted which led to small changes in the meaning of some items and answer options. The adapted EQ-5D-Y was satisfactorily understood by children and adolescents in different countries. It was better accepted and proved more feasible than the EQ-5D. The administration of the EQ-5D and of the EQ-5D-Y causes differences in frequencies of reported problems. The newly developed EQ-5D-Y is a useful tool to measure HRQOL in young people in an age-appropriate manner.


Lipid metabolism-related gene expression in the immune microenvironment predicts prognostic outcomes in renal cell carcinoma.
Rates of renal cell carcinoma (RCC) occurrence and mortality are steadily rising. In an effort to address this issue, the present bioinformatics study was developed with the goal of identifying major lipid metabolism biomarkers and immune infiltration characteristics associated with RCC cases. The Cancer Genome Atlas (TCGA) and E-MTAB-1980 were used to obtain matched clinical and RNA expression data from patients diagnosed with RCC. A LASSO algorithm and multivariate Cox regression analyses were employed to design a prognostic risk model for these patients. The tumor immune microenvironment (TIME) in RCC patients was further interrogated through ESTIMATE, TIMER, and single-cell gene set enrichment analysis (ssGSEA) analyses. Gene Ontology (GO), KEGG, and GSEA enrichment approaches were further employed to gauge the mechanistic basis for the observed results. Differences in gene expression and associated functional changes were then validated through appropriate molecular biology assays. Through the approach detailed above, a risk model based on 8 genes associated with RCC patient overall survival and lipid metabolism was ultimately identified that was capable of aiding in the diagnosis of this cancer type. Poorer prognostic outcomes in the analyzed RCC patients were associated with higher immune scores, lower levels of tumor purity, greater immune cell infiltration, and higher relative immune status. In GO and KEGG enrichment analyses, genes that were differentially expressed between risk groups were primarily related to the immune response and substance metabolism. GSEA analyses additionally revealed that the most enriched factors in the high-risk group included the stable internal environment, peroxisomes, and fatty acid metabolism. Subsequent experimental validation in vitro and in vivo revealed that the most significantly differentially expressed gene identified herein, ALOX5, was capable of suppressing RCC tumor cell proliferation, invasivity, and migration. In summary, a risk model was successfully established that was significantly related to RCC patient prognosis and TIME composition, offering a robust foundation for the development of novel targeted therapeutic agents and individualized treatment regimens. In both immunoassays and functional analyses, dysregulated lipid metabolism was associated with aberrant immunological activity and the reprogramming of fatty acid metabolic activity, contributing to poorer outcomes.


Hypothyroidism in children with the Down syndrome: report of three cases.
The cases of three patients with concurrent Down syndrome and hypothyroidism are reported. Review of these and 12 similar cases from the literature suggests an association between the Down syndrome and thyroid autoimmune disease. Studies of autoimmune thyroid antibodies in families of patients with the Down syndrome are also reviewed. Several questions as yet unanswered regarding the possible relationship of these studies to cases of concurrent Down syndrome and hypothyroidism are mentioned.


