Novel cold-sensitive cytosolic 3,5,3'-triiodo-L-thyronine-binding proteins in human red blood cell. Isolation and characterization.
Four cytosolic 3,5,3'-triiodo-L-thyronine-binding proteins (CTBP) were isolated from hemoglobin-free human erythrocyte on DEAE-cellulose column by linear gradient of NaCl (0-0.4 M). CTBP I, II, and IV underwent rapid loss of their activities at low temperatures, whereas CTBP III was cold-insensitive. Reactivation of cold-inactivated CTBPs by warming was obtained at 20 and 37 degrees C. CTBP I, II, and IV were not inhibited by thiol-blocking agents, whereas CTBP III was blocked. Scatchard analysis of L-3,5,3'-triodo-thyronine binding showed a high affinity site with Kd on the order of 10(-10) M for CTBP II and Kd values of about 10(-9) M for CTBP I and IV and of about 10(-8) M for CTBP III. The order of affinity of iodothyronine analogues to CTBPs was similar in CTBP I, II, and IV but different in CTBP III. Chromatography on Sephacryl S-200 HR showed the elution of a single peak for each CTBP. The apparent molecular weights were about 200,000, 200,000, 25,000, and 60,000 for CTBP I, II, III, and IV, respectively. The physiological relevance of these CTBPs is discussed.


[Risk factors for venous thromboembolism in hospitalized patients in internal medicine: case-control study of 150 patients].
Risk factors for the thrombo-embolic disease are not yet completely validated in medical setting. Indeed, there is a lack of scientific data concerning their prevalence and their thrombogenic weight. We carried out a prospective case-control study in an internal medicine unit where general acute pathologies are recruited. We have included two patients without thrombosis for each patient admitted for a thrombo-embolic event. In all patients, at admission, clinical and biological risk factors for thromboembolism were systematically analysed in a physiopathological and chronological way. 450 patients were included during the 27 months period of the study. Among these patients, 150 were hospitalised for a deep venous thrombosis of the leg or/and a pulmonary embolism. Height risk factors have demonstrated their high thrombogenic potential: paralysis of the legs (OR = 13; 95% CI: 1.4 to 5.1), post-thrombotic syndromes (OR = 13; CI: 1.7 to 4.3), extrinsic compressions (OR = 8; CI: 1.3 to 5.4), pregnancy (OR = 6; CI: 1.2 to 6), malignancy occurred one year before (OR = 4; CI: 1.1 to 6.7), personal history of deep vein thrombosis (OR = 3; CI: 1.6 to 4.5), varicosity (OR = 2.5; CI: 1.2 to 6.1) and venous insufficiency (OR = 1.7; CI: 1 to 7.4). Four parameters, generally considered as risk factors, didn't prove here their pathogenic power: the age over 60, obesity (BMI > 27), bedrest and the presence of an on-going malignancy. Only risk factors with high thrombogenic power (as paralysis or extrinsic compression for example) could be identified by this kind of study performed in polypathological patients. In this particular population, usually recognised risk factors as age, obesity and bedrest are not determinant parameters for the thomboembolic risk evaluation.


Mendelian Randomization With Repeated Measures of a Time-varying Exposure: An Application of Structural Mean Models.
Mendelian randomization (MR) is often used to estimate effects of time-varying exposures on health outcomes using observational data. However, MR studies typically use a single measurement of exposure and apply conventional instrumental variable (IV) methods designed to handle time-fixed exposures. As such, MR effect estimates for time-varying exposures are often biased, and interpretations are unclear. We describe the instrumental conditions required for IV estimation with a time-varying exposure, and the additional conditions required to causally interpret MR estimates as a point effect, a period effect or a lifetime effect depending on whether researchers have measurements at a single or multiple time points. We propose methods to incorporate time-varying exposures in MR analyses based on g-estimation of structural mean models, and demonstrate its application by estimating the period effect of alcohol intake, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol on intermediate coronary heart disease outcomes using data from the Framingham Heart Study. We use this data example to highlight the challenges of interpreting MR estimates as causal effects, and describe other extensions of structural mean models for more complex data scenarios.


The impact of set size on cumulative area judgments.
The ability to track number has long been considered more difficult than tracking continuous quantities. Evidence for this claim comes from work revealing that continuous properties (specifically cumulative area) influence numerical judgments, such that adults perform worse on numerical tasks when cumulative area is incongruent with number. If true, then continuous extent tracking abilities should be unimpeded by number. The aim of the present study was to determine the precision with which adults track cumulative area and to uncover the process by which they do so. Across two experiments, we presented adults with arrays of dots and asked them to judge the relative cumulative area of the displays. Participants performed worse and were slower on incongruent trials, in which the more numerous array had the smaller cumulative area. These findings suggest that number interferes with continuous quantity judgments, and that number is at least as salient as continuous variables, undermining claims in the literature that continuous properties are easier to represent, and more salient to adults. Our primary research question, however, pertained to how cumulative area representations were impacted by set size. Results revealed that the area of a single item was tracked much faster and with greater precision than the area of multiple items. However, for sets with more than one item, results revealed less accurate, yet faster responses, as set size increased, suggesting a speed-accuracy trade-off in judgments of cumulative area. Results are discussed in the context of two distinct theories regarding the process of tracking cumulative area.


The effect of early customized vestibular rehabilitation on balance after acoustic neuroma resection.
To compare the effect of early customized vestibular rehabilitation with general instructions in patients after acoustic neuroma surgery. Tertiary referral centre. Fifty-three patients after surgery. A prospective assessor-blinded, randomized controlled trial. After stratification for age (<50 years; >or=50 years), patients were randomly allocated into groups receiving general instructions or customized vestibular rehabilitation protocols for 12 weeks. Standing Balance Sum, Timed Up and Go test, Tandem Gait and Dynamic Gait Index. Balance performance was assessed preoperatively, at discharge (one week after surgery), three, six, nine, 12, 26 and 52 weeks after surgery. All subjects clearly improved within the first six weeks after surgery. However, older subjects receiving vestibular rehabilitation performed significantly (P<0.05) better on standing balance, Timed Up and Go test and Tandem Gait, when compared with the older group that received only general instructions. This effect persisted up to 12 weeks and also became apparent on the Dynamic Gait Index. In addition, the older vestibular rehabilitation group had better balance scores at 12 weeks when compared with their original preoperative scores (P<0.05). This pattern remained even up to one year after surgery (P<0.05). In patients over 50, early vestibular rehabilitation facilitates recovery of postural control after acoustic neuroma surgery. Customized vestibular rehabilitation should be given in addition to general instructions that stress the need of exposure to movement. Retention of the early beneficial effects even one year after surgery stresses the importance of customized vestibular rehabilitation.


No evidence of EMAST in whole genome sequencing data from 248 colorectal cancers.
Microsatellite instability (MSI) is caused by defective DNA mismatch repair (MMR), and manifests as accumulation of small insertions and deletions (indels) in short tandem repeats of the genome. Another form of repeat instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), has been suggested to occur in 50% to 60% of colorectal cancer (CRC), of which approximately one quarter are accounted for by MSI. Unlike for MSI, the criteria for defining EMAST is not consensual. EMAST CRCs have been suggested to form a distinct subset of CRCs that has been linked to a higher tumor stage, chronic inflammation, and poor prognosis. EMAST CRCs not exhibiting MSI have been proposed to show instability of di- and trinucleotide repeats in addition to tetranucleotide repeats, but lack instability of mononucleotide repeats. However, previous studies on EMAST have been based on targeted analysis of small sets of marker repeats, often in relatively few samples. To gain insight into tetranucleotide instability on a genome-wide level, we utilized whole genome sequencing data from 227 microsatellite stable (MSS) CRCs, 18 MSI CRCs, 3 POLE-mutated CRCs, and their corresponding normal samples. As expected, we observed tetranucleotide instability in all MSI CRCs, accompanied by instability of mono-, di-, and trinucleotide repeats. Among MSS CRCs, some tumors displayed more microsatellite mutations than others as a continuum, and no distinct subset of tumors with the previously proposed molecular characters of EMAST could be observed. Our results suggest that tetranucleotide repeat mutations in non-MSI CRCs represent stochastic mutation events rather than define a distinct CRC subclass.


Hysteroscopic treatment of severe Asherman's syndrome and subsequent fertility.
In a retrospective case report series, we evaluated the efficacy of hysteroscopic adhesiolysis in patients with severe Asherman's syndrome. In 31 patients with permanent severe adhesions, hysteroscopic treatment was performed. In all patients, uterine cavity with at least one free ostial area was restored after one (n = 16), two (n = 7), three (n = 7), and four (n = 1) surgical procedures. All previously amenorrhoeic patients (n = 16) had resumption of menses. Twenty-eight patients were followed-up with a mean time of 31 months (range 2-84). Fifteen pregnancies were obtained in 12 patients and the outcomes were the following: two first trimester missed abortions, three second trimester fetal losses, one second trimester termination of pregnancy for multiple fetal abnormalities and nine live births in nine different patients. Pregnancy rate after treatment was 12/28 (42.8%) and live birth rate was 9/28 (32.1%). In patients </=35 years, 10 out of 16 conceived (62.5%) versus two out of 12 (16.6%) in patients >35 years (P = 0. 01). Three patients were lost to follow-up and their results omitted. In nine patients with live births, one Caesarean hysterectomy for placenta accreta and one hypogastric arteries ligation for severe haemorrhage and placenta accreta were performed. Hysteroscopic treatment of severe Asherman's syndrome appeared to be effective for the reconstruction of a functional uterine cavity with a 42.8% pregnancy rate. However, these pregnancies were at risk for haemorrhage with abnormal placentation.


Neurocognitive aspects of pediatric sickle cell disease.
Studies pertaining to the neurocognitive functioning and learning of children in whom sickle cell disease is diagnosed are reviewed, and findings suggest diffuse neurocognitive deficits, with much variability across subjects. A hypothesis is presented about the cumulative nature of such deficits in children who have not sustained cerebral vascular accidents. Important methodological shortcomings in the literature are identified and recommendations are made for future neurocognitive research with children in whom sickle cell disease has been diagnosed. Studies pertaining to the psychosocial development of these children are also reviewed, and it is concluded that behavioral problems, low self-esteem, and disturbances of body image are frequently characteristic of these children. Recommendations are made including early special education and psychosocial intervention programs for children with sickle cell disease.


