[Antiangiogenic agents and gastrointestinal cancers].
The role of angiogenesis in tumor development and the identification of VEGF as a key factor in this process have recently led to the development of anti-angiogenic agents in the treatment of cancer. Among them, the major are those targeting the VEGF pathway, including anti-VEGF antibodies (bevacizumab) and VEGF receptor tyrosine kinase inhibitors (vatalanib, sorafenib, sunitinib...). Other therapeutic strategies inhibiting angiogenesis are under investigation, targeting the VEGF pathway or other crucial steps of angiogenesis. In digestive oncology, bevacizumab was the first anti-angiogenic agent to be registered in the fist-line treatment of metastatic colorectal cancer in which it was proved to be efficient in combination with a 5-fluorouracile (5FU)/acide folinique (AF) with or without irinotecan-based chemotherapy. Sunitinib and sorafenib have more recently been shown to be active in gastrointestinal stromal tumors and advanced hepatocellular carcinoma, respectively. Side effects associated with these anti-angiogenic agents are not those usually observed with conventional anticancer drugs and require a specific management. Many anti-angiogenic agents are currently under investigation in digestive tumors, opening new prospects but also raising many questions.


Occlusive ligature and standardized fenestration of a Baerveldt tube with and without antimetabolites for early postoperative intraocular pressure control.
To determine the effectiveness of a surgical modification for a nonvalved aqueous tube shunt in controlling intraocular pressure (IOP) in the early postoperative period. The effect of antimetabolite use on IOP also was studied. A retrospective study of consecutive patients who underwent modified Baerveldt 350-mm2 implant with varied, nonrandomized, exposure to antimetabolites. Fifty-one eyes of 46 patients with uncontrolled glaucoma were examined. Identical surgical modification of a Baerveldt 350-mm2 tube was performed in all cases and consisted of placement of an occlusive 7-0 polyglactin suture just anterior to the plate followed by a through-and-through penetration of the tube just anterior to the occlusive ligature with a standardized 15 degrees blade. Seventeen eyes were not exposed to antimetabolite, while 2 groups of 17 eyes had 3 minutes' episcleral exposure to either 5-fluorouracil 50 mg/ml or mitomycin C 0.4 mg/ml at the location corresponding to the fenestration. The Tenon's layer and conjunctiva were not exposed because of concerns regarding conjunctival erosion over the device. Intraocular pressure and number of antiglaucoma medications required were analyzed. For the group, mean IOP before surgery and on postoperative days 1, 4, 10, 21, 42, 63, 84, and 112 was (in millimeters of mercury) 34.6, 20.1, 17.0, 17.2, 22.0, 17.3, 18.7, 17.4, and 15.6, respectively. There was an elevation of IOP at day 21 relative to fibrotic blockage of the fenestration before suture autolysis. This was temporized with antiglaucoma medication until suture autolysis occurred or treated with laser suture lysis (8 eyes). On day 1, hypotony occurred in 3 (6%) eyes whereas IOP greater than 30 mmHg was observed in 13 (26%) eyes. By day 10, the frequency had decreased to one (2.1 %) eye and three (6.4%) eyes, respectively. The use of antimetabolites did not result in lower IOP or less medication needed for any group at any interval (analysis of variance). This modification of a nonvalved glaucoma tube shunt device provides adequate IOP control in the early postoperative period with a low rate of hypotony and surgical complications. If elevation of IOP occurs before suture autolysis, it generally is well controlled by antiglaucoma medications or laser suture lysis. Antimetabolite exposure did not influence early postoperative IOP in this study.


Who makes in-play bets? Investigating the demographics, psychological characteristics, and gambling-related harms of in-play sports bettors.
Sports betting has increased markedly in recent years, in part due to legislative changes and the introduction of novel forms of sports betting (e.g., in-play betting). Some evidence suggests that in-play betting is more harmful than other types of sports betting (i.e., traditional and single-event). However, existing research on in-play sports betting has been limited in scope. To address this gap, the present study examined the extent to which demographic, psychological, and gambling-related constructs (e.g., harms) are endorsed by in-play sports bettors relative to single-event and traditional sports bettors. Sports bettors (N = 920) aged 18+ from Ontario, Canada completed an online survey containing self-report measures of demographic, psychological, and gambling-related variables. Participants were classified as either in-play (n = 223), single-event (n = 533), or traditional bettors (n = 164) based on their sports betting engagement. In-play sports bettors reported higher problem gambling severity, endorsed greater gambling-related harms across several domains, and reported greater mental health and substance use difficulties compared to single-event and traditional sports bettors. There were generally no differences between single-event and traditional sports bettors. Results provide empirical support for the potential harms associated with in-play sports betting and inform our understanding of who may be at risk for increased harms associated with in-play betting. Findings may be important for the development of public health and responsible gambling initiatives to reduce the potential harms of in-play betting, particularly as many jurisdictions globally move towards legalization of sports betting.


[Mechanical ventilation of morbidly obese patients in anaesthesia and intensive care].
Sculptures from the Stone Age hint at the possibility that morbidly obese humans have always existed. Today, obesity represents a global epidemic with far-reaching consequences affecting health systems worldwide. Increasingly often, anaesthetists and intensivists are challenged with the treatment of extremely obese patients perioperatively. In addition to insufficient logistics and inappropriate technical equipment, the large number of obesity-related diseases, combined with the distinct pathophysiological changes of the respiratory system, put the morbidly obese patient at a significantly increased risk of perioperative complications. If, however, elaborate logistics and adequate airway management--followed by lung protective mechanical ventilation--are combined with appropriately conducted anaesthesia and intensive care, the morbidly obese patients' intensive care survival rates and hospital survival rates can be similar to those of patients of normal weight.


Characteristics of Pediococcus pentosaceus Q6 isolated from Elymus nutans growing on the Tibetan Plateau and its application for silage preparation at low temperature.
Characteristics of a strain Pediococcus pentosaceus Q6 isolated from Elymus nutans growing on the Tibetan plateau and its effects on E. nutans silage fermentation stored at low temperature were investigated. Sugar fermentation pattern and growth profiles of the strain Q6 and its reference strain APP were characterized. The strain Q6 and APP were inoculated to E. nutans at ensiling respectively; and ensiled at different temperatures (10, 15 and 25°C) for 30, 60 and 90 days. The results indicated that Q6 could grow at pH 3·0 and at 4°C. In contrast to APP, Q6 could ferment mannitol, saccharose, sorbitol and rhamnose. Lower pH in Q6-treated silages fermented for 60 days at 10 and 15°C was found compared with the control and APP-treated groups. For the silages that were stored at 10 or 15°C, the greatest lactic acid content were detected in Q6-inoculated silages ensiled for 30 and 60 days respectively. There were no differences in pH and lactic acid content between Q6- and APP-treated silages ensiled at 10 and 15°C for 90 days respectively. Inoculation of the strain P. pentosaceus Q6 could improve fermentation quality of ensiled E. nutans at the early stage of ensiling stored at low temperature (10 or 15°C). The selection of P. pentosaceus inoculants for improving silage quality at low temperature, which provides a candidate strain to make high-quality silage in regions with frigid climate.


Non-traditional roles of ubiquitin-proteasome system in fertilization and gametogenesis.
Fertilization and gametogenesis are key events in sexual reproduction. Our recent studies, together with several reports by other authors, demonstrated that the extracellular ubiquitin-proteasome system plays a role in fertilization and gametogenesis in addition to the traditional intracellular ubiquitin-proteasome system. Here, we summarize our recent results showing the importance of the extracellular ubiquitin-proteasome system in the sperm penetration through the vitelline coat of the egg during ascidian fertilization, together with our recent reports implicating the participation of a novel proteasome-associating complex PC530 in starfish oocyte maturation. We also describe the results by other authors showing the participation of the ubiquitin system both in the elimination of defective sperm in epididymis and in the elimination of paternal mitochondria in fertilized eggs. These are evidence of non-traditional extracellular functions of the ubiquitin system.


Elemental Profiling of North-East Indian Tea (Camellia sinensis) by ICP-MS and Assessment of Associated Health Risk.
Tea is a perennial crop that requires acidic soil for better plant growth. Due to the acidic nature of tea-growing soil, metals can be easily absorbed by tea plants from growing medium. Other anthropogenic activities are also the major contributor of element in the tea. This study provided a comprehensive database of 24 elements which were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Selected 24 elements belong to alkali metal (Li, Rb, Cs), alkaline earth metal (Be, Sr, Ba), transition metal (V, Cr, Mn, Co, Ni, Cu, Zn, Ag, Cd, Hg), basic metal (Al, Ga, Sn, Tl, Pb), metalloid (As), non-metal (Se), and actinide (U). Total 321 drier mouth samples were collected during 2020-2021 from eight different regions (Darjeeling, Terai, Dooars, North Bank, Upper Assam, South Bank, Cachar, and Tripura) of north-east India. No inorganic mercury as well as uranium was detected in any tested tea samples. Mean concentrations of Be, As, Ga, Tl, Li, Se, Cd, Ag, Cs, V, Co, and Pb were at trace level, whereas macro-element mean concentrations were distributed in the manner of Al > Mn > Rb > Ba > Zn > Cu > Sr > Cr > Ni > Sn. Human health risk for non-carcinogenic and carcinogenic metals was also assessed for the studied elements. Hazard quotients (HQs) and hazard index (HI) values (< 1) for non-carcinogenic elements indicated no risk. The incremental lifetime cancer risk (ILCR) values for carcinogenic elements indicated no risk for As, Cd, and Pb and medium level risk for Ni. Study concluded that north-east Indian tea would not pose any health hazard.


Health assessment of Black-crowned Night-herons (Nycticorax nycticorax) of the New York Harbor estuary.
Blood samples from 145 Black-crowned Night-heron (Nycticorax nycticorax, BCNH) chicks (mean age 3 weeks) were taken from four island colonies (Goose (2004), Canarsie Pol (2005), Hoffman (2004 and 2005) and North Brother (2004 and 2005)) in New York Harbor in 2004 and 2005 to establish baseline health reference ranges for this species and to compare health indices of birds reared on different islands. Packed cell volume (PCV) and total solids (TS) did not differ among islands in either year. Herons raised on Hoffman Island in 2004 had lower white blood cell count (WBC), and higher activities of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate amino transferase (AST), higher concentrations of potassium (K) and phosphorous (PHOS) and lower liver derived proteins (TP, prealbumin, albumin, alpha 1 globulins, alpha 2 globulins, beta globulins and gamma globulins) compared to herons from Goose and North Brother Islands. These changes suggest compromised health in chicks reared on Hoffman Island in 2004. On Hoffman in 2005, these biochemical analytes did not differ from concentrations and enzyme activities measured from birds on other islands. Although no single etiology can explain these extensive changes, it is likely that exposure to contaminants at foraging sites used by birds nesting on Hoffman and/or changes in prey availability and abundance causing birds to forage in different locations between years, led to differences measured in blood-based health indices. Avian health assessments coupled with foraging ecology serve as an excellent method for evaluating ecosystem health of the New York Harbor estuary system.