Optimization of Linezolid Dosing Regimens for Treatment of Vancomycin-Resistant Enterococci Infection.
Linezolid, an oxazolidinone antibiotic, is recommended for vancomycin-resistant enterococci (VRE). However, 100% free-drug concentration above the minimum inhibitory concentration (fT>MIC) and an area under the curve of free drug to MIC ratio (fAUC24/MIC) >100 were associated with favorable clinical outcome with less emerging resistance. A plasma trough concentration (Ctrough) of linezolid ≥9 μg/mL was also related to hematologic toxicity. Thus, linezolid dose optimization is needed for VRE treatment. The study aimed to determine the in vitro linezolid activity against clinical VRE isolates and linezolid dosing regimens in critically ill patients who met the target pharmacokinetics/pharmacodynamics (PK/PD) for VRE treatment. Enterococcal isolates from enterococcal-infected patients were obtained between 2014 and 2018 at Phramongkutklao Hospital. We used Monte Carlo simulation to calculate the probability of target attainment, and the cumulative fraction of response (CFR) of the free area under the curve to MIC ratio (fAUIC24) was used to calculate the fAUC24/MIC 80 - 100 and fT/MIC >85 - 100% of the interval time of administration for clinical response and microbiological eradication as well as the Ctrough ≥9 μg/mL for the probability of hematologic toxicity. For linezolid MIC determination, the MIC median (MIC50), MIC for 90% growth (MIC90), and range for linezolid were 1.5 μg/mL, 2 μg/mL, and 0.72 - 2 μg/mL, respectively. A dosing regimen of 1,200 mg either once daily or as a divided dose every 12 h gave target attainments of fAUC24/MICs >80 and >100, which exceeded 90% for MICs ≤1 and ≤1 μg/mL, respectively, with a rate of hematologic toxicity <15%. If the expected fT>MICs were >85% and 100%, a 1,200-mg divided dose every 12 h could cover VRE isolates having linezolid MICs ≤1 μg/mL and ≤0.75 μg/mL. Even 600 mg every 8 h and 1,200 mg as a continuous infusion gave a higher target attainment of fAUC24/MIC and a fT>MIC and the target CFR, but those regimens gave Ctrough ≥9 μg/mL rates of 40.7% and 99.6%. The current dosing of 1,200 mg/day might be optimal treatment for infection by VRE isolates with documented MICs ≤1 μg/mL. For treatment of VRE with a MIC of 2 μg/mL or to achieve the target CFR, the use of linezolid with other antibiotic combinations might help achieve the PK/PD target, provide better clinical outcome, and prevent resistance.


Prediction of sensory properties of Brazilian Arabica roasted coffees by headspace solid phase microextraction-gas chromatography and partial least squares.
Volatile compounds in fifty-eight Arabica roasted coffee samples from Brazil were analyzed by SPME-GC-FID and SPME-GC-MS, and the results were compared with those from sensory evaluation. The main purpose was to investigate the relationships between the volatile compounds from roasted coffees and certain sensory attributes, including body, flavor, cleanliness and overall quality. Calibration models for each sensory attribute based on chromatographic profiles were developed by using partial least squares (PLS) regression. Discrimination of samples with different overall qualities was done by using partial least squares-discriminant analysis (PLS-DA). The alignment of chromatograms was performed by the correlation optimized warping (COW) algorithm. Selection of peaks for each regression model was performed by applying the ordered predictors selection (OPS) algorithm in order to take into account only significant compounds. The results provided by the calibration models are promising and demonstrate the feasibility of using this methodology in on-line or routine applications to predict the sensory quality of unknown Brazilian Arabica coffee samples. According to the PLS-DA on chromatographic profiles of different quality samples, compounds 3-methypropanal, 2-methylfuran, furfural, furfuryl formate, 5-methyl-2-furancarboxyaldehyde, 4-ethylguaiacol, 3-methylthiophene, 2-furanmethanol acetate, 2-ethyl-3,6-dimethylpyrazine, 1-(2-furanyl)-2-butanone and three others not identified compounds can be considered as possible markers for the coffee beverage overall quality.


[Cortisol-induced changes in methylation of repeating sequences of transcriptionally active DNA from rat liver].
The m5C content was determined in three functionally different fractions of rat liver DNA isolated by a modified phenol fractionation. The transcriptionally active DNA-I contains up to 12-14% of hybrid RNA not hydrolyzed by RNAase, is enriched with unique sequences and makes up to about 20% of total DNA. In its total nucleotide content (43 mol.% of GC-pairs) DNA-I does not differ from the major fraction of DNA-II making up to about 70% of the genome, and from hardly extractable DNA-III, whose content in total DNA does not exceed 10%. However, the degree of methylation of the transcriptionally active DNA-I (1.28 mol.% of m5C) is higher than that of DNA-II and DNA-III (1.0 mol.% of m5C). Under cortisol-induced activation of transcription the number of repeating sequences in DNA-I is increased by about 10% concomitant with a decrease of these sequences in DNA-III. The hormone-induced changes in the transcriptionally active fraction of DNA are reversible. 4 hrs after cortisol injection a demethylation of highly repeating and supermethylation of normally repeating sequences in DNA-I are observed. The level of methylation of the unique sequences in DNA-I (Cot greater than 200) remains unchanged. The degree of methylation of various subfractions of nucleotide sequences of DNA-II and DNA-III afer cortisol injection does not differ from normal. Presumably the hormone-induced supermethylation of normally repeating sequences may control the transcription.