Bladder papillary urothelial neoplasm of low malignant potential in Chinese: a clinical and pathological analysis.
Papillary urothelial neoplasm of low malignant potential (PUNLMP) had the incidence of low and definitive recurrence. Therefore, few studies showed that the relationship between pathological factors and the prognosis of patients with PUNLMP. The aim of this study assessed the linkage of pathological factors and prognosis of patients with PUNLMP including the presence or absence of mitoses and the thickness of urothelium. A retrospective analysis of 71 patients with PUNLMP was enrolled between January 2007 and June 2013. The clinicopathological factors consisting of tumor diameter, multifocality, the presence or absence of mitoses and cell thickness of urothelium were retrieved, Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses to evaluate the associations of these factors with recurrence-free survival (RFS) and progression-free survival (PFS).The incidence of recurrence and progression for PUNLMP was 19.7% and 16.9%, respectively. Patients with grade progression represented 85.7% in the recurrent patients. No patients had stage progression and no cases died from invasive urothelial carcinoma. Univariate analysis showed that the presence of mitoses, tumor diameter greater than or equal to 0.8 cm, multifocality were significantly correlated with worse RFS (P<0.05) and PFS (P<0.05). Multivariate analysis demonstrated that the presence of mitoses, tumor multifocality were significantly independent biomarkers for worse RFS (P<0.05) and PFS (P<0.05). Although the rare and infrequent mitoses were found for PUNLMP, the presence of mitoses and tumor multifocality were still the independent and poor predictors for the prognosis of PUNLMP. In addition, once the PUNLMP appeared to the recurrence, the inevitable grade progression could be determined, herein, long-term follow-up was necessary to be warranted, especially for patients with multiple lesions and the presence of mitoses.


The effects of dry period length and dietary energy source on natural antibody titers and mammary health in dairy cows.
In earlier studies, natural antibodies (NAb) were related not only to the energy balance (EB) of dairy cows, but also to somatic cell count (SCC) and clinical mastitis (CM). The first objective of our study was to evaluate the effects of dry period length and dietary energy source on titers of NAb binding keyhole limpet hemocyanin (KLH) and lipopolysaccharide (LPS) in plasma and milk, SCC and CM occurrence in dairy cows in two subsequent lactations. Our second objective was to study the relationship between NAb levels and mammary health. Holstein-Friesian dairy cows (N=167) were randomly assigned to three dry period lengths (0, 30 or 60-d) and two early lactation rations (glucogenic or lipogenic). Treatments were repeated during two subsequent lactations (years 1 and 2). In year 2, 19 cows which were planned to have 0-d dry period dried off naturally and were assigned to an additional group 0→30-d dry period. In year 1, cows with a 0-d dry period had a higher SCC, a higher titer of immunoglobulin G (IgG) binding LPS in plasma, and higher titers of IgG and IgM binding KLH and LPS in milk compared with cows with a 30-d or 60-d dry period. In year 2, cows with a 60-d dry period had a lower SCC than cows with a 30-d and 0→30-d dry periods. In year 2, dry period length did not affect NAb titers in plasma or milk. The CM occurrence was 17 percent in year 1 of the experiment and 25 percent in year 2, and did not differ according to dry period lengths or rations. For both years, an increasing titer of IgG binding LPS in plasma was associated with decreased odds of a high SCC and decreased odds of CM occurrence. Also up to three weeks before the CM occurrence, an increasing titer of IgM binding KLH and LPS in plasma was associated with a decreased odds of CM occurrence. In conclusion, omitting the dry period increased SCC, NAb titers in milk and IgG binding LPS in plasma compared with a short (30-d) or conventional (60-d) dry period. The effects on NAb titers, however, were only present in the first year after omitting the dry period and disappeared after repeated omitting the dry period. Moreover, an increasing titer of IgG binding LPS in plasma was associated with decreased odds of high SCC and CM occurrence.


Beyond the Lungs: Systemic Manifestations of Pulmonary Arterial Hypertension.
Pulmonary arterial hypertension (PAH) is a disease characterized by progressive loss and remodeling of the pulmonary arteries, resulting in right heart failure and death. Until recently, PAH was seen as a disease restricted to the pulmonary circulation. However, there is growing evidence that patients with PAH also exhibit systemic vascular dysfunction, as evidenced by impaired brachial artery flow-mediated dilation, abnormal cerebral blood flow, skeletal myopathy, and intrinsic kidney disease. Although some of these anomalies are partially due to right ventricular insufficiency, recent data support a mechanistic link to the genetic and molecular events behind PAH pathogenesis. This review serves as an introduction to the major systemic findings in PAH and the evidence that supports a common mechanistic link with PAH pathophysiology. In addition, it discusses recent studies describing morphological changes in systemic vessels and the possible role of bronchopulmonary anastomoses in the development of plexogenic arteriopathy. On the basis of available evidence, we propose a paradigm in which metabolic abnormalities, genetic injury, and systemic vascular dysfunction contribute to systemic manifestations in PAH. This concept not only opens exciting research possibilities but also encourages clinicians to consider extrapulmonary manifestations in their management of patients with PAH.


Functional polymorphisms in dopamine and serotonin pathway genes.
There is mounting evidence on the functional significance of single nucleotide and simple repeat sequence polymorphisms in both the coding and regulatory regions of genes in the monoamine neurotransmitter pathways. Many of these gene variants have been associated with human behavioral disorders and traits, and thus have important clinical relevance. This review summarizes the literature on the published functional studies from a molecular, cellular, and neurobiological perspective, and notes their possible behavioral consequences. Functional studies have adopted a variety of strategies. Pharmacological studies have focused on the effects of gene variation at the protein level in terms of binding to ligands or drugs. Other key investigations have determined effects on gene expression at the level of transcription in mammalian cell cultures, lymphoblasts, and/or human postmortem brain tissue. This has enabled the comparison of in vitro and in vivo data, and furthermore provides an improved perceptive of their respective advantages. Additionally, molecular biological approaches have identified transcription factors (DNA-binding proteins) that interact with the motifs within the polymorphisms themselves. Various neuroimaging studies have further determined the relationship of genotype with protein availability in the brain, and thus have contributed to our understanding of the in vivo functional significance of gene variants. Finally, there is growing evidence from both human and animal studies on the interaction of functional polymorphisms with the environment in determining a behavioral outcome. Taken together, these findings have contributed to a greater understanding of the plausible molecular mechanisms that underpin the functional significance of polymorphisms in monoamine neurotransmitter pathway genes, and how they may influence behavioral phenotypes.


Developmental Regulation of beta-Conglycinin in Soybean Axes and Cotyledons.
Analysis of the expression of genes encoding the beta-conglycinin seed storage proteins in soybean has been used to extend our understanding of developmental gene expression in plants. The alpha, alpha', and beta subunits of beta-conglycinin are encoded by a multigene family which is organ-specific in its expression. In this study we report the differentially programmed accumulation of the alpha, alpha', and beta subunits of beta-conglycinin. Multiple isomeric forms of each subunit are present in the dry seed, but the timing of their accumulation is unique for each subunit. The previously reported variation in amount of alpha' and alpha subunits in axis and cotyledons is also reflected in the amount of subunit specific mRNA which is present in each tissue. The beta subunit, previously undetected in soybean axes, is found to be synthesized but rapidly degraded. These differences in beta-conglycinin protein accumulation may be reflected by the morphological differences observed in protein bodies between these two tissues.


Pretreatment of 2,4-dinitroanisole (DNAN) producing wastewater using a combined zero-valent iron (ZVI) reduction and Fenton oxidation process.
A combined zero-valent iron (ZVI) reduction and Fenton oxidation process was tested for the pretreatment of 2,4-dinitroanisole (DNAN) producing wastewater. Operating conditions were optimized and overall performance of the combined process was evaluated. For ZVI process, almost complete reduction of nitroaromatic compounds was observed at empty bed contact time (EBCT) of 8h. For Fenton process, the optimal pH, H₂O₂ to Fe(II) molar ratio, H₂O₂ dosage and hydraulic retention time (HRT) were found to be 3.0, 15, 0.216 mol/L and 5h, respectively. After pretreatment by the combined ZVI-Fenton process under the optimal conditions, aromatic organic compound removal was as high as 77.2%, while the majority of COD remained to be further treated by sequent biological process. The combined anaerobic-aerobic process consisted of an anaerobic baffled reactor (ABR) and a moving-bed biofilm reactor (MBBR) was operated for 3 months, fed with ZVI-Fenton effluent. The results revealed that the coupled ZVI-Fenton-ABR-MBBR system was significantly efficient in terms of correcting the effluent's main parameters of relevance, mainly aromatic compounds concentration, COD concentration, color and acute toxicity. These results indicate that the combined ZVI-Fenton process offers bright prospects for the pretreatment of wastewater containing nitroaromatic compounds.


Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists.
3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described. Developed by reasoned modification of the known anxiolytic benzodiazepines, these compounds provide highly potent, orally effective ligands selective for peripheral (CCK-A) receptors, with binding affinities approaching or equaling that of the natural ligand CCK-8. The distinction between CCK-A receptors on the one hand and CNS (CCK-B), gastrin, and central benzodiazepine receptors on the other is demonstrated by using the structure-activity profiles of the new compounds. Details of the binding of these agents to CCK-A receptors are examined, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.


