Degradation of trichloroethylene in aqueous solution by FeS2 catalyst under innovative oxic environments.
Rapid growth and industrialization have become a major threat to water contamination with carcinogenic chlorinated hydrocarbons such as trichloroethylene (TCE). Therefore, this study aims to assess the TCE degradation performance through advanced oxidation process (AOP) using catalyst FeS2 in combination with oxidants persulfate (PS), peroxymonosulfate (PMS), and hydrogen peroxide (H2O2) in PS/FeS2, PMS/FeS2, and H2O2/FeS2 systems, respectively. TCE concentration was analyzed using gas chromatography (GC). The results found the trend for TCE degradation by the systems was PMS/FeS2>PS/FeS2>H2O2/FeS2 (99.84, 99.63, and 98.47%, respectively). Degradation of TCE was analyzed at different pH ranges (3-11) and maximum degradation at a wide pH range was observed for PMS/FeS2. The analysis using electron paramagnetic resonance (EPR) and scavenging tests explored responsible reactive oxygen species (ROS) for TCE degradation and found that HO• and SO4-• played the most effective role. The results of catalyst stability showed PMS/FeS2 system the most promising with the stability of 99, 96 and 50% for the first, second and third runs, respectively. The system was also found efficient in the presence of surfactants (TW-80, TX-100, and Brij-35) in ultra-pure water (89.41, 34.11, 96.61%, respectively), and actual groundwater (94.37, 33.72, and 73.48%, respectively), but at higher reagents dosages (5X for ultra-pure water and 10X actual ground water). Furthermore, it is demonstrated that the oxic systems have degradation capability for other TCE-like pollutants. In conclusion, due to its high stability, reactivity, and cost-effectiveness, PMS/FeS2 system could be a better choice for the treatment of TCE contaminated water and can be beneficial for field application.


Patient experience and satisfaction with remote memory assessment: Responding to clinical need in times of COVID-19 restrictions.
The suspension of memory services during the COVID-19 pandemic delayed dementia diagnosis and access to early intervention. Some services responded to the challenge by developing a remote memory assessment pathway to comply with reduced social contact measures to protect vulnerable patients. The aim of the study was to establish whether remote model is considered a satisfactory experience within the context of the COVID-19 pandemic and to understand the factors associated with patient and carer satisfaction of remote pathway. 73 participants recruited from patients referred to memory clinic in West Sussex, who were assessed over a video or telephone. Participants completed an 11-item questionnaire capturing satisfaction across a range of elements, contextual items (the impact of the pandemic, loneliness, previous experience of using teleconference technology and diagnosis), as well as 3 dimensions from Patient Experience Questionnaire. Descriptive statistics are reported at a whole sample level, separated by patient and carer status. A hypothesis driven set of bivariate analyses (Spearman's rank) was used to understand the association between overall satisfaction and key independent factors across the whole sample. 73 participants were typically older adults (M=68.5, SD=13.3) and female (n=40, 54.8%). The patient was more likely to be older, feel lonely within the past week and to have used video call software when compared to the carer (p> 0.05). Participants were generally satisfied with the remote pathway with 95.8% (n=69) agreeing or strongly agreeing with the statement "Overall, I was satisfied with the assessment". Patients and carers did not significantly differ on any satisfaction response, apart from the ease of use of technology, in which carers were more likely to find the technology easy to use (U= 432.5; p=0.01). Worry about contracting COVID and communication experience was positively associated with overall satisfaction, whilst perceived communication barriers were significantly negatively associated with overall satisfaction. Remote memory assessment was a positive and satisfactory experience for most patient and carers. The remote pathway should be considered as an option available during and beyond the pandemic to improve access and patient choice of assessment modality.


Nuclear deoxyribonucleic acid polymerases of liver.
Hepatic nuclei that are isolated in aquenous solutions of low ionic strength or glycerol contain all or nearly all the nonmitochondrial DNA polymerase activity of the cell. The presence of polymerase activity in the cytoplasm is due to extraction of nuclear enzymes by buffer and inorganic salts. Even with low ionic strength solutions, some leaching of nuclear enzymes occurs if the concentration of liver in the homogenizing medium is greater than 10%. As defined by sucrose gradient analysis, the normal adult rat liver nucleus contains mainly or entirely a single species of DNA polymerase (3.2 S) whereas the regenerating nucleus after 70% hepatectomy has an additional enzyme (7.1 S). The total activity of regenerating nuclei is about twice the normal value. The increase resides in the 7.1 S activity. The 7.1 S DNA polymerase had been purified partially from regenerating liver nuclei (isolated in low ionic strength solutions) and cytosol (prepared under conditions of nuclear enzyme extraction). The properties of the activity from the two sources are indistinguishable. A mixture of albumin and spermidine enhances by several-fold the activities of the 3.2 S and 7.1 S DNA polymerases. In the presence of spermidine, but not in its absence, the activity of the 7.1 S DNA polymerase is strictly proportional to the amount of the enzyme preparation.


Studies of nuclear proteins in the skeletal muscle of the cardiomyopathic Syrian hamster.
Nonhistone nuclear proteins (NHNP) were isolated from the skeletal muscle of dystrophic hamsters and their respective paired controls. These proteins were extracted with phenol and fractionated by polyacrylamide gel electrophoresis. One-dimensional gel electrophoresis using either sodium-dodecylsulfate or isoelectrofocusing revealed quantitative changes between the two groups. An improved resolution using a two-dimensional system showed both quantitative and very limited qualitative differences. There are differences in proteins focusing at pH 5.0, molecular weight 55,000, in the dystrophic tissue. In addition proteins from dystrophic muscle focusing between pH 5.0 and 7.0, molecular weight 45,000, and proteins focusing between pH 7.0 and 9.0, molecular weights 35,000--45,000 and 60,000--70,000 were reduced as compared to the controls. There were no detectable differences in the electrophoretic patterns between the two groups of proteins derived from skeletal muscle homogenates. The differences in NHNP appear to be reflections of alterations in the nuclear composition of the dystrophic muscle cell. Some of these differences may represent changes secondary to the muscle disease. However, if NHNP interacting with DNA play a major role in the control of genetic expression, some of the manifestations of hamster dystrophy could be due to a different constitution of NHNP in the skeletal muscle.


Establishment of Plantago lanceolata L. and Plantago major L. among grass : II. Shade tolerance of seedlings and selection on time of germination.
Establishment of Plantago lanceolata and P. major ssp major among grass was studied in a field experiment in which survival and selection on date of seedling emergence and plant size was investigated in relation to the vegetation structure. P. major - in contrast to P. lanceolata - was not able to establish itself in grass because of its lower competitive ability caused by later germination, smaller seedling size, and shorter leaves. In both species there was selection for early germination. For P. lanceolata a significant correlation was found between the strength of selection and the light climate, determined by the structure of the grass sward. Plants that germinated early were at an advantage because they were larger, especially the leaves, when compared with plants that germinated late. It seems likely that selection was mainly by competition for light. Contrary to expectation P. major-seedlings had a higher shade tolerance than those of P. lanceolata. The performance of both species is discussed in relation to their different life strategies.


Depot medroxyprogesterone acetate: implications for weight status and bone mineral density in the adolescent female.
Depot medroxyprogesterone acetate (DMPA) is an effective and easy-to-use contraceptive method for adolescents. However, recent literature suggests that overweight teens may be at increased risk for weight gain while on this contraceptive method, and decreases in bone mineral density have been documented in adolescents on DMPA, particularly with longer duration of use. Consideration of this new literature on DMPA and its implications for clinical practice must be done in the context of the United States having the highest adolescent pregnancy rate in the industrialized world. Hence, potential DMPA risks need to be weighed against the risk of unintended pregnancy in an adolescent.


Protein kinase inhibitors of the quinazoline class exert anti-cytomegaloviral activity in vitro and in vivo.
Cytomegalovirus infection is associated with severe disease in immunocompromised individuals. Current antiviral therapy faces several limitations. In a search of novel drug candidates, we describe here the anti-cytomegaloviral properties of two compounds of the chemical class of quinazolines, gefitinib (Iressa) and Ax7396 (RGB-315389). Both compounds showed strong inhibitory effects in vitro against human and animal cytomegaloviruses with IC(50)s in a low micromolar range. Cytotoxicity did not occur at these effective concentrations. The antiviral mode of action was based on the inhibition of protein kinase activity, mainly directed to a viral target kinase (UL97/M97) in addition to cellular target candidates. This was demonstrated by a high sensitivity of the respective protein kinases in vitro and by infection experiments with viral mutants carrying genomic alterations in the ORF UL97/M97 modulating viral drug sensitivity. In a guinea pig model, gefitinib showed inhibition of cytomegaloviral loads in blood and lung tissue. Importantly, the rate of mortality of infected animals was reduced by gefitinib treatment. In contrast to the in vitro data, Ax7396 showed no significant antiviral activity in a mouse model. Further in vivo analyses have to assess the potential use of gefitinib in the treatment of cytomegalovirus disease.


Implementation and evaluation of a quality improvement project: carepaths for Early Psychosis Intervention Programmes in Northeastern Ontario.
This study aims to describe the implementation and evaluation of a quality improvement project, which aimed to standardize services and documentation across several district Early Psychosis Intervention Programmes in a rural region of Canada (Northeastern Ontario). A Carepath for early psychosis intervention (EPI), which outlined best practice EPI care pathways, was implemented across 12 EPI programme sites. It was hypothesized that the proportion of best practice interventions provided across the district programmes would increase after the implementation of the Carepath initiative and that documentation would be standardized. Pre-Carepath and post-Carepath chart audits evaluated the provision and documentation of EPI best practices that were specified in the Carepath. Pre-audits and post-audits were completed on 110 and 108 client files, respectively. Chi-squared tests revealed that the post-audit frequencies were significantly higher than the pre-audit frequencies for two of the 12 EPI best practices that were evaluated (i.e. assessed impact on family and assessment of substance use). Standardization of documentation did not improve significantly. The results are discussed in the context of barriers to implementing and evaluating the Carepaths. Various individual and agency level barriers are identified (e.g. staff resistance, resources and agency documentation parameters), and strategies to overcome them are discussed. It is concluded that, despite barriers to implementation and evaluation, Carepaths can be a useful tool for standardizing services and documentation across a network of EPI programmes and guiding programme evaluation and quality assurance.