Smart Information Management in Health Big Data.
The smart information management system (SIMS) is concerned with the organization of anonymous patient records in a big data and their extraction in order to provide needful real-time intelligence. The purpose of the present study is to highlight the design and the implementation of the smart information management system. We emphasis, in one hand, the organization of a big data in flat file in simulation of nosql database, and in the other hand, the extraction of information based on lookup table and cache mechanism. The SIMS in the health big data aims the identification of new therapies and approaches to delivering care.


Polymyalgia rheumatica and giant-cell arteritis.
Polymyalgia rheumatica and giant-cell arteritis are closely related disorders that affect people of middle age and older. They frequently occur together. Both are syndromes of unknown cause, but genetic and environmental factors might have a role in their pathogenesis. The symptoms of polymyalgia rheumatica seem to be related to synovitis of proximal joints and extra-articular synovial structures. Giant-cell arteritis primarily affects the aorta and its extracranial branches. The clinical findings in giant-cell arteritis are broad, but commonly include visual loss, headache, scalp tenderness, jaw claudication, cerebrovascular accidents, aortic arch syndrome, thoracic aorta aneurysm, and dissection. Glucocorticosteroids are the cornerstone of treatment of both polymyalgia rheumatica and giant-cell arteritis. Some patients have a chronic course and might need glucocorticosteroids for several years. Adverse events of glucocorticosteroids affect more than 50% of patients. Trials of steroid-sparing drugs have yielded conflicting results. A greater understanding of the molecular mechanisms involved in the pathogenesis should provide new targets for therapy.


Three-dimensional complex image coding using a circular Dammann grating.
Recently, optical image coding using a circular Dammann grating (CDG) has been proposed and investigated. However, the proposed technique is intensity based and could not be used for three-dimensional (3D) image coding. In this paper, we investigate an optical image coding technique that is complex-amplitude based. The system can be used for 3D image coding. The complex-amplitude coding is provided by a circular Dammann grating through the use of a digital holographic recording technique called optical scanning holography. To decode the image, along the depth we record a series of pinhole holograms coded by the CDG. The decoded reconstruction of each depth location is extracted by the measured pinhole hologram matched to the desired depth. Computer simulations as well as experimental results are provided.


Delivery of Glucosylceramidase Beta Gene Using AAV9 Vector Therapy as a Treatment Strategy in Mouse Models of Gaucher Disease.
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the GBA gene. Enzyme replacement treatment is the most effective therapy available for type 1 GD patients, but it is very expensive and does not improve neurologic outcomes in type 2 and 3 GD patients. This study evaluated the effectiveness of an adeno-associated virus 9 (AAV9) vector expressing the Gba gene delivered systemically in GD mouse models. To detect the therapeutic effects of the AAV9-mediated Gba transfer on the systemic symptoms of GD, an inducible whole-body Gba knockout mouse was developed in which tamoxifen effectively induced whole-body Gba gene deletion, and the mice displayed systemic symptoms of GD. The AAV9-CMV-Gba vector, with the expression of Gba driven by the universal CMV promoter, restored GCase activity in multiple organs and prolonged the lifespan in tamoxifen-induced GD mice after intravenous injection. Mice with brain-specific Gba deletion were also included in this study as a model of neuropathic GD (nGD) and injected intraperitoneally on postnatal day 5 with the AAV9-SYN-Gba vector; this improved the GCase activity, ameliorated the neuropathological changes and extended the mean lifespan two-fold. This study demonstrates that AAV9-mediated gene transfer is a potentially effective treatment for GD.