Organic triplet emissions of arylacetylide moieties harnessed through coordination to [Au(PCy(3))]+. Effect of molecular structure upon photoluminescent properties.
A family of mono- and binuclear Cy(3)P-supported gold(I) complexes containing various pi-conjugated linear arylacetylide ligands, including the two homologous series (Cy(3)P)Au(Ctbd1;CC(6)H(4))(n)()(-)(1)(Ctbd1;CPh) and (Cy(3)P)Au(Ctbd1;CC(6)H(4))(n)()Ctbd1;CAu(PCy(3)) (n = 1-4), have been prepared. X-ray crystal analyses revealed no intermolecular aurophilic interactions in their crystal lattice. The lowest-energy singlet transitions are predominately intraligand in nature and exhibit both phenyl and acetylenic (1)(pipi) character. Strong photoluminescence is detected in solid and solution states under ambient conditions, with lifetimes in the microsecond regime. For complexes with a single arylacetylide group, only phosphorescence from the arylacetylide (3)(pipi) state is observed. Vibrational spacings in the solid-state emission spectra can be attributed to a combination of phenyl ring deformation and symmetric phenyl ring and Ctbd1;C stretches. Additional delayed-fluorescence emission is recorded for complexes with multiple p-arylacetylide units, and this is attributed to a triplet-triplet annihilation process. The phosphorescence energy of these complexes are readily modified by altering the length of the conjugated arylacetylide system, while the intensity of phosphorescence relative to fluorescence decreases when the p-arylacetylide chain is elongated. Information regarding the nature and relative energies of arylacetylide singlet and triplet excited states has been derived from the two homologous series and extrapolated to polymeric arylacetylide species. The (3)(pipi) excited-state reduction potentials E degrees [Au(+)/Au] (Au = 1a, 2, and 4) are estimated to be -1.80, -1.28, and -1.17 V versus SSCE, respectively.


Psychological Antecedents and Consequences of Social Integration Based on Self-Disclosure in Virtual Communities: Empirical Evidence From Sina Microblog.
With the normalization of COVID-19 prevention and control, a large number of intergenerational audiences with different cognition preferences and value orientations have started to pour into non-acquaintance virtual communities (VCs) to address their social needs by disclosing their own thoughts, feelings and experiences toward certain topics. To avoid the negative impacts of self-disclosure, this study introduced the concept of social integration into cyber society among non-acquaintance VCs, such as the topic-based VCs. Our theoretical model considers both the psychological antecedents and consequences of VC audiences' social integration and our findings have implications for public online (and even offline) social life. Moreover, this research could play a guiding role in improving VC audiences' social integration status in future online learning and telecommuting scenarios. To assess the theoretical model constructed in this manuscript, we conducted an online survey in two different topic-based VCs among Microblog and yielded 472 useable responses from intergenerational audiences, among which 28.81% were born before 1985, 26.67% were born from 1985 to 1995, and 48.52% were born after 1995. Our sample consisted of 208 individuals from Health Regimen VC and 264 individuals from Star Chasing VC, 200 (42.37%) were men and 272 (57.63%) were women. Our structural equation model (SEM) indicated that individuals' self-disclosure in topic-based VCs might not directly guide them to acquire social integration. However, intimacy and cognitive communion derived from VC audiences' self-disclosure might not only enhance their social integration, but also improve their psychological well-being. In addition, VC audiences' social integration mediated the relationship between intimacy and psychological well-being, and the relationship between cognitive communion and psychological well-being. Moreover, VC audiences' intimacy was found to have a direct influence on their cognitive communion. In the context of topic-based VCs, audiences' self-disclosure could significantly foster their intimacy and cognitive communion with others, and both intimacy and cognitive communion are conductive to VC audiences' social integration. Thus, audiences in topic-based VCs who wish to improve their psychological well-being need to disclose themselves and build corresponding psychological foundations (i.e., intimacy and cognitive communion) to enhance their social integration. Meanwhile, topic-based VCs should pay attention to the cultivation of intimacy and cognitive communion among audiences while encouraging them to reveal themselves.


Stroke monitoring on a national level: PERFECT Stroke, a comprehensive, registry-linkage stroke database in Finland.
Stroke databases are established to systematically evaluate both the treatment and outcome of stroke patients and the structure and processes of stroke services. Comprehensive data collection on this common disease is resource-intensive, and national stroke databases often include only patients from selected hospitals. Here we describe an alternative national stroke database. We established a nationwide stroke database with multiple administrative registry linkages at the individual-patient level. Information on comorbidities; treatments before, during, and after stroke; living status; recurrences; case fatality; and costs were collected for each hospital-treated stroke patient. The current database includes 94 316 patients with incident stroke between January 1999 and December 2007, with follow-up until December 2008. Annually, 10 500 new patients are being added. One-year recurrence was 13% and case fatality was 27% during the study period. In 2007, 86% of patients survived 1 month and 77% were living at home at 3 months, but the proportion treated in stroke centers (62%) or with nationally recommended secondary preventive medication after ischemic stroke (49%) was still suboptimal. In comparison with other national stroke databases, our method enables higher coverage and more thorough follow-up of patients. Information on long-term recurrences, case fatality, or costs is not often included in national stroke databases. Our database has low maintenance costs, but it lacks detailed data on in-hospital processes. Use of national administrative data, where such linkage is possible, saves resources, achieves high rates of long-term follow-up, and allows for comprehensive monitoring of the burden of the disease.


Biocompatible and Antibacterial Nitric Oxide-Releasing Pluronic F-127/Chitosan Hydrogel for Topical Applications.
Nitric oxide (NO) is involved in physiological processes, including vasodilatation, wound healing and antibacterial activities. As NO is a free radical, designing drugs to generate therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL)-chitosan (CS) hydrogel, with an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL-1 of hydrogel, which corresponds to 1 mmol·L-1 of GSNO). Interestingly, the concentration range in which the NO-releasing hydrogel demonstrated an antibacterial effect was not found to be toxic to the Vero mammalian cell. Thus, the GSNO-PL/CS hydrogel is a suitable biomaterial for topical NO delivery applications.


Application of diffusional kurtosis imaging to detect occult brain damage in multiple sclerosis and neuromyelitis optica.
Multiple sclerosis (MS) and neuromyelitis optica (NMO) are two common types of inflammatory demyelinating disease of the central nervous system. Early distinction of NMO from MS is crucial but quite challenging. In this study, 13 NMO spectrum disorder patients (Expanded Disability Status Scale (EDSS) of 3.0 ± 1.7, ranging from 2 to 6.5; disease duration of 5.3 ± 4.7 years), 17 relapsing-remitting MS patients (EDSS of 2.6 ± 1.4, ranging from 1 to 5.5; disease duration of 7.9 ± 7.8 years) and 18 healthy volunteers were recruited. Diffusional kurtosis imaging was employed to discriminate NMO and MS patients at the early or stable stage from each other, and from healthy volunteers. The presence of alterations in diffusion and diffusional kurtosis metrics in normal-appearing white matter (NAWM) and diffusely increased mean diffusivity (MD) in the cortical normal-appearing gray matter (NAGM) favors the diagnosis of MS rather than NMO. Meanwhile, normal diffusivities and kurtosis metrics in all NAWM as well as increases in MD in the frontal and temporal NAGM suggest NMO. Our results suggest that diffusion and diffusional kurtosis metrics may well aid in discriminating the two diseases.


MyWelch: building an information portal system in a medical library environment.
MyWelch is a medical library portal system that users can use to create customized web sites that reflect their research needs and personal interests. In the MyWelch environment, faculty and students are empowered to take a greater role in identifying their needs and determining their requirements in the electronic environment. The portal system also facilitates interaction among library users and staff.


Non-Mendelian Inheritance of 3-(3,4-Dichlorophenyl)-1,1-dimethylurea-Resistant Thylakoid Membrane Properties in Chlamydomonas.
A uniparentally inherited 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)-resistant mutant of Chlamydomonas reinhardii, Dr2, which has a resistance mechanism of the type defined as ;primary,' has been isolated. In vitro Hill reactions catalyzed by isolated thylakoid membranes reveal a reduced apparent affinity of the thylakoids for DCMU. These changes in membrane properties quantitatively account for the resistance of mutant Dr2 to herbicide inhibition of growth. The properties of this mutant show that all of the Hill reaction-inhibiting DCMU binding sites are under identical genetic control. Mutant Dr2 is a useful new uniparental genetic marker, since it has a novel phenotype and it may be possible to identify its altered gene product. The low cross-resistance of Dr2 to atrazine suggests that there may be considerable flexibility in exploiting induced herbicide resistance of crop plants for improving herbicide specificity.Four mendelian mutants in at least three loci all have resistance mechanisms in the class we define as ;secondary.' They are as sensitive as wild type to in vitro inhibition of the Hill reaction, and must acquire resistance in vivo by preventing the active form of the herbicide from reaching the sensitive site.


'Inside-out', back-to-front: a model for clinical population genetic screening.
Developments in DNA technology have resulted in a dramatic increase in the number of genes identified. With the localisation of a gene it is possible to devise procedures suitable for mass carrier screening programmes. Until recently mass carrier screening was only possible for a limited number of disorders, for example, Tay-Sachs disease and haemoglobinopathies. Counselling possible carriers was based on estimations of risk. The momentum towards mass carrier screening is likely to be increased by gene therapy. Carrier screening for cystic fibrosis alone will have dramatic implications for genetic service provision as 4 to 5% of the UK population carry the CF gene. The potential for genetic screening of multifactorial diseases, for example, cancers, should also be considered. The existing organisation of genetic services is likely to be inadequate. A new specialty of clinical population genetics is required. A model is proposed of clinical population genetic screening programmes, organised under a 'common umbrella' led by a public health physician, while screening and follow up will remain the responsibility of the appropriate clinician.


Understanding Age-based Transition Needs: Perspectives from Adolescents and Adults with Congenital Heart Disease.
The purpose of this study was to explore the transition process in congenital heart disease (CHD) care through the perceived needs and concerns of adolescents (pretransition) and the experiential insight from adults (post-transition), in order to inform future transition initiatives and information delivery methods. In this cross-sectional study, adolescents and adults with moderate or complex CHD participated in semistructured telephone interviews. Interview transcripts were coded using NVivo qualitative data software. Single large urban tertiary care CHD center Adolescents (between 16 and 20 years of age) and adults (21-40 years of age) with moderate or complex CHD. Patients with global developmental delay or known chromosomal abnormalities were excluded. Twenty adolescents and 20 adults participated in the study; each interview allowed for participants to discuss issues relevant to them. Among adolescents, half wanted more CHD information and half were concerned about becoming adults with CHD. All adolescents had access to the Internet via a mobile phone, but only 55% had searched online for CHD information. Adolescents were interested in mentorship with other adolescents (90%) and adults (60%) with CHD either in person or via protected social media. Among adults, 55% were satisfied with the amount of information they had received as adolescents. Areas in which adults would have preferred additional information include longer-term implications of CHD, employment, insurance, family planning, and mental health. There are similarities and differences in the perceived transition needs of a diverse group of adolescents and adults with CHD. Both cohorts desire additional information during the transition process, including interest in use of a transition checklist to learn about managing their CHD. Adolescents are interested in interactions with other teens and adult mentors with CHD and are open to Internet-based interventions. Web-based initiatives could deliver CHD information and provide a platform for social media mentorship.


