Use of multiple radioligands to characterize adenosine receptors in human placenta.
To identify and characterize fully the adenosine receptor of human placenta, particulate preparations of placental parenchyma were examined using several adenosine receptor ligands, [3H]2-chloradenosine ([3H]2-Cl-ADO), [3H]N6-ethylcarboxamideadenosine ([3H]NECA), and [3H]N6-(L-phenylisopropyl)-adenosine ([3H]PIA). Each of the three ligands bound to the particulate preparations with unique binding characteristics. Binding of [3H]PIA characterized a high-affinity low-capacity receptor while the [3H]NECA displayed lower-affinity, higher-capacity binding. Saturation isotherms for [3H]2-Cl-ADO appeared intermediate in terms of affinity and binding capacity. Saturation isotherms of binding data also disclosed displaceable non-receptor binding at high labelled ligand concentrations. Competitive binding studies supported the observation that PIA and NECA bind to sites of high and low affinity, respectively. However, the multicomponent competition curves for [3H]2-Cl-ADO binding suggest binding to the receptors with differential affinity. These studies confirm the presence of adenosine receptors in the human placenta and suggest that these receptors are of both the high-and low-affinity subtypes.


[Determination of organochlorine pesticide residues in soil/sediment using isotope dilution gas chromatography-mass spectrometry].
A method was developed for the determination of organochlorine pesticide (OCP) residues in soil/sediment using high resolution gas chromatography coupled with low resolution mass spectrometry. The analytical procedures consisted of Soxhlet extraction, sulfur removal with copper powder, clean-up with gel permeation chromatography (GPC) and a florisil column of solid phase extraction (SPE). The analytes were separated on an HP-5MS capillary column, detected in selected ion monitoring ( SIM) mode and quantified using internal standard calibration curves of isotope dilution technique. The linear correlations of calibration standard solutions were good for all the OCPs. The recoveries and relative standard deviations of labeled compound solutions ranged from 60% to 110% and from 1.5% to 18%, respectively. The limits of detection ranged from 0.20 to 10.3 microg/kg were established for the 23 OCPs. The method showed satisfactory clean-up effect and precision quantification. It is suitable for the determination and confirmation of pesticides in complex matrices such as soil, sediment.


Plasma markers for identifying patients with metastatic melanoma.
With the rising incidence of melanoma, more patients are undergoing surveillance for disease recurrence. Our purpose was to study levels of proteins that might be secreted in the blood of patients with metastatic melanoma that can be used for monitoring these individuals. Genome-wide gene expression data were used to identify abundantly expressed genes in melanoma cells that encode for proteins likely to be present in the blood of cancer patients, based on high expression levels in tumors. ELISA assays were employed to measure proteins in plasma of 216 individuals; 108 metastatic melanoma patients and 108 age- and gender-matched patients with resected stage I/II disease split into equal-sized training and test cohorts. Levels of seven markers, CEACAM (carcinoembryonic antigen-related cell adhesion molecule), ICAM-1 (intercellular adhesion molecule 1), osteopontin, MIA (melanoma inhibitory activity), GDF-15 (growth differentiation factor 15), TIMP-1 (tissue inhibitor of metalloproteinase 1), and S100B, were higher in patients with unresected stage IV disease than in patients with resected stage I/II disease. About 81% of the stage I/II patients in the training set had no marker elevation, whereas 69% of the stage IV patients had elevation of at least one marker (P < 0.0001). Receiver operating characteristic curves for the markers in combination in these two patient populations had an area under curve (AUC) of 0.79 in the training set and 0.8 in the test set. A CART (Classification and Regression Trees) model developed in the training set further improved the AUC in the test set to 0.898. Plasma markers, particularly when assessed in combination, can be used to monitor patients for disease recurrence and can compliment currently used lactate dehydrogenase and imaging studies; prospective validation is warranted.


Cervical Cancer Screening Programs in Europe: The Transition Towards HPV Vaccination and Population-Based HPV Testing.
Cervical cancer is the fourth most frequently occurring cancer in women around the world and can affect them during their reproductive years. Since the development of the Papanicolaou (Pap) test, screening has been essential in identifying cervical cancer at a treatable stage. With the identification of the human papillomavirus (HPV) as the causative agent of essentially all cervical cancer cases, HPV molecular screening tests and HPV vaccines for primary prevention against the virus have been developed. Accordingly, comparative studies were designed to assess the performance of cervical cancer screening methods in order to devise the best screening strategy possible. This review critically assesses the current cervical cancer screening methods as well as the implementation of HPV vaccination in Europe. The most recent European Guidelines and recommendations for organized population-based programs with HPV testing as the primary screening method are also presented. Lastly, the current landscape of cervical cancer screening programs is assessed for both European Union member states and some associated countries, in regard to the transition towards population-based screening programs with primary HPV testing.


Facultative sex ratio adjustment in natural populations of wasps: cues of local mate competition and the precision of adaptation.
Sex ratio theory offers excellent opportunities to examine the extent to which individuals adaptively adjust their behavior in response to local conditions. Hamilton's theory of local mate competition, which predicts female-biased sex ratios in structured populations, has been extended in numerous directions to predict individual behavior in response to factors such as relative fecundity, time of oviposition, and relatedness between cofoundresses and between mates. These extended models assume that foundresses use different sources of information, and they have generally been untested or have only been tested in the laboratory. We use microsatellite markers to describe the wild oviposition behavior of individual foundresses in natural populations of the parasitoid wasp Nasonia vitripennis, and we use the data collected to test these various models. The offspring sex ratio produced by a foundress on a particular host reflected the number of eggs that were laid on that host relative to the number of eggs that were laid on that host by other foundresses. In contrast, the offspring sex ratio was not directly influenced by other potentially important factors, such as the number of foundresses laying eggs on that patch, relative fecundity at the patch level, or relatedness to either a mate or other foundresses on the patch.


[The use of the atropine test in patients with duodenal peptic ulcer].
Results of the studies made showed that among the examined patients who took part in the elimination of the aftermath of the Chernobyl accident, a positive atropin test was recordable in 38 (63%), a negative one in 16 (27%), weakly positive in 6(10%). In the control group of patients with duodenal ulcer a positive atropin test was in 73%, a negative one in 9%, and weakly positive in 18%. The difference between the frequency of a negative atropin test in the main and control groups was statistically significant (P < 0.05). The results obtained attest to the need for the atropin test to be done in patients with duodenal ulcer to prescribe pathogenetically substantiated therapy treatments tailored to the individual.


Epidemiology of primary tumours of the brain and spinal cord: a regional survey in southern England.
This survey is based upon 894 patients presenting with primary tumours of the brain, spinal cord, and meninges, over a nine year period in the Wessex population of about 1 1/2 million. All patients were 15 years of age or over. Each tumour type is characterized by age, sex, district, social class, and by rural or urban distribution. Standardized morbidity ratios for each tumour type are calculated for each health district. Gliomas are the commonest tumour with an average annual incidence of 3.94 per 100,000; they occur with a lower frequency in large urban areas. Grade 3-4 astrocytomas (glioblastoma multiforme) have a peak annual incidence of 7.53 per 100,000 in the 50-59 years age group and are more common in males. The peak incidence for oligodendrogliomas is also 50-59 years but for grade 1-2 astrocytomas it is 30-39 years. Meningiomas have an average annual incidence of 1.23 per 100,000 with a peak incidence of 2.48 per 100,000 at 60-69 years; they have a female predominance (female 1.76 per 100,000; male of 0.64 per 100,000). Rural districts have a lower incidence of meningiomas than urban areas. There is some variation in the distribution of gliomas, meningiomas, and Schwannomas throughout the Wessex region and there is a suggestion of geographical clustering of ependymomas, acoustic neuromas, and meningiomas. An excess of patients with grade 1-2 astrocytomas and oligodendrogliomas is seen in social classes 1 and 2 and a deficit in classes 4-5; a similar, but less marked, preponderance is seen with meningiomas.


