Effects of Chios Mastiha essential oil on cholesterol levels of healthy volunteers: A prospective, randomized, placebo-controlled study (MASTIHA-OIL).
Chios Mastiha essential oil (CMO) is a natural product extracted from the resin of Mastiha, possessing antioxidant, anti-microbial, anti-ulcer, anti-neoplastic, and cholesterol-lowering capabilities in vitro, and its hypolipidemic effect was confirmed in animal studies. Yet, there are no randomized, placebo-controlled clinical studies in the literature regarding CMO's hypolipidemic effects in humans. A prospective, randomized, placebo-controlled study was designed to study the hypolipidemic effect of CMO capsules on healthy volunteers with elevated cholesterol. 192 healthy volunteers were screened and 160 of them with total cholesterol> 200 mg/dl participated in the study. They were randomized with a 2:1 ratio of receiving CMO capsules (200 mg mastiha-oil/capsule) and placebo for 8 weeks respectively. 113 patients received CMO and 47 were randomized in the control group, and all of them completed the follow-up period. After 8 weeks of CMO administration, total and LDL cholesterol were significantly lower in the CMO compared to the placebo group 215.2 ± 27.5 vs 237.0 ± 27.9 mg/dl (p < 0.001) and 135.0 ± 26.1 vs 153.0 ± 23.3 mg/dl (p < 0.001) respectively. No gastrointestinal adverse events or liver or renal toxicity were reported. Additionally, in the CMO group total cholesterol was significantly decreased by 20.6 mg/dl (9%), LDL by 18.1 mg/dl (12%), triglycerides by 21.8 mg/dl (15%), and glucose by 4.6 mg/dl (5%) and HDL was increased by 2.4 mg/dl (5%), compared to their baseline values. The MASTIHA-OIL study showed the efficacy and safety of CMO in reduction of total and LDL cholesterol after 8 weeks of administration in healthy volunteers with elevated cholesterol levels.


An epidemiological study of Cryptosporidium parvum in two herds of adult beef cattle.
Prevalences of Cryptosporidium parvum oocysts in faeces and of isotype-specific anti-C. parvum antibodies in serum of apparently healthy adult cattle on two farms were determined. On Farm 1 cryptosporidial diarrhoea had been recorded in more than 80% of calves born over the previous 5 years, whereas on Farm 2 cryptosporidiosis had never been reported. No differences were demonstrated in oocyst excretion or presence of antibodies between the two farms. C. parvum oocysts were detected in 62.4% of faecal smears collected from a total of 553 apparently healthy adult cattle. Sucrose flotation was performed on a proportion of the faecal samples. This proved a more sensitive technique, detecting oocysts in 92% of the samples tested, and highlighting the insensitivity of direct smears for detecting oocysts. More than 90% of the cattle had specific anti-C. parvum IgG, IgG1, IgG2 and IgM antibodies and 58% specific anti-C. parvum IgA antibodies. Results suggest that asymptomatic adults may play an important role in the epidemiology of cryptosporidiosis in calves.


Alcohol is not associated with increased mortality in adolescent traumatic brain injury patients.
Compared to adults, there is a paucity of data regarding the association of a positive alcohol screen (PAS) and outcomes in adolescent patients with traumatic brain injury (TBI). We hypothesize adolescent TBI patients with a PAS on admission to have increased mortality compared to patients with a negative alcohol screen. The 2017 Trauma Quality Improvement Program database was queried for patients aged 13-17 years presenting with a TBI and serum alcohol screen. Patients with missing information regarding midline shift on imaging and Glasgow Coma Scale (GCS) score were excluded. A multivariable logistic regression analysis for mortality was performed. From 2553 adolescent TBI patients with an alcohol screen, 220 (8.6%) had a PAS. Median injury severity scores and rates of penetrating trauma (all p > 0.05) were similar between alcohol positive and negative patients. Patients with a PAS had a similar mortality rate (13.2% vs. 12.1%, p = 0.64) compared to patients with a negative screen. Multivariate logistic regression controlling for risk factors associated with mortality revealed a PAS to confer a similar risk of mortality compared to alcohol negative patients (p = 0.40). Adolescent TBI patients with a PAS had similar associated risk of mortality compared to patients with a negative alcohol screen.


Efficacy of postoperative adjuvant transfusion of cytokine-induced killer cells combined with chemotherapy in patients with colorectal cancer.
To assess the activity and safety of postoperative adjuvant immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined with chemotherapy in patients with colorectal cancer. We retrospectively studied 96 consecutive patients with colorectal cancer who were treated with resection between January 2010 and December 2012 as well as adjuvant chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune cells and treatment related side effects were assessed. The patients were followed up until May 2013. By the end of follow-up, 10 patients (10.42 %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK group had significantly longer DFS than those in the control group [HR = 0.28, 95 % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group and the control group were 59.65 ± 24.80 % and 29.35 ± 6.39 %, respectively. The CD4(+)/CD8(+) ratios were significantly lower during the period of chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were significantly higher during the period of CIK cell transfusion than those before CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK cell transfusions. Adjuvant transfusion of CIK cells prolongs DFS in patients with colorectal cancer.


Ethanol inhibition of vinyl chloride metabolism in isolated rat hepatocytes.
Isolated rat liver cells convert [14C]vinyl chloride into non-volatile metabolites. The metabolism is not increased by in vivo pretreatment with phenobarbital. It is sensitive to inhibition by ethanol, which at a concentration of 4 mM inhibits vinyl chloride metabolism to 50% in hepatocyte suspensions. The metabolic activity is NADPH-dependent and is localized in the microsomal fraction of the liver. The enzyme is also strongly inhibited by tetrahydrofuran, indicating that it could be identical to an ethanol-inducible cytochrome P-450 described in the literature [1].


Methicillin-resistant Staphylococcus aureus (MRSA) isolated in clinics and hospitals in the Fukuoka city area.
Bacteriological and clinical studies were carried out on 280 strains of Staphylococcus aureus isolated in clinics and hospitals in the Fukuoka city area from September 1990 to March 1991. The percentage of methicillin-resistant S. aureus (MRSA) strains studied was 41.4% (116 of 280). Of 116 MRSA strains, 48 (41.3%) produced coagulase VII and 21 (18.1%) produced coagulase II. The mean age of the patients who harboured MRSA, 70.5 +/- 16.9 years, was significantly higher than that of patients with methicillin-sensitive S. aureus (MSSA), 44.2 +/- 29.3 years (P < 0.001). MRSA was detected more frequently than MSSA in sputum (P < 0.01), while MSSA was detected more frequently than MRSA in pus (P < 0.01). Ninety (89.1%) of 101 strains of MRSA were isolated from inpatients and 98 (71.0%) of 130 strains of MSSA were isolated from outpatients. Similar number of MRSA strains were recovered in a variety of hospitals, indicating that there was no relationship between hospital size (number of beds) and the incidence of MRSA. As for drug susceptibility, coagulase VII-producing MRSA strains were more sensitive to clidamycin (P < 0.01) and more resistant to minocycline (P < 0.01) than were other MRSA strains.


Unravelling the metal uptake process in mosses: Comparison of aquatic and terrestrial species as air pollution biomonitors.
Transplanted mosses have been widely shown to be excellent tools for biomonitoring air pollution; however, it is not clear how the functional groups present on their surfaces affect the uptake of metal cations. In the present study, we examined differences in trace metal accumulation in two terrestrial and one aquatic moss species, and investigated whether the differences depended on their physico-chemical characteristics. In the laboratory, we determined C, N and H contents in their tissues and obtained the ATR-FTIR spectra (to identify the presence of functional groups). We also conducted surface acid-base titrations and metal adsorption assays with Cd, Cu and Pb. In the field, we exposed transplants of each species near different air-polluting industries, and determined the mosses enrichment of Al, Cd, Co, Cr, Cu, Fe, Ni, Pb and V. Laboratory results demonstrated higher metal uptake capacity in the terrestrial mosses Sphagnum palustre and Pseudoscleropodium purum, compared to that in the aquatic moss Fontinalis antipyretica, which can be attributed to a greater abundance of acidic functional groups (i.e. negatively charged binding sites) on the surface of the terrestrial mosses. The affinity of moss for certain elements depends on the abundance and nature of surface functional groups. Accordingly, the metal concentrations generally reached higher levels in S. palustre transplants compared to the other species, except for the uptake of Hg, which was higher in F. antipyretica. However, the findings also suggest an interaction between the type of environment (terrestrial or aquatic) and the moss characteristics that may influence the abovementioned trend. Thus, irrespective of the physico-chemical characteristics, metal uptake varied depending on the environment of origin of the mosses "i.e. atmospheric or aquatic". In other words, the findings suggest that species that accumulate more metals in terrestrial environments will accumulate lower amounts of metals in aquatic environments and vice versa.


Functional characterization of SdcF from Bacillus licheniformis, a homolog of the SLC13 Na⁺/dicarboxylate transporters.
The SdcF transporter from Bacillus licheniformis (gene BL02343) is a member of the divalent anion sodium symporter (DASS)/SLC13 family that includes Na⁺/dicarboxylate transporters from bacteria to humans. SdcF was functionally expressed in Escherichia coli (BL21) and assayed in right side out membrane vesicles. ScdF catalyzed the sodium-coupled transport of succinate and α-ketoglutarate. Succinate transport was strongly inhibited by malate, fumarate, tartrate, oxaloacetate and L-aspartate. Similar to the other DASS transporters, succinate transport by SdcF was inhibited by anthranilic acids, N-(p-amylcinnamoyl) anthranilic acid and flufenamate. SdcF transport was cation-dependent, with a K₀.₅ for sodium of ~1.5 mM and a K₀.₅ for Li⁺ of ~40 mM. Succinate transport kinetics by SdcF were sigmoidal, suggesting that SdcF may contain two cooperative substrate binding sites. The results support an ordered binding mechanism for SdcF in which sodium binds first and succinate binds last. We conclude that SdcF is a secondary active transporter for four- and five-carbon dicarboxylates that can use Na⁺ or Li⁺ as a driving cation.


Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication.
Genome-wide gene expression analyses of the human somatic cell cycle have indicated that the set of cycling genes differ between primary and cancer cells. By identifying genes that have cell cycle dependent expression in HaCaT human keratinocytes and comparing these with previously identified cell cycle genes, we have identified three distinct groups of cell cycle genes. First, housekeeping genes enriched for known cell cycle functions; second, cell type-specific genes enriched for HaCaT-specific functions; and third, Polycomb-regulated genes. These Polycomb-regulated genes are specifically upregulated during DNA replication, and consistent with being epigenetically silenced in other cell cycle phases, these genes have lower expression than other cell cycle genes. We also find similar patterns in foreskin fibroblasts, indicating that replication-dependent expression of Polycomb-silenced genes is a prevalent but unrecognized regulatory mechanism.


A comprehensive assessment on sludge conditioning by pyrite acid eluent-activated peroxymonosulfate based on dewaterability, heavy metals risk and ore recovery.
Wastewater activated sludge (WAS) has poor dewaterability and contains heavy metals (HMs), limiting its land application. Therefore, in this study, a novel pyrite acid eluent-activated peroxymonosulfate (Fe2+pyrite/PMS) conditioning approach that can completely recover the residual pyrite and greatly reduce acid use was developed to improve WAS dewaterability, and the HMs chemical speciation and risks of conditioned WAS were assessed. Our results showed that under the optimized operational parameters, the capillary suction time (CST) and water content (Wc) of WAS decreased by 46.03% and 7.75%, respectively. Furthermore, during Fe2+pyrite/PMS conditioning processing, sulfate radical (SO4-) destroyed the extracellular polymeric substances (EPS) matrix, causing bound water release and the decrease of proteins/polysaccharides in outer layered EPS, even the decomposition of some protein-N in tightly bound EPS (TB-EPS) into inorganic-N. In addition, although the total concentration of HMs in the conditioned WAS matrix increased, the Ni concentration decreased in the solid fraction. Further, the risk assessment code (RAC) levels did not increase, and the eco-toxicity of Cr became weakened after Fe2+pyrite/PMS conditioning. However, after acid extraction, the pyrite residue had worsened recycle performance because the passivation layer contained S0/Sn2- on its surface, and no additional elements were detected in the pyrite residue, which had almost no effect on its further usage.


Phylogeography of plastid DNA sequences suggests post-glacial southward demographic expansion and the existence of several glacial refugia for Araucaria angustifolia.
Despite the high diversity of the Southern South American environments, the patterns and processes driving both their species diversity and demographic history are still poorly known and are a challenging task. In this study, we evaluate plastid DNA sequences of the conifer species Araucaria angustifolia aiming to (i) assess the species genetic structure within its main range of occurrence, (ii) infer its population demographic history, looking for evidence of southward expansion, (iii) search for evidence of glacial refugia within the species distribution area and (iv) discuss some conservation and management strategies for this species. Twenty haplotypes were identified, revealing the presence of three distinct genetic groups across the geographic range of the species and structuring the populations into Northern, Central and Southern groups. Our results suggest the occurrence of post-glacial expansion of A. angustifolia towards the south, as well as the existence of at least three refugia within the species occurrence area. Testing the occurrence of historical demographic expansion, we suggest that genetic groups experienced fluctuations in effective size, associated to a structured distribution of populations. The identification of three genetic groups in this study corroborates the proposition of using the geographic distribution of A. angustifolia for selecting in situ conservation areas, for planning seed collection for ex situ conservation, as well as for the delineation of seed zones.


Determination of pesticides in compost by pressurized liquid extraction and gas chromatography-mass spectrometry.
A gas chromatographic-mass spectrometric method was developed for the determination of pesticides in compost. The investigated pesticides included two fungicides, two herbicides and 10 insecticides. The pesticides were extracted from the compost by pressurized liquid extraction. The extract was cleaned up by a partition between hexane and acetonitrile followed by a dispersive solid-phase extraction using a porous carbon made from Moso bamboo (Phyllostachys pubescens). The overall recoveries were 81-104% and the relative standard deviations (RSDs) ranged from 2.4 to 12%. The minimum detectable concentrations were 0.02-0.04 microg g(-1). This method was successfully applied to a compost sample from food waste as well as commercial compost.


Scaffolded biology.
Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.


An updated Italian normative dataset for the Stroop color word test (SCWT).
The Stroop color and word test (SCWT) is widely used to evaluate attention, information processing speed, selective attention, and cognitive flexibility. Normative values for the Italian population are available only for selected age groups, or for the short version of the test. The aim of this study was to provide updated normal values for the full version, balancing groups across gender, age decades, and education. Two kinds of indexes were derived from the performance of 192 normal subjects, divided by decade (from 20 to 90) and level of education (4 levels: 3-5; 6-8; 9-13; >13 years). They were (i) the correct answers achieved for each table in the first 30 s (word items, WI; color items, CI; color word items, CWI) and (ii) the total time required for reading the three tables (word time, WT; color time, CT; color word time, CWT). For each index, the regression model was evaluated using age, education, and gender as independent variables. The normative data were then computed following the equivalent scores method. In the regression model, age and education significantly influenced the performance in each of the 6 indexes, whereas gender had no significant effect. This study confirms the effect of age and education on the main indexes of the Stroop test and provides updated normative data for an Italian healthy population, well balanced across age, education, and gender. It will be useful to Italian researchers studying attentional functions in health and disease.


Association between chronic exposure to pesticides and recorded cases of human malignancy in Gaza Governorates (1990-1999).
Epidemiological association between chronic exposure to pesticides and recorded cases of human malignancy in Gaza Governorates during the years 1990-1999 was studied. The pesticide usage in Gaza Governorates was recorded in detail. It ranged from 216.9 to 393.3 t from 1990 to 1999, respectively. Banned and extremely hazardous pesticides are identified according to their carcinogenicity, genotoxicity and cytotoxicity. Hospital cases of cancers in men and women were recorded. Each tumor type was grouped according to sex and age group from 0 to > 65 years. Total cases recorded in males were 2277, with average annual incidence and age-adjusted rate/100,000 was 53.2 and 96.8 respectively, whereas the total for females was 2458 cases, average annual incidence and age-adjusted rate/100,000 was 59.7 and 105.3, respectively, over the same 10 years. Lung cancer, lymphomas, leukemia, cancers of the urinary bladder, prostate, brain, colon, stomach and liver were the most abundant among males, while breast cancer, leukemia, lymphomas, cancers of the brain, uterus, lung, thyroid gland and liver were the most abundant in females. Statistical analysis using correlation coefficients and P values showed highly significant positive correlations between the type of pesticide and cancer incidence for male, female and both sexes. Correlation coefficients and P values, respectively, for both sexes were: 0.992 and 0.000 for insecticides; 0.952 and 0.000 for fungicides; 0.812 and 0.004 for herbicides; 0.925 and 0.000 for nematicides; 0.992 and 0.000 for others; and 0.994 and 0.000 for all types of pesticides. In the densely populated agricultural areas, it is not possible to separate or differentiate between occupational and general public exposure. Consequently, the introduction of and heavy use and misuse of pesticides and other toxic substances in the Gaza environment is suspected to correlate with the growing incidence of cancer. Precise determination of the effects of chronic exposure is, therefore, urgently needed. Future legislation to stop and regulate the use of extremely hazardous compounds will be essential. Continuous records for chronic diseases and cancers are also required for future follow-ups and periodical risk-assessment evaluations. Hence, further epidemiological studies are needed with detailed exposure assessment for individual pesticides, taking measures to reduce risk into consideration.


The effect of corticosteroid injection for trigger finger on blood glucose level in diabetic patients.
To determine how corticosteroid injections for trigger finger affect the blood glucose level in diabetic patients and the clinical results of those injections. Eighteen diabetic patients receiving a methylprednisolone injection for a single trigger finger were studied. Six patients had type I (juvenile-onset) diabetes and 12 patients had type II (adult-onset) diabetes. Patients recorded their usual blood glucose measurements and then they recorded their blood glucose measurements for 5 days after injection. Clinical efficacy of the injections was measured by avoidance of surgery. There were 3 men and 15 women with an average age of 58 years. The blood glucose level increased after corticosteroid injection for all patients. The first morning after injection showed the biggest increase in blood glucose level: 73% more than the average preinjection levels. By the fifth morning after injection the blood glucose levels still were increased by 26% more than the preinjection levels. This trend was marked particularly in type I diabetic patients, who had an average blood glucose level increase the first morning after injection of 145%, which decreased over 5 days to 22% greater than baseline levels. Sixteen patients had follow-up evaluation over a period of 1 year and of these 16 patients 7 required surgery for this condition. A digital injection of the corticosteroid methylprednisolone acetate in diabetic patients with trigger finger causes a hyperglycemic effect that lasts for at least 5 days but can help prevent the need for surgery more than half the time. Therapeutic, Level IV.


Combined diffusing capacity for nitric oxide and carbon monoxide as predictor of bronchiolitis obliterans syndrome following lung transplantation.
There is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients. We studied whether the pulmonary diffusing capacity for inhaled nitric oxide is capable of detecting BOS stages. Sixty-one LTx patients were included into this cross-sectional study (19/29/7/3/3 in BOS stages 0/0-p/1/2/3). For analysis stages 0/0-p versus 1/2/3 ("BOS binary-early"), and stages 0/0-p/1 versus 2/3 ("BOS binary-late") were summarized. Measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were compared with spirometry and bodyplethysmography, and their relative importance was evaluated by discriminant analysis. Regarding the recognition of "BOS binary-early", among spirometric parameters forced expiratory volume in 1 s (FEV1) was best, among bodyplethysmographic parameters airway resistance, and among diffusing parameters DLNO. Regarding "BOS binary-late", DLNO was inferior to bodyplethysmographic parameters. Although the study comprised only measurements at a single time point and no follow-up, DLNO outperformed FEV1, the time course of which is used in detecting BOS. Together with its pathophysiological plausibility, this result suggests that the measurement of DLNO, possibly over time, could be an easily applicable tool for the monitoring of LTx patients and should be evaluated in larger studies.