[SDS-PAGE analysis of surface proteins and antigens evidences high heterogenity in natural clones of Trypanosoma cruzi, correlated with isoenzyme variability].
Surface protein and surface antigen patterns of 19 Trypanosoma cruzi laboratory clones, representing 17 different isozymic profiles (zymodemes), were compared by SDS-PAGE analysis. Surface protein patterns were found to be complex and heterogeneous. According to the number of common bands, we calculated similarity coefficients of surface protein patterns on the one hand, and of surface antigen patterns on the other hand, for 33 stock pairwise comparisons. In both cases, these coefficients were statistically correlated to the isozyme index of genetic identity. Such a correlation between independent genetic markers favours the clonal structure of T. cruzi natural populations previously evidenced. Moreover, we did not observe any notable differences in the surface antigen pattern among 4 T. cruzi cloned stocks precipitated by homologous as well as heterologous hyperimmune sera. The immunological significance of the molecular weight variability in surface antigen patterns among different zymodemes is discussed.


Different inoculum of Leishmania braziliensis concentrations influence immunopathogenesis and clinical evolution in the ear dermis hamster model of cutaneous leishmaniasis.
The golden hamster (Mesocricetus auratus) is commonly used as a promising model for Leishmania braziliensis infection developing skin-ulcerated lesions. However, different protocols using high concentration of parasites inoculated in the footpad result in severe clinical disease. Here, we further investigate the outcome of the site of infection and concentration of L. braziliensis parasites inoculated on the immunopathogenesis and clinical evolution. Initially, hamsters were infected in the ear dermis or hind footpad with a concentration of 1 × 105 parasites. Animals infected in the ear dermis developed a disease, with an increased parasite load that more closely resembled human cutaneous leishmaniasis lesions comparing to the group infected in the footpad. Next, we evaluated if different parasite concentrations (104 , 105 and 106 ) inoculated in the ear dermis would impact the course and clinical aspects of infection. Hamsters infected with 104 and 105 parasites developed mild lesions compared to the group infected with 106 that presented severe and persistent lesions. The parasite load varied between the different parasite concentrations. The inflammatory response was more intense when infection was initiated with 106 parasites accompanied by an increased initial expression of IL-4, IL-10 and arginase in the lymph node followed by expression of both pro-and anti-inflammatory cytokines comparing to groups infected with 104 and 105 parasites. In conclusion, the number of parasites inoculated, and the initial site of infection could influence the inflammatory response, and clinical presentation. Our results suggest that the ear dermis infection model induces a chronic disease that relates to immunopathological aspects of CL natural infection.


Oral health literacy and information sources among adults in Tehran, Iran.
To assess oral health literacy level and oral health information of Iranian adults in Tehran, and to determine the factors related to oral health literacy. A cross-sectional population study. A random sample of 1,031 adults in Tehran, Iran. Oral health literacy was measured using an oral health adult literacy questionnaire (OHL-AQ). Variation in use of information sources by socio-economic and demographic background was estimated by odds ratios. A multiple linear regression model served to determine predictor factors of OHL-AQ scores controlling for characteristics of the subjects and number of information sources. The mean OHL-AQ score was 10.5 (sd 3.0). Women (p < 0.001), younger (p < 0.001), and better educated participants (p < 0.001) had higher OHL-AQ scores. The most common sources of oral health information were dentists (52.6%), and TV/Radio (49.5%). According to the regression model, females (p = 0.001), high educational level (p < 0.001), and use of multiple information sources (two sources p = 0.01, three sources or more p = 0.002) were the main predictor factors of OHL-AQ scores. The average oral health literacy level of Iranian adults was low. Disseminating evidence-based oral health care information from multiple sources including TV/radio, dentists, and other health professionals in different settings should improve public oral health literacy.


Estimating costs of mental health and substance abuse coverage.
The cost of expanding mental health and substance abuse treatment coverage is a major impediment to reforming insurance coverage for these types of conditions. The recent experience with national health care reform offers a case study in cost estimation for mental health and substance abuse coverage. The impact of managed care and the cost of expanding coverage to currently uninsured persons introduced uncertainty into predictions. This paper critically reviews that experience and draws lessons for estimating future costs of policy initiatives.


Interest in new heterodinuclear transition-metal/main-group-metal complexes: DFT study of electronic structure and mechanism of fluoride sensing function.
Systematic DFT calculations were carried out on a series of heterodinuclear complexes [(o-(Ph2P)C6H4)3M(1)M(2)Cl](+) (M(1) = As, Sb, or Bi; M(2) = Pd or Pt) to investigate the mechanism of colorimetric sensing function for the fluoride anion. The fluoride anion binds with the M(1) center to afford a hypervalent M(1) species with large stabilization energy. For instance, the stabilization energy by the fluoride adduct formation is -15.5 kcal mol(-1) for 3 (M(1) = Sb; M(2) = Pd) and -16.2 kcal mol(-1) for 6 (M(1) = Sb; M(2) = Pt), where a negative value represents stabilization. Interestingly, the allosteric coordination of the third phosphine with the M(2) center is induced by the fluoride adduct formation. For chloride, bromide, and thiocyanide anions, the binding energies are positive (~4.5 kcal mol(-1)), and the allosteric coordination does not occur. The allosteric coordination plays a crucial role in the absorption spectrum change induced by the fluoride adduct formation. For instance, the fluoride adduct formation quenches the absorption band of 3 around 400 nm and newly exhibits two absorption peaks at longer wavelength, 475 and 451 nm. These two peaks are assigned to ligand-field transitions (d(xy)→ d(z(2)) and d(x(2)-y(2))→ d(z(2))) including metal-to-ligand charge transfer character. We discussed the reasons why the allosteric coordination can occur only in the fluoride adduct and induces these two absorptions in the longer wavelength region. In addition, the Bi-Pd combination is also recommended for a fluoride sensing material, while the Sb-Pt combination is recommended for cyanide sensing.


Quantifying water pathogen risk in an epidemiological framework.
Traditionally, microbial risk assessors have used point estimates to evaluate the probability that an individual will become infected. We developed a quantitative approach that shifts the risk characterization perspective from point estimate to distributional estimate, and from individual to population. To this end, we first designed and implemented a dynamic model that tracks traditional epidemiological variables such as the number of susceptible, infected, diseased, and immune, and environmental variables such as pathogen density. Second, we used a simulation methodology that explicitly acknowledges the uncertainty and variability associated with the data. Specifically, the approach consists of assigning probability distributions to each parameter, sampling from these distributions for Monte Carlo simulations, and using a binary classification to assess the output of each simulation. A case study is presented that explores the uncertainties in assessing the risk of giardiasis when swimming in a recreational impoundment using reclaimed water. Using literature-based information to assign parameters ranges, our analysis demonstrated that the parameter describing the shedding of pathogens by infected swimmers was the factor that contributed most to the uncertainty in risk. The importance of other parameters was dependent on reducing the a priori range of this shedding parameter. By constraining the shedding parameter to its lower subrange, treatment efficiency was the parameter most important in predicting whether a simulation resulted in prevalences above or below non outbreak levels. Whereas parameters associated with human exposure were important when the shedding parameter was constrained to a higher subrange. This Monte Carlo simulation technique identified conditions in which outbreaks and/or nonoutbreaks are likely and identified the parameters that most contributed to the uncertainty associated with a risk prediction.


Isolation and characterization of a novel microsomal membrane-bound phenol sulfotransferase from bovine liver.
A novel phenol sulfotransferase (PST) was detected in bovine liver microsomal membrane fraction. The enzyme was found to be capable of catalyzing the sulfation of simple phenolic compounds, with 3'-phosphoadenosine-5'-phosphosulfate as the sulfate donor. Detergent extracted PST showed a pH optimum of 5.7 and, among the simple phenols tested, the PST exhibited highest activity toward alpha-naphthol. No activities were detected when tyrosine and its derivatives were used as substrates. Both 2,6-dichloro-4-nitrophenol and chlorpromazine were capable of inhibiting the activity of the PST toward p-nitrophenol with inhibition Coefficient50 values of 100 nM and 4 mM, respectively.


Domain Selection in Metallothionein 1A: Affinity-Controlled Mechanisms of Zinc Binding and Cadmium Exchange.
Mammalian metallothioneins (MTs) are small, metal binding proteins implicated in cellular metal ion homeostasis and heavy metal detoxification. Divalent, metal-saturated MTs form two distinct domains; the N-terminal β domain binds three metals using nine Cys residues, and the C-terminal α domain binds four metals with 11 Cys residues. Domain selection during zinc binding and cadmium exchange to human MT1A was examined using a series of competition reactions with mixtures of the isolated domain fragments. These experiments were conducted at two biologically significant pH conditions where MTs exist in vivo. Neither zinc binding nor cadmium exchange showed any significant degree of specificity or selectivity based on detailed analysis of electrospray ionization mass spectrometric and circular dichroic data. Under acidic conditions, zinc binding and cadmium exchange showed slight α domain selectivity because of the increased preference for cooperative clustering of the α domain. Modeling of the reactions showed that at both physiological (7.4) and acidic (5.8) pHs, zinc binding and cadmium exchanges occur essentially randomly between the two fragments. The metal binding affinity distributions between the domain fragments are comingled and not significantly separated as required for a domain specific mechanism. The models show rather that the order of the binding events follows the order of the binding affinities that are distributed across both domains and that this can be considered quantitatively by the KF(Cd)/KF(Zn) binding constant ratio for each metal bound.