African adolescents and their teachers: sex and rural-urban comparisons in teachers' perceived behaviors.
This study investigated rural-urban differences in teachers' perceived behaviors among African adolescent boys and girls. On the Perceived Teacher Behavior Inventory administered to 354 boys and 530 girls from four rural and urban high schools in South Africa no significant sex differences were found on the subscales of Generalized Support, Positive Expectations, and Participation. Rural boys and girls scored significantly higher, however, than their urban peers on the Generalized Support and Participation.


A comparison of the effects of bradykinin, 5-hydroxytryptamine and histamine on the hepatic arterial and portal venous vascular beds of the dog: histamine H1 and H2-receptor populations.
1 The hepatic arterial and hepatic portal venous vascular beds of anaesthetized dogs were separately perfused in different experiments.2 From measurements of perfusion pressures and blood flows in the two series of experiments, hepatic arterial vascular resistance (HAVR) and hepatic portal venous vascular resistance (HPVR) respectively were calculated.3 Bradykinin, 5-hydroxytryptamine (5-HT) and histamine were injected intra-arterially and intra-portally and dose-response curves constructed from these data.4 Bradykinin injected intra-arterially caused dose-dependent hepatic arterial vasodilatation, and with an ED(50) of 2.66 x 10(-13) mol was more potent than any other vasodilator agent yet examined on this vascular bed.5 Bradykinin injected intraportally at doses up to 10 times those which were maximal on the arterial circuit did not alter the calculated HPVR.6 5-HT injected intra-arterially caused weak and variable rises in HAVR, indicating vasoconstriction. The maximum rise in HAVR was much less than that attained with noradrenaline in the same preparations.7 5-HT injected intraportally caused dose-dependent rises in HPVR indicating portal constriction at doses above 15-100 mug: in some experiments small doses of 5-HT resulted in reductions in calculated HPVR.8 Histamine has previously been shown to cause hepatic arterial vasodilatation: by intraportal injection, it caused dose-dependent rises in HPVR.9 In order to examine the receptors responsible for the effects of histamine, dose-response curves were constructed before and after mepyramine and metiamide.10 On the hepatic arterial vascular bed, metiamide did not antagonize the vasodilator effects of intra-arterial histamine, but these effects were antagonized by mepyramine.11 Similarly on the hepatic portal bed, the rises in HPVR due to histamine were antagonized by mepyramine but not by metiamide.12 The effects of histamine on both the hepatic arterial and portal venous vascular beds of the dog are therefore mediated predominantly by histamine H(1)-receptors.


Murine social stress results in long lasting voiding dysfunction.
Repeated exposure to social stress shifts the voiding phenotype in male mice leading to bladder wall remodeling and is associated with increased expression of the stress neuropeptide, corticotropin-releasing factor (CRF) in Barrington's nucleus neurons. In these studies, we set out to determine if the voiding phenotype could recover upon removal from the stressor. Male mice were exposed for 1h daily to an aggressor and the voiding phenotype was assessed at one month followed by randomization to three groups. One group underwent immediate sacrifice. Two groups were allowed a one month recovery from the social stress exposure with or without the addition of fluoxetine (1.2mg/ml) in their drinking water and repeat voiding patterns were measured prior to sacrifice. Social stress significantly increased bladder mass, bladder mass corrected for body weight, voided volumes, and decreased urinary frequency. The abnormal voiding phenotype persisted after a 1month recovery with no effect from the addition of fluoxetine. CRF mRNA in Barrington's nucleus was increased by social stress and remained elevated following recovery with no effect from the addition of fluoxetine. The mRNA and protein expression for the alpha 1 chains of type 1 and type III collagen was unchanged across all groups suggesting that changes in the extracellular matrix of the bladder are not responsible for the voiding phenotype. This persisting voiding dysfunction correlates with the persistent elevation of CRF mRNA expression in Barrington's nucleus.


Quantal analysis of transmitter release at an inhibitory synapse in the central nervous system of the leech.
The quantal nature of transmitter release has been analysed at central inhibitory synapses in the leech nervous system between an interneurone (HN) and a motoneurone (HE) that regulate the heartbeat. 1. Ganglia were bathed in leech Ringer fluid containing 20 mM-Mg and 1.8 mM-Ca and the membrane of the presynaptic HN interneurone was hyperpolarized by current injection. Under these conditions successive inhibitory potentials in the HE motoneurone, evoked by impulses in the HN interneurone, showed striking fluctuations in amplitude. 2. Assuming a Poisson distribution of the i.p.s.p.s and estimating the number of failures from the amplitude histograms of the observed responses, the mean size of the quantal unit was estimated as 0.25 +/- 0.015 mV (S.E. of mean, n = 26). When m, the mean number of quanta released per trial, was varied by changing the membrane potential of the presynaptic HN cell (Nicholls & Wallace, 1978), the experimentally observed amplitude distributions could be predicted by the Poisson theory. 3. An independent estimate of the unit size was obtained by noise analysis. A long subthreshold depolarizing pulse applied to the presynaptic HN interneurone evoked a sustained hyperpolarization of the HE motoneurone, apparently caused by an increase in the rate of on-going release of quanta by the HN cell terminals. From the mean change in membrane potential and the increase in variance, the size of the unit was calculated as 0.21 +/- 0.039 mV (S.E. of mean, n = 11). For ten pairs of cells an estimate of unit amplitude was made both from the Poisson analysis and the analysis of variance, again with good agreement. For these cells the estimated unit sizes were 0.24 +/- 0.023 mV (S.E. of mean, n = 10) from the failures and 0.21 +/- 0.043 m V (S.E. of mean, n = 10) from the noise. 4. A similar analysis was made of the inhibitory synaptic potentials evoked in one HN interneurone by stimulation of its contralateral homologue. Transmission again appeared to be qualtal; the mean unit amplitude from Poisson analysis was 0.31 +/- 0.022 mV (S.E. of mean, n = 19) and from the noise 0.29 +/- 0.027 mV (S.E. of mean, n = 3). 5. We conclude that transmitter is released from the terminals of the HN interneurone in quantal units that evoke miniature i.p.s.p.s of about 0.25 mV in the post-synaptic cells. Furthermore, modulation of transmission proudced by variation in the presynaptic resting potential and during presynaptic inhibition results from changes in the mean number of quanta released by each impulse.


Classification schema for anatomic variations of the inferior epigastric vasculature evaluated by abdominal CT angiograms for breast reconstruction.
Many studies demonstrate direct patient benefits from use of preoperative computed tomography angiograms (CTA) for abdominal tissue-based breast reconstruction. We present a novel classification schema to translate imaging results into further clinical relevance. Each hemiabdomen CTA was classified into a schema that addressed findings of expected anatomy, anatomy that necessitates a change in operative technique and anatomy that suggests less morbid procedures may be considered. Eighty-six patients (172 hemiabdomens) were available for study. Of the reconstructions performed in this time period, 40 (47%) were bilateral and 46 (53%) unilateral. Based on perforator size and location, relative perimuscular anatomy, and continuity of vessels, five categories were defined: type I "Traditional" anatomy (n = 150, 87%), type II "Highly Favorable" anatomy (n = 11, 6.4%), type III "Altered-Superiorly Translocated" anatomy (n = 9, 5.2%), type IV "Superficial Dominant" anatomy (n = 26, 15%), and type V "Hostile" anatomy (n = 4, 2.3%). The additive total is greater than 100%, because vessels may fall into more than one category. In providing the microsurgeon with a preoperative vascular map that has the potential to influence the preoperative, operative, and postoperative course, abdominal CTAs should be considered a worthy adjunct to the diagnostic armamentarium of the reconstructive surgeon. These classifications and their clinical impacts become even more important in centers performing increasing numbers of bilateral reconstructions. We believe that our simple schema can facilitate effective use of this powerful tool, aiding in overall care of the breast reconstruction patient.


Immunofluorescence study of the presence of herpes type 1 and type 2 antigens in patients with cancer of the uterine cervix.
The presence of herpes simplex virus (HSV) antigens was tested by direct immunofluorescence in 24 cases of cervical carcinoma and in 1 case of uterine leiomyosarcoma, in comparison with 34 uterine fibroma preparations that served as controls. HSV antigens type 1 and type 2 were detected in 8 cervical carcinoma cases and in the patient with uterine leiomyosarcoma.


Estimation of groundwater recharge variability using a GIS-based distributed water balance model in Makutupora basin, Tanzania.
Groundwater recharge estimation in the Makutupora basin (1500 km2) is vital considering the potentiality of the basin to Dodoma city. This study aims to apply the WetSpass model to estimate the long-term average seasonal (dry and wet) and annual groundwater recharge for the Makutupora basin. Data required for this study were biophysical data (topography, land use, soil, slope, and depth to the groundwater) and long-term hydro-meteorological data (2000-2020). Data were collected by using both field visits and disk transfer from respective institutions and websites. Hydro-meteorological data were prepared for dry and wet seasons. Raster maps were prepared in ArcMap 10.4 using the Inverse Distance Weighting (IDW) interpolation technique followed by resampling into a 200 × 200 m grid size. Resampled raster maps were converted from raster to ASCII format suitable to input in the WetSpass model. The findings indicated that more recharge was dominating in the wet season ranging between 0 and 120 mm/year with a mean value of 24.65 mm (99%) while less recharge occurs in the dry season ranging between 0 and 4.35 mm/year with a mean value of 0.24 mm/year (1%) and annually recharge ranges between 0 and 120.88 mm/year with a mean value of 24.88 mm. Mean annual precipitation computed from data for twenty (20) years was 694 mm/year out of which recharge accounted for 3.6%, surface runoff 33.9% and evapotranspiration 62.5%. The groundwater table receives total average volumetric recharge of 37.3 million m3 annually from precipitation for the entire basin area. The model was employed to realize the area's capacity for groundwater recharge to manage the water supply effectively, use it wisely, and plan for the future. Sustainable groundwater exploitation can be feasible only when there is knowledge of the rate at which groundwater is replenished annually. Therefore, the results of this study are useful in sustainable management plans, it may also be used as a benchmark for water supply authorities, policymakers and researchers to set proper protection measures and pumping policies.