Panax notoginseng saponins improve erectile function through attenuation of oxidative stress, restoration of Akt activity and protection of endothelial and smooth muscle cells in diabetic rats with erectile dysfunction.
Panax notoginseng saponins (PNS), which have an antioxidant property, are a widely used traditional Chinese medicine. In this study we investigated whether PNS can improve erectile function in rats with erectile dysfunction and the underlying mechanism by using a rat diabetic erectile dysfunction model. The rats were randomly divided into four groups: three PNS-treated groups (50, 100 and 150 mg/kg) and one saline-treated control group. Four weeks post treatment, electrostimulation was applied to the cavernous nerve and intracavernous pressure was measured to assess erectile function. Malondialdehyde, superoxide dismutase and glutathione were detected in the penises of all rats. Ultrastructural changes in the penises were examined by electron microscopy. Expression of Akt was detected by immunohistochemistry. The results showed that intracavernous pressure was increased in PNS-treated groups (100 and 150 mg/kg) compared to the control group. The levels of superoxide dismutase, glutathione and Akt were increased (p < 0.05) while that of malondialdehyde was decreased in the PNS groups. Ruptured endothelium, impaired smooth muscle cells and thrombus in the penises were detected by electron microscopy in the control group, but not in the PNS groups (10 and 150 mg/kg). The results suggest that PNS improves erectile function in diabetic rats. This improvement was associated with increased Akt expression, suppressed oxidative stress and restored functions of endothelial cells and smooth muscle cells in the penis.


Getting a Grip on the Grapevine: Extension and Factor Structure of the Motives to Gossip Questionnaire.
Gossip is condemned but also ubiquitous and thought to be essential for groups. This triggers the question of which motives explain gossip behavior. Hitherto, negative influence, social enjoyment, group protection, and information gathering and validation are established as motives to gossip. However, venting emotions-discussed as a potentially important motive-has been overlooked empirically. Furthermore, a lack of consensus about a definition of gossip may have affected previous conclusions about gossip motives. This study (N = 460) expands the Motives to Gossip Questionnaire (MGQ; Beersma and Van Kleef, 2012) by including a subscale measuring emotion venting, the desire to share emotionally evocative experiences. To validate the five motives to gossip across definitions, we asked participants to report the most recent gossip event they experienced, randomly assigning them to one of three instructions containing different gossip definitions commonly used in the literature: (1) broad instructions (sharing information about third parties who have no knowledge of the exchanged information), (2) narrower instructions (adding that the shared information must be evaluative), and (3) instructions using the word gossip. After participants recalled and described a gossip event, they completed the 25-item measure of five motives to gossip: social enjoyment, information gathering and validation, negative influence, group protection, and emotion venting. Confirmatory factor analysis confirmed the five-factor structure. Multi-group confirmatory factor analysis supported full invariance across the three definition conditions. This indicates the Motives to Gossip Questionnaire successfully measures the five dimensions argued to motivate gossip and can be applied in research conceptualizing gossip both narrowly and broadly.


SfiI genomic cleavage map of Escherichia coli K-12 strain MG1655.
An SfiI restriction map of Escherichia coli K-12 strain MG1655 is presented. The map contains thirty-one cleavage sites separating fragments ranging in size from 407 kb to 3.7 kb. Several techniques were used in the construction of this map, including CHEF pulsed field gel electrophoresis; physical analysis of a set of twenty-six auxotrophic transposon insertions; correlation with the restriction map of Kohara and coworkers using the commercially available E. coli Gene Mapping Membranes; analysis of publicly available sequence information; and correlation of the above data with the combined genetic and physical map developed by Rudd, et al. The combination of these techniques has yielded a map in which all but one site can be localized within a range of +/- 2 kb, and over half the sites can be localized precisely by sequence data. Two sites present in the EcoSeq5 sequence database are not cleaved in MG1655 and four sites are noted to be sensitive to methylation by the dcm methylase. This map, combined with the NotI physical map of MG1655, can aid in the rapid, precise mapping of several different types of genetic alterations, including transposon mediated mutations and other insertions, inversions, deletions and duplications.


Repertoire and organization of human T-cell receptor alpha region variable genes.
A contig of YAC, PAC, and cosmid clones that spanned the human T-cell receptor alpha variable (AV) gene region on chromosome 14 was assembled. PCR primers corresponding to the members of 32 different subfamilies were used to map AV genes on the genomic clones. Nucleotide sequencing of PCR products derived from different genomic clones was used to discriminate between related AV gene segments that coamplified. The presence of individual AV gene segments on genomic clones was further confirmed by hybridization both to clones and to human genomic DNA from several unrelated individuals. These results suggest that the T-cell receptor alpha (TCRA) region in humans contains at least 46 distinct AV gene segments that can be grouped into 32 subfamilies based on nucleotide homology. Several subfamilies appear to contain additional members detectable by hybridization that do not map to chromosome 14.


[An epidemiological study on erythromelalgia].
Erythromelalgia occurred in middle schools of many counties in Hubei province from February to March. A survey in 2 senior middle schools revealed that the total incidence of the disease was 13.1% (248/1892) the incidence of female was 30.7% (138/449) and that of male 7.9 (110/1443). The average course of the illness was 6.56 +/- 4.3 days. The study of meteorologic phenomenon, biological agents, nutrient etc shows that the factors of cold and humidity might play a leading role.


'Isolated' pulmonary valve stenosis as part of more widespread cardiovascular disease.
In 25 patients aged 6 days to 9 years presenting as 'isolated' pulmonary valve stenosis, histology of the myocardium of right and left ventricles, coronary arteries, and ascending aorta has shown abnormality in one or all these areas. Myocardial necrosis, old and recent, unrelated to coronary occlusion was frequent. Myocardial 'dysplasia' involving both ventricles, and resembling hypertrophic cardiomyopathy (HOCM, ASH) was found in 10 and a relation of this to myocardial injury in the fetus is postulated. Varying degrees of coronary occlusion were frequently seen in both right and left coronary arteries. The histology of the ascending aorta was abnormal showing 'higgledy-piggledy' disorder of smooth muscle components in 12 (48%). In a different series of 53 patients who had pulmonary valvotomy for apparent 'isolated' pulmonary valve stenosis there were 14 with clinical evidence of left ventricular abnormality consistent with the pathological changes described, 2 with the same aortic histological changes, and 2 with macroscopical left ventricular hypertrophy. Two of them developed classical hypertrophic cardiomyopathy years later. It is suggested that when pulmonary valve stenosis presents with a thick tricuspid poorly mobile valve, particularly in infants or in patients with evidence of other congenital stigmata, it may be part of a more widespread cardiovascular abnormality. This should be recognized and considered in the evaluation of surgical patients and late survivors who may show unexpected clinical features.