No source memory for unrecognized items when implicit feedback is avoided.
In a recent empirical study, Starns, Hicks, Brown, and Martin (Memory & Cognition, 36, 1-8 2008) collected source judgments for old items that participants had claimed to be new and found residual source discriminability depending on the old-new response bias. The authors interpreted their finding as evidence in favor of the bivariate signal-detection model, but against the two-high-threshold model of item/source memory. According to the latter, NEW responses only follow from the state of old-new uncertainty for which no source discrimination is possible, and the probability of entering this state is independent of the old-new response bias. However, when missed old items were presented for source discrimination, the participants could infer that the items had been previously studied. To test whether this implicit feedback led to second retrieval attempts and thus to source memory for presumably unrecognized items, we replicated Starns et al.'s (Memory & Cognition, 36, 1-8 2008) finding and compared their procedure to a procedure without such feedback. Our results challenge the conclusion to abandon discrete processing in source memory; source memory for unrecognized items is probably an artifact of the procedure, by which implicit feedback prompts participants to reconsider their recognition judgment when asked to rate the source of old items in the absence of item memory.


Women's preferences for water immersion during labor and birth: Results from a discrete choice experiment.
No discrete choice experiment study has been conducted to elicit women's preferences for water immersion during labor and birth. An online survey including sociodemographic questions and choice cards was conducted to explore women's preferences (i.e., factors that may influence their decision). Each participant responded to 12 choice cards with 6 attributes/factors (i.e., birth mode, duration of the labor phase, pain sensation, risk of severe perineal tears, risk of death of the newborn, and newborn general condition). Utilities were estimated using logit, latent class, and hierarchical Bayesian analyses. A total of 1088 subjects completed the survey in 2019. The risk of death of the newborn was given high priority by women in all but one analyses, while the risk of severe perineal tears was always considered the least important attribute. The latent class analysis clearly revealed three classes of women. The largest class including 52.9% of women was interested in water birth if it could reduce pain and would be risk-free for the newborn. The second class included 30.8% of women interested in water immersion but only during the labor phase. Finally, the third class (16.2%) did not want to consider water immersion during labor and birth, regardless of its risks and benefits. Follow-up questions revealed that many women were interested in water birth only if they could be assured that there would be no risk for the newborn. This study provided insights in favor of water immersion during labor and birth contingent upon the safety of the procedure for the newborn. No discrete choice experiment on women's preference for water immersion during childbirth was previously conducted. Six attributes/factors were used for the discrete choice experiment. Water immersion is poorly used in Quebec with only 49 (7.9%) women over 621 with childbirth experience reporting such immersion. A majority of women (70-80%) were in favor of water immersion.


Age-related immune alterations and cerebrovascular inflammation.
Aging is associated with chronic systemic inflammation, which contributes to the development of many age-related diseases, including vascular disease. The world's population is aging, leading to an increasing prevalence of both stroke and vascular dementia. The inflammatory response to ischemic stroke is critical to both stroke pathophysiology and recovery. Age is a predictor of poor outcomes after stroke. The immune response to stroke is altered in aged individuals, which contributes to the disparate outcomes between young and aged patients. In this review, we describe the current knowledge of the effects of aging on the immune system and the cerebral vasculature and how these changes alter the immune response to stroke and vascular dementia in animal and human studies. Potential implications of these age-related immune alterations on chronic inflammation in vascular disease outcome are highlighted.


All monofilament knots assume sliding conformation in vivo.
Surgeons are not always cognizant of the knots they tie. It has been thought that suture material does not determine what types of knots are tied. Experienced surgeons were asked to tie square monofilament knots that were salvaged and microscopically evaluated. Tightly cinched monofilament knots assume sliding conformation in vivo regardless of configuration, instrumentation, suture polymer, or surgeon. When monofilament suture is securely cinched in vivo, kinetic energy forces even a flat throw into sliding conformation. A well-crafted, intentionally sliding square knot appears compacter than any other monofilament knot.


Ultraviolet exposure and non-Hodgkin's lymphoma: beneficial and adverse effects?
Studies of risk of non-Hodgkin's lymphoma have found both direct and inverse correlations with respect to solar ultraviolet (UV) doses. Reduced risk is generally found in midlatitudes, while increased risk is generally found at higher latitudes. It is suggested that reduced risk arises from vitamin D production from UVB irradiance, while increased risk arises from immunosuppression associated with UVA irradiance. The ratio of UVA to UVB increases with increasing latitude.


Water relations and growth responses of Uniola paniculata (sea oats) to soil moisture and water-table depth.
This study examined the water relations and growth responses of Uniola paniculata (sea oats) to (1) three watering regimes and (2) four controlled water-table depths. Uniola paniculata is frequently the dominant foredune grass along much of the southeastern Atlantic and Gulf coasts of the United States, but its distribution is limited in Louisiana. Throughout most of its range, U. paniculata tends to dominate and be well adapted to the most exposed areas of the dune where soil moisture is low. Dune elevations in Louisiana, however, rarely exceed 2 m, and as a result the depth to the water table is generally shallow. We hypothesized that if U. paniculata grows very near the water-table, as it may in Louisiana, it will display signs of water-logging stress. This study demonstrated that excessive soil moisture resulting from inundation or shallow water-table depth has a greater negative effect on plant growth than do low soil moisture conditions. Uniola paniculata's initial response to either drought or inundation was a reduction of leaf (stomatal) conductance and a concomitant decrease in leaf elongation. However, plants could recover from drought-induced leaf xylem pressures of less than-3.3 MPa, but prolonged inundation killed the plants. Waterlogging stress (manifested in significantly reduced leaf stomatal conductances and reduced biomass production) was observed in plants grown at 0.3 m above the water table. This stress was relieved, however, at an elevation of 0.9 m above the water table. As the elevation was increased from 0.9 to 2.7 m, there were no signs of drought stress nor a stimulation in growth due to lower soil moisture. We concluded that although U. paniculata's moisture-conserving traits adapt it well to the dune environment, this species can grow very well at an elevation of only 0.9 m above the water table. Field measurements of water-table depth in three Louisiana populations averaged about 1.3 m. Therefore, the observed limited distribution of U. paniculata along the Louisiana coast apparently cannot be explained by water-logging stress induced by the low dune elevations and the corresponding shallow water-table depth.


Low-Dose DMC Significantly Enhances the Effect of TMZ on Glioma Cells by Targeting Multiple Signaling Pathways Both In Vivo and In Vitro.
Temozolomide (TMZ) is widely used for treating glioblastoma (GBM), which can effectively inhibit the GBM growth for some months; however, it still cannot prevent the invariable recurrence of GBM. Improving the chemotherapeutic sensitization becomes an urgent agenda. In this study, we found low-dose demethoxycurcumin (DMC) could enhance the sensitivity of TMZ on glioma cells, and high-dose DMC has more significant effects on GBM cells compared with TMZ treatment alone both in vitro and in vivo. And co-administration of DMC and TMZ resulted in a significant increase in GBM apoptosis and a marked inhibition of cell growth pathogenesis of GBM. Mechanistically, DMC and TMZ synergistically increase intracellular level of reactive oxygen species (ROS) production, activate caspase-3-dependent apoptotic pathway, and inactivate of JAK/STAT3 signaling pathway in GBMs, which account for the cell apoptosis and proliferation inhibition. Together, these data implicate that low-dose DMC combined with TMZ represents an effective therapy regimen against GBMs by targeting multiple signaling pathways.


Rate of disappearance of isethionic acid in the rat central nervous system.
The rates of disappearance of tritiated isethionic acid (2-hydroxyethanesulfonic acid) in eight regions of the rat central nervous system were studied. By utilizing the technique of graphical analysis ("curve peeling"), it was determined that seven areas (striatum, diencephalon, pons-medulla, midbrain, hippocampus, spinal cord, and cortex) exhibited triphasic (fast, intermediate, and slow) disappearance rates while only the cerebellum displayed a biphasic (fast, slow) rate. The half-lives for the fast component in the different regions of the central nervous system varied from 0.5 hr (midbrain and cortex) to 1.5 hr (diencephalon, cerebellum, and spinal cord): the half-lives for the intermediate component of the triphasic rate varied from 3.5 hr in the midbrain and spinal cord to 5.5 hr in the hippocampus. Half-lives estimated for the slow component of the multiphasic rate of disappearance of tritiated isethionic acid ([3H]ISA) varied from 28 hr (cerebellum) to 90 hr (spinal cord).


A role for matrix metalloproteinases in granulocyte infiltration and testicular remodelation in a seasonal breeding teleost.
The testicular cystic structure and the abrupt morphological changes that the fish testis undergoes during the reproductive cycle (RC) make it an interesting model for studying the regulation of spermatogenesis, in particular the role of matrix metalloproteinases (Mmps). The gilthead seabream is a seasonal breeding teleost whose testis undergoes drastic remodeling events, especially during the post-spawning stage when a massive infiltration of a immune cell type, the acidophilic granulocytes, occurred. Bearing this in mind, we studied the gilthead seabream testis gelatinolytic activities involved in migration and tissue remodeling and its regulation by endocrine, immune and tissue stimuli. Thus, we demonstrated that the germinal epithelium of the testis showed gelatinolytic activity during spermatogenesis and post-spawning but not during resting, when only scarce interstitial cells were stained. Moreover, the precursor and mature forms of two gelatinases, Mmp2- and Mmp9-like, were active in the gonad, whose activities were up-regulated by 17beta-estradiol (E(2)) but not by lipopolysaccharide (LPS)/bacterial DNA (VaDNA) in testicular cell suspensions. E(2) and LPS/VaDNA also up-regulated a variety of cytokines and chemokines. We also cloned mmp9, mmp13, tissue inhibitors of Mmps (timp)-2a and timp2b genes and found that all of them were expressed in the gonad in a RC stage-dependent manner. Interestingly, mmps and timps were highly expressed by the testicular acidophilic granulocytes. Moreover, in these cells, the gelatinolytic activity seemed to correspond to the precursor and mature forms of putative Mmp2 and Mmp9 gelatinases, while the main gelatinolytic activity seemed to correspond to the mature form of Mmp2 in head-kidney acidophilic granulocytes. Finally, although none of the stimuli used were able to induce the gelatinolytic activity of Mmp9-like in head-kidney acidophilic granulocytes, the expression of mmp9, timp2a and timp2b were all up-regulated by LPS/VaDNA in these cells, while only mmp9 and timp2a expression increased upon stimulation with gelatin.