NT-proBNP and the diagnosis of heart failure: a pooled analysis of three European epidemiological studies.
Many studies have shown that the B-type natriuretic peptides (BNP and NT-proBNP) are proven diagnostic markers for heart failure due to left ventricular systolic dysfunction. The manner in which they are to be used is still being unravelled; most single centre studies have chosen the best concentration of the peptide on ROC analysis as their cut-point resulting in numerous different values for both BNP and NT-proBNP appearing in the literature. We report a different approach of defining an age and sex corrected abnormal concentration for NT-proBNP, derived from normal individuals within a large sample of 3051 subjects pooled from three European epidemiology studies and applying that to the entire population to detect HF and LVD. Three thousand and fifty one subjects were studied. Of these 10% (305) had significant LVD and 3.1% (94) had HF. The median concentrations of NT-proBNP (IQR) in normals, those with LVD and in heart failure subjects were 20 pg/ml (10.30), 117.3 pg/ml (28.145) and 269.6 pg/ml (54.323), P<0.001, respectively. The area under the ROC curve for NT-proBNP for the detection of 'heart failure' was 0.85 and 0.69 for LVD. NT-proBNP was an independent predictor of the presence of HF on multivariate analysis. An abnormal NT-proBNP was defined as being >95th centile for normals, age and sex corrected, and diagnosed HF with a sensitivity of 75% and a negative predictive value of 99%. In an additional analysis in a breathless subgroup of our population, in 30% a raised NT-proBNP concentration could be explained by HF due to LVD, in another 64% the high BNP level was associated with some other structural of functional cardiac abnormality or renal impairment. We were unable to assign a possible cause to the high NT-proBNP values in 5.9% of this breathless subgroup of the population. An abnormal NT-proBNP concentration is an accurate diagnostic test both for the exclusion of HF in the population and in ruling out LVD in breathless subjects. An elevated NT-proBNP merely indicates the presence of 'cardio-renal distress' and should prompt referral for further investigation.


Differential polymerase chain reaction for detection of wild-type and a vaccine strain of Aujeszky's disease (pseudorabies) virus.
A polymerase chain reaction (PCR) strategy for differentiating between a vaccine mutant strain and wild-type (WT) strains of Aujesky's disease (pseudorabies) virus (ADV) was evaluated. With this approach, a single virus or a concurrent WT and vaccine virus infection could be distinguished by targeting the genomic alteration within the vaccine strain. PCR primers were designed for a recombinant vaccine virus that has almost all of the WT gX gene replaced by the lacZ gene. One primer, corresponding to a conserved sequence upstream of the altered region, was selected for common use. The differentiating primers were chosen from the unique WT gX and vaccine lacZ gene sequences. The sensitivity of the differential PCR was analyzed using extracted viral DNA and in vitro infected cell lysates. Approximately 10 and between 10 to 100 molecules of WT and vaccine viral DNAs, respectively, could be detected, regardless of the presence or absence of uninfected cell lysates. Detection of viral DNA from in vitro infected cell cultures approximated this level of sensitivity. The specificity of the amplifications was verified by restriction endonuclease analysis and Southern hybridization. Although the vaccine primer pair target was amplified to a lesser degree as compared to the WT primer pair product, utility of the differential PCR was demonstrated using trigeminal nerve ganglia from swine infected with vaccine virus and WT virus. Both viral targets were detected only by their specific primer pair, in either the single or dual infection.


Evaluation of two wild types of Pleurotus ostreatus (MCC07 and MCC20) isolated from nature for their ability to decolorize Benazol Black ZN textile dye in comparison to some commercial types of white rot fungi: Pleurotus ostreatus, Pleurotus djamor, and Pleurotus citrinopileatus.
Biological decolorization of Benazol Black ZN, a reactive azo-type textile dyestuff, was comparatively studied using 3 different commercial-type white rot fungi strains (Pleurotus ostreatus, Pleurotus cornucopiae var. citrinopileatus, Pleurotus djamor, and 2 wild types of P. ostreatus (MCC07 and MCC20) isolated from the nature. The initial dye concentrations in the medium were 500 and 1000 mg.L-1. All the organisms studied decolorized Benazol Black ZN to varying degrees. At low dye concentration, both commercial and wild type of P. ostreatus resulted in the best decolorization, conversely, wild-type P. ostreatus (MCC07) was found to be much more robust against increasing dye concentration and provided the best decolorization efficiency at high dye concentration.


Coagulation factor XIII polymorphisms and the risk of myocardial infarction and ischaemic stroke in young women.
The inconsistent findings among association studies that have examined the relationship between factor XIIIA Val34Leu and thrombosis may be owing to (1) population differences in the prevalence of other risk factors that modify the association with Val34Leu, or (2) linkage disequilibrium with other functional factor XIIIA polymorphisms. We therefore performed genotyping for factor XIIIA Val34Leu, Tyr204Phe and Pro564Leu in a population-based study of myocardial infarction (MI) and ischaemic stroke among white women <45-years of age and 345 demographically similar controls, and examined potential interactions with other risk factors. The presence of the factor XIIIA Leu34 allele was associated with a slight decreased risk of MI [odds ratio (OR) = 0.80] that was most pronounced among women with traditional cardiovascular risk factors. Paradoxically, women carrying two copies of the Leu34 allele had a nearly fourfold increased risk of ischaemic stroke relative to the Val34/Val34 genotype. Heterozygosity for factor XIIIA Phe204 was associated with a milder increased risk of ischaemic stroke, and analysis of a kindred with congenital dysfibrinogenaemia suggested that co-inheritance of the factor XIIIA Phe204 allele may increase susceptibility to ischaemic stroke. Our results suggest that the factor XIIIA Val34Leu variant may be associated with a decreased risk of MI among young women with other risk factors. The relationship of factor XIIIA polymorphisms to cerebrovascular disease requires further study.


Hyperprolactinemia is not associated with hyperestrogenism in noncycling African elephants (Loxodonta africana).
African elephants in US zoos are not reproducing at replacement levels. This is in part due to physiological problems, one of which is abnormal ovarian cyclicity that has been linked to increased prolactin secretion (hyperprolactinemia). A relationship between increased estrogen production (hyperestrogenism) and hyperprolactinemia has been found in other species. Therefore, the objective of this study was to determine if elevated prolactin was associated with increased estrogen concentrations in non-cycling African elephants. In cycling elephants (n=12), prolactin secretion followed a normal cyclic pattern, with higher concentrations observed during the follicular phase; overall mean concentration was ∼18ng/ml and baseline prolactin was ∼6ng/ml. Non-cycling females (n=18) were categorized into three groups: (1) low prolactin (<15ng/ml; n=3); (2) moderate hyperprolactinemia (16-30ng/ml; n=7); and marked hyperprolactinemia (>31ng/ml; n=8). Mean urinary estrogen conjugate concentrations ranged from 5.4 to 41.4ng/mg Crt, and were similar between normal cycling (15.4±1.5ng/mg Crt) and non-cycling, low prolactin elephants (18.4±7.3ng/mg Crt), but were lower in moderate (9.4±1.3ng/mg Crt) and marked hyperprolactinemic (9.8±1.1ng/mg Crt) groups (P<0.05). In conclusion, African elephants appear to be sensitive to alterations in prolactin production, with both low (e.g., a non-cycling pattern) and high prolactin secretion being associated with abnormal ovarian activity. However, hyperestrogenism was not related to hyperprolactinemia in the non-cycling females.


Doridosine derivatives: binding at adenosine receptors and in vivo effects.
Doridosine, an adenosine analogue, causes, in vivo, hypotension, reduction of heart rates, muscle relaxation and anti-inflammatory effects through adenosine A1 and A2 receptors. A series of doridosine derivatives was synthesized in a search for compounds with more selective adenosine A1 receptor activity. These derivatives were characterized for binding to the respective adenosine receptors and for their cardiovascular effects. We used competition binding studies with highly selective radioligands: [3H]cyclohexyladenosine for adenosine A1 and [3H]CGS 21680 for adenosine A2 binding assays. The results for eight doridosine derivatives revealed that 1-cyclopropylisoguanosine (BN-063) and 1-allylisoguanosine (AZ-108-1) were more selective for the adenosine A1 receptor. In vivo, both BN-063 and AZ-108-1 caused significant bradycardia but no obvious effect on blood pressure. The bradycardia was almost completely blocked by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, a specific adenosine A1 receptor antagonist).


Enhanced AOX accumulation and aquatic toxicity during 2,4,6-trichlorophenol degradation in a Co(II)/peroxymonosulfate/Cl⁻ system.
Chloride ion is known to affect on degradation kinetics in different ways during HO· and SO4(·-)-based advanced oxidation processes (AOPs). However, its effect on absorbable organic halogen (AOX) evolution and acute toxicity of treated water remains unknown, despite the importance of the two parameters in evaluating the applicability of AOPs. In the present study, Co/peroxymonosulfate (Co/PMS) and UV/hydrogen peroxide (UV/H2O2) treatment of 2,4,6-trichlorophenol was compared in terms of AOX formation, chlorinated byproducts and acute toxicity. Both Co/PMS and UV/H2O2 systems were more reactive under acidic conditions, resulting in elevated AOX levels when compared with those at neutral pH. The presence of high levels of chloride led to an accumulation and increase of AOX in the Co/PMS system. The toxicity of chlorinated byproducts was evaluated using Photobacterium phosphoreum, and the results revealed a sharp increase in acute toxicity of Co/PMS reaction solutions on addition of chloride ion. However, addition of Cl(-) had no apparent impact on AOX and toxicity of UV/H2O2 reaction solutions. These findings may have significant technical implications for selecting feasible technologies to treat high salinity wastewater.


First glanders cases detected in Nepal underscore the need for surveillance and border controls.
Glanders is a transmissible zoonotic disease caused by Burkholderia mallei that infects equids and humans. No glanders cases in equids were reported so far in Nepal. Following suspected glanders in animals with clinical signs in different regions in Nepal, serum samples were tested by CFT, ELISA and Luminex® tests. Two horses and a mule tested positive for glanders by all tests, while two other equids only tested positive by ELISA and Luminex®. Analysis of swabs and pus samples by a PCR system targeting B. mallei confirmed the presence of the bacterium in the samples collected from the 3 equids that yielded positive results in all serological tests. Genotyping of the three PCR positive samples with a SNP-based method identified a genotype closely related to the B. mallei strains circulating in India. Confirmation of glanders cases underscores the need of implementing a surveillance program in Nepal and a strict control of the animal movement across the borders.