Chromosome transfer in Rhodobacter sphaeroides: Hfr formation and genetic evidence for two unique circular chromosomes.
A 600-bp oriT-containing DNA fragment from the Rhodobacter sphaeroides 2.4.1 S factor (oriTs) (A. Suwanto and S. Kaplan, J. Bacteriol. 174:1124-1134, 1992) was shown to promote polarized chromosomal transfer when provided in cis. A Kmr-oriTs-sacR-sacB (KTS) DNA cassette was constructed by inserting oriTs-sacR-sacB into a pUTmini-Tn5 Km1 derivative. With this delivery system, KTS appeared to be randomly inserted into the genome of R. sphaeroides, generating mutant strains which also gained the ability to act as Hfr donors. An AseI site in the Kmr cartridge (from Tn903) and DraI and SnaBI sites in sacR-sacB (the levansucrase gene from Bacillus subtilis) were employed to localize the KTS insertion definitively by pulsed-field gel electrophoresis. The orientation of oriTs at the site of insertion was determined by Southern hybridization analysis. Interrupted mating experiments performed with some of the Hfr strains exhibited a gradient of marker transfer and further provided genetic evidence for the circularity and presence of two chromosomal linkage groups in this bacterium. The genetic and environmental conditions for optimized mating between R. sphaeroides strains were also defined. The results presented here and our physical map of the R. sphaeroides 2.4.1 genome are discussed in light of the presence of two chromosomes.


1.4 million Q factor Si3N4 micro-ring resonator at 780 nm wavelength for chip-scale atomic systems.
A silicon nitride micro-ring resonator with a loaded Q factor of 1.4 × 106 at 780 nm wavelength is demonstrated on silicon substrates. This is due to the low propagation loss waveguides achieved by optimization of waveguide sidewall interactions and top cladding refractive index. Potential applications include laser frequency stabilization allowing for chip-scale atomic systems targeting the 87Rb atomic transition at 780.24 nm. The temperature dependent wavelength shift of the micro-ring was determined to be 13.1 pm/K indicating that a minimum temperature stability of less than ±15 mK is required for such devices for wavelength locking applications. If a polyurethane acrylate top cladding of an optimized thickness is used then the micro-ring could effectively be athermal, resulting in reduced footprint, power consumption, and cost of potential devices.


Dietary patterns are associated with disease risk among participants in the Women's Health Initiative Observational Study.
Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women's Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infarct compared to 1224 WHI-OS controls matched for age, enrollment date, race/ethnicity, and absence of CHD at baseline or follow-up. The first six principal components explained >75% of variation in dietary intakes and K-mean analysis based on these six components produced three clusters. Diet cluster 1 was rich in carbohydrate, vegetable protein, fiber, dietary vitamin K, folate, carotenoids, α-linolenic acid [18:3(n-3)], linoleic acid [18:2(n-6)], and supplemental calcium and vitamin D. Diet cluster 2 was rich in total and animal protein, arachidonic acid [20:4(n-6)], DHA [22:6(n-3)], vitamin D, and calcium. Diet cluster 3 was rich in energy, total fat, and trans fatty acids (all P < 0.01). Conditional logistic regression analysis demonstrated diet cluster 1 was associated with lower CHD risk than diet cluster 2 (reference group) adjusted for smoking, education, and physical activity [OR = 0.79 (95% CI = 0.64, 0.99); P = 0.038]. This difference was not significant after adjustment for BMI and systolic blood pressure. Diet cluster 3 was associated with higher CHD risk than diet cluster 2 [OR = 1.28 (95% CI = 1.04, 1.57); P = 0.019], but this difference did not remain significant after adjustment for smoking, education, and physical activity. Within this WHI-OS cohort, distinct dietary patterns may be associated with subsequent CHD outcomes.


Transcriptional regulation of T helper type 2 differentiation.
Considerable progress has been made in recent years towards our understanding of the molecular mechanisms of transcriptional regulation of T helper type 2 (Th2) cell differentiation. Additional transcription factors and chromatin-modifying factors were identified and shown to promote Th2 cell differentiation and inhibit differentiation into other subsets. Analyses of mice lacking several cis-regulatory elements have yielded more insight into the regulatory mechanism of Th2 cytokine genes. Gene deletion studies of several chromatin modifiers confirmed their impact on CD4 T-cell differentiation. In addition, recent genome-wide analyses of transcription factor binding and chromatin status revealed unexpected roles of these factors in Th2-cell differentiation. In this review, these recent findings and their implication are summarized.


Three dimensional preparatory trunk motion precedes asymmetrical upper limb movement.
Three-dimensional trunk motion, trunk muscle electromyography and intra-abdominal pressure were evaluated to investigate the preparatory control of the trunk associated with voluntary unilateral upper limb movement. The directions of angular motion produced by moments reactive to limb movement in each direction were predicted using a three-dimensional model of the body. Preparatory motion of the trunk occurred in three dimensions in the directions opposite to the reactive moments. Electromyographic recordings from the superficial trunk muscles were consistent with preparatory trunk motion. However, activation of transversus abdominis was inconsistent with control of direction-specific moments acting on the trunk. The results provide evidence that anticipatory postural adjustments result in movements and not simple rigidification of the trunk.


Power quality affects teacher wellbeing and student behavior in three Minnesota Schools.
Poor power quality (dirty electricity) is ubiquitous especially in schools with fluorescent lights and computers. Previous studies have shown a relationship between power quality and student behavior/teacher health. The purpose of this study is to determine the ability of power line filters to reduce dirty electricity in a school environment and to document changes in health and behavior among teachers and students. We installed Graham Stetzer filters and dummy filters and measured power quality in three Minnesota Schools. Teachers completed a daily questionnaire regarding their health and the behavior of their students for an 8-week period. Teachers were unaware of which filters were installed at any one time (single blind study). Dirty electricity was reduced by more than 90% in the three schools and during this period teacher health improved as did student behavior in the middle/elementary schools. Headaches, general weakness, dry eyes/mouth, facial flushing, asthma, skin irritations, overall mood including depression and anxiety improved significantly among staff. Of the 44 teachers who participated 64% were better, 30% were worse, and 6% did not change. Behavior of high school students did not improve but elementary/middle school students were more active in class; more responsive, more focused; had fewer health complaints; and had a better overall learning experience. Dirty electricity in schools may be adversely affecting wellbeing of teachers and behavior of their students, especially younger students in middle and elementary school. Power line filters improve power quality and may also protect those who are sensitive to this energy. Work on electric and magnetic field metrics with and without Stetzer filters urgently needs to be carried out to determine just what characteristics of the dirty electricity may be interacting with the people.


Clouds of venus: a preliminary assessment of microstructure.
The multimodal microstructure of the Venus cloud system has been examined. In addition to confirmed H(2)SO(4) droplets and suspected elemental sulfur, a highly concentrated aerosol population has been observed extending above, within, and below the cloud system. These aerosols appear to cycle through the cloud droplets, but can never be removed by the weak precipitation mechanisms present. All cloud particles are likely laced with aerosol contaminants. Sedimentation and decomposition of H(2)SO(4) in the droplets of the lower cloud region contribute more than 7 watts per square meter of heat flux equaling one-fourth of the solar net flux at 50 kilometers.