Detection and discrimination between ochratoxin producer and non-producer strains of Penicillium nordicum on a ham-based medium using an electronic nose.
The aim of this work was to evaluate the potential use of qualitative volatile patterns produced by Penicillium nordicum to discriminate between ochratoxin A (OTA) producers and non-producer strains on a ham-based medium. Experiments were carried out on a 3% ham medium at two water activities (aw ; 0.995, 0.95) inoculated with P. nordicum spores and incubated at 25°C for up to 14 days. Growing colonies were sampled after 1, 2, 3, 7 and 14 days, placed in 30-ml vials, sealed and the head space analysed using a hybrid sensor electronic nose device. The effect of environmental conditions on growth and OTA production was evaluated based on the qualitative response. However, after 7 days, it was possible to discriminate between strains grown at 0.995 aw, and after 14 days, the OTA producer and non-producer strain and the controls could be discriminated at both aw levels. This study suggests that volatile patterns produced by P. nordicum strains may differ and be used to predict the presence of toxigenic contaminants in ham. This approach could be utilised in ham production as part of a quality assurance system for preventing OTA contamination.


Elucidating the unexplained underperformance syndrome in endurance athletes : the interleukin-6 hypothesis.
The unexplained underperformance syndrome (UPS), previously known as the overtraining syndrome (OTS), has been defined as a persistent decrement in athletic performance capacity despite 2 weeks of relative rest. It has been proposed that UPS may be caused by excessive cytokine release during and following exercise causing a chronic inflammatory state and 'cytokine sickness'. This article extends that hypothesis by proposing that time-dependent sensitisation could provide a model through which the aetiology of UPS may be explained. In this model, the principal abnormal factors in UPS are an increased production of and/or intolerance to interleukin (IL)-6 during exercise. Strategies to attenuate the IL-6 response to exercise that may also reduce an athlete's susceptibility to UPS are proposed.


Enteric-coated mycophenolate sodium containing GvHD prophylaxis reduces GvHD rate after allogeneic HSCT.
The aim of this study was to evaluate whether cyclosporine A (CsA)-based Graft vs. Host Disease (GvHD) prophylaxis with enteric-coated mycophenolate sodium (EC-MPS) instead of mycophenolate mofetil (MMF) or methotrexate (MTX) reduces the GvHD incidence and lowers gastrointestinal (GI-) toxicities. In a retrospective analysis of 102 allogeneic hematopoietic stem cell transplant (HSCT) patients, incidences of overall and severe aGvHD (>II°), cGvHD as well as overall and severe (CTC >II°) GI-toxicities were compared between GvHD prophylaxis containing EC-MPS vs. MMF or MTX (control group). The overall aGvHD rate was significantly lower in the EC-MPS group compared to the control (47% vs. 72%, P = 0.022) with lower rates of severe aGvHD (10% vs. 25%, P = 0.088) and cGvHD (20% vs. 39%, P = 0.065). Prophylaxis with EC-MPS remained significantly associated with a lower aGvHD rate in a multiple logistic regression model. GI-toxicities did not differ between both groups except for severe abdominal pain for which the incidence was increased in the EC-MPS group (17% vs. 3%, P = 0.022). This data support the hypothesis that replacement of MMF or MTX by EC-MPS reduces GvHD rates after HSCT. This appears not to be due to a reduced GI-toxicity of EC-MPS.


One-step labeling of degenerative neurons in unfixed brain tissue samples using Fluoro-Jade C.
Neurodegeneration is the underlying cause of a vast majority of neurological disorders and often a result of brain trauma, stroke, or neurotoxic insult. Here we describe a simple method for labeling degenerating neurons in unfixed brain tissue samples. This method could provide a new avenue for identifying and harvesting degenerative neurons from unfixed brain tissues for subsequent molecular analyses.


Impact of nutrients and trace elements on freshwater microbial communities in Croatia: identifying bacterial bioindicator taxa.
Since aquatic microbial communities promptly respond to environmental changes, it is now evident that they can complement traditional taxa such as fish, macroinvertebrates and algae as bioindicators of water quality. The aim of this study was to correlate the physico-chemical parameters of water with the microbial community structure and the occurrence of putative bioindicator taxa. Thirty-five water samples were collected throughout Croatia and their physico-chemical parameters, including the concentration of trace elements using the high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), and the composition of the microbial communities by high-throughput sequencing of the 16S rRNA marker gene, were analysed in parallel. Partial least squares regression (PLS-R) modelling revealed that a number of microbial taxa were positively correlated with some of the water parameters. For example, some taxa from the phylum Proteobacteria were positively correlated with the ion content of the water (e.g. Erythrobacter, Rhodobacteraceae, Alteromonadaceae), while some Firmicutes taxa, such as the well-known faecal indicators Enterococcus and Clostridium, were correlated with nutrient content (ammonium and total phosphorus). Among the trace elements, uranium was positively correlated with a highest number of microbial taxa. The results obtained will aid in development of protocols for eDNA-based biological assessment of water quality.


Exploring Newer Biosynthetic Gene Clusters in Marine Microbial Prospecting.
Marine microbes genetically evolved to survive varying salinity, temperature, pH, and other stress factors by producing different bioactive metabolites. These microbial secondary metabolites (SMs) are novel, have high potential, and could be used as lead molecule. Genome sequencing of microbes revealed that they have the capability to produce numerous novel bioactive metabolites than observed under standard in vitro culture conditions. Microbial genome has specific regions responsible for SM assembly, termed biosynthetic gene clusters (BGCs), possessing all the necessary genes to encode different enzymes required to generate SM. In order to augment the microbial chemo diversity and to activate these gene clusters, various tools and techniques are developed. Metagenomics with functional gene expression studies aids in classifying novel peptides and enzymes and also in understanding the biosynthetic pathways. Genome shuffling is a high-throughput screening approach to improve the development of SMs by incorporating genomic recombination. Transcriptionally silent or lower level BGCs can be triggered by artificially knocking promoter of target BGC. Additionally, bioinformatic tools like antiSMASH, ClustScan, NAPDOS, and ClusterFinder are effective in identifying BGCs of existing class for annotation in genomes. This review summarizes the significance of BGCs and the different approaches for detecting and elucidating BGCs from marine microbes.


A retrospective audit of anesthetic techniques and complications in children with mucopolysaccharidoses.
To document the incidence of difficult airway management and difficult intubation in the era of replacement therapy for Australian children with mucopolysaccharidosis (MPS). Medical treatment for MPS has developed significantly since 1980's with a large number of patients now being offered either bone marrow transplant or enzyme replacement. The impact of these therapies on the incidence of difficult airway management has not been adequately documented. Similarly, anesthesia techniques and airway devices have been developed, which are thought to have greatly increased the safety of managing these patients under anesthesia but their role in children with MPS has not been systematically described. A retrospective chart review of 17 patients with MPS who had received anesthetics at the Royal Children's Hospital during the time frame January 1998-January 2011. The primary outcome was the incidence of difficult or failed intubation. Secondary outcomes were the relationship between the incidence of difficult intubation and treatment with enzyme replacement therapy (ERT) or bone marrow transplantation. Seventeen patients received 141 anesthetics for 214 procedures. Difficult face mask ventilation occurred in 20 anesthetics (14.2%). Difficult intubation occurred in 40 anesthetics (25%). Failed intubation occurred in two cases (1.6%).The incidence of difficult intubation was 12% in MPS I, 35% MPS II, 86.7% in MPS VI, and 0% in MPS III and IV. Hematopoietic stem cell transplantation prior to 2 years of age reduces the incidence of difficult mask ventilation and difficult intubation in children with MPS I. ERT was initiated late in the clinical course of MPS II and VI and induced improvements in upper airway patency but did not reduce the incidence of difficult airway management.


Optimisation of multilinear gradient elutions in reversed-phase liquid chromatography using ternary solvent mixtures.
The multilinear gradient elution theory for binary mobile phases in reversed-phase liquid chromatography presented in [P. Nikitas, A. Pappa-Louisi, A. Papageorgiou, J. Chromatogr. A 1157 (2007) 178] is extended to ternary gradients. For the evaluation of this theory and the performance of the various fitting and optimisation algorithms we used 13 o-phthalaldehyde (OPA) derivatives of amino acids with mobile phases modified by acetonitrile and methanol. It is shown that the theory can lead to high quality predictions of the retention times under gradients elutions and optimisation of ternary gradients provided that we use a six-parameter expression for the logarithm of the retention factor, lnk, and the adjustable parameters of this expression are determined from ternary isocratic data.


Age and gender-based categorization of very premature, premature, and non-premature acute myocardial infarction: A comparison of clinical and angiographic profile and in-hospital outcomes.
In this study, we aimed to assess and compare the distribution of demographic and clinical characteristics and composite adverse clinical outcomes after primary percutaneous coronary intervention (PCI) among "very premature", "premature", and "non-premature" patients with "ST-segment elevation acute coronary syndrome (STE-ACS)" presented at a tertiary care center. We included consecutive patients diagnosed with STE-ACS undergoing primary PCI. The "very premature" was defined as ≤40 years for males and ≤ 45 years for females, "premature" as <55 years for males and < 65 years for females, and "non-premature" as ≥55 years for males and ≥ 65 years for females. Clinical characteristics, angiographic patterns, and hospital course were compared among the three groups. In a sample of 4686 patients, 78.8%(3691) were male, and the average age was 55.6 ± 11 years. In total, 12%(561) were categorized as very premature, 38.3%(1797) as premature, and 49.7%(2328) as non-premature. The distribution of clinical characteristics in very premature, premature, and non-premature groups were as follows; hypertension in 44.6% vs. 53.5% vs. 54.9%; p < 0.001, diabetes in 30.3% vs. 36.8% vs. 35.5%; p = 0.018, smoking in 29.6% vs. 23.3% vs. 26.3%; p = 0.005, obesity in 19.4% vs. 18.4% vs. 15.3%; p = 0.008, single vessel diseases in 58.8% vs. 37.8% vs. 28.8%; p < 0.001, and composite adverse clinical outcomes in 14.1% vs. 16.7% vs. 21.8%; p < 0.001, respectively. In conclusion, we have a substantial burden of premature STE-ACS. Very premature STE-ACS was found to be associated with a better prognosis, but a substantial burden of composite adverse clinical outcomes was also observed.


[Hygiene and asepsis in surgery: introduction (author's transl)].
Since the development of asepsis and clinical hygiene by European and American surgeons in the second half of the nineteenth century, the prevention of infection has been one of the most important concerns of surgical practice. However, owing to the rapid expansion of therapeutic methods, medical practice now makes greater demands on clinical hygiene than has hitherto been the case; it has not always been possible for developments in clinical hygiene to keep pace in this respect, and the closing of the resulting gap represents one of the most urgent tasks confronting medicine today.