Sublingual reactive histiocytosis in a dog.
Lingual lesions are relatively uncommon in dogs and are mostly represented by neoplasms and glossitis secondary to trauma or infections. Reactive histiocytosis is an uncommon, poorly understood, reactive disorder characterized by proliferation of activated, interstitial, dendritic, antigen-presenting cells associated with lymphocytes and neutrophils with a specific angiocentric orientation and occasional angioinvasion and angiodestruction. Clinically, the disease has a waxing and waning behavior with possible response to treatment and regression, or progression to multiple lesions and internal organ involvement. This case report describes an unusual sublingual presentation of reactive histiocytosis in a Miniature Pinscher dog. The diagnosis was obtained by clinical and histopathological exclusion of other causes, detection of the characteristic microscopic growth pattern, and by immunocytochemistry. Histiocytic cells were vimentin, CD18, CD11c, and CD1c positive consistent with a dendritic cell origin. Anti-BCG stain (Bacillus Calmette and Guerin) was negative for etiological agents. The dog was treated with oral administration of tetracycline and niacinamide during an 8-month period. There was no indication of recurrence of the sublingual mass 2-years following treatment.


Permeability of dormant spores of Bacillus subtilis to malachite green and crystal violet.
The permeability of dormant spores of Bacillus subtilis to malachite green (MG) and crystal violet (CV) was examined by using potassium trichloro(eta 2-ethylene)platinum(II) (KTPt) as an electron-opaque marker for the dyes. The spores were treated with the dyes and other substances at 30 degrees C for 30 min or at 80 degrees C for 5 min. When the spores were incubated in 50 mM-MG solution at 30 degrees C and in 50 mM-CV solution at 30 degrees C or 80 degrees C, many small electron-dense precipitates, which were chemical complexes of dyes and platinum, were seen, mainly around the boundary between the inner and outer coat regions. The spores treated under the above conditions were not stained. Treatment with 50 mM-MG alone or a mixture of 25 mM-oxalic acid and 50 mM-CV at 80 degrees C made the spores stainable and dye-TPt precipitates were observed mainly in the outer pericortex region. Pretreatment with 25 mM-oxalic acid and 5% (v/v) phenol at 80 degrees C followed by 50 mM-CV treatment at 30 degrees C gave the same results as above. It was considered from these results that the inner coat itself might function as the primary permeability barrier to MG and CV, and that a secondary barrier to the dyes might exist around the cortex region.


Effects of Electrospinning on the Viability of Ten Species of Lactic Acid Bacteria in Poly(Ethylene Oxide) Nanofibers.
Lactic acid bacteria can have beneficial health effects and be used for the treatment of various diseases. However, there remains the challenge of encapsulating probiotics into delivery systems with a high viability and encapsulation efficacy. The electrospinning of bacteria is a novel and little-studied method, and further investigation of its promising potential is needed. Here, the morphology, zeta potential, hydrophobicity, average cell mass, and growth characteristics of nine different species of Lactobacillus and one of Lactococcus are characterized. The electrospinning of polymer solutions containing ~10 log colony forming units (CFU)/mL lactic acid bacteria enabled the successful incorporation of all bacterial species tested, from the smallest (0.74 µm; Lactococcus lactis) to the largest (10.82 µm; Lactobacillus delbrueckii ssp. bulgaricus), into poly(ethylene oxide) nanofibers with an average diameter of ~100 nm. All of these lactobacilli were viable after incorporation into nanofibers, with 0 to 3 log CFU/mg loss in viability, depending on the species. Viability correlated with the hydrophobicity and extreme length of lactic acid bacteria, whereas a horizonal or vertical electrospinning set-up did not have any role. Therefore, electrospinning represents a promising method for the incorporation of lactic acid bacteria into solid delivery systems, while drying the bacterial dispersion at the same time.


'It depends': Characterizing speech and language therapy for preschool children with developmental speech and language disorders.
Several studies have suggested that practitioners hold speech and language therapy (SLT) practice as tacit and consequently it is difficult for the therapist to describe. The current study uses a range of knowledge elicitation (KE) approaches, a technique not used before in SLT, as a way of accessing this tacit knowledge. There is currently no agreed framework that establishes key factors underpinning practice for preschool children with speech and language disorders. This paper attempts to address that gap. To develop a framework of SLTs' practice when working with preschool children with developmental speech and language disorders (DS&LD). A mixed-methods approach was adopted for this study. Data were collected iteratively, from 245 SLTs with experience of working with preschool children with DS&LD across sites in England, by means of focus groups and national events. There were three stages of data collection: local sites, specific-interest groups and two national events. KE techniques were used to gather data, with initial data being collected in local site focus groups. Findings from groups were taken to subsequent larger groups where a combination of concept mapping, teach-back and sorting exercises generated a more detailed description of practice, using discussion of consensus and disagreement to stimulate further exploration and definition and provide validatory evidence. This paper provides a high-level framework of therapy for preschool children with DS&LD that makes practice explicit in this area. The framework proposes that therapists' aims for this group of children fall into three categories: addressing children's areas of impairment and skills; achieving functionally meaningful skills and carryover; and supporting adults to provide a supportive communication environment. The exact configuration is shaped by the child's context and needs. The framework highlights themes that are well researched in the literature (e.g., speech) and others that have been little studied (e.g., adult understanding), indicating a disconnect between research evidence and practice. The research also highlights the complex nature of interventions for preschool children with DS&LD and the importance therapists attribute to tailoring therapy to individual needs. The framework provides a scaffold upon which SLTs can focus their clinical practice and encourages the profession to understand and explore better the gaps between research evidence and clinical practice for preschool children with DS&LD.


Design and preliminary evaluation of an expert system for platelet request evaluation.
In spite of growing awareness of the potential risks associated with transfusion, the number of platelet units transfused in the United States continues to increase each year. There is a growing interest in ensuring that all transfusions are administered for appropriate reasons. Prospective review of requests for transfusions has been used to accomplish this goal. Although successful in reducing the number of inappropriate transfusions, this review method requires great time commitments by blood bank personnel and physicians. A knowledge-based system (ESPRE) that aids hospital blood bank personnel in the review of requests for platelet transfusions has been developed. The system automatically obtains most of the required patient data via a direct link to the hospital's main laboratory computers. The system generates a printed report that includes a list of patient-specific data, a list of the conditions for which a transfusion would be appropriate for the particular patient (given the clinical condition), and the conclusions drawn by the system. During a preliminary clinical evaluation of ESPRE, 73 randomly selected platelet transfusion requests were evaluated for approval by laboratory personnel and ESPRE. Overall, ESPRE would have approved 71 of the requests and laboratory staff would have approved 72. Forty-four percent of the requests would have been approved for the same reasons given by the staff. There were only three disagreements on final approval between ESPRE and blood bank personnel. This computerized expert system is a promising approach to the prospective review of all platelet transfusions.


Three new platinum complexes containing fluoroquinolones and DMSO: Cytotoxicity and evaluation against drug-resistant tuberculosis.
This work describes the synthesis, characterization and biological evaluation of three platinum complexes of the type [Pt(DMSO)(L)Cl]Cl, in which L represents a fluoroquinolone, namely, ciprofloxacin (cpl), ofloxacin (ofl), or sparfloxacin (spf). The new complexes were characterized by elemental analysis, high-resolution mass spectrometry (HRESIMS) and 1H, 13C and 195Pt NMR (nuclear magnetic resonance). The spectral data suggest that the fluoroquinolones act as bidentate ligands coordinated to Pt(II) through the nitrogen atoms of the piperazine ring. Microbiological assays against wild type Mycobacterium tuberculosis (ATCC 27294) showed that all complexes have been very potent, exhibiting antitubercular potency at concentrations <2 μM, although none of the complexes presented higher potency than established anti-TB drugs. As to the resistant strains, the complex with sparfloxacin, [Pt(DMSO)(spf)Cl]Cl exhibited the best potential against most Mycobacterium tuberculosis clinical isolates. The cytotoxicity of these compounds was also evaluated in three breast cell lines: MCF-10 (a healthy cell), MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both tumor cell lines, [Pt(DMSO)(spf)Cl]Cl was more active and more selective than cisplatin. Flow cytometry analysis revealed that [Pt(DMSO)(spf)Cl]Cl induced late apoptotic cell death in MDA-MB-231 cells.


Eukaryotic DNA replication.
The past decade has witnessed an exciting evolution in our understanding of eukaryotic DNA replication at the molecular level. Progress has been particularly rapid within the last few years due to the convergence of research on a variety of cell types, from yeast to human, encompassing disciplines ranging from clinical immunology to the molecular biology of viruses. New eukaryotic DNA replicases and accessory proteins have been purified and characterized, and some have been cloned and sequenced. In vitro systems for the replication of viral DNA have been developed, allowing the identification and purification of several mammalian replication proteins. In this review we focus on DNA polymerases alpha and delta and the polymerase accessory proteins, their physical and functional properties, as well as their roles in eukaryotic DNA replication.


Inflammatory pseudotumor of the lacrimal sac.
A case of inflammatory pseudotumor of the lacrimal sac is presented. The patient was first consulted for epiphora and swelling of the right lacrimal sac region. A mass was found on computed tomography (CT) and finally it was removed by dacryocystectomy. The diagnosis of inflammatory pseudotumor was confirmed by histopathological sections.