Transperitoneal Versus Extraperitoneal Approach for Laparoscopic and Robot-Assisted Radical Prostatectomy: A Systematic Review and Meta-Analysis.
To conduct a comparative analysis of outcomes from 2 different surgical approaches, transperitoneal radical prostatectomy (TP-RP) and extraperitoneal radical prostatectomy (EP-RP) in minimally invasive surgery. A comprehensive search was conducted up to September 2022 using 5 online databases, namely PubMed, Cochrane, Scopus, EMBASE, and Science Direct. Studies were screened per the eligibility criteria, and outcomes included operative duration, estimated blood loss (EBL), hospital stay, operative complication, and positive surgical margin. Total of 13 studies compiled of 2387 patients were selected, with TP-RP and EP-RP performed on 1117 (46.79%) and 1270 (53.21%) patients, respectively. Six laparoscopy radical prostatectomy (LRP) studies and 7 robotassisted radical prostatectomy (RARP) studies with 1140 and 1247 patients, respectively, were also included. The EP-RP demonstrated a marked advantage in terms of operative complications (Risk Ratio [RR]=0.78, 95% CI=0.62, 0.98; P=.04), but no significant difference concluded for operative duration, EBL, hospital stay, and surgical margin. In the RARP group, there was a significant difference in operative duration for EP-RARP and TP-RARP (Mean difference [MD]=-17.27, 95% CI=-26.89, -7.65; P=.0004), hospital stay (MD=-0.54, 95% CI=-0.94, -0.14; P=.008), and operative complications (RR=0.7, 95% CI=0.49, 0.99; P=.04). There were no noteworthy variations identified in EBL and surgical margin. Furthermore, the LRP group did not show any significant differences. This study shows that regardless of the techniques used, EP-RP has a lower risk of operative complications than TP-RP, with no significant difference in other outcomes.


Metabolic effects of a high-fat diet post-weaning after low maternal dietary folate during pregnancy and lactation.
Investigate the influence of low-folate supply during pregnancy and lactation on obesity and markers of the metabolic syndrome in offspring, and how provision of a high-fat diet post weaning may exacerbate the resultant phenotype. Female C57Bl/6 mice were randomized to low or normal folate diets (0.4 or 2 mg folic acid/kg diet) prior to and during pregnancy and lactation. At 4 wk of age, offspring were randomized to high- or low-fat diets, weighed weekly and food intake assessed at 9 and 18 wk old. Adiposity was measured at 3 and 6 months. Plasma glucose and triacylglycerol (TAG) concentrations were measured at 6 months. Maternal folate supply did not influence adult offspring body weight or adiposity. High-fat feeding post weaning increased body weight and adiposity at 3 and 6 months (p > 0.001). Maternal low folate lowered plasma glucose (p = 0.010) but increased plasma TAG (p = 0.048). High-fat feeding post weaning increased plasma glucose and TAG (p = 0.023, p = 0.049 respectively). Offspring from folate-depleted (but not folate-adequate) dams had 30% higher TAG concentration when fed the high-fat diet from weaning (p = 0.005 for interaction). Inadequate maternal folate intake has long-term effects on offspring metabolism, manifested as increased circulating TAG, particularly in offspring with high-fat intake post weaning.


Intraoperative dosimetric representation of the real-time ultrasound-guided prostate implant.
To describe a method of creating an intraoperative dosimetric representation of the real-time ultrasound-guided prostate implant. An intraoperative dosimetry system (Multi Media Systems [MMS]) captures transverse ultrasound images after peripheral needles have been implanted in the prostate. The prostate contour and needle positions are outlined on the system. The volume of the prostate with needles in place is calculated. As seeds are deposited in the actual implant, the positions of the seeds are marked on the intraoperative system. Following implantation of the peripheral needles, the resulting isodose lines are displayed. The interior needles are inserted into the prostate, and these positions are captured on the system. As seeds are deposited through these needles into the prostate, their positions are captured on the planning system. When the implant is complete, the final dose coverage and dose volume histogram can be visualized. Ten consecutive patients underwent iodine 125 implants using real-time intraoperative isodose generation. The ratio of the preneedle prostate volume to postneedle prostate volume ranged from 0.89 to 1.0 (median 0.97). The calculated dose delivered to 90% of the prostate volume from the dose volume histogram (D90) ranged from 146.5 to 194 Gy (median 174.75 Gy). The percentage of the prostate covered by 240 Gy ranged from 14.6% to 59% (median 40.75%). Dosimetric representation of the real-time ultrasound-guided prostate implant can be achieved and demonstrates the efficacy of this brachytherapy technique.


Preferential alkylation of mitochondrial deoxyribonucleic acid by N-methyl-N-nitrosourea.
The reaction of the carcinogen N-methyl-N-nitrosourea with mitochondrial DNA from various rat tissues was examined in vivo and in vitro. After incubation of isolated mitochondria or cell nuclei with N[(14)C]-methyl-N-nitrosourea in vitro and subsequent isolation and purification of the DNA the specific radioactivity of the mitochondrial DNA was 3-7 times that of the nuclear DNA. The incorporation of (14)C into embryonic mitochondrial DNA in vitro was about twice that into the liver mitochondrial DNA. Identical incorporation rates, however, were found for the reaction of isolated mitochondrial DNA or nuclear DNA respectively with N[(14)C]-methyl-N-nitrosourea. After intraperitoneal injection of 43.3-58.5mg of N[(14)C]-methyl-N-nitrosourea/kg body wt. to adult rats the labelling of the mitochondrial DNA was on average 5 times that of the nuclear DNA. A smaller specific labelling was observed for the ribosomal RNA, transfer RNA, and mitochondrial RNA as well as for the mitochondrial protein as compared with the mitochondrial DNA. After hydrolysis of the alkylated nucleic acids with hydrochloric acid, fractionation was carried out on Dowex 50 cation-exchange columns. In most experiments 70-80% of the input (14)C radioactivity was eluted in the 7-methylguanine fraction. The preferential alkylation of the mitochondrial DNA by N-methyl-N-nitrosourea in situ is discussed in connexion with the cytoplasmic-mutation hypothesis of carcinogenesis.


Design and development of integrase inhibitors as anti-HIV agents.
A review is presented on different categories of compounds that have been studied for the inhibition of the HIV-1 integrase to develop anti-HIV agents. These compounds are: oligonucleotides (double-stranded, triplex, and G-quartet), curcumin analogues, polyhydroxylated aromatic compounds, diketo acids, caffeoyl- and galloyl - based compounds, hydrazides and amides, tetracyclines, and depsides and depsidones. For all these compounds, the important structural features essential for the inhibition of the integrase are pointed out.


Differential brain activations during intentionally simulated and subjectively experienced paralysis.
Distinguishing conversion disorder from malingering presents a significant challenge as the diagnosis ultimately depends on the patient's subjective report and the clinician's suspicion of an intention to deceive. Using hypnosis to manipulate the intentionality of movement inhibition in the same subjects, we used positron emission tomography (PET) to determine whether failure to move during intentionally simulated and subjectively experienced paralysis is mediated by different neural structures. Using a within-subject design, 12 normal, hypnotised subjects were tested under two paralysis conditions during the same scanning session. Half of the scans were performed with the suggestion that the left leg was paralysed (subjectively experienced paralysis condition) and half with the leg normal but with the instruction that paralysis should be feigned (intentionally simulated paralysis condition). Relative increases in brain activation were seen in the right orbitofrontal cortex, right cerebellum, left thalamus, and left putamen during subjectively experienced paralysis compared to intentionally simulated paralysis, although a previously reported activation of the right anterior cingulate cortex was not seen. During intentionally simulated paralysis compared to subjectively experienced paralysis relative increases in brain activation were seen in the left ventrolateral prefrontal cortex, and a number of right posterior cortical structures. Our results suggest that subjectively experienced paralysis has a different neural basis to intentionally simulated paralysis. These findings have theoretical and clinical implications for malingering and related attempts to unravel the neuropsychological basis for conversion hysteria.