Phosphorus 31 nuclear magnetic resonance examination of female reproductive tissues.
Nuclear magnetic resonance spectroscopy is a powerful method of investigating the relationship between metabolism and function in living tissues. We present evidence that the phosphorus 31 spectra of myometrium and placenta are functions of physiologic state and gestational age. Specific spectroscopic abnormalities are observed in association with disorders of pregnancy and gynecologic diseases. Our results suggest that noninvasive nuclear magnetic resonance spectroscopy examinations may sometimes be a useful addition to magnetic resonance imaging examinations, and that nuclear magnetic resonance spectroscopy of biopsy specimens could become a cost-effective method of evaluating certain biochemical abnormalities.


Sites of the neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the macaque monkey include the ventral tegmental area and the locus coeruleus.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a profound parkinsonian state when systemically administered in monkeys and man. Previous studies have shown MPTP to be toxic to only the dopamine (DA) cells in the substantia nigra pars compacta and not to other catecholamine (CA)-containing cells. The data presented here suggest that MPTP also has a specific neurotoxic effect on the DA-containing cells of the ventral tegmental area and the noradrenaline-containing cells of the locus coeruleus in macaque monkeys with a moderate-to-severe parkinsonian syndrome. The results suggest that MPTP-induced parkinsonism in the monkey more closely replicates the neurochemical changes seen in idiopathic Parkinson's disease than previously thought.


CYP1A and POR gene mediated mitochondrial membrane damage induced by carbon nanoparticle in human mesenchymal stem cells.
Nanoparticles (NPs) can cause respiratory and cardiovascular problems, furthermore small carboxyl polystyrene NPs induce hemolysis, activate platelets and induce inflammation in human blood. Carbon nanoparticles (CNPs) are known to interfere with cellular metabolism, specific cellular functions and moreover may cause cellular toxicity. We aimed to study the influence of CNPs on oxidative stress, mitochondrial membrane damage and intracellular gene expression in human mesenchymal stem cells (hMSCs). CNPs cause a dose and time dependent growth inhibition in hMSCs at a dose range from 50 to 400μg/mL. Exposure of CNPs toxic doses viz., 50μg/mL (D1) and 100μg/mL (D2) decreased intracellular mitochondrial membrane potential compared to control. CNPs treated cells were found to lose their morphology due to cell membrane damage have been confirmed by propidium iodide staining and fluorescence microscopic analysis. Oxidative stress responsive genes like GSTM3 and GSR1 expression have increased a fold when compared to control, interim there is no change were observed in SOD and GPx. We found an increased expression of CYP1A and POR genes by at least 2- fold, which is involved in mitochondrial trans-membrane potential. In conclusion, routine and high exposure of CNPs to hMSCs increased oxidative stress and mitochondrial membrane damage.


Selective vagal postganglionic innervation of the sinoatrial and atrioventricular nodes in the non-human primate.
The distribution of parasympathetic postganglionic nerves to the atrioventricular (AVN) and sinoatrial nodal (SAN) regions was investigated in the non-human primate heart. Eight male monkeys (Macaca fascicularis) weighing 5.5-7.0 kg. were anesthetized (alpha-chloralose, 50 mg/kg and urethane, 500 mg/kg) and instrumented to measure arterial pressure, electrocardiogram, atrial and ventricular electrograms. The cervical vagi were electrically stimulated (20 Hz, 4 V, 2 ms) before and after selective denervation (D) of the AVN and/or SAN. Vagal stimulation was repeated during atrial pacing to assess parasympathetic modulation of AVN conduction. Ablation of parasympathetic pathways to the AVN, accomplished by the disruption of the epicardial fat and surface muscle layer at the junction of the inferior vena cava and inferior left atrium eliminated (P less than 0.01) the dromotropic effects of vagal stimulation without affecting the heart rate response (right vagus, before D, paced: atrial rate 218.0 +/- 6.3, ventricular rate 67.1 +/- 23.7; after D: atrial rate 210.3 +/- 6.4, ventricular rate 210.3 +/- 6.4 beats/min, means +/- S.D.). In sharp contrast, surgical dissection of the fat pad overlying the right pulmonary vein-superior vena cava junction significantly (P greater than 0.01) attenuated negative chronotropic effects of vagal stimulation (left vagus, before D the R-R interval increased by 832.7 +/- 146.4 ms, 209.5% increase; after D 37.4 +/- 18.0 ms, 8.8% increase). These data demonstrate discrete vagal efferent pathways innervate both the SAN and AVN regions of the non-human primate heart.


Inflammatory Diseases, Inflammatory Biomarkers, and Alzheimer Disease: An Observational Analysis and Mendelian Randomization.
Whether chronic autoimmune inflammatory diseases causally affect the risk of Alzheimer disease (AD) is controversial. We characterized the relationship between inflammatory diseases and risk of AD and explored the role of circulating inflammatory biomarkers in the relationships between inflammatory diseases and AD. We performed observational analyses for chronic autoimmune inflammatory diseases and risk of AD using data from 2,047,513 participants identified in the UK Clinical Practice Research Datalink (CPRD). Using data of a total of more than 1,100,000 individuals from 15 large-scale genome-wide association study data sets, we performed 2-sample Mendelian randomizations (MRs) to investigate the relationships between chronic autoimmune inflammatory diseases, circulating inflammatory biomarker levels, and risk of AD. Cox regression models using CPRD data showed that the overall incidence of AD was higher among patients with inflammatory bowel disease (hazard ratio [HR] 1.17; 95% CI 1.15-1.19; p = 2.1 × 10-4), other inflammatory polyarthropathies and systematic connective tissue disorders (HR 1.13; 95% CI 1.12-1.14; p = 8.6 × 10-5), psoriasis (HR 1.13; 95% CI 1.10-1.16; p = 2.6 × 10-4), rheumatoid arthritis (HR 1.08; 95% CI 1.06-1.11; p = 4.0 × 10-4), and multiple sclerosis (HR 1.06; 95% CI 1.04-1.07; p = 2.8 × 10-4) compared with the age (±5 years) and sex-matched comparison groups free from all inflammatory diseases under investigation. Bidirectional MR analysis identified relationships between chronic autoimmune inflammatory diseases and circulating inflammatory biomarkers. Particularly, circulating monokine induced by gamma interferon (MIG) level was suggestively associated with a higher risk of AD (odds ratio from inverse variance weighted [ORIVW] 1.23; 95% CI 1.06-1.42; p IVW = 0.007) and lower risk of Crohn disease (ORIVW 0.73; 95% CI -0.62 to 0.86; p IVW = 1.3 × 10-4). Colocalization supported a common causal single nucleotide polymorphism for MIG and Crohn disease (posterior probability = 0.74), but not AD (posterior probability = 0.03). Using a 2-sample MR approach, genetically predicted risks of inflammatory diseases were not associated with higher AD risk. Our data suggest that the association between inflammatory diseases and risk of AD is unlikely to be causal and may be a result of confounding. In support, although inflammatory biomarkers showed evidence for causal associations with inflammatory diseases, evidence was weak that they affected both inflammatory disease and AD.


[Serological evaluation of the efficacy of an antirabies vaccine in field dogs in Tunisia].
We have vaccinated with an inactivated experimental vaccine, Rabi Rabta, prepared in lamb brain 52 dogs from the field in Tunisia and we tested by recommended serological methods the production of specific antibodies. The animals (35) received a boost injection after one year and the control of the immunological response was done on the same way after one month. This work done on 27 dogs showed very low serological data. A comparable batch of 42 dogs was immunised with a commercial vaccine with the same procedure; the results obtained from 17 dogs were not very different. This is apparently in contradiction with the success obtained by the National Program against Rabies launched in Tunisia since 1982.


Replacing Pumps with Light Controlled Insulin Delivery.
The aim of this review is to summarize the development of the photoactivated depot (PAD) approach for the minimally invasive and continuously variable delivery of insulin. Using an insulin PAD, we have demonstrated that we can release native, bioactive insulin into diabetic animals in response to light signals from a small external LED light source. We have further shown that this released insulin retains bioactivity and reduces blood glucose. In addition, we have designed and constructed second generation materials that have high insulin densities, with the potential for multiple day delivery. The PAD approach for insulin therapy holds promise for addressing the pressing need for continuously variable delivery methods that do not rely on pumps, and their myriad associated problems.


Potential Substitutes for Replacement of Lead in Perovskite Solar Cells: A Review.
Lead halide perovskites have displayed the highest solar power conversion efficiencies of 23% but the toxicity issues of these materials need to be addressed. Lead-free perovskites have emerged as viable candidates for potential use as light harvesters to ensure clean and green photovoltaic technology. The substitution of lead by Sn, Ge, Bi, Sb, Cu and other potential candidates have reported efficiencies of up to 9%, but there is still a dire need to enhance their efficiencies and stability within the air. A comprehensive review is given on potential substitutes for lead-free perovskites and their characteristic features like energy bandgaps and optical absorption as well as photovoltaic parameters like open-circuit voltage (V OC), fill factor, short-circuit current density (J SC), and the device architecture for their efficient use. Lead-free perovskites do possess a suitable bandgap but have low efficiency. The use of additives has a significant effect on their efficiency and stability. The incorporation of cations like diethylammonium, phenylethyl ammonium, phenylethyl ammonium iodide, etc., or mixed cations at different compositions at the A-site is reported with engineered bandgaps having significant efficiency and stability. Recent work on the advancement of lead-free perovskites is also reviewed.


The contribution of mixed dishes to vegetable intake among US children and adolescents.
To describe the contribution of mixed dishes to vegetable consumption and to estimate vegetable intake according to specific types of vegetables and other foods among US children and adolescents. The 2003-2008 National Health and Nutrition Examination Survey (NHANES), a nationally representative probability survey conducted in the USA. Civilian non-institutionalized US population. All children and adolescents aged 2-18 years who met eligibility criteria (n 9169). Approximately 59 % of total vegetable intake came from whole forms of vegetables with 41 % coming from a mixed dish. White potatoes (10·7 (SE 0·6) %), fried potatoes (10·2 (SE 0·4) %), potato chips (8·6 (SE 0·5) %) and other vegetables (9·2 (SE 0·5) %) accounted for most vegetables in their whole forms, whereas pasta dishes (9·5 (SE 0·4) %), chilli/soups/stews (7·0 (SE 0·5) %), pizza/calzones (7·6 (SE 0·3) %) and other foods (13·7 (SE 0·6) %) accounted for most mixed dishes. Usual mean vegetable intake was 1·02 cup equivalents/d; however, after excluding vegetables from mixed dishes, mean intake fell to 0·54 cup equivalents/d and to 0·32 cup equivalents/d when fried potatoes were further excluded. Mixed dishes account for nearly half of overall vegetable intake in US children and adolescents. It is critical for future research to examine various components of vegetable intake carefully in order to inform policy and programmatic efforts aimed at improving dietary intake among children and adolescents.