Hepatitis B virus is associated with the clinical features and survival rate of patients with intrahepatic cholangiocarcinoma.
The pathogenesis and development of intrahepatic cholangiocarcinoma (ICC) may be triggered by hepatitis B virus (HBV). We conducted this retrospective study to explore the potential association between HBV infection and the clinical features and survival rate of patients with ICC. Patients with ICC who had undergone a curative resection were enrolled and divided into three groups according to the seropositivity of the hepatitis B surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). The groups were as follows: group I, HBsAg (+)/anti-HBc (+); group II, HBsAg (-)/anti-HBc (+); group III HBsAg (-)/anti-HBc (-). The symptoms, pathologic findings, and outcome information of all patients were retrospectively reviewed. The patient sera were isolated to detect anti-HCV, HBsAg, and anti-HBc. Surgical specimens were assessed by hematoxylin and eosin (HE) staining. The expression of cytokeratin 7 was evaluated by immunohistochemistry. Finally, the 1-, 3-, and 5-year cumulative survival rates were analyzed. Ninety-seven patients with ICC were enrolled in group I (n=26); group II, (n=50), and group III (n=21). A total of 26.8% (26/97) patients with ICC were positive for HBsAg. Patients with HBV-associated ICC tended to be younger (P=0.018), have lower CA19-9 levels (P=0.000), a higher alpha fetal protein (AFP) level (P=0.012) and prothrombin time (P=0.030), a higher risk of hepatic cirrhosis (P=0.001), and poor differentiation (P=0.028). The 1-, 3-, and 5-year cumulative survival rates for patients within the three groups were as follows: 27.3%, 0%, and 0% for group I, respectively; 62.5%, 30.0%, and 0% for group II, respectively; and 87.5%, 66.7%, and 50.0% for group III, respectively. The results were significantly different in an overall comparison (P=0.000). Patients with HBV-associated ICC showed different clinicopathological features and lower survival rates compared to patients with ICC without HBV infection.


The profit of senescence in phytoseiid mites.
A long post-reproductive period in females under optimal conditions is common among phytoseiid mites which are specialized predators of Tetranychus-species. The resulting long life span provides the possibility to postpone or delay egg production during periods of prey scarcity, theoretically in both virgin and fertilized females. The latter are better as colonists. These specialized predators are also the most prolific phytoseiids. The unusual combination of large reproductive capacity and long life might be explained as an adaptation to widely fluctuating prey densities.


Serum concentration of placental proteins in non-pregnant and pregnant subjects.
Chorionic gonadotrophin (hCG) and Schwangerschaftsprotein 1 (SP1) were measured in 35 menstrual cycles in 20 women. During the follicular phase, 3 samples were positive for hCG and two of these were also positive for SP1. All these positives occurred on the day of ovulation or immediately before. In the luteal phase 25 specimens showed both hCG and SP1 and two showed only SP1, the positive results occurring 3-15 days after ovulation. The placental proteins were also measured in a further eight women who became pregnant. The pattern in these was quite different. The first positives were detected 8 days after ovulation and by 12 days all the subjects were positive for both proteins. Thereafter both proteins increased sharply in concentration. A group of 139 subjects who, on biological grounds, could not have conceived, showed no positive results.


Decreased flow-mediated dilation in healthy Chinese adolescent with a family history of type 2 diabetes.
Endothelial dysfunction appears early in the development of cardiovascular disease and is associated with type 2 diabetes. We, therefore, tested the hypothesis that endothelial dysfunction is already present in healthy Chinese adolescent participants at risk of type 2 diabetes and associates with physical activity. We investigated the flow-mediated dilation in 65 first-degree relatives (normal tension, normal glucose tolerance) and 62 age-, sex- and BMI-matched controls without a family history of type 2 diabetes by ultrasound. Physical activity level was assessed using the Global Physical Activity Questionaire and type 2 diabetes family history through self-reporting. The association between physical activity and flow-mediated dilation was evaluated by Pearson correlations and multiple regressions in adolescents with or without a family history of type 2 diabetes. Female adolescents display better flow-mediated dilation than males. Adolescents with a family history of type 2 diabetes had significantly impaired flow-mediated dilation than healthy controls. Among the parameter detection in the blood, the flow-mediated dilation is only positively associated with high-density lipoprotein cholesterol level, but not others. Interestingly, flow-mediated dilation is positively corrected with physical activity scores in both the male and female adolescents, while slightly impaired but not significant in adolescents with a family history of type 2 diabetes. Studies in adolescents are important to understand the early pathogenesis of type 2 diabetes. Findings of this investigation suggest that family history of type 2 diabetes may play a role in regulating the vascular function in Chinese adolescents. Given the impaired flow-mediated dilation in individuals with family history and the effects of physical activity in improved flow-mediated dilation, people with a family history of type 2 diabetes may need higher physical activity levels to attenuate their susceptibility to impaired flow-mediated dilation.


The C-terminal domain of p53 catalyzes DNA-renaturation and strand exchange toward annealing between intact ssDNAs and toward eliminating damaged ssDNA from duplex formation through preferential recognition of damaged DNA by a duocarmycin.
The C-terminal domain of p53 may bind single-stranded (ss) DNA ends and catalyze renaturation of ss complementary DNA molecules, suggesting a possible direct role for p53 in DNA repair (Proc. Natl. Acad. Sci. USA, 92, 9455-9459, 1995). We found that DU-86, a duocarmycin derivative which alkylates DNA, bound ssDNA and enhanced the DNA binding activity of the p53 C-terminus. DU-86 weakened p53-mediated catalysis of complementary ssDNA renaturation. p53 C-terminus catalyzed DNA strand transfer toward annealing between intact ssDNAs and toward eliminating DU-86-damaged ssDNA from duplex formation. These results suggest that p53, via the C-terminal domain, may play a direct role in DNA repair by preferential recognization and elimination of damaged DNA.


Phenological calendar in some walnut genotypes grown in Romania and its correlations with air temperature.
Phenology is the study of periodic biological events in the plant world that are influenced by the environment. Temperature increase in spring season can advance the spring phases, but warming in autumn and winter may slow the fulfillment of chilling requirements and lead to later onset of spring events. This study examined different genotypes of walnut trees under environmental conditions, and measured the cold demand, heat requirements, and average time from budburst till flowering for 28 walnut genotypes. The information obtained provides a better understanding of the phenological temperature response of walnuts that will be useful for walnut production and will also contribute to the development of adaptation measures in the light of the expected climate change.


Effects of low temperature and highlight stress on lipid accumulation and cell structure of Tropidoneis maxima.
Tropidoneis maxima is a marine diatom with a rapid growth rate that produces high levels of lipids. To explore whether the lipid content could be further enhanced, cultures were first incubated under optimal conditions and then stressed under low temperature (10°C), a high light intensity level (80 μmol/m2 ·s), and the two factors together (interaction treatment). The results indicated that high light intensity and the temperature-light interaction exhibited greater impacts on lipid synthesis of T. maxima than low temperature. The two stress treatments increased lipid content by 17.16% and 16.6% compared to the control. In particular, higher biomass concentration was obtained with high light intensity (1.082 g L-1 ) and low temperature (1.026 g L-1 ). Moreover, high light intensity (9.06%) and interaction (10.3%) treatments yielded lower starch content compared to low temperature (14.27%) at the end of the stress culture. After 3 days of stress culture, the high light intensity treatment resulted in a 97.01% increase in cell wall thickness and an 18.46% decrease in cell diameter. The results suggest that high light intensity stress on T. maxima would open a new approach to cost-effective biolipid production.


Molecular effects of polystyrene nanoplastics toxicity in zebrafish embryos (Daniorerio).
Plastics pose a health hazard to living beings and the environment. Plastic degradation produces nano-sized plastic particles (NPs) that end up in terrestrial and aquatic ecosystems, including oceans, rivers, and lakes. Their presence in air, drinking water, sediments, food, and personal care products leads to a variety of exposure routes for living beings, including humans. The toxicity mechanisms of these nanomaterials (NMs) in living organisms and ecosystems are currently unknown, making it a priority to understand their effects at the molecular and cellular levels. The zebrafish (Zf) (Danio rerio) is a model organism which has a high homology with humans and has been widely used to assess the hazard of different xenobiotics. In this study, the expression changes of different genes in 120 hpf Zf embryos (Zfe) after exposure to polystyrene (PS) NPs (30 nm) at concentrations of 0.1, 0.5 and 3 ppm were investigated. The results showed that the gene encoding heat shock protein (hsp70) was down-regulated in a dose-dependent manner. The genes encoding superoxide dismutase (SOD 1 and SOD 2), apoptotic genes (cas 1 and cas 8) and interleukin 1-β (il1β) were activated at the concentration of 3 ppm PS NP, while the anti-apoptotic gene Bcl2α was inhibited at 0.5 and 3 ppm. In addition, the neurotransmitter-related gene Acetyl-Cholinesterase (ache) was significantly inhibited and the DNA repair genes (gadd45α and rad51) were also down-regulated. In contrast, the mitochondrial metabolism-related gene cox1 did not alter its expression in any of the treatments. Most of the changes in gene expression occurred at the highest concentration of NPs. Overall, the results indicated that NPs generated cellular stress that caused certain alterations in normal gene expression (oxidative stress, apoptotic and inflammatory processes, neurotoxicity and anti-apoptotic proteins), but did not cause any mortality after 120 hpf exposure at the three concentrations assayed. These results highlight the need for further studies investigating the effects, at the molecular level, of these materials in humans and other living organisms.


Studies on the molecular organization of cytochromes P-450 and b5 in the microsomal membrane.
1. The relative orientations of the heme groups of cytochromes P-450 and b5 in the microsomal membrane have been studied by the technique of electron paramagnetic resonance. The results show that the heme plane of cytochrome P-450 lies in the same plane as the membrane surface, whereas the cytochrome b5 heme plane has a random orientation. 2. No significant broadening or change in relaxation properties of the gz component of low spin cytochrome P-450 occurred when cytochrome b5 was reduced by redox poising. It is concluded that there is little or no paramagnetic coupling between the heme groups of the two species. 3. The results favor a model in which no tight complex between cytochromes P-450 and b5 is present, the species being independent and interacting only by random molecular collisions or via other intermediate species.