Clinical characteristics and risk factors of diabetic foot ulcers with PAD.
This study aimed to analyze the clinical characteristics of patients with diabetic foot ulcers combined with peripheral arterial disease (PAD) and the risk factors. A retrospective study was conducted on 120 patients with diabetic foot ulcers in the Second Affiliated Hospital of Dalian Medical University from October 2018 to February 2021. The patients were divided into uncombined with the PAD group (42 cases) and combined with the PAD group (78 cases). The baseline information and clinical indicators were measured from two groups. Univariate and binary logistic regression was used to analyze the risk factors of PAD in patients with diabetic foot ulcers. The proportion of patients with age ≥ 60 years, Wagner grade 4-5 and smoking history in the combined group was higher than that in the uncombined group (p < 0.05). The diastolic blood pressure (DBP) of the combined group was lower than that of the uncombined group, while the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and glycated hemoglobin (HbA1c) levels of the combined group were higher than those of the uncombined group (p < 0.05). Binary logistic regression analysis showed that age ≥ 60 years, high Wagner grade, smoking, elevated CRP, NLR and HbA1c levels were risk factors for patients with diabetic foot ulcer combined with PAD (OR > 1, p < 0.05). An elevated DBP level was the protective factor for PAD in patients with diabetic foot ulcer (OR < 1, p < 0.05). Patients with diabetic foot ulcer combined with PAD have the clinical characteristics of poor blood pressure control, long course of disease, and low ABI value. Age ≥ 60 years, high Wagner grade, smoking history, elevated CRP, NLR and HbA1c levels are the risk factors of PAD in patients with diabetic foot ulcer. Increased DBP is protective for PAD in patients with diabetic foot ulcer.


Genetic liability to disability pension in women and men: a prospective population-based twin study.
Previous studies of risk factors for disability pension (DP) have mainly focused on psychosocial, or environmental, factors, while the relative importance of genetic effects has been less studied. Sex differences in biological mechanisms have not been investigated at all. The study sample included 46,454 Swedish twins, consisting of 23,227 complete twin pairs, born 1928-1958, who were followed during 1993-2008. Data on DP, including diagnoses, were obtained from the National Social Insurance Agency. Within-pair similarity in liability to DP was assessed by calculating intraclass correlations. Genetic and environmental influences on liability to DP were estimated by applying discrete-time frailty modeling. During follow-up, 7,669 individuals were granted DP (18.8% women and 14.1% men). Intraclass correlations were generally higher in MZ pairs than DZ pairs, while DZ same-sexed pairs were more similar than opposite-sexed pairs. The best-fitting model indicated that genetic factors contributed 49% (95% CI: 39-59) to the variance in DP due to mental diagnoses, 35% (95% CI: 29-41) due to musculoskeletal diagnoses, and 27% (95% CI: 20-33) due to all other diagnoses. In both sexes, genetic effects common to all ages explained one-third, whereas age-specific factors almost two-thirds, of the total variance in liability to DP irrespective of diagnosis. Sex differences in liability to DP were indicated, in that partly different sets of genes were found to operate in women and men, even though the magnitude of genetic variance explained was equal for both sexes. The findings of the study suggest that genetic effects are important for liability to DP due to different diagnoses. Moreover, genetic contributions to liability to DP tend to differ between women and men, even though the overall relative contribution of genetic influences does not differ by sex. Hence, the pathways leading to DP might differ between women and men.


The impact of arbuscular mycorrhizal symbiosis, Funneliformis mosseae, on rosemary phytoremediation ability under urban traffic.
The aim of this study was to investigate the symbiotic relationship between arbuscular mycorrhizae (Funneliformis mosseae) and the ability of rosemary (Rosmarinus officinalis) to mitigate urban traffic pollution. A factorial experiment with three replications and three factors (inoculated/non-inoculated with G. mosseae, traffic volume, and pot type) was conducted in Shiraz, a metropolis in south-central Iran. Inoculation with F. mosseae led to a 33% increase in root weight and a 20% increase in root length under a traffic volume of 4,200 Vehicles/H. Additionally, as traffic volume increased, stem length and dry weight of the entire plant inoculated with the fungus increased by 8.33% and 29.53%, respectively. The presence of fungus in the rosemary plant decreased the accumulation of Cd and increased the accumulation of Pb by 12.82% and 55.82%, respectively under traffic conditions of 4,200 Vehicles/H. The transfer factor (TF) of Cd and Pb in rosemary plant inoculated under these traffic conditions decreased by 25.74% and 25.24%, respectively. These findings indicate that mycorrhiza-inoculated rosemary plants can thrive in Cd- and Pb-contaminated soils, effectively remediating heavy metals, particularly Pb, with a TF >1.