The diagnostic value of component-resolved diagnostics in peanut allergy in children attending a Regional Paediatric Allergology Clinic.
To date, diagnosing food allergies in children still presents a diagnostic dilemma, leading to uncertainty concerning the definite diagnosis of peanut allergy, as well as to the need for strict diets and the potential need for adrenalin auto-injectors. This uncertainty in particular is thought to contribute to a lower quality of life. In the diagnostic process double-blind food challenges are considered the gold standard, but they are time-consuming as well as potentially hazardous. Other diagnostic tests have been extensively studied and among these component-resolved diagnostics appeared to present a promising alternative: Ara h2, a peanut storage protein in previous studies showed to have a significant predictive value. Sixty-two out of 72 children, with suspected peanut allergy were analyzed using serum specific IgE and/or skin prick tests and specific IgE to several components of peanut (Ara h 1, 2, 3, 6, 8, 9). Subsequently, double-blind food challenges were performed. The correlation between the various diagnostic tests and the overall outcome of the double-blind food challenges were studied, in particular the severity of the reaction and the eliciting dose. The double-blind provocation with peanut was positive in 33 children (53 %). There was no relationship between the eliciting dose and the severity of the reaction. A statistically significant relationship was found between the skin prick test, specific IgE directed to peanut, Ara h 1, Ara h 2 or Ara h 6, and the outcome of the food challenge test, in terms of positive or negative (P < .001). However, we did not find any relationship between sensitisation to peanut extract or the different allergen components and the severity of the reaction or the eliciting dose. There was no correlation between IgE directed to Ara h 3, Ara h 8, Ara h 9 and the clinical outcome of the food challenge. This study shows that component-resolved diagnostics is not superior to specific IgE to peanut extract or to skin prick testing. At present, it cannot replace double-blind placebo-controlled food challenges for determination of the eliciting dose or the severity of the peanut allergy in our patient group.


Minimum 15-year follow-up for clinical outcomes of arthroscopic rotator cuff repair.
Arthroscopic rotator cuff repair surgery is one of the most common shoulder procedures performed in the United States. Although several studies have shown considerable symptomatic relief in the short term following surgery, a relatively high rate of recurrent defects has led surgeons to question the long-term durability of this operation. We hypothesized that outcomes at a minimum of 15 years of follow-up in patients who underwent all-arthroscopic rotator cuff repair would be maintained and would remain significantly improved compared with the preoperative status. All-arthroscopic rotator cuff repairs were performed in 193 patients from 2003 to 2005. Patient-reported outcomes were collected preoperatively and at 1, 2, 5, and ≥15 years postoperatively. The primary outcome was the American Shoulder and Elbow Surgeons (ASES) score. Secondary outcomes included Single Assessment Numeric Evaluation (SANE), Shoulder Activity Scale (SAS), visual analog scale, and Patient-Reported Outcomes Measurement Information System (PROMIS)-Upper Extremity (UE) scores. Patient demographic characteristics, revision surgical procedures, and complications were recorded. Generalized estimating equations were used to model scores over time, and multiple comparisons between time points were performed using Tukey adjustment. This study included 60 patients with a mean follow-up period of 16.5 years (range, 15.8-17.7 years). The mean ASES score improved from 60.2 ± 18.8 preoperatively to 93.0 ± 9.4 at ≥15 years (P < .0001). The mean visual analog scale pain score decreased from 4.1 ± 0.7 preoperatively to 0.7 ± 0.3 at ≥15 years (P < .0001). The average SANE, SAS, and PROMIS-UE scores at ≥15 years were 87.8 ± 14.8, 8.8 ± 4.3, and 49.6 ± 10.2, respectively. Of 60 patients, 7 underwent revision surgery. Older age and female sex were associated with lower SAS scores at 15 years, whereas female sex was associated with lower PROMIS-UE scores. There were no factors predictive of ASES or SANE scores. At long-term follow-up (≥15 years), the patient-reported outcomes of all-arthroscopic rotator cuff repair show significant improvement from baseline preoperative function and remain durable over a period of 15 years. This information is useful in counseling patients regarding the long-term results of this procedure.


Optimization of conditions for supercritical fluid extraction of flavonoids from hops (Humulus lupulus L.).
Waste hops are good sources of flavonoids. Extraction of flavonoids from waste hops (SC-CO(2) extracted hops) using supercritical fluids technology was investigated. Various temperatures, pressures and concentrations of ethanol (modifier) and the ratio (w/w) of solvent to material were tested in this study. The results of single factor and orthogonal experiments showed that at 50 degrees C, 25 MPa, the ratio of solvent to material (50%), ethanol concentration (80%) resulted in maximum extraction yield flavonoids (7.8 mg/g). HPLC-MS analysis of the extracts indicated that flavonoids obtained were xanthohumol, the principal prenylflavonoid in hops.


Evolutionary fates and origins of U12-type introns.
U2-type and U12-type introns are spliced by distinct spliceosomes in eukaryotic nuclei. A classification method was devised to distinguish these two types of introns based on splice site sequence properties and was used to identify 56 different genes containing U12-type introns in available genomic sequences. U12-type introns occur with consistently low frequency in diverse eukaryotic taxa but have almost certainly been lost from C. elegans. Comparisons with available homologous sequences demonstrate subtype switching of U12 introns between termini of AT-AC and GT-AG as well as conversion of introns from U12-type to U2-type and provide evidence for a fission/fusion model in which the two splicing systems evolved in separate lineages that were fused in a eukaryotic progenitor.


Effect of Shift Work on Nocturia.
To identify the circadian sensitive component of nocturia by comparing nocturia in patients who voluntarily choose a disrupted circadian rhythm, that is, shift workers, with those who maintain normal day-night cycles. Between 2011 and 2013, a total of 1741 untreated patients, 1376 nonshift workers and 365 shift workers, were compared for nocturia indices based on frequency volume charts (FVCs). General linear model of 8-hour interval urine production and frequency were compared between FVCs of nonshift workers, FVCs of night-shift workers, and FVCs of day-shift workers. Nocturia frequency was increased in the night-shift workers (2.38 ± 1.44) compared with nonshift workers (2.18 ± 1.04) (P <.01). Whereas nocturnal polyuria index did not increase significantly (0.33 ± 0.19 for night-shift workers, 0.34 ± 0.13 for nonshift workers, P = .24), nocturnal bladder capacity index increased significantly (1.41 ± 1.06 for night-shift workers, 1.26 ± 0.92 for nonshift workers, P <.01). Eight-hour interval indices show that urine production changed with shift (P <.01), whereas voiding frequency remains unchanged despite shift changes (P = .35). Patients in alternating work shifts showed increased nocturia, especially during their night shift. These changes tended to be more associated with decreased nocturnal bladder capacity than increased nocturnal polyuria.


Acantholysis induced by proteolytic enzymes. II. Enzyme fractions produced by Trichophyton mentagrophytes.
Trichophyton mentagrophytes produces three enzyme fractions of molecular weight 65,000, 92,000 and 18,000, respectively. Normal human skin was cultivated and the specimens were subjected to electron microscopy. Enzyme fraction I showed the capacity to induce epidermal acantholysis and dermo-epidermal separation, while the other two fractions showed no proteolytic nor keratinolytic action in cultivated skin.


STING-dependent autophagy suppresses Nosema bombycis infection in silkworms, Bombyx mori.
Nosema bombycis is a unicellular spore-forming obligate parasite, related to fungi, and causes infections in economically important animals and are opportunistic human pathogens. However, the mechanisms of host response to N. bombycis remain unclear. STING (stimulator of interferon genes) is an adapter protein involved in the innate immune response to pathogens. In this study, a transgenic gRNA vector containing BmSTING was constructed and microinjected to generate the transgenic line BmSTINGΔ6bp/WT and BmSTINGΔ5bp/WT in silkworms. The expression of BmSTING was significantly reduced in BmSTINGΔ5bp/WT compared to non-transgenic silkworm. The mortality and LC3 (microtubule-associated protein 1 light chain 3) level in BmSTINGΔ6bp/WT and BmSTINGΔ5bp/WT was significantly decreased in the early infection stage of N. bombycis, but the transgenic silkworms died rapidly in the later stage. Furthermore, both BmSTING and LC3 were increased in BmE cell lines after infection with N. bombycis. This study highlights the role of STING-dependent pathways response to microsporidia in silkworm, Bombyx mori.


Histone deacetylase inhibitor FK228 suppresses the Ras-MAP kinase signaling pathway by upregulating Rap1 and induces apoptosis in malignant melanoma.
Histone deacetylase (HDAC) inhibitors are expected to be effective for refractory cancer because their mechanism of action differs from that of conventional antineoplastic agents. In this study, we examined the effect of the HDAC inhibitor FK228 on malignant melanoma, as well as its molecular mechanisms. FK228 was highly effective against melanoma compared with other commonly used drugs. By comparing the gene expression profiles of melanoma cells and normal melanocytes, we defined a subset of genes specifically upregulated in melanoma cells by FK228, which included Rap1, a small GTP-binding protein of the Ras family. The expression of Rap1 mRNA and protein increased in FK228-treated melanoma cells in both a dose- and a time-dependent manner. A decrease in the phosphorylation of c-Raf, MEK1/2, and ERK1/2 was accompanied by an increase in Rap1 expression in both FK228-treated and Rap1-overexpressing cells. Inhibition of Rap1 upregulation by small interfering RNA (siRNA) abrogated the induction of apoptosis and suppression of ERK1/2 phosphorylation in FK228-treated melanoma cells. These results indicate that the cytotoxic effects of FK228 are mediated via the upregulation of Rap1. Furthermore, we found that Rap1 was overexpressed and formed a complex with B-Raf in melanoma cell lines with a V599E mutation of B-Raf. The siRNA-mediated abrogation of Rap1 overexpression increased the viability of these cells, suggesting that Rap1 is also an endogenous regulator of Ras-MAP kinase signaling in melanomas.