One-Pot Synthesis of Phosphinylphosphonate Derivatives and Their Anti-Tumor Evaluations.
This paper reports on the synthesis of new hydroxymethylene-(phosphinyl)phosphonates (HMPPs). A methodology has been developed to propose an optimized one-pot procedure without any intermediate purifications. Various aliphatic and (hetero)aromatic HMPPs were synthesized in good to excellent yields (53-98%) and the influence of electron withdrawing/donating group substitution on aromatic substrates was studied. In addition, the one-pot synthesis of HMPP was monitored by 31P NMR spectroscopy, allowing effective control of the end of the reaction and identification of all phosphorylated intermediate species, which enabled us to propose a reaction mechanism. Optimized experimental conditions were applied to the preparation of biological relevant aminoalkyl-HMPPs. A preliminary study of the complexation to hydroxyapatite (bone matrix) was carried out in order to verify its lower affinity towards bone compared to bisphosphonate molecules. Moreover, in vitro anti-tumor activity study revealed encouraging antiproliferative activities on three human cancer cell lines (breast, pancreas and lung).


Diversity and prevalence of nuisance arthropods detected by sticky traps in apartments in New Jersey.
Many nuisance arthropods occur in homes. In this study, nuisance arthropods are defined as any arthropod other than cockroaches and bed bugs. We examined nuisance arthropods found on sticky traps in 1,581 low-income apartments in four cities in New Jersey during 2018-2019 as part of a study for monitoring cockroach infestations. Four sticky traps (three in the kitchen, one in the bathroom) were placed in each apartment for approximately two weeks. Forty two percent of the apartments had nuisance arthropods on sticky traps. The relative abundance of different groups of arthropods were flies-36%, beetles-23%, spiders-14%, ants-10%, booklice-5%, and others-12%. The flies were further grouped into the following subgroups and their relative abundance were fungus gnats-42%, phorid flies-18%, moth flies-17%, fruit flies-10%, midges-8%, and others-5%. Among the beetles, 82% were stored product beetles (including spider beetles). Summer months (May-July) had a much higher frequency of nuisance arthropods occurrence than winter months (November-January). In addition to installing sticky traps, we also conducted interviews with 1,020 residents. Only 13% of the interviewed residents indicated sightings of nuisance arthropods. Resident interviews revealed a much higher relative frequency of sightings for flies (58%), much lower frequency for beetles (4%), and much higher frequency for mosquitoes compared to those captured on sticky traps. We conclude that sticky traps provide much more accurate information on indoor nuisance arthropod abundance and diversity than resident interviews and are a valuable tool for monitoring indoor nuisance arthropods.


Extraordinarily high rates of male circumcision in South Korea: history and underlying causes.
To investigate the high circumcision rate in South Korea and its rapid increase in the short period since its introduction. From January to December 2000, 5434 South Korean males (or their parents) aged 0-92 years were interviewed in detail about their circumcision status, their age at circumcision, and the possible effect of circumcision on their sexuality. In addition, 267 practising medical doctors were surveyed about their basic understanding of circumcision and phimosis. Currently the circumcision rate for high-school boys is > 90% and for those > 70 years old is < 10%. The circumcision rate in 1945 was < 0.1%. When averaged over the whole population, the present South Korean circumcision rate is approximately 60%; the rate has increased dramatically with time and particularly in the past 20 years, when the estimated number of male circumcisions has exceeded the number of male births. Although circumcision in South Korea has been strongly influenced by American culture, it has never been predominantly neonatal. The age at circumcision has continued to decrease and boys are now circumcised at approximately 12 years old. Of those who were circumcised long after they had been sexually active, > 80% reported no noticeable difference in sexuality, but a man was twice as likely to have experienced diminished sexuality than improved sexuality. Of the doctors who were surveyed, 41% carried out circumcision but, unlike in America, gynaecologists and paediatricians rarely did so. Among the doctors, basic knowledge on circumcision and phimosis was generally lacking, regardless of whether they practised circumcision or not. Amongst the factors contributing to the high circumcision rate was the mistaken notion held by both doctors and the general public that circumcision is directly correlated with industrialization and general progress of living standards. Many doctors believe the out-dated and sometimes controversial benefits of circumcision, i.e. prevention of cervical cancer and sexually transmitted diseases, and improved sexuality. Thus the vast majority of doctors recommend circumcision regardless of the patient's age. Peer pressure was also an important contributing factor. South Korea has an unusual history of circumcision. The mistaken and out-dated notions about circumcision and lack of knowledge of phimosis by physicians seem to be a leading contributory factor to the extraordinarily high circumcision rate.


Intestinal phospholipase A2 from Sparidae species: Functional properties and cytotoxic potential evaluation.
Marine species have gained significant attention as potential source for a broad spectrum of bioactive proteins. Fish phospholipases A2 (PLA2) have attracted renewed interest due to their excellent properties in lipid digestion. Herein, we report for the first time the catalytic properties of two intestinal secreted PLA2 (sPLA2) identified from Diplodus sargus (IDsPLA2) and Sparus aurata (ISaPLA2). The highest sequence identity was obtained with recently isolated Sparidae digestive PLA2 (45%) and Human pancreatic PLA2 (42%). IDsPLA2 and ISaPLA2 were overexpressed in E. coli as inclusion bodies, refolded and purified. Both enzymes have improved thermostability compared to mammalian pancreatic sPLA2 since they are active and stable at 55 °C, with specific activities of 320 and 190 U mg-1 measured on phosphatidylcholine, respectively. Interestingly, IDsPLA2, but not ISaPLA2, revealed weak toxicity towards macrophages and suggests its involvement in cell membrane degradation. ISaPLA2 was found to be more active than IDsPLA2 when using the monolayer technique at 20 mN m-1. Structural models of both enzymes revealed their differences. In silico docking of phospholipids with both models allowed proposing key amino-acids in substrate binding and selectivity. Overall, these results provide insight into the enzymatic and structural properties of two novel sPLA2 with potential for future applications.


Discovery of novel N-substituted carbazoles as neuroprotective agents with potent anti-oxidative activity.
Carbazole moiety is an important scaffold with a variety of biological applications, for example, anti-oxidative stress. Our previous synthesized carbazoles were screened for their neuroprotective properties against two individual oxidative stresses. Some of the new carbazole derivatives were observed with modest to good neuroprotective effects on neuronal cells HT22 against cell injury induced by glutamate or homocysteic acid (HCA). Substituents introduced to the carbazole ring system play crucial roles in their biological activities. In particular, a bulky group favors the neuroprotective activity of the compounds. One of the new compounds, 6, showed the best neuroprotective effects, which might result from its anti-oxidative activity with a GSH-independent mechanism. These findings might provide an alternative strategy for the development of novel carbazole derivatives for the treatment of CNS diseases such as Alzheimer's disease.


EEG correlates (event-related desynchronization) of emotional face elaboration: a temporal analysis.
An EEG frequency band analysis was conducted, in order to explore the significance of brain oscillations (delta, theta, alpha and beta) for emotional face comprehension during different post-stimulus time intervals (50-150; 150-250; 250-350; and 350-450 ms). The study was conducted on twenty adults who looked at emotional (happy, sad, angry, fearful) or neutral faces. The results showed that motivational significance of the stimulus can modulate the power synchronization (event-related desynchronization (ERD) decrease) within the frequency band of delta and theta. We propose that delta and theta respond to variations in processing stage of emotional face: whereas, delta reflects updating of the stimulus, theta responds to the emotional significance of face. The findings revealed that emotional discrimination by theta is observable mainly within 150-250 time interval and that it is more distributed on anterior regions, whereas delta is maximally synchronized within 250-350 interval and more posteriorly distributed for all the stimulus type. Finally, a right-hemisphere dominance was found for theta during emotional face comprehension.


Congenital bile duct cysts: Classification, operative procedures, and review of thirty-seven cases including cancer arising from choledochal cyst.
Congenital bile duct cysts are observed in any part of the bile duct from the liver to the duodenum. Reports of cases of cancer arising from it are increasing. Excision of the choledochal cyst seems to be the treatment of choice and partial resection of the intrahepatic cyst followed by intrahepatic cystoenterostomy at the porta hepatis is necessary for type IV-A cysts.


Transfer of the efficiency calibration of Germanium gamma-ray detectors using the GESPECOR software.
The GESPECOR software was extended to incorporate procedures for the computation of the efficiency transfer factor for cases of practical interest: (a) sources with identical geometry, but different matrices, (b) sources with similar (but not identical) geometry; and (c) transfer from a point source to a volume source. Fast and accurate algorithms. based on correlated sampling, were implemented for solving the first two cases. A procedure to take into account the imperfect charge collection in the detector was implemented.


New fluorenyl-substituted ditopic dioxotetraamine ligands and their copper(II) complexes--synthesis, crystal structure, magnetic properties and solution behavior.
A new fluorenyl-substituted dioxotetraamine salicylaldehyde Schiff-base ligand (L1) has been synthesized by the non-template 1 + 2 condensation of ligand 6-(9-fluorenyl)-1,4,8,11-tetraazaundecane-5,7-dione (L) with salicylaldehyde. From reduction of L1 with an excess of NaBH4, a ditopic dioxotetraamine ligand (L2) has been obtained. The copper(II) complex of L1 has been synthesized and its properties were examined by ES-MS and variable-temperature magnetic susceptibility as well as its crystal structure being determined. Detailed studies have been made on solution chemistry of Cu(II) complex of L2 by pH-potentiometric and fluorometric titration.


Selective stabilization of multiple promoter G-quadruplex DNA by using 2-phenyl-1H-imidazole-based tanshinone IIA derivatives and their potential suppressing function in the metastatic breast cancer.
The G-quadruplex (G4) DNA, which has been developed as a potential anticancer target in drug screening and design, plays a crucial role in the oncogene transcription and translation. Tanshinone IIA derivatives with a planar heterocycle structure may function as G4 stabilizers. We present an innovative case of imidazole-based tanshinone IIA derivatives (1-8) especially compound 4 that improve the selectivity and the binding affinity with G4 DNA and enhance the target tumor inhibition. Cellular and in vivo experiments indicate that the tanshinone IIA derivative 4 inhibits the growth, metastasis, and angiogenesis of triple-negative breast cancer cells possibly through the stabilization of multiple G4 DNAs (e.g., c-myc, K-ras, and VEGF) to induce DNA damage. Further investigation of the intermolecular interaction and the molecular docking indicates that tanshinone IIA derivatives have better selective binding capability to various G4 DNAs than to double-stranded DNA. These findings provide guidance in modifying the molecular structures of tanshinone IIA derivatives and reveal their potential to function as specific G4 stabilizers.