Working toward the future: insights into Francisella tularensis pathogenesis and vaccine development.
Francisella tularensis is a facultative intracellular gram-negative pathogen and the etiological agent of the zoonotic disease tularemia. Recent advances in the field of Francisella genetics have led to a rapid increase in both the generation and subsequent characterization of mutant strains exhibiting altered growth and/or virulence characteristics within various model systems of infection. In this review, we summarize the major properties of several Francisella species, including F. tularensis and F. novicida, and provide an up-to-date synopsis of the genes necessary for pathogenesis by these organisms and the determinants that are currently being targeted for vaccine development.


The Usefulness of the TAPSE/sPAP Ratio for Predicting Survival in Medically Treated Chronic Thromboembolic Pulmonary Hypertension.
The ventriculoarterial uncoupling has been linked with unfavorable results as measured noninvasively by tricuspid annular plane systolic excursion divided by systolic pulmonary artery pressure (TAPSE/sPAP). However, its prognostic importance in chronic thromboembolic pulmonary hypertension (CTEPH) is limited. Thus, we determine the effect of the TAPSE/sPAP ratio on outcomes and predictors of all-cause mortality in these patients. We analyzed 56 subjects with medically treated CTEPH. Two-dimensional echocardiographic examination and right heart catheterization findings were recorded from the hospital database. Baseline New York Heart Association functional class (NYHA-FC), 6-min walk distance (6MWD), and brain natriuretic peptide (BNP) test results were recorded. The median age was 65.5 years. Over a median follow-up time of 27 months, 29 (51.8%) patients died. BNP values were higher (P = 0.008), 6MWD values were lower (P = 0.004), and NHYA-FC (P = 0.0001) was worse in the non-survivor group. TAPSE (P = 0.0001) and TAPSE/sPAP ratio (P = 0.001) were significantly lower and pulmonary vascular resistance (PVR) was higher in the non-survivor group (P = 0.03). The best cut-off value for the TAPSE/sPAP ratio for predicting mortality was 0.20 mm/mmHg and the survival rates were significantly lower in the TAPSE/sPAP ratio ≤0.20 group (log-rank P = 0.012). 6MWD (P = 0.005), NHYA-FC III-IV (P = 0.0001), TAPSE/sPAP ratio ≤0.20 (P = 0.017), PVR (P = 0.008), and TAPSE/sPAP ratio ≤0.20 combined with NYHA-FC III-IV (P = 0.0001) were significant determinants and TAPSE/sPAP ratio ≤0.20 combined with NYHA-FC III-IV was the only independent predictor of mortality (P = 0.003). Medically treated CTEPH patients with a TAPSE/sPAP ratio ≤0.20 had lower survival rates. TAPSE/sPAP ratio≤0.20 combined with NYHA-FC III-IV was the independent predictor of poor prognosis.


Assessment of Childhood Depression.
Depression as a disorder in childhood began to be increasingly recognised in the 1970s. Epidemiologic community and clinic-based studies have characterised the prevalence, clinical course, and complications of this illness throughout childhood and adolescence into adulthood. This paper reviews two instruments for assessing depression in prepubertal children - the Dominic Interactive and The Preschool Age Psychiatric Assessment. Both instruments are useful in screening for psychiatric disorders and reliably identifying the presence of depressive symptoms in young children.


Total angular momentum sorting in the telecom infrared with silicon Pancharatnam-Berry transformation optics.
Parallel sorting of orbital angular momentum (OAM) and polarization has recently acquired paramount importance and interest in a wide range of fields ranging from telecommunications to high-dimensional quantum cryptography. Due to their inherently polarization-sensitive optical response, optical elements acting on the geometric phase prove to be useful for processing structured light beams with orthogonal polarization states by means of a single optical platform. In this work, we present the design, fabrication and test of a Pancharatnam-Berry optical element in silicon implementing a log-pol optical transformation at 1310 nm for the realization of an OAM sorter based on the conformal mapping between angular and linear momentum states. The metasurface is realized in the form of continuously variant subwavelength gratings, providing high-resolution in the definition of the phase pattern. A hybrid device is fabricated assembling the metasurface for the geometric-phase control with multi-level diffractive optics for the polarization-independent manipulation of the dynamic phase. The optical characterization confirms the capability to sort orbital angular momentum and circular polarization at the same time.


Learning language from the input: why innate constraints can't explain noun compounding.
Do the production and interpretation of patterns of plural forms in noun-noun compounds reveal the workings of innate constraints that govern morphological processing? The results of previous studies on compounding have been taken to support a number of important theoretical claims: first, that there are fundamental differences in the way that children and adults learn and process regular and irregular plurals, second, that these differences reflect formal constraints that govern the way the way regular and irregular plurals are processed in language, and third, that these constraints are unlikely to be the product of learning. In a series of seven experiments, we critically assess the evidence that is cited in support of these arguments. The results of our experiments provide little support for the idea that substantively different factors govern the patterns of acquisition, production and interpretation patterns of regular and irregular plural forms in compounds. Once frequency differences between regular and irregular plurals are accounted for, we find no evidence of any qualitative difference in the patterns of interpretation and production of regular and irregular plural nouns in compounds, in either adults or children. Accordingly, we suggest that the pattern of acquisition of both regular and irregular plurals in compounds is consistent with a simple account, in which children learn the conventions that govern plural compounding using evidence that is readily available in the distribution patterns of adult speech.


Utility and significance of ureteric frozen section analysis during radical cystectomy.
To assess the utility of routine frozen section analysis of ureters at the time of radical cystectomy (RC) for urothelial cancer (UC), and the long-term outcomes of adverse ureteric pathology. Pathological data on 2 047 patients undergoing RC for UC with routine frozen section analysis of ureters (January 1971 to December 2009) were analysed. Univariate and multivariable logistic and Cox proportional hazards models were used to determine the risk of upper tract UC (UTUC) recurrence, local recurrence and overall survival in those identified as having adverse pathology (severe atypia/carcinoma in situ [CIS] or UC) at time of frozen section analysis. Adverse pathology was identified by frozen section analysis in 178 patients (8.6%). Frozen section analysis was found to have poor sensitivity in identifying adverse pathology (59.1%), which was improved in patients with preoperative CIS (68.0%). After a median (interquartile range) follow-up of 12.4 (1.9-10.1) years, 28 patients (1.4%) developed UTUC recurrence. There were no uretero-enteric anastomotic recurrences. Adverse pathology on frozen section analysis was associated with UTUC recurrence on univariate analysis (hazard ratio [HR] 6.2, 95% confidence interval [CI] 2.9-13.5), but 15/28 patients (54%) with UTUC recurrence had benign ureteric frozen section analysis on initial sectioning. Adverse pathology on frozen section analysis was not independently associated with the risk of local recurrence (HR 1.08, 95% CI 0.61-1.89) or overall survival (HR 1.12, 95% CI 0.94-1.35) in multivariate models. Ureteric frozen section analysis has poor sensitivity and may be marginally improved in pre-existing CIS. UTUC recurrence is rare and can occur despite negative frozen section analysis. Our data question the utility of routine frozen section analysis of the distal ureteric margin at the time of RC.


Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen.
Intratesticular testosterone (ITT) is thought to play a key role in the control of spermatogenesis in man but is rarely measured. The purposes of this study were 1) to examine the relationship between intratesticular fluid and serum testosterone (T) at baseline and during treatment with a contraceptive regimen known to suppress spermatogenesis and 2) to measure intratesticular fluid androgenic bioactivity. Seven men received 6 months of T enanthate (TE) 100 mg weekly intramuscularly plus levonorgestrel (LNG) 62.5 or 31.25 microg orally daily. Testicular fluid was obtained by percutaneous aspiration at baseline and during month 6. Mean luteinizing hormone (LH) was suppressed 98% from 3.79 +/- 0.80 IU/L at baseline to 0.08 +/- 0.03 IU/L. Mean follicle stimulating hormone (FSH) was suppressed 97%, from 3.29 +/- 0.67 IU/L to 0.10 +/- 0.03 IU/L. Mean serum T levels were similar before (22.8 +/- 1.9 nmol/L) and during treatment (28.7 +/- 2.0 nmol/L) (P = .12). ITT (822 +/- 136 nmol/L) was approximately 40x higher than serum T (P < .001) at baseline. ITT was suppressed 98% during treatment to 13.1 +/- 4.5 nmol/L, a level similar to baseline serum T (P = .08) but significantly lower than on-treatment serum T (P = .01). At baseline, intratesticular fluid androgenic bioactivity (583 +/- 145 nmol/L) was 70% of the ITT concentration measured by radioimmunoassay. Intratesticular androgenic bioactivity was suppressed 93% to 40 +/- 22 nmol/L (P < .01) during treatment, but was 3x higher than ITT (13.1 +/- 4.5 nmol/L). Sperm counts declined from 65 +/- 15 million/mL to 1.3 +/- 1.3 million/mL. In summary, TE plus LNG dramatically suppressed ITT (98%) and intratesticular androgenic bioactivity (93%) to levels approximating those in serum. ITT levels comparable with serum T were insufficient to support normal spermatogenesis. Intratesticular androgenic bioactivity was higher than ITT during treatment, suggesting that other androgens may be prevalent in the low-ITT environment.


Mitochondrial phosphagen kinases support the volatile power demands of motor nerve terminals.
Motor neurons are the longest neurons in the body, with axon terminals separated from the soma by as much as a meter. These terminals are largely autonomous with regard to their bioenergetic metabolism and must burn energy at a high rate to sustain muscle contraction. Here, through computer simulation and drawing on previously published empirical data, we determined that motor neuron terminals in Drosophila larvae experience highly volatile power demands. It might not be surprising then, that we discovered the mitochondria in the motor neuron terminals of both Drosophila and mice to be heavily decorated with phosphagen kinases - a key element in an energy storage and buffering system well-characterized in fast-twitch muscle fibres. Knockdown of arginine kinase 1 (ArgK1) in Drosophila larval motor neurons led to several bioenergetic deficits, including mitochondrial matrix acidification and a faster decline in the cytosol ATP to ADP ratio during axon burst firing. KEY POINTS: Neurons commonly fire in bursts imposing highly volatile demands on the bioenergetic machinery that generates ATP. Using a computational approach, we built profiles of presynaptic power demand at the level of single action potentials, as well as the transition from rest to sustained activity. Phosphagen systems are known to buffer ATP levels in muscles and we demonstrate that phosphagen kinases, which support such phosphagen systems, also localize to mitochondria in motor nerve terminals of fruit flies and mice. By knocking down phosphagen kinases in fruit fly motor nerve terminals, and using fluorescent reporters of the ATP:ADP ratio, lactate, pH and Ca2+ , we demonstrate a role for phosphagen kinases in stabilizing presynaptic ATP levels. These data indicate that the maintenance of phosphagen systems in motor neurons, and not just muscle, could be a beneficial initiative in sustaining musculoskeletal health and performance.


IL-21 Induces an Imbalance of Th17/Treg Cells in Moderate-to-Severe Plaque Psoriasis Patients.
Background: Psoriasis is a chronic immune-mediated inflammatory skin disease, with over-activated interleukin (IL)-17-producing CD4+ T cells (Th17) and repressed regulatory T (Treg) cells. IL-21 is a Th17-related cytokine and plays an important role in the pathogenesis of psoriasis. However, the mechanism by which IL-21 affects the pathogenic progress of psoriasis remains poorly understood. Methods: IL-21 and IL-21 receptor (IL-21R) expression in normal and psoriatic lesional skin were determined by immumohistochemical staining, immunofluorescence staining, and western blotting. The levels of IL-21, IL-17A, and IL-22 in the culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). The level of IL-10 in the culture supernatants was measured by cytometric bead array (CBA). The mRNA expression levels were assessed by quantitative polymerase chain reaction (qPCR). CD4+ T cells were isolated from the peripheral blood mononuclear cells (PBMCs) from the psoriasis patients and healthy individuals and then treated with or without IL-21 for 3 days. The proportions of Th17 and Treg cells were determined by flow cytometric analysis. Results: IL-21 and IL-21R were highly expressed in the lesional skin and peripheral blood of psoriasis patients. IL-21 promoted CD4+ T cells proliferation and Th17 cells differentiation and inhibiting Treg cells differentiation by upregulating RORγt expression and downregulating Foxp3 expression, with increased expression and secretion of IL-17A and IL-22. The proportion of Treg cells was negatively correlated with that of Th17 cells in psoriasis patients. Conclusion: Our results suggest that IL-21 may promote psoriatic inflammation by inducing imbalance in Th17 and Treg cell populations.


pH-Responsive Nanoprobe for In Vivo Photoacoustic Imaging of Gastric Acid.
In vivo real-time monitoring gastric acid is of great importance for diagnosis and treatment of gastrointestinal diseases. Herein, we synthesized a pH-responsive photoacoustic (PA) nanoprobe (denoted as LET-4) based on near-infrared (NIR) dye (IR1061) for in vivo photoacoustic imaging (PAI) of gastric acid in living subjects. In the acidic condition, the protonated LET-4 nanoprobe has a strong absorbance peak at 808 nm, followed by a strong PA signal output at 808 nm. The PA808 signal at pH 3 is 3.45-fold higher than the signal at pH 7. More importantly, the LET-4 nanoprobe could monitor in vivo gastric acid secretion assessment in animal model using PAI. This organic small molecule NIR dye-based probe with simple components, facile preparation, good biocompatibility, and rapid excretion has great potential for gastrointestinal disease diagnosis.