Natural killer-like activity in human cultured lymphoid cells propagated in the presence of interleukin-2: acquired resistance to prostaglandin E2- or dexamethasone-mediated suppression.
The cytotoxic activity of human peripheral blood lymphocytes against the natural killer-sensitive target K562 was suppressed both by prostaglandin E2 and dexamethasone. On the other hand, cultured lymphoid cells propagated in the presence of interleukin-2 showed strong cytotoxic reactivity against K562 targets, and were resistant to prostaglandin E2- or dexamethasone-mediated suppression.


Two-dimensional speckle technique for slope error measurements of weakly focusing reflective X-ray optics.
Speckle-based at-wavelength metrology techniques now play an important role in X-ray wavefront measurements. However, for reflective X-ray optics, the majority of existing speckle-based methods fail to provide reliable 2D information about the optical surface being characterized. Compared with the 1D information typically output from speckled-based methods, a 2D map is more informative for understanding the overall quality of the optic being tested. In this paper, we propose a method for in situ 2D absolute metrology of weakly focusing X-ray mirrors. Importantly, the angular misalignment of the mirror can be easily corrected with the proposed 2D processing procedure. We hope the speckle pattern data processing method presented here will help to extend this technique to wider applications in the synchrotron radiation and X-ray free-electron laser communities.


New fluorescent chemosensors based on mononuclear copper complex for highly selective and sensitive detection of phosphate anion in aqueous solution and living cells.
Three new probes, named, [Cu(L1)2]Cl2 (C1), [Cu(L2)2]Cl2 (C2) and [Cu(L3)2]Cl2 (C3) were synthesized and well characterized. The probes C1, C2 and C3 were successfully achieved for the efficient detection of PO43- as turn-on fluorescence chemosensors in DMSO/H2O (v:v = 2:8, Tris-HCl pH = 7.20). The limit of detection (LOD) of probes C1, C2 or C3 for PO43- could be as low as 0.029 μM, 0.048 μM, 0.079 μM, respectively, which were effectively applied for the determination of the PO43- concentration in environmental water of swimming pool. What's more, the binding constant between probes C1, C2, C3 and PO43- are estimated to be 3.11 × 107 M-1 (R2 = 0.9992), 1.84 × 107 M-1 (R2 = 0.9956), 1.93 × 107 M-1 (R2 = 0.9976), respectively. The proposed mechanism for the "on-off-on" fluorescence response was confirmed by ESI-MS and fluorescence spectrum. Moreover, the membrane-permeable probe C1 was successfully demonstrated in monitoring of PO43- in cultured HepG2 cells.


Caseous mitral annular calcification: Is it a benign condition?
Caseous mitral annular calcification (CMAC) is a variant of mitral annular calcification (MAC) with a central liquefaction necrosis. The echocardiographic prevalence of CMAC is approximately 0.6% in patients with MAC and 0.06-0.07% in large series of patients of all ages. However, the prevalence in necropsy series has been reported to be 2.7%, which indicates that this condition is yet under-recognized. Furthermore CMAC is probably underappreciated as a source of potentially serious conditions. We report a case of recent stroke associated with CMAC diagnosed by trans-thoracic and confirmed by trans-esophageal echocardiogram (TEE). The importance of correct diagnosis of CMAC extends beyond the possible complications; since several misdiagnoses of CMAC as abscesses and cardiac tumors have been reported leading to inappropriate interventions.


Aflatoxin contamination in different fractions of rice from Pakistan and estimation of dietary intakes.
The purpose of this study was to determine the distribution of aflatoxins in rice milling fractions and to estimate dietary intakes. A total of 413 rice samples (paddy 58, parboiled 69, brown 84, white 93, and broken 109) were analyzed by HPLC with fluorescence detector. The results showed that 64 % paddy (16.35 ± 1.67 μg/kg), 38 % parboiled (14.20 ± 2.04 μg/kg), 33 % brown (9.85 ± 1.25 μg/kg), 42 % white (7.10 ± 1.39 μg/kg), and 50 % broken (8.5 ± 1.71 μg/kg) rice samples were contaminated with aflatoxins. It was found that paddy rice was most contaminated with aflatoxins while white rice was least contaminated. The percentage of samples exceeding EU maximum contents for total aflatoxins in rice (4 μg/kg) varied from 14 to 36 % when compared to the analyzed rice fractions. The total estimated amount of aflatoxin intake for average rice consumers ranged from 19.1 to 26.6 ng/kg body weight/day, much higher than the reference value of 1 ng/kg body weight/day. This is the first report discovering that rice is a major contributor to the dietary intake of aflatoxins in Pakistan.


Ocular axial length changes in a pediatric patient with aphakia and pseudophakia.
Excessive eye elongation can be induced in experimental animals by visual deprivation. A tendency toward myopic refraction or shift in pediatric aphakia has been recorded in some children. In this report, we present the case of an 18-year-old patient who had developmental cataracts treated at seven years of age with bilateral cataract extraction and implantation of an intraocular lens in one eye only. Axial length of the eye with a contact lens increased compared with the eye with the intraocular lens.


[Morphological data on the reproductive characteristics of the LEIV-108A and LEIV-3306 Uz strains of the Baku virus in chick fibroblast cell culture].
Electron microscopic examinations of chick fibroblast cells 24 hours after inoculation with LEIV-108A and LEIV-3306 Uz strains of Baku virus revealed the following: in the nuclei of the cells infected with the LEIV-108A strain fine granular matrices were found and virus particles were forming at the periphery of the nucleus; in the LEIV-3306Uz-infected cells virus particles were found budding from the plasma membrane of the cell.


Real-world pharmacological treatment patterns of patients with threatened miscarriage in China from 2014 to 2020: A cross-sectional analysis.
Approximately half of the patients with threatened miscarriage suffer an abortion, and consistent medication therapy to prevent threatened miscarriage is lacking. Our goal was to investigate the real-world pharmacological treatment patterns of patients with threatened miscarriage in China, with a focus on the trend and rationality of progestogen use over the last 7 years. We performed a cross-sectional analysis of data from the Hospital Prescription Analysis Cooperation Project that is overseen by the Chinese Pharmaceutical Association. Information was extracted from prescriptions of outpatients with threatened miscarriage between January 2014 and December 2020. We quantified the types of medications using the first level anatomical therapeutic chemical (ATC) classification code and the frequency of use of medicines classified as category X by the United States Food and Drug Administration (FDA). We also calculated the prevalence of the most frequently used progestogens by assessing prescription rates, determined the sum of the defined daily doses (DDDs) and defined daily cost (DDC) and evaluated the rationality of progestogens according to drug labels and guidelines. Of the 91,464 patients included in this study, 69.4% were from the eastern region, 92.5% were from tertiary hospitals, and 72.9% were between 25 and 34 years old. The average number of medications per patient was 1.4. The following types of medicines were the most prevalent: "genitourinary system and sex hormones" (90.7%), "alimentary tract and metabolism" (10.8%) and "blood and blood-forming organs" (9.9%). Progestogens were prescribed for 81,080 patients (88.6%), among which oral progesterone (39.7%) was the most commonly used, followed by oral dydrogesterone (34.4%), progesterone injection (26.0%), oral allylestrenol (0.7%) and progesterone gel (0.4%). In other words, 10,991 (12.0%) patients used more than one progestogen, and the top three combinations were oral dydrogesterone plus progesterone injection (5.6%), oral progesterone plus progesterone injection (4.7%) and oral dydrogesterone plus oral progesterone (1.1%). The prescription rate of dydrogesterone increased gradually, whereas that of progesterone, especially progesterone injection, obviously decreased. Among 34,760 prescriptions of progestogens with complete usage information, the primary errors of progestogen use were "low frequency" (18.4%), "high single dose" (15.9%) and "low single dose" (11.3%). In addition, 137 prescriptions were identified with drug-progestogen interactions, and 61 were identified with contraindications for progestogens. A total of 4.5% of prescriptions included FDA category X medicines. Our findings are the first to provide information on medication use in patients with threatened miscarriage over the last seven years in China. Medicines targeting the "genitourinary system and sex hormones," especially progestogens, were the most commonly prescribed medications, among which dydrogesterone was the most prevalent. However, it is remarkable that the use of progestogens for the treatment of threatened abortion is still controversial; thus, high-quality large sample studies are still required, especially among Chinese patients. Since usage errors in progestogen records and exposure to category X medicines were common, more efforts are needed to guarantee the safety and rationality of medicines used in pregnant women.


Total hip arthroplasty-related osteogenic osteosarcoma: case report and review of the literature.
Orthopedic implant-related sarcoma is an exceedingly rare, but a known complication of total hip arthroplasty (THA). The authors describe clinical and radiologic features, histologic appearance, and treatment of osteogenic osteosarcoma located in the proximal femoral diaphysis associated with an unstable femoral prosthesis following THA in a 65-year-old male patient. The patient with HLA-B27 positive ankylosing spondylitis underwent arthroplasty 15 years ago. The neoplastic process may be considered as an extraordinary complication of THA and might just be coincidental or the result of some derangement of the healing process in host tissue with no definitely proven hypothesis that the implants or their by-products are carcinogenic. The soluble chemical substances from the implanted prosthetic material are, at least in animals, suspected to play a vital role in the pathogenesis of the neoplastic transformation of the bone tissue. The presented case shall alert orthopedic surgeons to clinical, radiologic, and macroscopic similarities between a malignant tumor and benign lesions caused by wear debris at THA sites. At the examination of plane X-rays of patients with THA loosening, the differential diagnosis should always include osteogenic sarcoma, as well. To our knowledge, there have been only nine cases of THA-related osteogenic osteosarcomas described in the English-language literature.