Synthesis and skin gene analysis of 4'-acetoxy-resveratrol (4AR), therapeutic potential for dermal applications.
Resveratrol (RV) 1, a plant polyphenol, has proven effective in commercial products yet drawbacks include low bioavailability due to rapid metabolism. Structural modifications have led to a 4'-acetoxy analog 2 (4AR) now produced using a selective one-step esterification reaction. The one-step synthesis is shown together with expression of skin genes using human dermal models to establish 4AR 2 benefits to skin health. 4AR 2 at 1% in qPCR experiments using a human skin model significantly increased gene expression of the anti-aging factor, SIRT 1 by over 3.3-fold, extracellular matrix proteins collagen III, IV, elastin and tissue inhibitors of metalloproteinases (TIMP 1, 2), anti-oxidants CAT, LOX, superoxide dismutase (SOD 1, 2), metallothioneins (MT1H, MT1H), skin aging biomarkers fibrillin (FBN1), laminin (LAMB1), proliferating cell nuclear antigen (PCNA), skin growth factors (HBEGF, IGF1, NGF and TGF). 4AR 2 also decreased gene expression of inflammatory and skin-aging molecules (IL-1, IL-6, IL-8, COX-2, TNGRSF) and S100 calcium binding proteins A8, A9. These findings suggest that 4AR 2 has potential for topically treatment and prevention of skin aging.


Circulating tumor cells are associated with poor outcomes in early-stage hepatocellular carcinoma: a prospective study.
Previous studies evaluating association between circulating tumor cells (CTCs) and clinical outcomes in hepatocellular carcinoma (HCC) have shown inconsistent results due to suboptimal detection methods and patient heterogeneity. Patients undergoing surgery for early-stage HCC were prospectively enrolled. The CTC numbers were determined using a tapered slit platform, which detects CTCs based on the cell size and morphology. Survival and recurrence were evaluated, and Cox proportional hazards models were used to demonstrate the prognostic significance of CTC. Of 105 patients, 25 had increased CTC numbers after surgery (ΔCTC > 0, defined as positive) and a significantly higher level of recurrence (p = 0.042). A positive ΔCTC was seen to be an independent predictor of recurrence (hazard ratio 2.28), along with hepatitis B virus infection, alanine aminotransferase level, and the presence of satellite nodules (all p < 0.05). Subgroup analyses showed that a positive ΔCTC was associated with lower survival and higher recurrence among patients with low alpha-fetoprotein levels and cirrhosis (all p < 0.05). Calculation of ΔCTC based on the physical properties of the cells is predictive of recurrence in patients with early HCC undergoing surgery.


Effects of adrenergic drugs on sheep oviduct motility.
Recordings of electrical activity of the oviduct in conscious ewes fitted with an extracellular multi-electrode assembly confirm the presence of alpha- and beta-adrenergic receptors in both the ampullary and isthmic portions. Regional differences in response to noradrenaline and isoprenaline were observed particularly during oestrus. In all cases the lowest threshold of sensitivity was exhibited by the isthmic portion of the oviduct.


A two-phase model for drug release from microparticles with combined effects of solubilisation and recrystallisation.
The present study aims to provide a comprehensive mathematical model for drug release from microparticles to the adjacent tissues. In the elucidation of drug release mechanisms, the role of mathematical modelling has been depicted thereby facilitating the development of new therapeutic drug by a systematic approach, rather than expensive experimental trial-and-error methods. In order to study the whole process, a two-phase mathematical model describing the dynamics of drug transport in two coupled media is presented. Drug release is described taking into consideration both solubilisation dynamics of drug crystallites and diffusion of the solubilised drug through the microparticle. In the coupled media, reversible dissociation/recystallisation processes are taking place. The model has led to a system of partial differential equations that are solved analytically. The model points out the important roles played by the diffusion, mass-transfer and reaction parameters, which are the main architects behind drug kinetics across two layers. The dependence of drug masses on the main parameters is also analysed.


Structured treatment interruptions (STIs) in HIV-1 infected pediatric populations increases interferon gamma production and reduces viremia.
We assessed the effect of progressively longer antiretroviral structured treatment interruptions (STIs) starting with 3 days, increasing by 2 days in length each cycle on HIV-specific immune responses. As well, we correlated these responses with control of HIV viremia. Eight individuals became viremic and reached cycle 13 with an STI of > or =27 days. HIV-specific gamma-interferon production to inactivated HIV and vaccinia vectors expressing gag, env, nef, and pol increased (>10-fold) in six of eight subjects. Median plasma RNA levels peaked @ cycle 7 and declined to levels <10(4)cp/ml after cycle 10. In a subset of five who reached cycle 17, HIV-specific IFN-gamma frequencies increased from cycle 8 to cycle 17 with evidence of improved virologic control over comparable periods off antiretroviral therapy. This allowed us to conclude that exposure to autologous virus increased HIV-specific immune responses and decreased HIV RNA were seen in those who have had >13 interruptions, with STI intervals that exceeded 27 days.


Oral Phyto-thymol ameliorates the stress induced IBS symptoms.
Physical stressors play a crucial role in the progression of irritable bowel syndrome (IBS). Here we report a heterogeneous physical stress induced IBS rat model which shows depression and subsequent modulation of IBS by oral treatment of thymol. Oral administration of Thymol reduces the stress induced IBS significantly altering the stress induced gastrointestinal hypermotility, prolonged the whole gut transit time, and increased abdominal withdrawal reflex suggesting gastrointestinal hypermotility and visceral discomfort caused the onset of depression. Immunohistochemical analysis in small intestine and colon of rats shows the decreased 5-HT3AR expression level while thymol treatment normalized the 5-HT3AR expression in the stressed rats. Molecular docking studies showed that thymol competes with endogenous serotonin and an antagonist, Tropisetron and all have similar binding energies to 5-HT3AR. Molecular dynamics simulations revealed that thymol and tropisetron might have similar effects on 5-HT3AR. Our study suggest that thymol improves IBS symptoms through 5-HT3AR, could be useful for the treatment of IBS.


Kinetics analysis of oxygen vacancies in TiO2 solar water reduction: Revealing effects and eliminating disadvantages.
A consensus is yet to be reached on the effects of oxygen vacancy (VO) on the performance of TiO2 for photocatalytic water splitting as contrasting viewpoints have been presented in the latest researches. Herein, a comprehensive set of spectroelectrochemical methods are deployed to clearly reveal the advantages and disadvantages of VO on the performance of TiO2. The results indicate that surface VO improves the photocatalytic activity while bulk VO has a negative effect on the water reduction performance of TiO2. Intensity-modulated photocurrent spectroscopy (IMPS) and UV-vis spectroscopy provide compelling evidence that the improvement of H2 evolution can be attributed to the presence of defect level, while the low interface charge transfer efficiency caused by surface VO limits the further improvement of photocatalytical H2 evolution, which can be alleviated by an organic hole transport coating. The density functional theory (DFT) and surface photovoltaic (SPV) analyses confirm that the built-in field between TiO2 and hole molecules is the reason for the interface charge transfer efficiency improvement. Our findings provide a comprehensive understanding of VO in TiO2 by carrier behavior analysis and a scheme to further promote the photocatalytic performance.


Photosynthetic and ultrastructural responses of Ulva australis to Zn stress.
This research evaluated the effect of zinc (Zn) on the ultrastructure and the photosynthetic efficiency of a common green alga. Ulva australis was grown in the laboratory for 7days under a range of different Zn concentrations (0, 25, 50 and 100μgL-1). Growth rate (Gr), photosynthetic efficiency (Fv/Fm and ETRmax), photosynthetic pigments, and metal accumulation were measured. Samples of 1mm length were taken to analyse the effect of Zn on the ultrastructure using transmission electron microscopy (TEM) and cytochemical responses (TB-O and PAS) were evaluated by light microscopy (LM). There were no significant differences in the growth rate, Fv/Fm, ETRmax and the photosynthetic pigments chlorophyll a, chlorophyll b and carotenoids (p>0.05) after 7days of Zn exposure. However, TEM revealed cytoplasm retraction, compression of cellulose fibrils, dissembled thylakoids and electron-dense bodies suggesting ultrastructural impacts from metal exposure and accumulation. Cytological analysis demonstrated that Zn affected U. australis cells at the three concentrations tested. The main effect was cytoplasm retraction and a decrease on the amount of starch granules, following exposure at 25μgL-1 and 50μgL-1 of Zn. We conclude that concentrations of Zn assessed in U. australis in this research has a short-term cellular effect as revealed by TEM and cytological analysis, demonstrating the importance of measuring a broad suite of endpoints to better understand species responses to environmentally relevant concentrations of Zn. However, U. australis was able to physiologically tolerate adverse conditions, since there was no effect on the photosynthetic performance and growth.


An approach towards Zero-Waste wastewater technology: Fluoxetine adsorption on biochar and removal by the sulfate radical.
The appearance of pharmaceuticals in the aquatic environments has become a serious problem because of their hazardous effect on the biota. Therefore, great efforts are focussed in the removal to these pollutants from wastewaters. In this study, an innovative technology based on the principles of Zero-Waste for the management of wastewater streams is presented. Hence, adsorption of fluoxetine (FLX), selected as a model pollutant, in an eco-friendly adsorbent, biochar, was followed by an in situ removal of the pharmaceutical in the solid matrix by the action of sulfate radicals. Initially, an in-depth characterisation of the adsorbent and the adsorption process was carried out. The pseudo-second order kinetic and Freundlich isotherm described well the process, and the electrostatic attractions were revealed as the primary adsorption mechanism. Later, the removal of the FLX was studied by the sulfate radicals, in the presence of activators (Fe2+ and citric acid), in liquid and onto the biochar medium. It was concluded that in order to enhance the pollutant removal it is necessary the presence of both activators in liquid media. However, in in situ removal onto biochar, it was not necessary the Fe2+ presence and only the addition of complexing agents was required as a result of biochar's mineral content. Finally, the applicability of the proposed approach was studied in fixed-bed column assays where the adsorption and the removal of the pollutant were efficiently accomplished. This fact confirms the suitability of the developed process as a viable alternative in the treatment of wastewaters.