Monolithic anion-exchange chromatography yields rhinovirus of high purity.
For vaccine development, 3D-structure determination, direct fluorescent labelling, and numerous other studies, homogeneous virus preparations of high purity are essential. Working with human rhinoviruses (RVs), members of the picornavirus family and the main cause of generally mild respiratory infections, we noticed that our routine preparations appeared highly pure on analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), exclusively showing the four viral capsid proteins (VPs). However, the preparations turned out to contain substantial amounts of contaminating material when analyzed by orthogonal analytical methods including capillary zone electrophoresis, nano electrospray gas-phase electrophoretic mobility molecular analysis (nES GEMMA), and negative stain transmission electron microscopy (TEM). Because these latter analyses are not routine to many laboratories, the above contaminations might remain unnoticed and skew experimental results. By using human rhinovirus serotype A2 (RV-A2) as example we report monolithic anion-exchange chromatography (AEX) as a last polishing step in the purification and demonstrate that it yields infective, highly pure, virus (RV-A2 in the respective fractions was confirmed by peptide mass fingerprinting) devoid of foreign material as judged by the above criteria.


Biomarker discovery in neurodegenerative diseases: a proteomic approach.
Biomarkers for neurodegenerative disorders are essential to facilitate disease diagnosis, ideally at early stages, monitor disease progression, and assess response to existing and future treatments. Application of proteomics to the human brain, cerebrospinal fluid and plasma has greatly hastened the unbiased and high-throughput searches for novel biomarkers. There are many steps critical to biomarker discovery, whether for neurodegenerative or other diseases, including sample preparation, protein/peptide separation and identification, as well as independent confirmation and validation. In this review we have summarized current proteomics technologies involved in discovery of biomarkers for neurodegenerative diseases, practical considerations and limitations of several major aspects, as well as the current status of candidate biomarkers revealed by proteomics for Alzheimer and Parkinson diseases.


Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management.
Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100,000 adults, and accounts for ∼15% of newly diagnosed cases of leukemia in adults. CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR-ABL fusion oncogene, which in turn translates into a Bcr-Abl oncoprotein. Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib have been approved by the US Food and Drug Administration for the first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses; their impact on long-term survival remains to be determined. For patients who fail frontline therapy, second-line options include second and third generation TKIs. Although second and third generation TKIs are potent and specific BCR-ABL TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as patients comorbidities, disease stage, and BCR-ABL mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib. Allogeneic transplantation remains an important therapeutic option for CML-CP who have failed at least 2 TKIs, and for all patients in advanced phase disease.


Metabolic and process engineering of Clostridium cellulovorans for biofuel production from cellulose.
Production of cellulosic biofuels has drawn increasing attention. However, currently no microorganism can produce biofuels, particularly butanol, directly from cellulosic biomass efficiently. Here we engineered a cellulolytic bacterium, Clostridium cellulovorans, for n-butanol and ethanol production directly from cellulose by introducing an aldehyde/alcohol dehydrogenase (adhE2), which converts butyryl-CoA to n-butanol and acetyl-CoA to ethanol. The engineered strain was able to produce 1.42 g/L n-butanol and 1.60 g/L ethanol directly from cellulose. Moreover, the addition of methyl viologen as an artificial electron carrier shifted the metabolic flux from acid production to alcohol production, resulting in a high biofuel yield of 0.39 g/g from cellulose, comparable to ethanol yield from corn dextrose by yeast fermentation. This study is the first metabolic engineering of C. cellulovorans for n-butanol and ethanol production directly from cellulose with significant titers and yields, providing a promising consolidated bioprocessing (CBP) platform for biofuel production from cellulosic biomass.


Epidemiology and microbiology of cellulitis and bacterial soft tissue infection during HIV disease: a 10-year survey.
Cellulitis and soft tissue infection are underestimated complications of HIV disease. Sixty-seven bacteriologically proven consecutive episodes were identified among 2221 HIV-infected patients hospitalized in a 10-year period, and assessed according to several epidemiological, microbiological and clinical variables. Staphylococcus aureus was the most frequently cultured pathogen (50% of 92 isolates), followed by Pseudomonas spp., Escherichia coli and Streptococcus pyogenes; a polymicrobial infection was present in 38.1% of episodes. Drug addiction (p < 0.003) and male gender (p < 0.04) were significantly associated with the occurrence of these complications, which were community-acquired in 83.6% of cases. While a remarkable variation in the severity of underlying immunodeficiency was shown, hematogenous dissemination occurred in 25.4% of episodes, and proved significantly related to a low CD4+ lymphocyte count, and neutropenia. A 21.7% methicillin-resistance rate was shown among S. aureus isolates. All episodes were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam-aminglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in four patients only. Skin and soft tissue infections are continuing causes of morbidity in HIV-infected patients, even in the highly active antiretroviral therapy era.


Adenovirus or HA-2 fusogenic peptide-assisted lipofection increases cytoplasmic levels of plasmid in nondividing endothelium with little enhancement of transgene expression.
Adenovirus-assisted lipofection has been reported to increase transfection efficiency through mechanisms potentially involving endosome escape and/or nuclear targeting activity. Similarly, transfection with the viral fusogenic peptide HA-2 of the influenza virus hemagglutinin can increase transfection efficiency. However, there are few studies examining the mechanism and intracellular trafficking of these viral and/or viral fusogenic peptide-assisted lipofections. Endosome escape was directly assayed with T7 RNA polymerase bound to plasmid (pTM beta gal) expressing beta-galactosidase under a T7 promoter to detect transcribable plasmid that escapes the endosomal compartment. Lipofection of pTM beta gal with replication-deficient adenovirus (Ad5-null) at a multiplicity of infection (MOI) of 100 and 1000 increased cytoplasmic levels of transcribable plasmid by 24- and 117-fold, respectively, over lipofection alone, without an effect on total plasmid uptake. However, lipofection of pCMV beta gal with Ad5-null at a MOI of 100 and 1000 increased transgene expression only seven- and eight-fold, respectively, over lipofection alone. Thus, a 24-fold increase in endosome escape saturated expression from pCMV beta gal and provided only a seven-fold benefit in nondividing cells, which was not significantly increased with further increases in endosome escape. A cationic form of HA-2 (HA-K(4)) also caused significant enhancements in endosome escape, as detected with the cytoplasmic transcription assay. However, HA-K(4) enhancement of endosome escape did not correlate with transgene expression from pCMV beta gal, consistent with the detection of HA-K(4)-mediated partitioning of plasmid to the insoluble fraction of the cell lysate. These results indicate that enhancement of endosome escape in nondividing cells does not fully alleviate rate limits related to nuclear import of the plasmid.


Hidden Reservoir: An Outbreak of Tuberculosis in Hospital Employees with No Patient Contact.
We describe an outbreak of tuberculosis (TB) in the food preparation area of a hospital, which demonstrates that employees in healthcare settings may serve as potential risks for spread of TB even if they have no direct patient contact. Infect Control Hosp Epidemiol 2016;37:1111-1113.


Nasal Tip Deficiency.
Nasal tip deficiency can be congenital or secondary to previous nasal surgeries. Underdeveloped medial crura usually present with underprojected tip and lack of tip definition. Weakness or malposition of lateral crura causes alar rim retraction and lateral nasal wall weakness. Structural grafting of alar cartilages strengthens the tip framework, reinforces the disrupted support mechanisms, and controls the position of the nasal tip. In secondary cases, anatomic reconstruction of the weakened or interrupted alar cartilages and reconstitution of a stable nasal tip tripod must be the goal for a predictable outcome.


Prevalence of intimate partner violence against infertile women in low-income and middle-income countries: a systematic review and meta-analysis.
Infertility and intimate partner violence (IPV) are of serious concern globally, yet the prevalence of IPV against infertile women has not been quantified at the regional or global level. We aimed to estimate the prevalence of IPV against infertile women and its variation in low-income and middle-income countries (LMICs). We did a systematic literature search of 11 databases for articles published between database inception and Sept 30, 2021, and performed meta-analyses to estimate the pooled prevalence and 95% CI of IPV against infertile women in LMICs. We used subgroup analyses and meta-regressions to explore variation in the prevalence by study period (2010 and before vs after 2010), study region (Africa, west Asia, south Asia, and east Asia), type of infertility (primary or secondary), risk of bias (high, moderate, or low), sample size (continuous variable), and measuring tools (the modified Abuse Assessment Screen, the WHO Violence Against Women instrument, or the revised Conflict Tactics Scales). This study is registered with PROSPERO, CRD42021248448. Of 2661 references identified (2637 via database searches and 24 via secondary searches), 120 full-text articles were reviewed, and we identified 30 relevant studies conducted in nine LMICs between 2000 and 2019. 25 studies met the inclusion criteria for meta-analysis, with a total sample size of 7164 participants. The 12-month prevalence of IPV among infertile women was 36·0% (95% CI 20·4-55·2), compared with a lifetime prevalence of 47·2% (31·7-63·3). The most common type of IPV was psychological violence, with a prevalence of 24·6% (11·3-45·6) over 12 months and 51·5% (38·8-64·0) over a lifetime (slightly higher than the pooled overall rate due to different data sources), respectively; followed by physical violence (11·9% [5·2-25·1] and 20·2% [12·1-31·7]); sexual violence (8·7% [2·6-25·0] and 11·5% [6·1-20·7]); and economic coercion (2·6% [0·4-13·7] and 9·8% [5·7-16·5]). Significant variations of lifetime prevalence estimates were presented by study period (R2=39·46%), region (R2=50·95%), and measuring tools (R2=54·27%). A high prevalence of IPV against infertile women is evident despite heterogeneity across studies. IPV screening, counselling, and structural interventions should be tailored to address this urgent issue at multiple levels of society. China Medical Board and WHO.


[Ophthalmologic vascular occlusions and oral contraceptives].
PURPOSE/MATERIAL AND METHOD: We present two cases of vascular ocular occlusion occurring during oral contraceptive use. Different contraceptive related risk factors are discussed. Although ocular complications are rare, they should be kept in mind since these drugs (contraceptives) are not recommended when vascular occlusion risk factors are present.