High-Dose Busulfan-Fludarabine Conditioning and Low Alveolar Volume as Predictors of Pulmonary Complications after Allogeneic Peripheral Blood Stem Cell Transplantation in Children.
This study was conducted to investigate risk factors and predictors of infectious and noninfectious pulmonary complications (PCs) after allogeneic hematopoietic stem cell transplantation in children. We conducted a retrospective analysis of the post-transplantation PCs of 240 patients who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) between 2009 and 2018. Transplantation-related variables, pretransplantation baseline spirometry, body plethysmography, and CO diffusing capacity were analyzed for association with the development of infectious PCs (IPCs) and noninfectious PCs (NIPCs). Compared with the control group, the PC group had statistically significantly lower overall survival (50.6% versus 77.8%; P < .001), higher disease-related mortality (26.6% versus 54.4%; P < .001), and higher nonrelapse mortality (31.6% versus 5.9%; P < .001). A greater number of patients received pretransplantation conditioning with high-dose busulfan (520 mg/m2; Bu 520) and fludarabine (160 mg/m2; Flu 160) in both the IPC and NIPC groups. In the multivariate Cox hazard regression analysis, Bu 520 significantly increased the risk of NIPCs (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.13 to 3.49; P = .016), and Flu 160 was a predictor of IPCs (HR, 1.99; 95% CI, 1.13 to 3.49; P = .016). The Bu 520 + Flu 160 regimen was associated with a statistically significant increase in the risk of NIPC (HR, 1.92; 95% CI, 1.09 to 3.37; P = .023). In a multivariate analysis using pretransplantation baseline lung function, alveolar volume (VA) grades 3 and 4 and lung function score (LFS) VA categories III and IV were associated with increased risk for both IPCs and NIPCs. Our data identify receipt of the high-dose Bu-Flu conditioning regimen as an independent risk factor for NIPCs after allo-PBSCT. Impaired CO diffusing capacity before transplantation, especially VA reduction, contributes to the risk of post-transplantation pulmonary complications, and pretransplantation risk can be estimated by grading the degree of insufficiency of VA and LFS VA.


Proteomic profiling of gill GSTs in Mytilus galloprovincialis from the North of Portugal and Galicia evidences variations at protein isoform level with a possible relation with water quality.
Glutathione transferases (GSTs) are key for xenobiotic detoxification at the molecular level across phyla. These enzymes are therefore likely to be part of the defence mechanisms used by marine organisms, such as mussels, that thrive in highly polluted environments. Taking this hypothesis into account, we used proteomics to characterize the profile of GSTs from the gills of marine mussel Mytilus galloprovincialis in order to discriminate natural mussel populations exposed to different levels of pollution. Samples were collected between Cabo Home (Spain) and Matosinhos (Portugal) covering a north-south transect of approximately 122 Km of the Atlantic Ocean along the Western Coast of the Iberian Peninsula. GSTs from mussel gills were extracted and purified by affinity chromatography with glutathione as the binding substrate to the solid medium. We studied the abundance of GST isoforms by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight mass spectrometry and assessed total activity. Eleven putative individual GSTs from classes Mu, Pi and Sigma were identified by proteomics. Few variations were observed in total GST activity of post-mitochondrial samples between sampling sites, with animals from Matosinhos (polluted site) showing highest GST activity and Cabo Home (clean site) showing lowest. This contrasts with the increased number of differences in the individual GST isoforms. Each mussel population showed unique GST proteomic profiles. Based on the results we conclude that proteomics surpasses the conventional GST enzymatic activity method to discriminate natural mussel populations and has potential application in environmental monitoring. It is reasonable to suggest that the GST proteomic profiles observed may reflect differences in contamination levels.


A protective role for the embryo surrounding region of the maize endosperm, as evidenced by the characterisation of ZmESR-6, a defensin gene specifically expressed in this region.
A Zea mays cDNA clone, ZmESR-6, was isolated as a gene specifically expressed at the basal region of immature kernels. ZmESR-6 cDNA encoded for a small (11.1 kDa) protein homologous to plant defensins. As for other defensins, the protein contained an N-terminal signal peptide signature and a C-terminal acidic peptide, the mature peptide has a molecular mass of 5.5 kDa. ZmESR-6 was highly expressed in developing kernels but the transcript could not be detected in any other maize tissue. The recombinant ZmESR-6 protein, purified from E. coli, showed strong in vitro inhibitory activity against bacterial and fungal plant pathogens, suggesting a role for ZmESR-6 in plant defence. The distribution of the transcripts was restricted to the embryo surrounding region (ESR) of the kernel. Immunolocalisation experiments revealed, however, that at the grain filling phase ZmESR-6 was accumulated in the placentochalaza-cells, rather than in the ESR cells that produce it. Our results suggest that the ESR has a role in protecting the embryo at the very early stages of seed development, whilst contributes to the general defence mechanism of the kernel at later developmental stages.


Occlusive patch method for skin sensitization in guinea pigs: the Buehler method.
Currently, the European Community is in the process of discussing the details of how to conduct various protocols for safety assessment. Additionally, there is a desire that these protocols be harmonized internationally. This presentation attempts to describe the critical and non-critical parameters of the protocol for detecting potential contact allergens in the guinea pig and also discusses some controversial issues. It is also emphasized that the identification of a test material as a potential sensitizer is only the first step in the risk-assessment exercise.


Cell cycle control by Ca2+ in Saccharomyces cerevisiae.
We established an experimental system suitable for study of cell cycle regulation by Ca2+ in the yeast Saccharomyces cerevisiae. Systematic cell cycle analysis using media containing various concentrations of Ca2+, a Ca2(+)-ionophore (A23187), and a Ca2(+)-chelator [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) revealed that simultaneous addition of 10 microM A23187 and 10 mM EGTA to cells growing in a Ca2(+)-deficient medium at 22 degrees C caused rapid decrease in intracellular Ca content and resulted in transient G1 arrest followed by block mostly at G2/M, as revealed by flow cytometry. Recovery from G1 arrest was not due to coordinated initiation of DNA synthesis and bud emergence: unbudded cells with S or G2/M DNA were observed. Examination of terminal phenotype suggested that Ca2+ was required at all the stages of the cell cycle except for the initiation of DNA synthesis. The intracellular cAMP level decreased within 10 min of addition of A23187 and EGTA. No significant transient G1 arrest was observed in cells incubated with 8-Br-cAMP, or RAS2val19 and delta bcy1 mutants, which produce a high level of cAMP and have constitutively activated cAMP-dependent protein kinase, respectively. These results indicate that Ca2+ is essential for cell cycle progression and suggest that Ca2+ may regulate the cAMP level. This system will be useful for genetic and molecular studies on cell cycle events regulated by Ca2+.


Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox.
The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is four or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection - thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals.


Radiological analysis of hyaline membrane disease after exogenous surfactant treatment.
Exogenous surfactant treatment of hyaline membrane disease is known to modify the pattern of radiological changes on the chest radiograph. To analyse and attempt to explain the radiological changes observed after exogenous surfactant treatment. Materials and methods. Thirty-nine premature infants with typical hyaline membrane disease. Transient asymmetrical clearing with better aeration of the right lung in the absence of malposition of the tip of the endotracheal tube was observed in nine cases (23 %). This asymmetry was patchy in one case. It was due to a complication of mechanical ventilation in three cases [pneumothorax (n = 2) and pneumomediastinum (n = 1)]. In the other six cases, asymmetrical clearing could be related to the anatomical position of the right main bronchus, which facilitates distribution of surfactant to the right lung. However, the course of these premature infants was similar to that of infants with symmetrical chest radiological findings after treatment. Asymmetrical clearing of chest radiographs, sometimes patchy, after surfactant treatment requires exclusion of pneumothorax or infection but has no influence on clinical outcome.


Amplification loop cascade for increasing caspase activity induced by docetaxel.
The hierarchy of events accompanying induction of apoptosis by the microtubule inhibitor docetaxel was investigated in HL-60 human leukemia cells. Treatment of HL-60 cells with docetaxel resulted in the production of reactive oxygen species (ROS), activation of caspase-3 (-like) protease, c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activation, bcl-2 phosphorylation and apoptosis. Docetaxel elicited ROS production from NADPH oxidase as demonstrated by specific oxidase inhibitor diphenylene iodonium (DPI). ROS mediated the caspase-3 activation and apoptosis in HL-60 cells. The caspase inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) effectively inhibited JNK/SAPK activation, bcl-2 phosphorylation and partially attenuated the ROS production induced by docetaxel. Docetaxel-induced bcl-2 phosphorylation was completely blocked by expression of dominant negative JNK or the JNK/SAPK inhibitor SP600125. Overexpression of bcl-2 partially prevented docetaxel-mediated ROS production and subsequent caspase-3 activation, thereby inhibiting apoptotic cell death. It is thus conferred that such sequent events as ROS production, caspase activation, JNK/SAPK activation, bcl-2 phosphorylation and the further generation of ROS should be parts of an amplification loop to increase caspase activity, thereby facilitating the apoptotic cell death process.


[Diagnostic image (174). A Nicaraguan man with an epileptic seizure. Neurocysticercosis].
A 56-year-old Nicaraguan man was referred because of a generalised seizure. CT revealed neurocysticercosis.


Structural Variation of the Turtle Mitochondrial Control Region.
The present study describes the most comprehensive comparison of turtle mtD-loop regions to date. The primary structure was compared from DNA sequences accessed from GenBank from 48 species in 13 families of extant turtles, and secondary structures of the mtD-loop region were inferred from thermal stabilities, using the program Mfold, for each superfamiliy of turtles. Both primary and secondary structures were found to be highly variable across the order. The Cryptodira showed conservation in the primary structure at conserved sequence blocks (CSBs), but the Pleurodira displayed limited conservation of primary structural characters, other than the coreTAS, a binding site for the helicase TWINKLE, which was highly conserved in the Central and Right Domains across the order. No secondary structure was associated with a TAS, but an AT-rich fold (secondary structure) near the 3' terminus of the mtD-loop region was detected in all turtle superfamilies. Mapping of character states of structural features of the mtD-loop region revealed that most character states were autapomorphies and inferred a number of homoplasies. The Left Domain of turtles, containing no highly conserved structural elements, likely does not serve a functional role; therefore, the Central Domain in turtles is likely equivalent to the Left Domain of mammals. The AT-rich secondary structural element near the 3' terminus of the mtD-loop region may be conserved across turtles because of a functional role, perhaps containing the Light Strand Promotor, or perhaps interacting with the TWINKLE-coreTAS complex in the Central and Right Domains to regulate mtDNA replication and transcription.