Debrisoquine hydroxylation phenotype, acetylation phenotype, and ABO blood groups as genetic host factors of lung cancer risk.
Bronchogenic carcinoma is closely associated with cigarette smoking although additional environmental or individual factors might regulate a person's susceptibility to that disease. To further define such risk factors, the prevalence of the genetic debrisoquine 4-hydroxylation deficiency was determined before therapeutic intervention in 270 lung cancer patients. Nineteen homozygous carriers of this defect (poor metabolizers) were found (7.0%, 95% confidence limits 4.3%-10.8%), a number being lower than 30 out of 270 reference patients (11.1%, 95% confidence limits 7.6%-15.5%). The odds ratio of 0.61 was of marginal statistical significance (P = 0.067). Subdividing the collective according to histology revealed a trend towards underrepresentation of poor metabolizers especially among patients with adenocarcinoma (1 out of 37, P = 0.086) and among young patients not older than 50 years (none out of 32, P = 0.028). All poor metabolizers (PMs) in the cancer group were smokers. In 18 patients the phenotype assignment was confirmed by a second test several weeks after surgical or other treatment. In 220 of the lung cancer patients the N-acetyltransferase polymorphism was evaluated by means of the molar ratio of 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine after ingestion of caffeine (coffee). There were 111 (50.5%) slow acetylators and 109 (49.5%) fast acetylators. A statistically significant clustering of either phenotype after stratification according to histology, or debrisoquine hydroxilator status was lacking. Moreover, there was no difference in the ratio of both phenotypes as compared to the reference collective of 245 patients (53.5% slow and 46.5% fast acetylators). As a third genetic host factor the AB0 blood group frequencies were evaluated in 263 lung cancer patients. The frequency ratio of A/O was significantly higher as compared to 41,423 blood donors (odds ratio 1.37, 95% confidence limits 1.02-1.84, P less than 0.05). A/O tended to be especially high in young patients not older than 50 years. The ratio B/O in bronchial cancer was significantly higher than expected. The results suggest that the debrisoquine hydroxilator status might have an impact on an individual's susceptibility to lung cancer. This association is either a weak one and/or is restricted to certain histological cancer types or to patients with certain characteristics. The acetylator phenotype could not be established as a risk factor, whereas AB0 blood groups seem to influence lung cancer susceptibility.


Muscle opacity (mo), a new mutant gene in Xenopus laevis, linked to the rusty locus.
A new developmental mutant is described in Xenopus laevis (Amphibia, Anura): muscle opacity (mo). Homozygotes die at larval stage 48. The underlying defect, visible at stage 47, is a degeneration of cephalic musculature. The mo gene is linked to the rusty locus, with a map distance of 6.1%.


Facial Shape, Size, and Gender.
Traditional ways of visualizing the differences between male and female faces are often based on single-subject exemplars or artist depictions of hypermasculine and hyperfeminine faces. By equalizing the sizes of male and female facial averages, the authors analyzed the influences of intrinsic shape and size on the architecture of the face.


The host targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum.
During the blood stage of its lifecycle, the malaria parasite resides and replicates inside a membrane vacuole within its host cell, the human erythrocyte. The parasite exports many proteins across the vacuole membrane and into the host cell cytoplasm. Most exported proteins are characterized by the presence of a host targeting (HT) motif, also referred to as a Plasmodium export element (PEXEL), which corresponds to the consensus sequence RxLxE/D/Q. During export the HT motif is cleaved by an unknown protease. Here, we generate parasite lines expressing HT motif containing proteins that are localized to different compartments within the parasite or host cell. We find that the HT motif in a protein that is retained in the parasite endoplasmic reticulum is cleaved and N-acetylated as efficiently as a protein that is exported. This shows that cleavage of the HT motif occurs early in the secretory pathway, in the parasite endoplasmic reticulum.


High-Performance Nonfullerene Organic Photovoltaics Applicable for Both Outdoor and Indoor Environments through Directional Photon Energy Transfer.
With the advent of the smart factory and the Internet of Things (IoT) sensors, organic photovoltaics (OPVs) gained attention because of their ability to provide indoor power generation as an off-grid power supply. To satisfy these applications, OPVs must be capable of power generation in both outdoor and indoor at the same time for developing environmentally independent devices. For high performances in indoor irradiation, a strategy that maximizes photon utilization is essential. In this study, graphene quantum dots (GQDs), which have unique emitting properties, are introduced into a ZnO layer for efficient photon utilization of nonfullerene-based OPVs under indoor irradiation. GQDs exhibit high absorption properties in the 350-550 nm region and strong emission properties in the visible region due to down-conversion from lattice vibration. Using these properties, GQDs provide directional photon energy transfer to the bulk-heterojunction (BHJ) layer because the optical properties overlap. Additionally, the GQD-doped ZnO layer enhances shunt resistance (RSh) and forms good interfacial contact with the BHJ layer that results in increased carrier dissociation and transportation. Consequently, the fabricated device based on P(Cl-Cl)(BDD = 0.2) and IT-4F introduces GQDs exhibiting a maximum power conversion efficiency (PCE) of 14.0% with a superior enhanced short circuit current density (JSC) and fill factor (FF). Furthermore, the fabricated device exhibited high PCEs of 19.6 and 17.2% under 1000 and 200 lux indoor irradiation of light emitting diode (LED) lamps, respectively.


Differences in Accelerometer-Measured Patterns of Physical Activity and Sleep/Rest Between Ethnic Groups and Age: An Analysis of UK Biobank.
Physical activity and sleep are important for health; whether device-measured physical activity and sleep differ by ethnicity is unclear. This study aimed to compare physical activity and sleep/rest in white, South Asian (SA), and black adults by age. Physical activity and sleep/rest quality were assessed using accelerometer data from UK Biobank. Linear regressions, stratified by sex, were used to analyze differences in activity and sleep/rest. An ethnicity × age group interaction term was used to assess whether ethnic differences were consistent across age groups. Data from 95,914 participants, aged 45-79 years, were included. Overall activity was 7% higher in black, and 5% lower in SA individuals compared with white individuals. Minority ethnic groups had poorer sleep/rest quality. Lower physical activity and poorer sleep quality occurred at a later age in black and SA adults (>65 y), than white adults (>55 y). While black adults are more active, and SA adults less active, than white adults, the age-related reduction appears to be delayed in black and SA adults. Sleep/rest quality is poorer in black and SA adults than in white adults. Understanding ethnic differences in physical activity and rest differ may provide insight into chronic conditions with differing prevalence across ethnicities.


[Reactivation of Epstein-Barr virus is involved in the pathogenesis of lymphomatoid granulomatosis].
Recent studies point to a role of Epstein-Barr virus in the pathogenesis of lymphomatoid granulomatosis. Little is however known about the association of the pathogenesis of the disease with Epstein-Barr virus reactivation. A 46-year-old man presented with fever and general malaise. He had been admitted with fever of unknown origin 10 years previously. Chest radiographs and CT scans showed multiple nodular shadows in both lung fields. PET/CT showed strong accumulation in lung nodules, femoral muscle, lumbar subcutaneous nodule. He died of rapidly progressive neurological lesions. The definitive diagnosis of lymphomatoid granulomatosis was made from histological findings of the surgical biopsy specimen and at autopsy. Elevation of early antigen-IgG titer in serum was shown in this case. This result suggests that reactivation of Epstein-Barr virus is involved in the development of the disease.


Metrics Used to Quantify Fecal Incontinence and Constipation.
While fecal incontinence and constipation can be measured through physiological testing, the subjective experience of severity and impact on health-related quality of life lead to both being most effectively captured through patient-reported measures. Patient-reported measures of severity and impact help to determine baseline symptoms, guide clinical decision making, and compare various treatments. Here, we take pause to review the psychometric qualities that make effective instruments, and discuss some of the most commonly used instruments along with the reasons behind their use. In addition, we highlight the benefits of a standardized instrument designed to evaluate the major symptoms of patients presenting with pelvic floor disorders (including fecal incontinence and constipation). Ultimately, we aim to provide guidance in choosing appropriate instruments for clinical and research use.


Non-resolving periapical inflammation: a malignant deception.
To report a case of oral non-Hodgkin's lymphoma with a delayed diagnosis. Non-Hodgkin's lymphoma of the oral cavity is an uncommon but important condition. Early diagnosis is complicated when the presenting signs and symptoms are similar to those of odontogenic infections. This report describes the case of a 38-year-old female patient who presented to her dentist complaining of pain in her upper jaw. Subsequent dental treatment, including extraction, root canal treatment and apicectomy including biopsy were carried out by the patient's dentist and local dental hospital. Nine months elapsed before a more extensive surgical exploration established a diagnosis of lymphoma.


Phosphorus additions imbalance terrestrial ecosystem C:N:P stoichiometry.
Carbon (C):nitrogen (N):phosphorus (P) stoichiometry in plants, soils, and microbial biomass influences productivity and nutrient cycling in terrestrial ecosystems. Anthropogenic inputs of P to ecosystems are increasing; however, our understanding of the impacts of P addition on terrestrial ecosystem C:N:P ratios remains elusive. By conducting a meta-analysis with 1413 paired observations from 121 publications, we showed that P addition significantly decreased plant, soil, and microbial biomass N:P and C:P ratios, but had negligible effects on C:N ratios. The reductions in N:P and C:P ratios became more evident as the P application rates and experimental duration increased. The P addition effects on terrestrial ecosystem C:N:P stoichiometry did not vary with ecosystem types or climates. Moreover, the responses of N:P and C:P ratios in soil and microbial biomass were associated with the responses of soil pH and fungi:bacteria ratios. Additionally, P additions increased net primary productivity, microbial biomass, soil respiration, N mineralization, and N nitrification, but decreased ammonium and nitrate contents. Decreases in plant N:P and C:P ratios were both negatively correlated to net primary productivity and soil respiration, but positively correlated to ammonium and nitrate contents; microbial biomass, soil respiration, ammonium contents, and nitrate contents all increased with declining soil N:P and C:P ratios. Our findings highlight that P additions could imbalance C:N:P stoichiometry and potentially impact the terrestrial ecosystem functions.