The Contribution of Noradrenergic Activity to Anxiety-Induced Freezing of Gait.
Freezing of gait is a complex paroxysmal phenomenon that is associated with a variety of sensorimotor, cognitive and affective deficits, and significantly impacts quality of life in patients with Parkinson's disease (PD). Despite a growing body of evidence that suggests anxiety may be a crucial contributor to freezing of gait, no research study to date has investigated neural underpinnings of anxiety-induced freezing of gait. Here, we aimed to investigate how anxiety-inducing contexts might "set the stage for freezing," through the ascending arousal system, by examining an anxiety-inducing virtual reality gait paradigm inside functional magnetic resonance imaging (fMRI). We used a virtual reality gait paradigm that has been validated to elicit anxiety by having participants navigate a virtual plank, while simultaneously collecting task-based fMRI from individuals with idiopathic PD with confirmed freezing of gait. First, we established that the threatening condition provoked more freezing when compared to the non-threatening condition. By using a dynamic connectivity analysis, we identified patterns of increased "cross-talk" within and between motor, limbic, and cognitive networks in the threatening conditions. We established that the threatening condition was associated with heightened network integration. We confirmed the sympathetic nature of this phenomenon by demonstrating an increase in pupil dilation during the anxiety-inducing condition of the virtual reality gait paradigm in a secondary experiment. In conclusion, our findings represent a neurobiological mechanistic pathway through which heightened sympathetic arousal related to anxiety could foster increased "cross-talk" between distributed cortical networks that ultimately manifest as paroxysmal episodes of freezing of gait. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Could it be osteoarthritis? How dog owners and veterinary surgeons describe identifying canine osteoarthritis in a general practice setting.
Canine osteoarthritis is a common, painful condition that is typically managed in a general practice setting. Osteoarthritis may have significant negative impacts on the welfare of both dogs and their owners. Anticipated early clinical signs of canine osteoarthritis and the preferred route to its diagnosis are well described by veterinary subject experts in published literature. However, little is known about changes owners first recognise in a dog ultimately diagnosed with osteoarthritis, how they make decisions about when to present that dog to a general practitioner, or whether the described diagnostic pathways are followed by general practitioners. The aim of this research was to investigate how dog owners and veterinary surgeons describe identifying and diagnosing canine osteoarthritis. Owners of osteoarthritic dogs were recruited for semi-structured interview, and veterinary surgeons working in general practice were invited to take part in practice-based focus groups. Transcripts from both datasets were thematically analysed using a contextualist epistemology with an ontology based on critical realism to construct convergent themes from latent and semantic codes. Thirty-two interviews were completed with 40 owners from 32 households who discussed 35 dogs with osteoarthritis, and 26 veterinary surgeons engaged in four practice-based focus groups. Owners described identifying a wide range of acute and chronic, typically subtle and intermittent, behavioural and demeanour changes prior to their dogs' osteoarthritis diagnosis. Few attributed these changes to canine osteoarthritis, and some waited many months before presenting their dog to a veterinary practice. Veterinary surgeons described a consistent 'typical osteoarthritis' presentation that they recognised through history taking and clinical examination. Their diagnostic work-up rarely followed that advocated by subject experts for reasons including lack of time and perceptions that it would not change the outcome. Many veterinary surgeons described frustration that some owners did not accept their recommendations to provide analgesia for affected dogs. Short consultation lengths, poor awareness of owner knowledge levels, and lack of recognition of the importance of owners' prior knowledge, beliefs and assumptions may contribute to these consultations being perceived as challenging by some veterinary surgeons and owners. This research demonstrates that veterinary surgeons and owners want dogs with clinical signs of osteoarthritis to be happy and comfortable, but that ineffective communication and lack of trust in the consulting room may be a barrier. Our data identifies many new avenues for future research and improved communication strategies that could facilitate earlier identification and treatment of canine osteoarthritis in general practice.


In by helicopter out by cab: the financial cost of aeromedical overtriage of trauma patients.
Helicopter transport of injured patients is controversial and costly. This study aims to show that a complex trauma algorithm leads to significant aeromedical overtriage at substantial cost. Our secondary outcomes were to compare adjusted mortality and outcomes between air and ground transport and determine predictors of overtriage. A 6-y retrospective analysis was conducted of all trauma activations at a Level I center. Patients were dichotomized by transportation method as well as trauma activation criteria. Overtriage was defined as those who were discharged from the emergency department, medically admitted without injuries, or admitted to observation status only. Overtriage and associated charges were calculated for each patient cohort, and multivariate regression models were created to derive adjusted mortality rates and predictors of overtriage. A total of 4218 patients were treated with 28% arriving by helicopter. Overtriage increased significantly from 51% to 77% with lower tier activation criteria (P < 0.001). Median charges for air-evacuated patients was $10,478 (versus $1008 ground). Eliminating overtriage of air patients would result in a cost savings of $1,316,036 annually. Adjusted mortality between air and ground transport was not significantly different (8.5% versus 10.9%, P = 0.548). Predictors of overtriage included decreasing age, Injury Severity Score, Head Abbreviated Injury Score, nonoperative treatment, and lower tier activation criteria. Significant overtriage (52%) and unnecessary air evacuation of minimally injured patients occurs at great financial cost. Revision of trauma activation protocols may result in more judicious air transport use and significant reductions in health care costs.


GSK-3β inhibition elicits a neuroprotection by restoring lysosomal dysfunction in neurons via facilitation of TFEB nuclear translocation after ischemic stroke.
Lysosomal dysfunction is an essential pathogenesis of autophagic neuronal injury after ischemic stroke. As a result of cerebral ischemia, transcription factor EB (TFEB) is greatly phosphorylated by prominently activated glycogen synthase kinase-3β (GSK-3β). This increased TFEB phosphorylation decreases its nuclear translocation and subsequently leads to reduced lysosomal biosynthesis, which ultimately results in lysosomal dysfunction. The present study is to investigate whether the lysosomal dysfunction in neurons can be restored to alleviate post-stroke damage by GSK-3β inhibition. The GSK-3β activity was inhibited by pre-treatment with CHIR-99021 (CHIR) for 3 days before middle cerebral artery occlusion (MCAO) surgery in rats. Besides, the lysosomal capacity was altered by pre-administration with Bafilomycin A1 (Baf-A1) and EN6, respectively. Twenty-four hours after MCAO/reperfusion, the penumbral tissues were obtained to detect the GSK-3β, cytoplasmic and nuclear TFEB, and proteins in autophagic/lysosomal pathway by western blot and immunofluorescence, respectively. Meanwhile, the infarct volume, neurological deficits and neuron survival were assessed to evaluate the neurological outcomes elicited by GSK-3β inhibition. The results demonstrated that the neurological injury could be significantly mitigated by GSK-3β inhibition in MCAO + CHIR group, compared with that in MCAO group. Moreover, CHIR-facilitated TFEB nuclear translocation in neurons was coupled with reinforced lysosomal activities and attenuated autophagic substrates. However, GSK-3β inhibition-induced neuroprotection was greatly counteracted by Baf-A1-weakened lysosomal capacity. Conversely, EN6-reinforced lysosomal activities further ameliorated the autophagic/lysosomal signaling, and synergistically alleviated the neurological damage upon GSK-3β inhibition after MCAO/reperfusion. Our data suggests that GSK-3β inhibition-augmented neuroprotection against ischemic stroke is elicited by restoring the lysosomal dysfunction in neurons.


Olfactory dysfunction in type II diabetes: Therapeutic options and lessons learned from other etiologies - A scoping review.
Olfactory dysfunction (OD) is highly prevalent amongst type 2 diabetes mellitus (DM2) patients and has many associated health risks. For example, OD can lead to poor nutrition, safety issues related to diminished hazard detection, and increased mortality rates. While limited research exists about therapeutics for DM2-associated OD, recovery of olfactory function is better studied in other pathologic states. The objectives of this scoping review are to synthesize the existing data on interventions for DM2-associated OD and present the evidence for therapies that have been utilized for non-DM2-associated causes of OD. Additionally, the potential therapeutic opportunities for patients with DM2 are explored. A scoping review was conducted with a medical librarian to identify studies investigating treatments of DM2-related OD. 6 databases were searched (Embase, CINAHL, the Cochrane Library, Google Scholar, OVID Medline, and Web of Science). Studies were eligible if the primary discussion involved treatment of olfactory deficits in the context of DM2. All publication dates were included, and studies published in languages other than English were excluded. 3631 articles were identified; 3 articles met inclusion criteria and underwent full text review. Hyperbaric oxygen (HBO), the DPP-4 inhibitor Linagliptin and the GLP-1 agonists Exenatide and Liraglutide are the only therapeutics that have been used in the context of DM2. Only HBO and GLP-1 agonists produced statistically significant improvements in olfactory identification. The literature regarding non-DM2-associated OD supports interventions such as olfactory training, dietary supplements, and intranasal insulin. Specifically, olfactory training was very effective in many contexts such as post-viral and traumatic OD while being affordable and non-invasive. This scoping review of olfactory rehabilitation options for DM2-induced OD demonstrates a paucity of prospective investigations of plausible therapeutics. Additionally, treatments for OD related to non-DM2-associated etiologies, such as olfactory training, are well-studied, efficacious, and should be investigated in the context of DM2. Future investigation has the potential to enhance the quality of clinical intervention for OD and improve short- and long-term outcomes for DM2 patients.


Simultaneous presence, in one serum, of four monoclonal antibodies that might correspond to different steps in a clonal evolution from polyreactive to monoreactive antibodies.
Three monoclonal IgG of different subclasses (IgG1, IgG2, and IgG4) and one IgA1 were isolated from the serum of patient Per suffering from an immunocytic sarcoma. All four monoclonal Ig shared the same N-terminal sequence of their H chains (VH3). Furthermore, their kappa-chains exhibited identical isoelectric charges and N-terminal sequences (VK2) and expressed the same private idiotope. A strong antitubulin activity was found in IgA1Per and in two of the three monoclonal IgGPer. The specificity was restricted to tubulin for IgA1Per and IgG4Per, whereas IgG1Per also displayed significant polyreactive bindings and IgG2Per failed to react with any of the Ag tested. The monoreactive IgG4Per, as well as the polyreactive IgG1Per, bound a large peptide in the central part of both alpha and beta subunits of tubulin (amino acid position 100 to 300). In contrast, the monoreactive IgA1Per bound to a rarely detected epitope close to residue 310 of these subunits. The tubulin epitope recognized by polyreactive IgG1Per was similar to that of germ-line-encoded polyreactive antibodies. It is hypothesized that IgG4Per- and IgA1Per-producing cells derive from the IgG1Per polyreactive clone after somatic events leading to the production of monoreactive antibodies.