[Do scoliotic patients need increased orthodontic treatment? A comparative study on 104 cases].
The diagnosis of scoliosis during orthodontic treatment is often attributed to orthodontic treatment, which may be a simple confounding factor. Do scoliotic patients require increased orthodontic treatment? Is the extent of their need for orthodontic treatment correlated with the severity of their scoliosis? The authors conducted a comparative multicenter epidemiological study between a group of patients with a proven diagnosis of scoliosis objectified by the Cobb angle and a control group recruited from the general population. The endpoint was the Index Of Orthodontic Treatment Need (IOTN). The calculation of the number of subjects was made a priori. A statistical significance threshold of 5% was used for the statistical analysis. In this study, 104 patients were included: 36 patients (10 boys, 26 girls) with an average age of 12.1 years (+/-2.3 years) in the scoliosis group (mean Cobb angle = 21°) versus 69 patients (20 boys, 49 girls) with an average age of 12 years (+/-2.7 years) in the control group. Patients with scoliosis have a significantly higher need for orthodontic treatment than the general population. The study did not correlate the severity of scoliosis with the increased need for orthodontic treatment. Thus, the diagnosis of scoliosis during orthodontic treatment should not systematically result in the removal of the orthodontic appliance over-hastily held responsible for the scoliotic condition.


Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.
Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.


Cell-type-specific differentiation and molecular profiles in skin transplantation: implication of medical approach for genetic skin diseases.
Skin is highly accessible and valuable organ, which holds promise to accelerate the understanding of future medical innovation in association with skin transplantation, engineering, and wound healing. In skin transplantation biology, multistage and multifocal damages occur in both grafted donor and perilesional host skin and need to be repaired properly for the engraftment and maintenance of characteristic skin architecture. These local events are more unlikely to be regulated by the host immunity, because human skin transplantation has accomplished the donor skin engraftment onto the immunocompromised or immunosuppressive animals. Recent studies have emerged the importance of α-smooth muscle actin- (SMA-) positive myofibroblasts, via stage- and cell-specific contribution of TGFβ, PDGF, ET-1, CCN-2 signalling pathways, and mastocyte-derived mediators (e.g., histamine and tryptase), for the functional reorganisation of the grafted skin. Moreover, particular cell lineages from bone marrow (BM) cells have been shown to harbour the diferentiation capacity into multiple skin cell phenotypes, including epidermal keratinocytes and dermal endothelial cells and pericytes, undercontrolled by chemokines or cytokines. From a dermatological viewpoint, we review the recent update of cell-type- and molecular-specific action associated with reconstitution of the grafted skin and also focus on the novel application of BM transplantation medicine in genetic skin diseases.


A simplified and rapid in situ hybridization protocol for planarians.
Whole-mount in situ hybridization is a critical technique for analyzing gene expression in planarians. While robust in situ protocols have been developed, these protocols are laborious, making them challenging to incorporate in an academic setting, reducing throughput and increasing time to results. Here, the authors systematically tested modifications to all phases of the protocol with the goal of eliminating steps and reducing time without impacting quality. This modified protocol allows for whole-mount colorimetric in situ hybridization and multicolor fluorescence in situ hybridization to be completed in two days with a significant reduction in steps and hands-on processing time.


Aerosol therapy with Sch 1000. Short-term mucociliary clearance in normal and bronchitic subjects and toxicology in normal subjects.
The anticholinergic bronchodilator drug, Sch 1000, was administered as an aerosol by a metered-dose inhaler (200 microgram) to six normal and six bronchitic subjects. The short-term effect on mucociliary clearance was assessed and compared to a placebo (propellant and dispersal agent) in a double-blind crossover study. Mucociliary clearance in the normal group was significantly faster with administration of Sch 1000 than with placebo (P less than 0.01). There was no significant difference between the effects of administration of Sch 1000 and placebo on mucociliary clearance in the bronchitic group. Pulmonary function was significantly increased by therapy with Sch 1000 (as compared to administration of placebo) in the bronchitic group for two hours (P less than 0.05) and in the normal group for one hour (P less than 0.05). In another study, 12 normal subjects inhaled aerosols containing 40 microgram of placebo or 400 microgram of Sch 1000 from metered-dose inhalers on separate days in a randomized double-blind fashion. A significant sustained improvement in pulmonary function (P less than 0.05) and a transient fall in diastolic blood pressure were observed after administration of Sch 1000.


Effect of progesterone on embryo survival.
Increased genetic selection over the past 40 years has resulted in a dairy cow with an improved biological efficiency for producing milk but with an associated reduced fertility. Embryo loss is the greatest factor contributing to the failure of a cow to conceive. The extent and timing of embryo loss indicates that 70% to 80% of this loss occurs in the first 2 weeks after artificial insemination (AI). This is the period when a number of critical phases in embryo development occur and where protein accretion, substrate utilization and embryo metabolism increase dramatically. During this time the early embryo is completely dependent on the oviduct and uterine environment for its survival and it is likely that the embryo requires an optimal uterine environment to ensure normal growth and viability. There is increasing evidence of an association between the concentration of systemic progesterone and early embryo loss and that progesterone supplementation of cows, particularly those with low progesterone, can reduce this loss. While progesterone is known to affect uterine function and embryo growth, little is known about the uterus during the period of early embryo loss and how this is affected by changes in the concentration of systemic progesterone. The expression of uterine genes encoding the transport protein retinol binding protein (RBP) and the gene for folate binding protein (FBP) appear to be sensitive to changes in systemic progesterone, particularly during the early luteal phase of the cycle. Uterine concentrations of proteins also seem to be regulated by stage of cycle; however, their relationship with the systemic concentration of progesterone is unclear. There is an urgent need to characterize the uterine environment from a functional perspective during the early part of the luteal phase of the cycle, particularly in the high-producing cow, in order to understand the factors contributing to early embryo loss and in order to devise strategies to minimize or reduce this loss.


Non-regulated haloaromatic water disinfection byproducts act as endocrine and lipid disrupters in human placenta cells.
The disinfection of drinking water generates hundreds of disinfection byproducts (DBPs), including haloaromatic DBPs. These haloaromatic DBPs are suspected to be more toxic than haloaliphatic ones, and they are currently not regulated. This work investigates their toxicity and ability to interfere with estrogen synthesis in human placenta JEG-3 cells, and their genotoxic potential in human alveolar A549 cells. Among the haloaromatic DBPs studied, halobenzoquinones (2,6-dichloro- and 2,6-dibromo-1,4-benzoquinone (DCBQ, DBBQ)) showed the highest cytotoxicity (EC50: 18-26 μg/mL). They induced the generation of very high levels of reactive oxygen species (ROS) and up-regulated the expression of genes involved in estrogen synthesis (cyp19a1, hsd17b1). Increased ROS was linked to significant depletion of polyunsaturated lipid species from inner cell membranes. The other DBPs tested showed low or no significant cytotoxicity (EC50 ≥ 100 μg/mL), while 2,4,6-trichloro-, 2,4,6-tribromo-phenol (TCP, TBP) and 3,5-dibromo-4-hydroxybenzaldehyde (DCHB) induced the formation of micronuclei at concentrations much higher than those typically found in water (100 μg/mL). This study reveals the different modes of action of haloaromatic DBPs, and highlights the toxic potential of halobenzoquinones, which had a significant impact on the expression of placenta steroid metabolism related genes and induce oxidative stress, implying potential adverse health effects.