Plasminogen-based capture combined with amplification technology for the detection of PrP(TSE) in the pre-clinical phase of infection.
Variant Creutzfeldt-Jakob disease (vCJD) is a neurodegenerative infectious disorder, characterized by a prominent accumulation of pathological isoforms of the prion protein (PrP(TSE)) in the brain and lymphoid tissues. Since the publication in the United Kingdom of four apparent vCJD cases following transfusion of red blood cells and one apparent case following treatment with factor VIII, the presence of vCJD infectivity in the blood seems highly probable. For effective blood testing of vCJD individuals in the preclinical or clinical phase of infection, it is considered necessary that assays detect PrP(TSE) concentrations in the femtomolar range. We have developed a three-step assay that firstly captures PrP(TSE) from infected blood using a plasminogen-coated magnetic-nanobead method prior to its serial amplification via protein misfolding cyclic amplification (PMCA) and specific PrP(TSE) detection by western blot. We achieved a PrP(TSE) capture yield of 95% from scrapie-infected material. We demonstrated the possibility of detecting PrP(TSE) in white blood cells, in buffy coat and in plasma isolated from the blood of scrapie-infected sheep collected at the pre-clinical stage of the disease. The test also allowed the detection of PrP(TSE) in human plasma spiked with a 10(-8) dilution of vCJD-infected brain homogenate corresponding to the level of sensitivity (femtogram) required for the detection of the PrP(TSE) in asymptomatic carriers. The 100% specificity of the test was revealed using a blinded panel comprising 96 human plasma samples. We have developed a sensitive and specific amplification assay allowing the detection of PrP(TSE) in the plasma and buffy coat fractions of blood collected at the pre-clinical phase of the disease. This assay represents a good candidate as a confirmatory assay for the presence of PrP(TSE) in blood of patients displaying positivity in large scale screening tests.


Caries prevalence in non-syndromic patients with cleft lip and/or palate: a meta-analysis.
To evaluate caries prevalence in non-syndromic patients with cleft lip and/or palate (CLP) in comparison with a matched non-CLP population. A literature search was conducted in order to identify articles reporting on the prevalence of caries in CLP versus non-CLP individuals. The related citations function in PubMed and reference lists of retrieved articles were used to expand the search. Only studies with a suitable matched control group were included. From each included study, study and sample characteristics were extracted, as were results. The main outcome was the score given for caries prevalence in each study, using a well-defined index. The data were entered into meta-analysis software and a meta-analysis performed using the random-effects model. From the 592 articles initially identified, 7 were chosen according to preset inclusion and exclusion criteria. All of the studies were cross-sectional in nature, and used the decayed, missing, and filled (DMF/dmf) indices as the final outcomes. The included studies involved a total of 474 CLP patients aged 1.5-29 years. When looking at permanent teeth, data from 5 studies suggest that CLP patients have a higher number of DMF teeth than the controls (mean difference 1.38; p = 0.003). For deciduous teeth, data from 4 studies suggest that CLP patients have a higher number of dmf teeth than the controls (mean difference 1.51; p = 0.03). Non-syndromic patients with CLP tend to have higher caries prevalence, both in the permanent and the deciduous dentition, in comparison with matched non-CLP controls.


[Emergency hospitalization for acute, non-accidental abdominal pain. Prospective data of a surgical university clinic].
During a 19-month period 549 patients (278 women, 271 men) suffering from abdominal pain unrelated to trauma (mean age 48.2 years) entered the emergency room of the Department of Surgery of the University Hospital Zürich. 43% presented during business hours, whereas 57% were admitted during nighttime and/or weekends. Clinical examination, abdominal roentgenograms (upright and supine) as well as sonography were the most commonly used diagnostic tools. 40% suffered from abdominal pain of unknown cause. The most common diagnosis on admission was appendicitis. Only half of these cases really proved to be an appendicitis. In 36% the diagnosis on admission corresponds both to the initial diagnosis made by a member of staff during his first visit, as well as to the final diagnosis. The initial diagnosis agrees in 57% with the final diagnosis. In 10% of the patients the cause of pain was not elucidated despite extensive diagnostic procedures. High technology and sophisticated diagnostics are less important than the clinical evaluation. The decision between operative or nonoperative treatment was mainly based on clinical findings.


Thallium myocardial perfusion scans for the assessment of right ventricular hypertrophy in patients with cystic fibrosis. A comparison with other noninvasive techniques.
The incidence of right ventricular hypertrophy in 32 patients with cystic fibrosis was studied using thallium 201 (TI-201) myocardial perfusion scans, and compared with other noninvasive techniques including electrocardiography, vectorcardiography, and M-mode echocardiography. The patients (mean age, 17.3 yr; range, 7 to 33) had a wide range of clinical and pulmonary abnormalities (mean Shwachman-Kulczycki score, 66.6). In the total study group, TI-201 scans, like the vectorcardiograms and the M-mode echocardiograms, gave a surprisingly high proportion of positive predictions for right ventricular hypertrophy (RVH) (44%). The correlations with all other noninvasive methods were uniformly poor, so caution must be exercised in using this technique to predict early RVH in order to follow the natural history of cor pulmonale in cystic fibrosis. At the time of the study, 6 patients had clinical evidence of right ventricular failure, and in this disease setting must have had RVH. In 3 patients, RVH was confirmed at autopsy, and it was successfully predicted by TI-201 scans in 5 of the 6 patients. The false negative scan may have been due to regional myocardial ischemia secondary to severe right ventricular failure. In contrast, the vectorcardiogram, using Fowler's new criteria, made a successful prediction of RVH in all 6 patients, and the electro cardiogram in only 3. Although the M-mode echocardiogram was abnormal in all patients, it would have predicted RVH (with increased right ventricular anterior wall thickness) in only 1 patient. We concluded that TI-201 myocardial perfusion cans are good at confirming RVH in cases with established right ventricular failure, but have no advantage over vectorcardiographic assessments, which are logistically easier to perform and carry no radiation risks.


A dosimetric characterization of a novel linear accelerator collimator.
The aim of this work is to characterize a new linear accelerator collimator which contains a single pair of sculpted diaphragms mounted orthogonally to a 160 leaf multileaf collimator (MLC). The diaphragms have "thick" regions providing full attenuation and "thin" regions where attenuation is provided by both the leaves and the diaphragm. The leaves are mounted on a dynamic leaf guide allowing rapid leaf motion and leaf travel over 350 mm. Dosimetric characterization, including assessment of leaf transmission, leaf tip transmission, penumbral width, was performed in a plotting tank. Head scatter factor was measured using a mini-phantom and the effect of leaf guide position on output was assessed using a water phantom. The tongue and groove effect was assessed using multiple exposures on radiochromic film. Leaf reproducibility was assessed from portal images of multiple abutting fields. The maximum transmission through the multileaf collimator is 0.44% at 6 MV and 0.52% at 10 MV. This reduced to 0.22% and 0.27%, respectively, when the beam passes through the dynamic leaf guide in addition to the MLC. The maximum transmission through the thick part of the diaphragm is 0.32% and 0.36% at 6 and 10 MV. The combination of leaf and diaphragm transmission ranges from 0.08% to 0.010% at 6 MV and 0.10% to 0.14% depending on whether the shielding is through the thick or thin part of the diaphragm. The off-axis intertip transmission for a zero leaf gap is 2.2% at 6 and 10 MV. The leaf tip penumbra for a 100 × 100 mm field ranges from 5.4 to 4.3 mm at 6 and 10 MV across the full range of leaf motion when measured in the AB direction, which reduces to 4.0-3.4 mm at 6 MV and 4.5-3.8 mm at 10 MV when measured in the GT direction. For a 50 × 50 mm field, the diaphragm penumbra ranges from 4.3 to 3.7 mm at 6 MV and 4.5 to 4.1 mm at 10 MV in the AB direction and 3.7 to 3.2 mm at 6 MV and 4.2 to 3.7 mm when measured in the GT direction. The tongue and groove effect observed from exposure of a radiochromic film to two abutting fields is an underdose of 25%. The head scatter factor at both 6 and 10 MV is similar to that from the MLCi2 collimator to within 0.8%. The uncertainty in the leaf position reproducibility is 0.05 mm (2σ). The Agility collimator is a low leakage, high definition collimator where both the MLC and the sculpted diaphragm have been optimized for dynamic treatments.


Astaxanthin ameliorates damage to the cerebral cortex, hippocampus and cerebellar cortex caused by methotrexate.
We investigated the ameliorating effects of astaxanthin (AXA) on methotrexate (MTX) induced damage to the cerebral cortex, hippocampus, cerebellar cortex and blood. We used 24 female Wistar albino rats divided into three groups of eight as follows: sham/control group, single dose of saline intraperitoneally (i.p.) and 7 days orally; MTX group, single dose of 20 mg/kg MTX (i.p.); MTX + AXA group, single dose of 20 mg/kg MTX i.p.+ 100 mg/kg AXA orally for 7 days. For all groups we measured total oxidant status (TOS) and total antioxidant status (TAS) in the cerebral cortex, hippocampus and blood. Histological sections of cerebral cortex, hippocampus and cerebellar cortex were inspected microscopically. Caspase-3 (cas-3), granulocyte colony-stimulating factor (GCSF), growth related oncogene (GRO), inducible nitric oxide synthase (iNOS) and myelin basic protein (MBP) were estimated immunohistochemically in the cerebral cortex, hippocampus and cerebellar cortex. In the MTX group, TAS was decreased significantly in the cerebral cortex, hippocampus and blood, while TOS was significantly increased. AXA significantly ameliorated oxidative stress parameters in the cerebral cortex and hippocampus. Histopathological examination revealed degeneration, edema and hyperemia in the cerebral cortex, hippocampus and cerebellar cortex in the MTX group. AXA treatment ameliorated histopathological changes. MTX decreased MBP expression in cerebral cortex. Although MBP expression was decreased in the cerebral cortex, hippocampus and cerebellar cortex stimulated with MTX, the expressions of cas-3, GCSF, GRO and iNOS were significantly increased. AXA ameliorated the expression of cas-3, GCSF, GRO, iNOS and MBP. AXA exhibits anti-inflammatory, antioxidant and anti-apoptotic effects on MTX induced toxicity in the cerebral cortex, hippocampus and cerebellar cortex by increasing MBP expression, regulating inflammatory cytokine release and reducing oxidative stress.