Polyploidy, EZH2 upregulation, and transformation in cytomegalovirus-infected human ovarian epithelial cells.
Human cytomegalovirus (HCMV) infection has been implicated in epithelial ovarian cancer (OC). Polyploidy giant cancer cells (PGCCs) have been observed in high-grade serous ovarian carcinoma (HGSOC); they possess cancer stem cell-like characteristics and give rise to progeny cells expressing epithelial-mesenchymal transition (EMT) markers. EZH2 plays a potential oncogenic role, correlating with high proliferative index and tumor grade in OC. Herein, we present the experimental evidence for HCMV as a reprogramming vector that elicited human ovarian epithelial cells (OECs) transformation leading to the generation of "CMV-transformed Ovarian cells" (CTO). The infection with the two high-risk clinical strains, namely HCMV-DB and BL provoked a distinct cellular and molecular mechanisms in infected OECs. EZH2 upregulation and cellular proliferation were curtailed by using EZH2 inhibitors. The HGSOC biopsies were characterized by an elevated EZH2 expression, possessing a strong positive correlation between the aforementioned marker and HCMV. From HGSOC biopsies, we isolated three HCMV clinical strains that transformed OECs generating CTO cells which displayed proliferative potentials in addition to EZH2 upregulation and PGCCs generation; these features were reduced upon EZH2 inhibition. High-risk HCMV strains transformed OECs confirming an HCMV-induced epithelial ovarian cancer model and highlighting EZH2 tumorigenic properties. Our findings might be highly relevant in the pathophysiology of ovarian tumors thereby nominating new targeted therapeutics.


Racial and regional disparities in deaths in breast cancer.
Breast cancer is the second most diagnosed malignancy in American women with a lifetime occurrence of 1 in 8 women in the United States. There has been a dearth of research focusing on regional differences in breast cancer mortality with respect to race in the US. It is crucial to identify regions that are lagging to uplift the outreach of breast cancer care to certain races. Data for this study were obtained from the 2016-2018 Nationwide Inpatient Sample. In-hospital mortality, race and hospital regions for the patients with the primary diagnosis of Malignant Neoplasms of Breast were studied. Baseline characteristics of participants were summarized using descriptive statistics. The patient population was stratified as per race, hospital region, gender, therapy received and family history. Logistic regression was performed to derive the odds ratio while adjusting for different variables. 99, 543 patients with metastatic breast cancer were identified. African Americans (AAs) were found to have the highest reported deaths at 5.54%, followed by Asians and Pacific Islanders at 4.80% and Caucasians 4.09% (p < 0.0001). The odds of dying were significantly higher in the AA population when compared to Caucasian population (OR 1.391 (1.286-1.504)), and the odds were consistently higher across all regions of the US. In terms of regional disparities with respect to race, AA's had highest mortality in the south whereas all other races had the highest mortality in the west. It was seen that races identifying as "others" had significantly higher odds of dying in the Northeast. It is crucial to identify racial differences in the various regions across the US in order to implement appropriate outreach strategies to tackle these disparities.


Identification of a novel allele, HLA-B*52:01:24, by sequence-based typing in a Chinese individual.
HLA-B*52:01:24 has one synonymous nucleotide change from HLA-B*52:01:01:01 at nucleotide 384 (codon 104 Glycine).


Modulation of the effects of extracellular ATP on [Ca2+]i in rat brain microvacular endothelial cells.
This study examined the intracellular regulation of signal transduction initiated by activation of the P2Y2 purinoceptor in a cultured rat brain microvascular endothelial cell line (RBE4). Intracellular free Ca2+ ([Ca2+]i) was monitored in single cells, using FURA-2 fluorimetry. As previously described [Nobles, M., Revest, P.A., Couraud, P.-O., Abbott, N.J., 1995. Characteristics of nucleotide receptors that cause elevation of cytoplasmic calcium in immortalized rat brain endothelial cells, RBE4, and in primary cultures. Br. J. Pharmacol., 115, 1245-1252], extracellular ATP (100 microM, 20 s) evoked a transient increase in intracellular free calcium concentration ([Ca2+]i). The amplitude of the Ca2+ transient evoked by ATP decreased with successive applications (desensitisation), as expected for a P2 purinoceptor. The modulation of the Ca2+ signal downstream to the activation of the ATP receptor was investigated, using agents selected for their ability to interfere with the intracellular pathways activated by ATP. The amplitude of the Ca2+ transient observed on the second application of ATP was compared in the presence and absence of these agents. The Ca2+ transient triggered by ATP was decreased by the inhibitor of nitric oxide synthesis, N-omega-nitro-L-arginine methyl ester (L-NOARG). The inhibition induced by 100 microM L-NOARG was reversed by coapplication of the permeant cGMP analogue 8-brcGMP (100 microM). 8-BrcGMP caused a transient increase in [Ca2+]i when applied alone, and a dose-dependent inhibition of the increase in [Ca2+]i elicited by ATP. Indomethacin, an inhibitor of prostaglandin synthesis, inhibited the response to ATP. The inhibition caused by 10 microM indomethacin was reversed by coapplication of the permeant analogue of cAMP, 8-brcAMP (100 microM). 8-BrcAMP caused a transient rise in [Ca2+]i when applied alone, and a dose-dependent inhibition of the Ca2+ response evoked by ATP. The non-permeant cyclic nucleotides cAMP and cGMP did not affect the desensitising response to ATP, nor did they reverse the inhibitory actions of L-NOARG or indomethacin. It is concluded that cyclic nucleotides, nitric oxide, and prostaglandin synthesis pathways are able to interact with the Ca2+ second messenger pathway in rat brain endothelial cells activated by extracellular ATP.


Measuring single-virus fusion kinetics using an assay for nucleic acid exposure.
The kinetics by which individual enveloped viruses fuse with membranes provide an important window into viral-entry mechanisms. We have developed a real-time assay using fluorescent probes for single-virus genome exposure than can report on stages of viral entry including or subsequent to fusion pore formation and prior to viral genome trafficking. We accomplish this using oxazole yellow nucleic-acid-binding dyes, which can be encapsulated in the lumen of target membranes to permit specific detection of fusion events. Since increased fluorescence of the dye occurs only when it encounters viral genome via a fusion pore and binds, this assay excludes content leakage without fusion. Using this assay, we show that influenza virus fuses with liposomes of different sizes with indistinguishable kinetics by both testing liposomes extruded through pores of different radii and showing that the fusion kinetics of individual liposomes are uncorrelated with the size of the liposome. These results suggest that the starting curvature of such liposomes does not control the rate-limiting steps in influenza entry.


[Immunology and deafness. Manifestations of relapsing polychondritis in the ENT area. A case report].
Relapsing polychondritis is a rare episodic systemic disorder characterised by recurrent, widespread, and potentially destructive inflammatory lesions involving cartilaginous structures, the cardiovascular system, and organs of special sense, such as the eyes and ears. Although the aetiology is unknown and its pathogenesis is incompletely understood, experimental evidence strongly suggests that immunological mediated mechanisms are operative. The following case report adds some considerations to the discussion about the immunopathology of the inner ear.


Entropic electrolytes for anodic cycloadditions of unactivated alkene nucleophiles.
Unactivated alkenes were previously found to be effective carbon nucleophiles for anodic cycloadditions in lithium perchlorate/nitromethane electrolyte solution. Herein, 7Li NMR analysis and calorimetric studies clearly illustrate that the entropic effect is essential for these anodic cycloadditions, which has led to the successful screening of novel effective electrolytes.


Caspofungin in a pediatric patient with persistent candidemia.
To describe the response of a child with persistent fungemia to caspofungin, a member of the echinocandin class of antifungals. Descriptive case report. Pediatric intensive care unit at a university teaching hospital. A 3-yr-old female with persistent candidemia. After >5 wks of persistent candidemia, caspofungin was added to an antifungal regimen that included amphotericin B and flucytosine. The addition of caspofungin resulted in rapid clearance of the candidemia. The child recovered without evidence of further fungal infection or overt toxicity. Caspofungin was administered safely in this pediatric patient and possibly contributed to her clinical improvement. Caspofungin may be considered in children with severe persistent fungal infections that are not responsive to standard therapy. More study in pediatric patients is necessary before recommending its general use.


Characterization of human alpha fetoprotein charge microheterogeneity during fetal development.
Aliquotes of human amniotic fluid (AF), fetal serum (FS), and cord blood (CB) were obtained as by-products of routine clinical diagnostic procedures at term or in the second trimester of pregnancy. When samples of CB were applied to a pH 5.5-4 chromatofocusing gradient, three isoforms of AFP could be resolved; a pl 4.57 form (isoform IA, 52% AFP), a pl 4.27 form (isoform IB, 43% AFP), and one species that was bound to the column but could be eluted with 1.0 M NaCl (isoform II, pl less than 4.00, 5% AFP). Term AF displayed a profile similar to that observed in term CB. When samples of 15-20-week gestation AF were chromatofocused, the immunoreactive AFP recovered was distributed between isoform IA and IB (60%) and isoform II (40%). FS and AF obtained from same pregnancy (23-26 weeks) displayed an identical chromatofocusing profile. Aliquotes of AF subjected to conA revealed 83% reactive variants compared with greater than 95% reactive variants for CB. FS displayed a conA profile identical to CB. When individual CB charge isoforms were isolated and subjected to conA analysis, greater than 97% of the AFP bound to conA. In contrast, when AFP isoform IA and IB were isolated from midgestation AF, approximately 22% of the AFP did not bind to the lectin while 100% of isolated AFP isoform II eluted as the reactive variant. These data suggest that human AFP exists as at least three charge and two lectin variants and that the charge profile may change during fetal development.


Performance evaluation of a wood-chip based biofilter using solid-phase microextraction and gas chromatography-mass spectroscopy-olfactometry.
A pilot-scale mobile biofilter was developed where two types of wood chips (western cedar and 2 in. hardwood) were examined to treat odor emissions from a deep-pit swine finishing facility in central Iowa. The biofilters were operated continuously for 13 weeks at different air flow rates resulting in a variable empty bed residence time (EBRT) from 1.6 to 7.3 s. During this test period, solid-phase microextraction (SPME) PDMS/DVB 65 microm fibers were used to extract volatile organic compounds (VOCs) from both the control plenum and biofilter treatments. Analyses of VOCs were carried out using a multidimentional gas chromatography-mass spectrometry-olfactometry (MDGC-MS-O) system. Results indicated that both types of chips achieved significant reductions in p-cresol, phenol, indole and skatole which represent some of the most odorous and odor-defining compounds known for swine facilities. The results also showed that maintaining proper moisture content is critical to the success of wood-chip based biofilters and that this factor is more important than media depth and residence time.