Financial development and innovation: Do institutions and human capital matter?
This paper explores the dynamic link between financial development and innovation, while accounting for human capital and institutional quality for 29 OECD countries spanning 40 years (1980-2019). The findings based on Generalized Method of Moments (GMM) and the Fully Modified Ordinary Least Squares (FMOLS) estimators show that trade, institutional quality, human capital and financial development promote innovation activities, while foreign direct investment has the opposite effect. Further, the findings show a non-linear relationship between finance and innovation.


Compound treatment of thiolated citrus high-methoxyl pectin and sodium phosphate dibasic anhydrous improved gluten network structure.
The effects of pectin or thiolated pectin alone and combined with sodium phosphate dibasic anhydrous (Na2HPO4) on the performances of gluten were studied. Results showed that compared with pectin treated gluten, the thiols of thiolated pectin treated gluten increased by 8.7 times. Analysis of the extensibility and rheological properties revealed that pectin reduced gluten strength, whereas thiolated pectin improved the strength and viscoelasticity of gluten, especially with the assistance of Na2HPO4. Furthermore, thiolated pectin and Na2HPO4 compound increased enthalpy (ΔH, from 150.42 to 168.60 J/g) and decreased Imax (from 5255.33 to 2775.33) markedly, indicating gluten aggregation. The highest β-sheet (76.47%) and the lowest α-helix/β-sheet ratio (0.11) were found in gluten treated with thiolated pectin and Na2HPO4 and suggested gluten stability was enhanced. SEM observation confirmed that thiolated pectin and Na2HPO4 compound strengthened the gluten structure. These results are of great significance for the supplementation of pectin in wheat products.


EPIDEMIOLOGY OF UNDERFIVE MALNUTRITION : SEX DIFFERENTIAL IN HEALTH CARE AND NUTRITIONAL STATUS (UNDERFIVE MALNUTRITION).
Under five children of defence personnel attending an immunisation clinic in a peace station over a three year period were screened for malnutrition and hemoglobin status. One thousand two hundred and forty eight underfives attended the clinic, out of which 703 (56.33%) were boys and 545 (43.67%) were girls. Girls showed a greater prevalence of various grades of malnutrition (28.9%) compared to boys (21.9%), (p=0.01335458). Mean hemoglobin level was marginally lower in girls at 10.8 gm per cent, compared to boys at 11.2 gm per cent (p=0.000001). Overall 25 per cent of underfives were suffering from various grades of malnutrition which is much lower than the national malnutrition rate of 63 per cent among underfives.


Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk.
Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies. IV analyses in the Health and Retirement Study cohort (1998-2010) used two sets of instruments: (1) a genetic risk score constructed from three single-nucleotide polymorphisms (SNPs; n = 7981); and (2) compulsory schooling laws (CSLs) and state school characteristics (term length, student teacher ratios, and expenditures; n = 10,955). Using the genetic risk score as an IV, there was a 1.1% reduction in dementia risk per year of schooling (95% confidence interval, -2.4 to 0.02). Leveraging compulsory schooling laws and state school characteristics as IVs, there was a substantially larger protective effect (-9.5%; 95% confidence interval, -14.8 to -4.2). Analyses evaluating the plausibility of the IV assumptions indicated estimates derived from analyses relying on CSLs provide the best estimates of the causal effect of education. IV analyses suggest education is protective against risk of dementia in older adulthood.


New modeling of scattering behaviors of argon atoms on tungsten substrate.
In this study argon beam-tungsten surface scattering processes were investigated numerically by applying molecular dynamics simulations. Energy transfer, momentum change and the scattering processes of argon gas atoms from the W(110) surface were discussed. The molecular dynamics results showed that Maxwell boundary conditions fail to describe the behaviors of a high mean kinetic energy argon beam impinging on a tungsten surface. A new three-dimensional model of argon-tungsten interaction was thus proposed, and its results proved to be in line with experimental and theoretical results that have been obtained previously by other researchers. Specifically, we developed a method for the normalization of the parameters of a gas beam scattered by a metal surface. We found that the ratio of the average velocity of the scattered beam to the appropriate root mean square deviation (RMSD) allowed us to determine whether the distribution of the scattered atoms was Maxwellian or not. We found that the shape of the functions representing the angular distributions of the scattered Ar atoms could be determined using the ratio of the RMSD of an angle (azimuthal or polar) of the scattered beam to the RMSD of a uniform distribution. The distribution of the azimuthal angle of the scattered atoms was found to be uniform regardless of the incident's kinetic energy, when the incident of the beam on the surface was normal.


First Presentation and Diagnosis of a Rare Advanced Gynaecological Cancer in Emergency Department: A Case Report.
A case of rare endometrial carcinosarcoma with locoregional spread and sigmoid fistula presenting for the very first time at a hospital emergency department (ED). A 56-year-old female presented with abdominal pain, diarrhea, fever, and pancytopenia, which was diagnosed as advanced gynaecological cancer following assessment, imaging, and tissue biopsy. Increased pressure on the ED owing to coronavirus disease 2019 pandemic may cause the first presentation of gynae-oncology cases to ED physician. A full return of all primary care services may reduce such pressure, improve early detection of gynaecological malignancies, allow early multidisciplinary team care, and result in better patient experience in the long run.


Effect of allergic conjunctival inflammation on the allogeneic response to donor cornea.
Immunologic rejection is the most common cause of corneal allograft rejection. Ipsilateral ocular inflammation has been identified as a predictor of future corneal graft failure. This study investigates the effect of perioperative allergic conjunctivitis on corneal allograft survival. C57BL6 donor corneas were transplanted into naive A/J mice, A/J mice sensitized to short ragweed (SRW) pollen by intraperitoneal injection and then challenged with topical SRW to induce allergic conjunctivitis (Sens(+)Chall(+)), and A/J mice sensitized to SRW and challenged with topical PBS (Sens(+)Chall(-)). Syngeneic grafts were also performed in eyes with allergic conjunctivitis. Graft survival and infiltrating cell phenotype in rejected grafts were compared between groups. Mice with allergic conjunctivitis (Sens(+)Chall(+)) rejected corneal allografts significantly more quickly than naive mice. Syngeneic grafts in allergic eyes survived indefinitely. The rate of rejection in Sens(+)Chall(-) mice was similar to that in naive mice. There were no significant differences, between groups, in the numbers of infiltrating CD4(+) cells, CD8(+) cells, and macrophages at the time of graft rejection. Eosinophils were seldom observed in rejected grafts in naive and Sens(+)Chall(-) mice but were observed consistently in Sens(+)Chall(+) eyes. Eosinophils were also found consistently in the ciliary body of Sens(+)Chall(+) eyes at the time of graft rejection. Active allergic conjunctivitis at the time of transplantation accelerates corneal allograft rejection. Local conjunctival inflammation is an important factor in accelerating rejection.


RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers.
NRG1 gene fusions are rare, therapeutically relevant, oncogenic drivers that occur across solid tumor types. To understand the landscape of NRG1 gene fusions, 4397 solid tumor formalin-fixed, paraffin-embedded samples consecutively tested by comprehensive genomic and immune profiling during standard care were analyzed. Nineteen NRG1 fusions were found in 17 unique patients, across multiple tumor types, including non-small-cell lung (n = 7), breast (n = 2), colorectal (n = 3), esophageal (n = 2), ovarian (n = 1), pancreatic (n = 1), and unknown primary (n = 1) carcinomas, with a cumulative incidence of 0.38%. Fusions were identified with breakpoints across four NRG1 introns spanning 1.4 megabases, with a mixture of known (n = 8) and previously unreported (n = 11) fusion partners. Co-occurring driver alterations in tumors with NRG1 fusions were uncommon, except colorectal carcinoma, where concurrent alterations in APC, BRAF, and ERBB2 were present in a subset of cases. The overall lack of co-occurring drivers highlights the importance of identifying NRG1 gene fusions, as these patients are unlikely to harbor other targetable alterations. In addition, RNA sequencing is important to identify NRG1 gene fusions given the variety of fusion partners and large genomic areas where breakpoints can occur.


The enrichment of more functional microbes induced by the increasing hydraulic retention time accounts for the increment of autotrophic denitrification performance.
With pyrite (FeS2) and polycaprolactone (PCL) as electron donors, three denitrification systems, namely FeS2-based autotrophic denitrification (PAD) system, PCL-supported heterotrophic denitrification (PHD) system and split-mixotrophic denitrification (PPMD) system, were constructed and operated under varying hydraulic retention times (HRT, 1-48 h). Compared with PAD or PHD, the PPMD system could achieve higher removals of NO3--N and PO43--P, and the effluent SO42- concentration was greatly reduced to 7.28 mg/L. Similarly, the abundance of the dominant genera involved in the PAD (Thiobacillus, Sulfurimonas, and Ferritrophicum, etc.) or PHD (Syntrophomonas, Desulfomicrobium, and Desulfovibrio, etc.) process all increased in the PPMD system. Gene prediction completed by PICRUSt2 showed that the abundance of the functional genes involved in denitrification and sulfur oxidation all increased with the increase of HRT. This also accounted for the increased contribution of autotrophic denitrification to total nitrogen removal in the PPMD system. In addition, the analysis of metabolic pathways disclosed the specific conversion mechanisms of nitrogen and sulfur inside the reactor.