The role of selectins and CD18 in leukotriene B4-mediated white blood cell emigration in human skin grafts transplanted on SCID mice.
The purpose of this study was to examine the role of selectins and CD18 cell adhesion molecules (CAMs) in inflammation induced by injection of leukotriene B4 (LTB4) into human skin. To accomplish this, the expression of CAMs and the ability of specific antibodies against CAMs to block white blood cell (WBC) transmigration were studied in an in vivo model consisting of human skin transplanted onto mice with the severe combined immune deficiency (SCID) mutation. The results indicate that LTB4-induced WBC transmigration in the human/SCID model is rapid and pronounced; however, it is not accompanied by a significant upregulation of the baseline expression of endothelial P-selectin, E-selectin, ICAM-1 or VCAM-1. An anti-murine CD18 mAb markedly inhibited white cell infiltration (89% inhibition) confirming the importance of beta 2 integrins in the process. The role of selectins was also examined. MEL-14, a bioactive antibody against murine L-selectin inhibited transmigration by 66%. A significant, but smaller, effect (39% inhibition) was observed by blocking E-selectin function. These results indicate that LTB4-induced inflammation does not require upregulation of endothelial CAM expression and, in contrast to TNF alpha-induced transmigration, is only partially blocked by anti-E-selectin antibodies.


Duality of Interactions Between TGF-β and TNF-α During Tumor Formation.
The tumor microenvironment is essential for the formation and development of tumors. Cytokines in the microenvironment may affect the growth, metastasis and prognosis of tumors, and play different roles in different stages of tumors, of which transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α) are critical. The two have synergistic and antagonistic effect on tumor regulation. The inhibition of TGF-β can promote the formation rate of tumor, while TGF-β can promote the malignancy of tumor. TNF-α was initially determined to be a natural immune serum mediator that can induce tumor hemorrhagic necrosis, it has a wide range of biological activities and can be used clinically as a target to immune diseases as well as tumors. However, there are few reports on the interaction between the two in the tumor microenvironment. This paper combs the biological effect of the two in different aspects of different tumors. We summarized the changes and clinical medication rules of the two in different tissue cells, hoping to provide a new idea for the clinical application of the two cytokines.


Characterization by enzyme-linked immunosorbent assay of monoclonal antibodies to pisum and Avena phytochrome.
Nine monoclonal antibodies to pea (Pisum sativum L.) and 16 to oat (Avena sativa L.) phytochrome are characterized by enzyme-linked immunosorbent assay against phytochrome from six different sources: pea, zucchini (Cucurbita pepo L.), lettuce (Lactuca sativa L.), oat, rye (Secale cereale L.), and barley (Hordeum vulgare L.). All antibodies were raised against phytochrome with a monomer size near 120,000 daltons. Nevertheless, none of them discriminated qualitatively between 118/114-kilodalton oat phytochrome and a photoreversible, 60-kilodalton proteolytic degradation product derived from it. In addition, none of the 23 antibodies tested discriminated substantially between phytochrome-red-absorbing form and phytochrome-far red-absorbing form. Two antibodies to pea and six to oat phytochrome also bound strongly to phytochrome from the other species, even though these two plants are evolutionarily widely divergent. Of these eight antibodies, two bound significantly to all of the six phytochrome preparations tested, indicating that these two may recognize highly conserved regions of the chromoprotein. Since the molecular function of phytochrome is unknown, these two antibodies may serve as unique probes for regions of this pigment that are important to its mode of action.


Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.
Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.


A potential anti-cancer agent: 5-chloro-7-iodo-8-hy-droxy-quinolinium dichlorido(5-chloro-7-iodo-quinolin-8-olato-κN,O)palladium(II) dihydrate.
The title Pd(II) coordination compound, (C(9)H(6)ClINO)[PdCl(2)(C(9)H(4)ClINO)]·2H(2)O, was prepared as a potential anti-cancer agent. Its structure is ionic and consists of a square-planar [PdCl(2)(CQ)](-) complex anion (CQ is 5-chloro-7-iodo-quinolin-8-olate), with the Pd(II) atom surrounded by two chloride ligands in a cis configuration and one N,O-bidentate CQ mol-ecule, a protonated anion of CQ as counter-cation and two non-coordinated water mol-ecules. The water mol-ecules are involved in O-H⋯O and N-H⋯O hydrogen bonds, which inter-connect the HCQ(+) cations into a chain parallel to [010]. Apart from these inter-actions, the structure is also stabilized by face-to-face π-π inter-actions [centroid-centroid = 3.546 (3) Å], which occur between the phenolic parts of the complex anions and cations.


Field studies on dominant rodents and the efficacy of certain insecticides to their fleas in Dakahlia Governorate, Egypt.
A preliminary survey of domestic rodent and the efficacy of bendiocarb, diazinon and pirimiphos-methyl insecticides to their fleas were carried out in Dakahlia Governorates (Aga, Meet-Ghamr, El-Senbellawen, Temi El-Amded, Beni-Abed, Dekernes, Nabarow, Talkha, Menia El-Nasr and El-Kordy). Rodent index (number of rodent/trap) and percentage frequency of drodent species were recorded from October 2010 to May 2011. The main rodent species found were the Norway rat, Rattus norvegicus, the grey-bellied rat, R. rattus alexandrinus, the white-bellied rat, R. r. frugivorus and the house mouse, Mus musculus. The rodent index at Beni-Abed, Nabarow, Meet-Ghamr, Dekernes and El-Kordy centers showed 0.46, 0.39, 0.34, 0.33 & 0.33, respectively, while Menia El-Nasr center showed the lowest (0.08). Aga, Talkha, El-Senbellawen, and Temi El-Amded centers showed moderate (0.25, 0.21, 0.2 & 0.16, respectively). The commonest flea species was the oriental rat flea, Xenopsylla cheopis, the mouse flea, Leptopsylla segnis, the dog flea, Ctenocephalides canis and the sticktight flea Echidnophaga gallinacea. The highest number of fleas was on R. norvegicus (Flea index=10.9) while lowest number was on Mus musculus (Flea index=0.1). X. cheopis was the highest frequency distributed for all domestic rodent species (60.9%), while, C. canis was the lowest (1.6%). The results showed that bendiocarb was effective (Lc50=0.389%) than diazinon (Lc50=1.039%) and pirimiphosmethyl (Lc50=2.056 %).


Extracellular-purine metabolism in blood vessels (part I). Extracellular-purine level in blood of patients with abdominal aortic aneurysm.
Adenosine and adenosine derivatives are the main regulators of purinoceptors (P1 and P2) mediated hemostasis and blood pressure. Since impaired hemostasis and high blood pressure lead to atherosclerosis and to the development of aneurysm, in this study we tested and compared the concentration of extracellular purines (e-purines) in the blood in of patients having abdominal aortic aneurysm with that from healthy volunteers. Whereas adenine nucleosides and nucleotides level in human blood plasma was analysed using reverse phase high performance liquid chromatography (HPLC), cholesterol concentration was estimated by an enzymatic assay. We did not find any correlation between e-purines concentration and the age of healthy volunteers. Furthermore, the sum level of e-purines (ATP, ADP, AMP, adenosine, and inosine) in the control group did not exceed 70 microM, while it was nearly two-fold higher in the blood of patients having abdominal aortic aneurysm, (123 microM). In a special case of people with Leriche Syndrome, a disease characterized by deep atherosclerotic changes, the e-purines level had further increased. Additionally, we also report typical atherosclerotic changes in the aorta using histological assays as well as total cholesterol rise. The significant rise in cholesterol concentration in the blood of the patients with abdominal aortas aneurysm, compared with the control groups, was not unique since 23% of the healthy people also exceeded the normal level of cholesterol. Therefore, our results strongly indicate that the estimation of e-purines concentration in the blood may serve as another indicator of atherosclerosis and warrant further consideration as a futuristic diagnostic tool.


Splenic metastases from cervical carcinoma: a case report.
Splenic metastasis from squamous cell carcinoma of the uterine cervix is an unusual event in the natural history of the disease. The authors report one such uncommon occurrence in a 41-year-old female who presented initially with cervical carcinoma (stage IIB) and was treated with radical radiotherapy with concurrent weekly chemotherapy. Following a disease-free interval of less than a year, she developed hepatosplenic metastases despite being locally controlled. The literature relevant to the report is also discussed. This report reaffirms the notion that splenic metastases from cervical carcinoma are rare events but can occur as part of widespread dissemination.


[5-(2-bromovinyl)-2'-deoxyuridine therapy of herpes zoster diseases in patients with malignant primary diseases].
BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine] has proved effective in the treatment of varicella-zoster virus diseases in patients with malignancies. In 13 out of 20 patients a prompt cessation of new vesicle formation accompanied by rapid resolution of fever, crusting and complete epithelialisation of cutaneous lesions were noted. Only in few cases a prolonged recovery from the severe zoster occurred. When starting the treatment later than 48 hours after the onset of initial rash the dissemination of epithelial lesions could not be prevented. BVDU was well tolerated. Laboratory abnormalities were observed only in some cases and did not result in interruption of treatment.


Excessive Game Playing Is Associated with Poor Toothbrushing Behavior among Athletic Children: A Cross-Sectional Study in Miyagi, Japan.
Dental problems among athletes have been cautioned due to negative impacts not only on their oral health but also on athletic performance. Acquirement of appropriate oral health behavior mainly composed of toothbrushing in childhood can be one of the most important strategies for advancing children's athletic possibilities. Although habits of screen viewing, including game playing, and TV viewing have direct impacts on children's health and behavioral development, little is known about the association between these habits and toothbrushing frequency. A cross-sectional survey examining sports activities was conducted using a self-report questionnaire among school-aged athletic children belonging to the Miyagi Amateur Sports Association (n = 6,658). All statistical analyses were performed with SPSS, and P-values less than 0.05 were considered statistically significant. The association between a lower brushing frequency (< 2 times a day) and screen-viewing behavior was examined using multivariate logistic models after adjusting for sex, age, body mass index (BMI), studying time, and sleep duration. After adjustment for all covariates, longer game playing (> 2 hrs a day), but not TV viewing, significantly correlated with lower brushing frequency (P for trend < 0.001). Importantly, longer game-playing behavior was also associated with unhealthy dental behavior defined as a lower brushing frequency regardless of the awareness of dental caries (P for trend < 0.001). In conclusion, this is the first study indicating a type-specific unfavorable impact of screen viewing on oral health behavior among athletic children. Excessive game playing may adversely affect oral health literacy more strongly than TV viewing.