Modes of antibacterial action of curcumin under dark and light conditions: A toxicoproteomics approach.
Curcumin is a potent natural food-grade antimicrobial compound. Exposure to light further enhances its antimicrobial capacity. Proteomic methods were used in this study for investigating the mechanistic aspects of the antibacterial curcumin effects in the dark and upon illumination. Escherichia coli cells exposed to water-dispersible curcumin-methyl-β-cyclodextrin inclusion complex under dark and light conditions were compared with the non-treated cells kept under the same illumination regimes. Curcumin treatment in the dark evoked adaptive responses aimed at mitigation of oxidative stress, DNA protection, proteostasis, modulation of redox state via changing NADH level, and gasotransmitter (H2S and NH3) biosynthesis. Although part of these phenomena were also present in E. coli treated under light, the light-induced curcumin toxicity was prevailed by maladaptive responses. The ROS burst induced upon curcumin treatment under light overrode the cellular adaptive mechanisms disrupting the iron metabolism, deregulating the iron-sulfur cluster biosynthesis and eventually leading to cell death. The toxicoproteomic findings were validated by transcriptomic analysis and by assessment of intracellular ROS, NADH, NADPH and iron levels. The results of this study elucidate putative mechanistic basis of antibacterial effects of curcumin, suggesting ways towards more efficient contamination control. In particular, the antimicrobial efficacy of curcumin can be potentiated by targeting bacterial systems that remediate its dark toxicity by free radical detoxification and modulation of cell redox status. To the best of the authors' knowledge, this is the first proteomic study differentiating between the dark and light-induced antimicrobial activity of curcumin.


Competition between hydrogen bonds and halogen bonds in complexes of formamidine and hypohalous acids.
Quantum chemical calculations have been per-formed for the complexes of formamidine (FA) and hypohalous acid (HOX, X = F, Cl, Br, I) to study their structures, properties, and competition of hydrogen bonds with halogen bonds. Two types of complexes are formed mainly through a hydrogen bond and a halogen bond, respectively, and the cyclic structure is more stable. For the F, Cl, and Br complexes, the hydrogen-bonded one is more stable than the halogen-bonded one, while the halogen-bonded structure is favorable for the I complexes. The associated H-O and X-O bonds are elongated and exhibit a red shift, whereas the distant ones are contracted and display a blue shift. The strength of hydrogen and halogen bonds is affected by F and Li substitutents and it was found that the latter tends to smooth differences in the strength of both types of interactions. The structures, properties, and interaction nature in these complexes have been understood with natural bond orbital (NBO) and atoms in molecules (AIM) theories.


The dual-gate lumen model of renal monoamine transport.
The three-phase response of urinary serotonin and dopamine in subjects simultaneously taking amino acid precursors of serotonin and dopamine has been defined.1,2 No model exists regarding the renal etiology of the three-phase response. This writing outlines a model explaining the origin of the three-phase response of urinary serotonin and dopamine. A "dual-gate lumen transporter model" for the basolateral monoamine transporters of the kidneys is proposed as being the etiology of the three-phase urinary serotonin and dopamine responses. The purpose of this writing is to document the internal renal function model that has evolved in research during large-scale assay with phase interpretation of urinary serotonin and dopamine. In excess of 75,000 urinary monoamine assays from more than 7,500 patients were analyzed. The serotonin and the dopamine phase were determined for specimens submitted in the competitive inhibition state. The phase determination findings were then correlated with peer-reviewed literature. The correlation between the three-phase response of urinary serotonin and dopamine with internal renal processes of the bilateral monoamine transporter and the apical monoamine transporter of the proximal convoluted renal tubule cells is defined. The phase of urinary serotonin and dopamine is dependent on the status of the serotonin gate, dopamine gate, and lumen of the basolateral monoamine transporter while in the competitive inhibition state.


Reinvestigation of the photophysics of 3-aminobenzoic acid in neat and mixed binary solvents.
The present study elucidates the reinvestigation of the photophysical behavior of 3-aminobenzoic acid (3ABA) in solvents of different polarities using the steady-state spectroscopic techniques. Kamlet-Taft and Catalan solvatochromic models have been used to analyze the solvatochromic changes in neat solvents. The hydrogen bond donating ability of the solvent was found to be the main parameter affecting the spectral behavior of 3ABA. The solvatochromic characteristics of 3ABA have also been examined in binary solvent mixtures viz. acetonitrile (ACN)-methanol (MeOH) and benzene (BEN)-MeOH using the concept of preferential solvation. The preferential solvation of 3ABA shows unusual behavior for BEN-MeOH binary mixture and described unnoticed sigmoidal behavior in the ground state and synergistic impact in the excited state. Besides, the 3ABA was studied theoretically by quantum chemical calculations using (HF) Hartree-Fock and (DFT/B3LYP) density functional theories and its electronic absorption bands have been assigned by time-dependent density functional theory (TD-DFT). The effect of solvents on 3ABA was considered using a IEF-PCM-TDDFT (integral equation formalism of the polarizable continuum model- TDDFT) method. Thus, the theoretical results were found to be closer to the experimental results.


Improving Performance of Breast Cancer Risk Prediction by Incorporating Optical Density Image Feature Analysis: An Assessment.
The purpose of this study is to improve accuracy of near-term breast cancer risk prediction by applying a new mammographic image conversion method combined with a two-stage artificial neural network (ANN)-based classification scheme. The dataset included 168 negative mammography screening cases. In developing and testing our new risk model, we first converted the original grayscale value (GV)-based mammographic images into optical density (OD)-based images. For each case, our computer-aided scheme then computed two types of image features representing bilateral asymmetry and the maximum of the image features computed from GV and OD images, respectively. A two-stage classification scheme consisting of three ANNs was developed. The first stage included two ANNs trained using features computed separately from GV and OD images of 138 cases. The second stage included another ANN to fuse the prediction scores produced by two ANNs in the first stage. The risk prediction performance was tested using the rest 30 cases. With the two-stage classification scheme, the computed area under the receiver operating characteristic curve (AUC) was 0.816 ± 0.071, which was significantly higher than the AUC values of 0.669 ± 0.099 and 0.646 ± 0.099 achieved using two ANNs trained using GV features and OD features, respectively (P < .05). This study demonstrated that applying an OD image conversion method can acquire new complimentary information to those acquired from the original images. As a result, fusion image features computed from these two types of images yielded significantly higher performance in near-term breast cancer risk prediction.


Temporal changes in survival among adult patients with acute myeloid leukaemia in the period 2000-2016: a Danish population-based study.
In the present study, we quantify the progress in overall survival (OS) during the period 2000-2016 among Danish patients with acute myeloid leukaemia (AML). This population-based study, including 3820 adult patients with AML, demonstrates a significantly improved OS over time with the 2-year age-standardised OS increasing from 22% in 2002 to 31% in 2016. The improvement in OS was exclusively seen in patients with AML aged ≥50 years, with absolute improvements in 2-year OS from 2002 to 2016 of ≥10% among patients aged 50-75 years and a small absolute increase in those aged >75 years.


Lung cancer chemotherapy decisions in older patients: the role of patient preference and interactions with physicians.
Lung cancer chemotherapy decisions in patients ≥ 70 years old are complex because of toxicity, comorbidity and the limited data on patient preferences. We examined the relationships between preferences and chemotherapy use in this group of patients. We used a questionnaire describing four hypothetical lung cancer treatment options. Eighty-three elderly (≥ 70 years old) lung cancer patients were informed about their diagnosis and therapeutic choices and then asked to choose one of the four options. Patients had previously been included in a prospective study to explore geriatric evaluation in an oncology unit and all had given written informed consent. Older patients (n=83) diagnosed with lung cancer (non-small- and small-cell lung cancer) from January 2006 to February 2008 were recruited from a single centre. The mean patient age was 77 years (range: 70-91). Eighty-one patients (97.6%) were men. Non-small-cell lung cancer (NSCLC) was the diagnosis in 63 patients (76%). Most patients selected active treatment (38.6% most survival benefit, 18% less survival benefit) and 31.3% selected no active treatment. Elderly lung cancer patients were significantly more likely to accept aggressive treatments despite high reported toxicities. Although most of the patients were symptomatic at diagnosis, the "symptom relief" option was chosen less frequently than the options that could prolong survival. Factors significantly related to patients' attitude toward chemotherapy were age (p<0.001), frailty (p=0.0039), depression and poor performance status (PS). Elderly lung cancer patients want to be involved in the decision-making process. Survival was the main treatment objective for more than half of the patients in this study. We have not found other published studies about elderly lung cancer patients' decisions about chemotherapy.


Interspecific size regularities in tropical felid assemblages.
I extend an earlier analysis of size relationships in Neotropical cats to felid assemblages in tropical Africa and Asia. Jaw length is the size measure, which apparently correlates well with modal prey size. Each assemblage contains two species ("convergents") that are indistinguishable in jaw length. When, the convergent species are treated as separate entities, there is little evidence of even ratios, but there is a tendency for ratios to be larger on average than expected by random assembly, especially among the larger species. This tendency may reflect greater prey size variance for the large species or fewer alternatives to prey size as a basis for niche segregation among large species. Extreme evenness in size ratios observed among the larger Neotropical cats is not repeated in the other assemblages. Because demonstration of strong size ratio evenness depends on merging the convergents, the significance of such regularity must await greater knowledge of the habits of the convergent species. Differences between the convergent species in habitat use or predatory behavior are suggested by the fact that in each convergent pair, one species has dappled (striped or spotted) coat coloration and the other a plain coat.


Renal malposition in patients with omphalocele.
We describe a boy with a history of omphalocele who presented with gross hematuria. Subsequent evaluation revealed a cephalad right kidney malposition and the hematuria was of lower tract origin. To investigate the frequency of this radiographic finding the medical records of 15 patients with omphalocele who presented between 1979 and 1985 were reviewed. Studies of the urinary tract were performed after omphalocele closure. Of 7 cases (46 per cent) with abnormal cephalad renal displacement the kidney was on the right side only in 3 and it was bilateral in 4. The omphalocele contents consisted of gastrointestinal tract only in 9 patients, and liver and gastrointestinal tract in 6. All 6 patients with omphaloceles that included the liver had cephalad renal displacement. One patient with small bowel alone in the omphalocele had right kidney displacement. Clinicians should be aware of this variation to avoid confusion and further unnecessary evaluation.