Lipid biosynthesis in the marine flatworm Convoluta roscoffensis and its algal symbiont Platymonas convoluta.
As a part of an investigations on the lipid metabolism in Platyhelminthes, the acoel Convoluta roscoffensis, which harbors the green alga Platymonas convoluta as a symbiont, was studied. Isotopic tracer experiments established that the acoel lacks the ability to synthesize de novo long-chain saturated and unsaturated fatty acids and depends on its algal symbiont for these compounds. The acoel's fatty acid composition closely resembles that of the alga but differs from those of other animals; the acoel's polyunsaturated fatty acids are of the plant type (omega 3 family) rather than of the animal type (omega 6 family). The acoel also lacks the ability to synthesize sterols de novo. It contains 24-methylenecholesterol synthesized by the algae and, in addition, significant amounts of cholesterol, which is probably a host modification product of the algal sterol. With fatty acids provided by the symbiont, the acoel has the ability to synthesize its own complex lipids. The acoel contains relatively large amounts of triglyceride, phosphatidylcholine, and ethanolamine plasmalogen. These compounds are either not present at all or present only in minute amounts in the symbiotic alga. Since acoels belong to the most primitive forms of the present-day flatworms, the observed metabolic defects in this organism suggest that mechanisms for the biosynthesis of fatty acids and sterols were lost early during the evolution of the Platyhelminthes, and that this phenomenon is widespread within the phylum.


The genetic legacy of African Americans from Catoctin Furnace.
Few African Americans have been able to trace family lineages back to ancestors who died before the 1870 United States Census, the first in which all Black people were listed by name. We analyzed 27 individuals from Maryland's Catoctin Furnace African American Cemetery (1774-1850), identifying 41,799 genetic relatives among consenting research participants in 23andMe, Inc.'s genetic database. One of the highest concentrations of close relatives is in Maryland, suggesting that descendants of the Catoctin individuals remain in the area. We find that many of the Catoctin individuals derived African ancestry from the Wolof or Kongo groups and European ancestry from Great Britain and Ireland. This study demonstrates the power of joint analysis of historical DNA and large datasets generated through direct-to-consumer ancestry testing.


Vitiligo: treatment by dermabrasion and epithelial sheet grafting.
Several years ago, a surgical technique for treating depigmentation resulting from burn injuries was developed. The treatment of this problem in the patient with burns was consistently successful. The purpose of this study was to investigate the usefulness of the surgical technique developed for patients with burn injuries to determine whether the same technique would be useful in treating patients with vitiligo whose skin did not repigment with conventional medical treatments. Five patients with stable vitiligo were treated. The epithelium of the vitiliginous areas was removed by dermabrasion. The dermabraded area was then reepithelialized with epithelial sheet grafts sufficient to cover the entirety of the vitiliginous dermabraded region. Each operation was successful. Scarring did not develop in the repigmented or donor site regions. The final color match has been good to excellent in all patients. Good to excellent repigmentation was observed in each patient. We believe our results, to date, are more successful than the results of other procedures reported previously in the medical literature.


Cerebral abscess associated with an intrauterine contraceptive device.
The present communication is the first report of a metastatic brain abscess occurring as a complication of severe intrauterine device (IUD)-related pelvic inflammatory disease (PID). The diagnostic and therapeutic problems are discussed, and a suggestion is made for the reporting of all IUD-associated infections to a central agency.


Packing procedure effective for liver transplantation in hemophilic patients with HIV/HCV coinfection.
We herein report an effective procedure for liver transplantation (LT) for severe cirrhotic patients with hemophilia. Three hemophilic patients suffering from liver cirrhosis due to human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection underwent deceased donor LT in our institute. Basic clotting parameters were measured and evaluated during LT to determine the optimal packing procedure. All patients were treated with a gauze packing procedure to ensure stable hemostasis in relation to hemophilia during the peri-transplant period. The graft function of all patients recovered well upon gauze removal (depacking) procedure and the patients were finally discharged to home. The administration of clotting factor was discontinued on day 3 after deceased donor LT. No infectious complications occurred in any of the 3 patients. This technique could be an option for achieving successful LT in these patients. Cooperation between transplant surgeons and anesthesiologists can make this challenging operation possible.


Catalytic function of a newly purified exo-β-D-glucosaminidase from the entomopathogenic fungus Paecilomyces lilacinus.
An entomopathogenic fungus, Paecilomyces lilacinus, was found to grow on chitosanase-detecting plates. Besides an endo-chitosanase, an exo-β-D-glucosaminidase was purified by cation-exchange chromatography from this microorganism cultivated in M9 minimal media containing 0.5% chitosan as the sole carbon source. The molecular weight of the enzyme is 95kDa; the optimum pH and temperature for activity are 6.0 and 45°C, respectively. The purified exo-β-D-GlcNase promotes the hydrolysis of 95% deacetylated chitosan from its non-reducing end and liberates 2-amino-2-deoxy-D-glucopyranose (GlcN) as the sole product; however, 2-acetamido-2-deoxy-D-glucopyranose (GlcNAc) was not detected when chitin was used as the substrate. The cleavage pattern confirmed using real-time mass spectrometry shows that exo-β-D-glucosaminidase cleaves the glycosidic bonds between GlcN-GlcN and GlcN-GlcNAc but not between GlcNAc-GlcN or GlcNAc-GlcNAc. In the presence of a 10% solution of various alcohols, many alkyl-β-D-glucosaminides were obtained, indicating that exo-β-D-glucosaminidase is a retaining enzyme.


Laryngoscope blades and handles as sources of cross-infection: an integrative review.
The lack of standardization of efficient procedures to clean and disinfect laryngoscope blades and handles, which may be important sources of infection during their clinical use, has been reported previously, revealing contamination with blood, body fluids and micro-organisms. This paper aimed to evaluate the evidence available in the literature regarding the risk of laryngoscope blades and handles as a source of patient contamination. An integrative review of the literature was performed using databases such as Medline, LILACS, SciELO, Cochrane Library, BDENF and PubMed, and keywords in Medical Subject Headings (MeSH). The sample comprised 20 articles published between 1994 and 2012. The studies demonstrated risk of cross-infection and no consensus in current guidelines regarding cleaning and disinfection of this equipment. It was concluded that there are important gaps to be filled and urgent investigations required in order to facilitate standardization of efficient procedures to clean and disinfect laryngoscope blades and handles, and in turn to reduce the potential risk to which the patient and/or health team is exposed.


miR-34a/SIRT1/HIF-1α axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise.
Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders worldwide. Recent research has indicated that sodium butyrate (NaB) affects glucose metabolism and exercise has an anti-hyperglycemic effect in diabetes. This study aimed to evaluate the effects of NaB and treadmill exercise on heart angiogenesis through the miR-34a/SIRT1/FOXO1-HIF-1α pathway. Diabetic animals received NaB (400 mg/kg daily, orally) and treadmill exercise for 6 weeks. The effect of NaB and treadmill exercise, alone or combined, on miR-34a expression, SIRT1, FOXO1, HIF-1α levels, and angiogenesis in diabetic heart tissue was measured. Diabetes caused increased miR-34a (p < 0.01) and FOXO1 (p < 0.001) expression levels. Also, SIRT1 (p < 0.001) and HIF-1α (not significant) expression levels were reduced in diabetic rats. NaB and treadmill exercise decreased miR-34a (respectively p < 0.05 and not significant) and FOXO1 (both p < 0.001) expression levels and improved SIRT1 (both not significant) and HIF-1α (respectively p < 0.01 and p < 0.001) levels. Also, NaB combined with treadmill exercise decreased miR-34a (p < 0.001) and FOXO1 (p < 0.001) expression levels, and elevated SIRT1 (p < 0.05) and HIF-1α (p < 0.001) levels in comparison with the diabetic group. NaB and treadmill exercises modulate the expression of miR-34a and the levels of SIRT1, FOXO1, and HIF-1α proteins, thus increasing angiogenesis in the heart tissue of diabetic rats. It can be concluded that NaB and treadmill exercise, alone or combined, may be useful in the treatment of diabetes through the miR-34a/SIRT1/FOXO1-HIF-1α pathway.


Fruit ripening under heat stress: The intriguing role of ethylene-mediated signaling.
Crop production is significantly influenced by climate, and even minor climate changes can have a substantial impact on crop yields. Rising temperature due to climate change can lead to heat stress (HS) in plants, which not only hinders plant growth and development but also result in significant losses in crop yields. To cope with the different stresses including HS, plants have evolved a variety of adaptive mechanisms. In response to these stresses, phytohormones play a crucial role by generating endogenous signals that regulate the plant's defensive response. Among these, Ethylene (ET), a key phytohormone, stands out as a major regulator of stress responses in plants and regulates many plant traits, which are critical for crop productivity and nutritional quality. ET is also known as a ripening hormone for decades in climacteric fruit and many studies are available deciphering the function of different ET biosynthesis and signaling components in the ripening process. Recent studies suggest that HS significantly affects fruit quality traits and perturbs fruit ripening by altering the regulation of many ethylene biosynthesis and signaling genes resulting in substantial loss of fruit yield, quality, and postharvest stability. Despite the significant progress in this field in recent years the interplay between ET, ripening, and HS is elusive. In this review, we summarized the recent advances and current understanding of ET in regulating the ripening process under HS and explored their crosstalk at physiological and molecular levels to shed light on intricate relationships.


Effect of cytomegalovirus infection on post-transplant hospitalization days among children undergoing allogeneic hematopoietic cell transplantation: A marginal structural model approach.
Cytomegalovirus (CMV) commonly reactivates after allogeneic hematopoietic cell transplant (HCT), potentially leading to CMV disease and significant morbidity and mortality. To reduce morbidity and mortality, many centers conduct weekly CMV blood polymerase chain reaction (PCR) surveillance testing with subsequent initiation of antiviral therapy upon CMV DNAemia detection. However, the impact of CMV DNAemia on subsequent hospitalization risk has not been assessed using models accounting for the time-varying nature of the exposure, outcome, and confounders. All allogeneic HCTs at the Children's Hospital of Philadelphia from January 2004-April 2017 were considered for inclusion. Patients were monitored with CMV surveillance via PCR testing for up to 105 days after HCT receipt. We estimated the association between CMV DNAemia and rate of hospitalization using marginal structural models (MSM). There were 343 allogeneic HCT episodes in 330 with CMV surveillance; median age was 9.0 (range: 0.1-26.2) and 46.5% were female. And 24.1% of HCT patients had at least one positive CMV blood PCR during the follow-up period. Median time to CMV DNAemia detection was 19 days (range: 4-97). The MSM estimated the incidence rate ratios for an association of CMV DNAemia with hospitalization to be 1.24, (95% confidence interval: 1.04-1.47). CMV DNAemia was associated with an increased hospitalization in the post-HCT period. The MSM accounted for time-varying nature of the outcome, exposure and confounders. The findings support prevention of CMV DNAemia in this population. We recommend further investigation into the effectiveness and safety of prophylaxis versus pre-emptive CMV prevention approaches.