Standard donor lung procurement with normothermic ex vivo lung perfusion: A prospective randomized clinical trial.
Ex vivo lung perfusion (EVLP) was primarily developed for evaluation of impaired donor lungs. The good clinical results raise the question for its possible impact on lungs meeting standard criteria. Before application of EVLP on such lungs enters routine clinical practice, it must be demonstrated whether EVLP would affect or improve outcome when used in standard donor lungs. We performed a prospective randomized trial to investigate the role of EVLP in standard lung transplantation (Tx). This prospective randomized clinical trial compared patients who underwent Tx with ex vivo evaluated donor lungs with an equivalent patient population without previous EVLP. From October 2013 to May 2015, 193 lung Tx were performed at the Medical University of Vienna. During this period, 80 recipient/donor pairs that met the inclusion criteria were included in this trial, 41 pairs in the control group, and 39 in the EVLP group. In the EVLP group, 4 lungs (10.2%) ultimately did not qualify for Tx and were rejected for lung Tx owing to technical reasons (n = 2) and quality criteria (n = 2). Donor and recipient characteristics were comparable in both groups. Total cold ischemic time in the EVLP group was significantly longer for both implanted lungs (first side, 372 minutes vs 291 minutes, p < 0.001; second side, 437 minutes vs 370 minutes, p = 0.001); median duration of surgery showed no differences (277 minutes vs 275 minutes). Median oxygen partial pressure/fraction of inspired oxygen ratio at 24 hours after Tx was 516 (range, 280-557) in the EVLP group and 491 (range, 352-575) in the control group (p = 0.63). Incidence of primary graft dysfunction >1 was lower in the EVLP group at all time points compared with the control group (24 hours, 5.7% vs 19.5%, p = 0.10), and need for post-operative prolonged extracorporeal membrane oxygenation was lower in the EVLP group (5.7% vs 12.2%, p = 0.44). Short-term clinical outcomes did not differ between recipients in the 2 groups. Patients remained intubated (1.6 days vs 1.6 days, p = 0.67), in the intensive care unit (6 days vs 6 days, p = 0.76), and in the hospital (23 days vs 19 days, p = 0.42) for a comparable period of time. The 30-day survival was 97.1% vs 100% (p = 0.46). This study provides evidence that EVLP can safely be used in standard donor lungs. Functional results and perioperative outcome are comparable to those achieved with standard donor lung preservation techniques. As an evaluation tool, EVLP allows clinicians to identify and to possibly exclude lungs with functional impairment. Finally, EVLP can safely extend total preservation time.


A comparison of carbamazepine divitabs with carbamazepine normal formulation in psychiatric and oligophrenic patients. Preliminary pharmacokinetic results.
In an open, randomized, two-centre, cross-over study 20 patients formerly adjusted to a stable oral twice daily 200-600 mg carbamazepine dose, used ordinary tablets and divitabs (a new sustained-release formulation) for periods of three weeks, whereafter the serum level courses of carbamazepine and its metabolite carbamazepine-10,11-epoxide were measured. The mean peak/mean trough carbamazepine-serum concentration ratio was slightly lower after the intake of divitabs in comparison to normal formulation: 1.14 +/- 0.447 versus 1.23 +/- 0.545 (mean +/- SD). The mean trough levels of carbamazepine and its metabolite were 9% and 16% lower in the case of divitabs. In patients with peak/trough carbamazepine-serum level ratios of at least 1.30 after the intake of normal formulation, divitabs had a significant advantage.


Expression of genes containing the IgH enhancer in non-lymphoid cells.
Nuclear run-on experiments were used to verify the hypothesis that extinction of expression of Ig synthesis in L cell x myeloma hybrids occurs at the transcriptional level. Both the H chain enhancer and promoter have been shown to be the targets for extinction in myeloma x T cell hybrids. To examine the expression of genes containing the immunoglobulin heavy chain gene (IgH) enhancer in stably transfected non-B cells, we used a vector with two selectable markers, one of which (gpt providing resistance to mycophenolic acid) either lacks an enhancer or contains the IgH enhancer, the other (neo providing resistance to G418) contains an SV40 enhancer. Stable transfectants of both myeloma (J558L) and L cells selected using G418 were tested to determine if they are also mycophenolic acid resistant. When the IgH enhancer is positioned 3' to the gpt gene, transfected J558L are mycophenolic acid resistant whereas stably transfected L-cells are mycophenolic acid sensitive. However, when large numbers of L cell transfectants are exposed to mycophenolic acid for a prolonged period, resistant subclones emerge. When the 700-bp IgH enhancer fragment was used, the majority of the subclones examined had amplified the vector, between 3 and 38 copies; when a 400-bp subfragment was used no change in the integrated genes was seen. In both cases, in the mycophenolic acid resistant subclones, increased accumulation of gpt and neo mRNA is seen. However, the gpt specific transcripts are heterogeneous in size whereas the neo transcripts are of a discrete size. The heterogeneity of the gpt transcripts results at least in part from heterogeneous initiation. When HXM-resistant L cell subclones are fused to the gamm 2b, k myeloma 4T001, extinction of Ig production occurs; therefore these cells are still capable of negatively regulating Ig expression. These results are discussed from the standpoint of both cis and trans regulatory elements and factors in non-lymphoid cells.


Assessment of changes in biophysical parameters by dermocosmetic emulgel loaded with Cinnamomum tamala extract: A split-faced and placebo-controlled study.
Phenolic and flavonoid compounds found in plants alleviate the photo-damaging skin conditions by playing a major role in skin rejuvenation. The aim of the study was to explore the cosmeceutical effects of Cinnamomum tamala extract. Recent research was aimed to quantify phenols and flavonoids in the natural extract of C tamala leaves, to develop its phyto-cosmetic emulgel and to assess effects of emulgel on healthy human skin. Phenols and flavonoids in C tamala (CT) extract were quantified by using ELISA assay. Emulgel formulation loaded with 4% C tamala (CT emulgel) was developed, and its cosmetic effects were evaluated on the cheeks of 13 healthy female test volunteers by comparing with placebo (base). Facial parameters including melanin, erythema, sebum, and visible facial pores (size and area) were studied by using Mexameter® , Sebumeter® , and VisioFace® at regular interval for 90 days. Total phenolic content and total flavonoids content of C tamala leaves extract were found to be 73.08 ± 0.0078 mg GAE/g and 52.63 ± 0.0060 mg QE/g CT extract respectively. As compared to placebo (base), CT emulgel was found to be significantly (P ≤ .05) effective in minimizing skin photo-damaging effects by reducing the levels of melanin, erythema, and sebum and size and count of both fine and large facial pores. Cinnamomum tamala leaves extract, being a rich source of phenols and flavonoids minimized the photo-damaging effects by reducing skin melanin, erythema, and excess sebum; improving the skin imperfections by reducing facial pore count and area as assessed by advanced imaging and bioengineering techniques.


Unraveling the Cyclization of l-Argininosuccinic Acid in Biological Samples: A Study via Mass Spectrometry and NMR Spectroscopy.
Since l-argininosuccinic acid (ASA) is the characteristic biomarker for the diagnosis of certain diseases, its reliable detection in complex biological samples is necessary to obtain a complete evaluation with greater specificity and accuracy. ASA can undergo intramolecular cyclization, yielding an equilibrium with the resulting cyclic forms, which can predominate under different analytical conditions. In this work, the appearance and transformation of the different forms of ASA have been studied and a strategy for targeted screening analysis of ASA and its cyclic forms using capillary electrophoresis-electrospray ionization-time-of-flight mass spectrometry (CE-ESI-TOF-MS) has been developed. The data and spectra obtained allowed us to gain further insight into accurate identification, concluding that there is a dynamic equilibrium depending on the pH. Moreover, one- and two-dimensional NMR spectroscopy experiments have allowed us to determine the predominant tautomeric structure for the major cyclic ASA derivative, confirming the importance of intramolecular hydrogen bonds.


In situ phytoremediation of heavy metal-contaminated soil and groundwater: a green inventive approach.
The heavy metal contamination of soil and groundwater is a serious threat to environment worldwide. The survival of human being primarily relies upon soil and groundwater sources. Therefore, the remediation of heavy metal-contaminated soil and groundwater is a matter of utmost concern. Heavy metals are non-degradable and persist in the environment and subsequently contaminate the food chain. Heavy metal pollution puts a serious impact on human health and it adversely affects our physical body. Although, numerous in situ conventional technologies have been utilized for the treatment purpose, but most of the techniques have some limitations such as high cost, deterioration of soil properties, disturbances to soil native flora and fauna and intensive labour. Despite that, in situ phytoremediation is a cost-effective, eco-friendly, solar-driven and novel approach with significant public acceptance. The past research reflects rare discussion addressing both (heavy metal in situ phytoremediation of soil and groundwater) in one platform. The present review article covers both the concepts of in situ phytoremediation of soil and groundwater with major emphasis on health risks of heavy metals, enhanced integrated approaches of in situ phytoremediation, mechanisms of in situ phytoremediation along with effective hyperaccumulator plants for heavy metals remediation, challenges and future prospects.


Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury.
Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions. Wild-type and miR-30a-/- neonatal mice were exposed to hyperoxia [95% FiO2, postnatal day [PND1-5] or room air before being euthanized on PND21. Alveolarization, pulmonary microvascular development, differences in lung transcriptome, and miR-30a expression were assessed in lungs from WT and miR-30a-/- mice of either sex. Blood transcriptomic signatures from preterm newborns (with and without BPD) were correlated with WT and miR-30a-/- male and female lung transcriptome data. Significantly, the sex-specific differences observed in WT mice were abrogated in the miR-30a-/- mice upon exposure to hyperoxia. The loss of miR-30a expression eliminated the protective effect in females, suggesting that miR-30a plays an essential role in regulating alveolarization and angiogenesis. Transcriptome analysis by whole lung RNA-Seq revealed a significant response in the miR-30a-/- female hyperoxia-exposed lung, with enrichment of pathways related to cell cycle and neuroactive ligand-receptor interaction. Gene expression signature in the miR-30a-/- female lung associated with human BPD blood transcriptomes. Finally, we showed the spatial localization of miR-30a transcripts in the bronchiolar epithelium. miR-30a could be one of the biological factors mediating the resilience of the female preterm lung to neonatal hyperoxic lung injury. A better understanding of the effects of miR-30a on pulmonary angiogenesis and alveolarization may lead to novel therapeutics for treating BPD.