Renal prostaglandins: relationship to the development of blood pressure and concentrating capacity in pre-term and full term healthy infants.
The relationships between urinary prostaglandins (PGs)E2 and F2 alpha and the postnatal development of blood pressure and renal concentrating capacity were investigated in 14 pre-term and 32 full term healthy infants. Mean PGE2 and PGF2 alpha excretion was 18.9 and 10.1 ng/h/1.73 m2, respectively, in pre-term infant. In full term infants mean urinary PGE2 was significantly lower (13.4 ng/h/1.73 m2) and PGF2 alpha significantly higher (22.2 ng/h/1.73 m2). The decrease of the PGE2/PGF2 alpha ratio (P less than 0.001) was accompanied by an increase in blood pressure. High PGE2 levels in pre-term infants were inversely correlated with urinary cAMP excretion. A decreasing PGE2/PGF2 alpha ratio in full term infants was associated with increasing urinary osmolality. After intranasal administration of antidiuretic hormone (DDAVP) in 8 full term infants the increase in urinary osmolality and cAMP excretion was accompanied by a drop in PGE2 excretion to less than half the basal values. These findings suggests that the postnatal changes in urinary PG excretion are associated with a concomittant increase in blood pressure and in the concentrating capacity of the neonatal kidney.


The Pseudomonas putida NfnB nitroreductase confers resistance to roxarsone.
Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, Rox) has been used for decades as an antimicrobial growth promoter for poultry and swine. Roxarsone is excreted in chicken manure unchanged and can be microbially transformed into a variety of arsenic-containing compounds such as 3-amino-4-hydroxyphenylarsonic acid (HAPA(V)) that contaminate the environment and present a potential health hazard. To cope with arsenic toxicity, nearly every prokaryote has an ars (arsenic resistance) operon, some of which confer resistance to roxarsone. Pseudomonas putida KT2440 is a robust environmental isolate capable of metabolizing many aromatic compounds and is used as a model organism for biodegradation of aromatic compounds. Here we report that P. putida KT2440 (ΔΔars) in which the two ars operons had been deleted retains resistance to highly toxic trivalent Rox(III), the likely active form of roxarsone. In this study, a genomic library constructed from P. putida KT2440 (ΔΔars) was used to screen for resistance to Rox(III) in Escherichia coli. One gene, termed, PpnfnB, was identified that encodes a putative 6,7-dihydropteridine reductase. Cells expressing PpnfnB reduce the nitro group of Rox(III), and purified NfnB catalyzes FMN-NADPH-dependent nitroreduction of Rox(III) to less toxic HAPA(III). This identifies a key step in the breakdown of synthetic aromatic arsenicals.


Inventory of potential vectors of trypanosoma and infection rate of the Tsetse fly in the National Park of Ivindo, Gabon.
Trypanosoma's vectors distribution is poorly investigated in Gabon, where Trypanosomiasis historical foci exist. Thus, an active detection of Trypanosoma sp transmission needs to be assessed. The present study aims to identify potential vectors of Trypanosoma sp and to evaluate the infection rate of the Tsetse fly in an area of Gabon. An entomological survey was conducted in the National Park of Ivindo in May 2012 using Vavoua traps. All captured insects were identified. Tsetse were dissected and organs were microscopically observed to detect the presence of Trypanosoma sp. 247 biting flies known as vectors of Trypanosomiasis were caught including 189 tsetse flies, 32 Tabanid and 26 Stomoxys. Tsetse flies had the highest bulk densities per trap per day (ADT = 3 tsetse / trap / day), while the lowest density was found among Stomoxys (ADT= 0.41 Stomoxys / trap / day). The infection rate of flies was 6.3%. Infectious organs were midguts and to a lesser extent salivary glands and proboscis. The presence of Tsetse infected by Trypanosoma highlights an existing risk of trypanosomiasis infection in the National Park of Ivindo.


Identifying management opportunities to combat climate, land, and marine threats across less climate exposed coral reefs.
Conserving coral reefs is critical for maintaining marine biodiversity, protecting coastlines, and supporting livelihoods in many coastal communities. Climate change threatens coral reefs globally, but researchers have identified a portfolio of coral reefs (bioclimatic units [BCUs]) that are relatively less exposed to climate impacts and strongly connected to other coral reef systems. These reefs provide a proactive opportunity to secure a long-term future for coral reefs under climate change. To help guide local management efforts, we quantified marine cumulative human impact (CHI) from climate, marine, and land pressures (2013 and from 2008 to 2013) in BCUs and across countries tasked with BCU management. Additionally, we created a management index based on common management measures and policies for each pressure source (climate, marine, and land) to identify a country's intent and commitment to effectively manage these pressures. Twenty-two countries (79%) had increases in CHI from 2008 to 2013. Climate change pressures had the highest proportional contribution to CHI across all reefs and in all but one country (Singapore), but 18 BCUs (35%) and nine countries containing BCUs (32%) had relatively high land and marine impacts. There was a significant positive relationship between climate impact and the climate management index across countries (R2 = 0.43, p = 0.02), potentially signifying that countries with greater climate impacts are more committed to managing them. However, this trend was driven by climate management intent in Fiji and Bangladesh. Our results can be used to guide future fine-scale analyses, national policies, and local management decisions, and our management indices reveal areas where management components can be improved. Cost-effectively managing local pressures (e.g., fishing and nutrients) in BCUs is essential for building a climate-ready future that benefits coral reefs and people.


The prevalence of atrial fibrillation in a geographically well-defined population in northern Sweden: implications for anticoagulation prophylaxis.
The aims of this study were to evaluate the community-based prevalence of atrial fibrillation (AF) in a western society using a geographically well-defined population in the northern part of Sweden as a reference and to estimate the proportion of patients eligible for oral anticoagulation (OAC) prophylactic therapy according to the stroke risk indices CHADS2 and CHA2 DS2 -VASc. Bleeding risk was assessed using the HAS-BLED score. The study population was recruited from AURICULA, a Swedish national quality register for patients receiving anticoagulation treatment. All patients with the diagnosis AF in the catchment area are registered in AURICULA. Of the 65 532 inhabitants in the catchment area, 1616 were diagnosed with AF (1200 cases were characterized as chronic AF). Thus, the overall prevalence of AF was 2.5%. The prevalence increased with age from 6.3% in patients over 55 years of age to 13.8% in those over 80 years. The prevalence was higher in men than in women in all age groups. Overall, 56.3% and 85.1% of the population were at high risk of stroke (≥2 points) according to CHADS2 and CHA2 DS2 -VASc, respectively. In addition, 26.9% had an increased bleeding risk according to HAS-BLED. Within this large Caucasian population, we identified the highest community-based prevalence of AF to date. The prevalence was strongly associated with increasing age and male gender. Using CHA2 DS2 -VASc instead of CHADS(2) widened the indication for OAC prophylactic therapy of AF in this population.


Effects of lanthanum nitrate on behavioral disorder, neuronal damage and gene expression in different developmental stages of Caenorhabditis elegans.
Rare earth elements (REEs) are widely used in the industry, agriculture, biomedicine, aerospace, etc, and have been shown to pose toxic effects on animals, as such, studies focusing on their biomedical properties are gaining wide attention. However, environmental and population health risks of REEs are still not very clear. Also, the REEs damage to the nervous system and related molecular mechanisms needs further research. In this study, the L1 and L4 stages of the model organism Caenorhabditis elegans were used to evaluate the effects and possible neurotoxic mechanism of lanthanum(III) nitrate hexahydrate (La(NO3)3·6H2O). For the L1 and L4 stage worms, the 48-h median lethal concentrations (LC50s) of La(NO3)3·6H2O were 93.163 and 648.0 mg/L respectively. Our results show that La(NO3)3·6H2O induces growth inhibition and defects in behavior such as body length, body width, body bending frequency, head thrashing frequency and pharyngeal pumping frequency at the L1 and L4 stages in C. elegans. The L1 stage is more sensitive to the toxicity of lanthanum than the L4 stage worms. Using transgenic strains (BZ555, EG1285 and NL5901), we found that La(NO3)3·6H2O caused the loss or break of soma and dendrite neurons in L1 and L4 stages; and α-synuclein aggregation in L1 stage, indicating that Lanthanum can cause toxic damage to dopaminergic and GABAergic neurons. Mechanistically, La(NO3)3·6H2O exposure inhibited or activated the neurotransmitter transporters and receptors (glutamate, serotonin and dopamine) in C. elegans, which regulate behavior and movement functions. Furthermore, significant increase in the production of reactive oxygen species (ROS) was found in the L4 stage C. elegans exposed to La(NO3)3·6H2O. Altogether, our data show that exposure to lanthanum can cause neuronal toxic damage and behavioral defects in C. elegans, and provide basic information for understanding the neurotoxic effect mechanism and environmental health risks of rare earth elements.


Systematic evaluations regarding interparticular mass transfer in spheronization.
Pellets are frequently used in pharmaceutical applications. The extrusion-spheronization process is a well-established technique used to produce pellets of a spherical shape and narrow size distribution. In this process, cylindrical extrudates are transformed into spherical pellets by spheronization. Most established mechanisms consider only breakage and deformation to explain pellet formation. An interaction between the rounding extrudates via adhesion of fine particles was not considered for many years. This study deals with the evolution of pellet properties over time during the spheronization process in order to quantify the influence of pellet interactions on their properties. Therefore the most important pelletization aids (MCCI, MCCII and κ-carrageenan) were investigated using acetaminophen as a model drug and lactose as a filler. In the first seconds of the spheronization process, a high fine fraction was seen which decreased during the process. Simultaneously, the material transferred between the pellets increased. However the fine fraction is not high enough to explain the mass transfer; therefore a direct transfer between the pellets was assumed. The pelletization aid has a huge influence on the amount of mass transferred. Whereas κ-carrageenan leads to a quite low mass transfer of 15%, MCCI and MCCII show higher values up to 25%.


How soccer players head the ball: a test of Optic Acceleration Cancellation theory with virtual reality.
We measured the movements of soccer players heading a football in a fully immersive virtual reality environment. In mid-flight the ball's trajectory was altered from its normal quasi-parabolic path to a linear one, producing a jump in the rate of change of the angle of elevation of gaze (alpha) from player to ball. One reaction time later the players adjusted their speed so that the rate of change of alpha increased when it had been reduced and reduced it when it had been increased. Since the result of the player's movement was to regain a value of the rate of change close to that before the disturbance, the data suggest that the players have an expectation of, and memory for, the pattern that the rate of change of alpha will follow during the flight. The results support the general claim that players intercepting balls use servo control strategies and are consistent with the particular claim of Optic Acceleration Cancellation theory that the servo strategy is to allow alpha to increase at a steadily decreasing rate.


Severe congenital X-linked myopathy with excessive autophagy secondary to an apparently synonymous but pathogenic novel variant.
X-linked myopathy with excessive autophagy is a rare inherited disease characterized by aberrant accumulation of autophagic vacuoles in skeletal muscle. Affected males usually show a slow progression and the heart is characteristically spared. We present four male patients from the same family with an extremely aggressive form of this disease, requiring permanent mechanical ventilation from birth. Ambulation was never achieved. Three died, one in the first hour of life, one at 7 years and one at 17 years, the last death being a consequence of heart failure. Muscle biopsy showed pathognomonic features of the disease in the 4 affected males. Genetic study found a novel synonymous variant in VMA21, c.294C>T (Gly98=). Genotyping was consistent with co-segregation with the phenotype in an X-linked recessive manner. An alteration of the normal splice pattern was confirmed by transcriptome analysis, proving that the apparently synonymous variant was the cause of this extremely severe phenotype.


Purification and properties of heat-resistant exotoxin produced by Macrophomina phaseolina (Tassi) Goid in culture.
A partially purified preparation of a water-soluble, heat-resistant, nonspecific exotoxin produced by a strain of Macrophomina phaseolina, isolated from Phaseolus mungo L. could reduce Cu++ ions and produced a red colour with 2,4-dinitrophenyl hydrazine reagent. It caused inhibition of seed germination, wilting of cult seedlings, stunted growth of young seedlings and loss of permeability of the cell membrane. Seedlings of P. mungo, grown in presence of the toxin showed a slight increase in the contents of protein and total RNA over control, but a significant increase in the specific activities of F-1, 6-BP aldolase and G-6-P isomerase.


Conformational transition of hyaluronic acid: carboxylic group participation and thermal effect.
The chiroptical, viscosity and titration studies of hyaluronic acid in mixed organic/water solvent show a reversible conformational transition of the molecule depending upon pH, solvent composition, temperature, and molecular weight. Neither methylhyaluronate nor chondroitin undergoes conformational transition of this type. These results indicate that hydrogen bonding between the protonated carboxylic group and carbonyl oxygen of the acetamido group is directly involved in the conformational change. Results with chondroitin provide further support for the 4-fold helical structure that we have proposed for hyaluronic acid in mixed organic/water solvent. The thermal stability of the conformation has been studied under various pH values and solvent compositions.


Extracellular pH influences the mode of cell death in human colon adenocarcinoma cells subjected to photodynamic treatment with chlorin p6.
Effect of varying extracellular pH on mode of cell death induced by photodynamic action of chlorin p6 was investigated in human colon carcinoma (Colo-205) cells. At an extracellular pH of 7.4, compared to cells treated with chlorin p6 in dark, the photodynamically treated cells showed reduction in mitochondrial membrane potential, an increase in ADP/ATP ratio (1:2) and a large percentage of cells with chromatin condensation. In contrast, when photodynamic treatment and post irradiation incubation was carried out in acidic medium (pH 6.5), total loss of mitochondrial membrane potential, a marked increase in ADP/ATP ratio (1:33) and increased damage to plasma membrane were observed. Further, cells subjected to photodynamic treatment in a medium of pH 7.4 showed twofold increase in caspase-3 activity as compared to photodynamic treatment at pH 6.5. These results suggest that chlorin p6 mediated photodynamic action induces apoptotic cell death when extracellular pH is 7.4 whereas necrosis is more predominant under condition when extracellular pH is 6.5.


Ionic liquid phase microextraction combined with fluorescence spectrometry for preconcentration and quantitation of carvedilol in pharmaceutical preparations and biological media.
Carvedilol belongs to a group of medicines termed non-selective beta-adrenergic blocking agents. In the presented approach, a practical and environmentally friendly microextraction method based on the application of ionic liquids (ILs) was followed by fluorescence spectrometry for trace determination of carvedilol in pharmaceutical and biological media. A rapid and simple ionic liquid phase microextraction was utilized for preconcentration and extraction of carvedilol. A hydrophobic ionic liquid (IL) was applied as a microextraction solvent. In order to disperse the IL through the aqueous media and extract the analyte of interest, IL was injected into the sample solution and a proper temperature was applied and then for aggregating the IL-phase, the sample was cooled in an ice water-bath. The aqueous media was centrifuged and IL-phase collected at the bottom of the test tube was introduced to the micro-cell of spectrofluorimeter, in order to determine the concentration of the enriched analyte. Main parameters affecting the accuracy and precision of the proposed approach were investigated and optimized values were obtained. A linear response range of 10-250 μg I(-1) and a limit of detection (LOD) of 1.7 μg I(-1) were obtained. Finally, the presented method was utilized for trace determination of carvedilol in commercial pharmaceutical preparations and biological media.


Global translational control by the transcriptional repressor TrcR in the filamentous cyanobacterium Anabaena sp. PCC 7120.
Transcriptional and translational regulations are important mechanisms for cell adaptation to environmental conditions. In addition to house-keeping tRNAs, the genome of the filamentous cyanobacterium Anabaena sp. strain PCC 7120 (Anabaena) has a long tRNA operon (trn operon) consisting of 26 genes present on a megaplasmid. The trn operon is repressed under standard culture conditions, but is activated under translational stress in the presence of antibiotics targeting translation. Using the toxic amino acid analog β-N-methylamino-L-alanine (BMAA) as a tool, we isolated and characterized several BMAA-resistance mutants from Anabaena, and identified one gene of unknown function, all0854, named as trcR, encoding a transcription factor belonging to the ribbon-helix-helix (RHH) family. We provide evidence that TrcR represses the expression of the trn operon and is thus the missing link between the trn operon and translational stress response. TrcR represses the expression of several other genes involved in translational control, and is required for maintaining translational fidelity. TrcR, as well as its binding sites, are highly conserved in cyanobacteria, and its functions represent an important mechanism for the coupling of the transcriptional and translational regulations in cyanobacteria.


Influence of movement parameters on area 18 neurones in the cat.
In cats, 107 area 18 neurones with identified FR type, 10-50 degrees from the visual axis, were tested for the influence of direction, velocity and amplitude of movement. These three parameters are believed to be the primary parameters of a movement analysing system. 94% of the neurones were influenced by the direction of movement, all of them by the angular velocity and 16% by the amplitude of movement. For each of the primary parameters, tuning curves were established. Angular velocity influenced not only the response magnitude but also the response latency and the direction bias. By preparing response amplitude functions at different velocities the influence of movement duration was ruled out. The association of functional properties and RF organization suggests a model of information processing in area 18 of the cat.


Traumatic intraspinal pneumocele.
Traumatic intraspinal pneumocele (TIP) is a radiologic finding in which air is visualized within the spinal canal on routine cervical spine x-rays following a head injury. TIP may be the initial radiologic evidence of a severe central nervous system injury. The presence of TIP will alert a physician to the severity of the head injury, as well as the need for further radiologic investigations.


Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis.
This Chapter has reviewed the literature concerning VPF/VEGF as a potent vascular permeabilizing cytokine. In accord with this important role, microvessels have been found to be hyperpermeable to plasma proteins and other circulating macromolecules at sites where VPF/VEGF and its receptors are overexpressed, i.e., in tumors, healing wounds, retinopathies, many important inflammatory conditions and in certain physiological processes, such as ovulation and corpus luteum formation. Moreover, microvascular hyperpermeability to plasma proteins was shown to have an important consequence: the laying down of a fibrin-rich extracellular matrix. This provisional matrix, in turn, favors and supports the ingrowth of fibroblasts and endothelial cells which, together, transform the provisional matrix into the mature stroma characteristic of tumors and healed wounds. Finally, we have considered the pathways by which these and other circulating macromolecules cross the endothelium of normal and VPF/VEGF-permeabilized microvessels. These pathways include VVOs and trans-endothelial openings that have been variously interpreted as inter-endothelial cell gaps or trans-endothelial cell pores. At least some trans-endothelial cell pores may arise from VVOs. In conclusion, these data provide new insights into the mechanisms of angiogenesis and stroma formation, insights which are potentially applicable to a wide variety of disease states and which may lead to identification of new targets for therapeutic intervention.


Molecular origin of polyglutamine aggregation in neurodegenerative diseases.
Expansion of polyglutamine (polyQ) tracts in proteins results in protein aggregation and is associated with cell death in at least nine neurodegenerative diseases. Disease age of onset is correlated with the polyQ insert length above a critical value of 35-40 glutamines. The aggregation kinetics of isolated polyQ peptides in vitro also shows a similar critical-length dependence. While recent experimental work has provided considerable insights into polyQ aggregation, the molecular mechanism of aggregation is not well understood. Here, using computer simulations of isolated polyQ peptides, we show that a mechanism of aggregation is the conformational transition in a single polyQ peptide chain from random coil to a parallel beta-helix. This transition occurs selectively in peptides longer than 37 glutamines. In the beta-helices observed in simulations, all residues adopt beta-strand backbone dihedral angles, and the polypeptide chain coils around a central helical axis with 18.5 +/- 2 residues per turn. We also find that mutant polyQ peptides with proline-glycine inserts show formation of antiparallel beta-hairpins in their ground state, in agreement with experiments. The lower stability of mutant beta-helices explains their lower aggregation rates compared to wild type. Our results provide a molecular mechanism for polyQ-mediated aggregation.