Impaired class II expression and antigen uptake in monocytic cells after HIV-1 infection.
Using the human macrophage hybridoma cell line 43 and primary monocytes, we investigated the regulation of class II expression and intracellular Ag trafficking after HIV-1 infection. The HIV-1-infected human macrophage hybridoma cell line, 43HIV, lost class II Ag expression, as determined by immunofluorescence, immunoprecipitation, and Northern blot analysis, 2 wk after infection. Class II expression could be restored by transfection with the full-length HLA-DR4 cDNA driven by a CMV IE promotor. However, even after transfection, the 43HIV cells were incapable of presenting Ag to MHC-matched Ag-specific T cells. This defect was associated with decreased formation of class II-Ag complexes, and similar findings were observed in primary HIV-1BaL-infected monocytes. We investigated Ag uptake using FITC-labeled tetanus, OVA, and keyhole limpet hemocyanin. There was decreased uptake of all three Ags after HIV-1 infection at different time points after Ag pulsing in the 43HIV cells and in primary HIV-1BaL-infected monocytes. There was colocalization of the FITC-labeled Ags with early (cathepsin D) and late endosomal markers (anti-mannose-6-phosphate receptor), lysosomal markers (CD-63), and acidic compartment markers (3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine) in the uninfected cells, but the level of colocalized Ag was reduced in the 43HIV cells and HIV-1BaL-infected monocytes. Our data suggest that class II expression, formation of class II-Ag complexes, and Ag uptake are impaired in chronically HIV-1-infected monocytic cells, which may contribute to the global immunosuppression observed in AIDS.


A New Class of Allosteric HIV-1 Integrase Inhibitors Identified by Crystallographic Fragment Screening of the Catalytic Core Domain.
HIV-1 integrase (IN) is essential for virus replication and represents an important multifunctional therapeutic target. Recently discovered quinoline-based allosteric IN inhibitors (ALLINIs) potently impair HIV-1 replication and are currently in clinical trials. ALLINIs exhibit a multimodal mechanism of action by inducing aberrant IN multimerization during virion morphogenesis and by competing with IN for binding to its cognate cellular cofactor LEDGF/p75 during early steps of HIV-1 infection. However, quinoline-based ALLINIs impose a low genetic barrier for the evolution of resistant phenotypes, which highlights a need for discovery of second-generation inhibitors. Using crystallographic screening of a library of 971 fragments against the HIV-1 IN catalytic core domain (CCD) followed by a fragment expansion approach, we have identified thiophenecarboxylic acid derivatives that bind at the CCD-CCD dimer interface at the principal lens epithelium-derived growth factor (LEDGF)/p75 binding pocket. The most active derivative (5) inhibited LEDGF/p75-dependent HIV-1 IN activity in vitro with an IC50 of 72 μm and impaired HIV-1 infection of T cells at an EC50 of 36 μm The identified lead compound, with a relatively small molecular weight (221 Da), provides an optimal building block for developing a new class of inhibitors. Furthermore, although structurally distinct thiophenecarboxylic acid derivatives target a similar pocket at the IN dimer interface as the quinoline-based ALLINIs, the lead compound, 5, inhibited IN mutants that confer resistance to quinoline-based compounds. Collectively, our findings provide a plausible path for structure-based development of second-generation ALLINIs.


A rice gene for microbial symbiosis, Oryza sativa CCaMK, reduces CH4 flux in a paddy field with low nitrogen input.
Plants have mutualistic symbiotic relationships with rhizobia and fungi by the common symbiosis pathway, of which Ca(2+)/calmodulin-dependent protein kinase (encoded by CCaMK) is a central component. Although Oryza sativa CCaMK (OsCCaMK) is required for fungal accommodation in rice roots, little is known about the role of OsCCaMK in rice symbiosis with bacteria. Here, we report the effect of a Tos17-induced OsCCaMK mutant (NE1115) on CH4 flux in low-nitrogen (LN) and standard-nitrogen (SN) paddy fields compared with wild-type (WT) Nipponbare. The growth of NE1115 was significantly decreased compared with that of the WT, especially in the LN field. The CH4 flux of NE1115 in the LN field was significantly greater (156 to 407% in 2011 and 170 to 816% in 2012) than that of the WT, although no difference was observed in the SN field. The copy number of pmoA (encodes methane monooxygenase in methanotrophs) was significantly higher in the roots and rhizosphere soil of the WT than in those of NE1115. However, the mcrA (encodes methyl coenzyme M reductase in methanogens) copy number did not differ between the WT and NE1115. These results were supported by a (13)C-labeled CH4-feeding experiment. In addition, the natural abundance of (15)N in WT shoots (3.05‰) was significantly lower than in NE1115 shoots (3.45‰), suggesting greater N2 fixation in the WT because of dilution with atmospheric N2 (0.00‰). Thus, CH4 oxidation and N2 fixation were simultaneously activated in the root zone of WT rice in the LN field and both processes are likely controlled by OsCCaMK.


A novel porous Ti6Al4V: characterization and cell attachment.
For the first time, a highly porous strong Ti6Al4V was produced by using a "polymeric sponge replication" method. A polymeric sponge, impregnated with a Ti6Al4V slurry prepared from Ti6Al4V powders and binders, was subjected to drying and pyrolyzing to remove the polymeric sponge and binders. After sintering at a high temperature and under high vacuum, a porous Ti6Al4V was produced. Optical microscopical observation, environmental scanning electron microscopy observation (with energy-dispersive micro X-ray analysis), mechanical tests, and metallurgical analyses were performed on the obtained porous Ti6Al4V with regard to the porous structure (both macropores and micropores), mechanical properties, chemical composition, phase compositions, and cell attachment behavior. The porous Ti6Al4V made by this method had a three-dimensional trabecular porous structure with interconnected pores mainly ranging from 400 to 700 microm and a total porosity of about 90%. The compressive strength was 10.3 +/- 3.3 MPa and the elastic constant 0.8 +/- 0.3 GPa. MC3T3-E1 cells attached and spread well in the inner surface of pores. Being similar to cancellous bone with regard to both interconnected porous structure and mechanical properties, the resulting porous Ti6Al4V is expected to be a promising biomaterial for biomedical applications.


Rat ovarian follicle bioassay reveals adverse effects of cadmium chloride (CdCl2) exposure on follicle development and oocyte maturation.
Rat ovarian follicle culture, as a novel bioassay, is adopted in this study to explore the effects of cadmium chloride (CdCL(2)) on folliculogenesis and oocyte maturation in vitro; the feasibility for its application on detection of possible effects of chemicals on reproduction is discussed and evaluated as well. The results showed that follicle growth, differentiation, and steroidogenesis were significantly disturbed by ≥ 1.2 μg/mL CdCl(2). The germinal vesicle breakdown of oocyte was also disturbed dose-dependently after the culture follicles were exposed to ≥ 1.6 μg/mL CdCl(2). Exposure to CdCl(2) with concentrations of 1.6 μg/mL on day 2 had caused significant reduced (p < 0.05) survival rate and rate of antral follicles, and increased abnormal follicle rate significantly, compared to the group exposed on day 6. Rat preantral follicle culture is a potential tool to assess the hazards of chemical compounds on female fertility and can be used to elucidate their mechanisms of actions.


Prior exposure to chronic stress results in enhanced synthesis and release of hippocampal norepinephrine in response to a novel stressor.
The release and synthesis of norepinephrine (NE) in hippocampus were measured in naive and chronically cold-stressed rats in response to acute tail-shock stress. Using in vivo microdialysis, it was determined that the basal extracellular concentrations of NE and 3,4-dihydroxyphenylacetic acid (DOPAC) in hippocampus were the same in the two groups. However, 30 min of intermittent tail shock produced a greater elevation of extracellular NE and 3,4-dihydroxyphenylacetic acid in the chronically cold-stressed rats than in the native controls. In hippocampus, the extracellular concentration of DOPAC may reflect NE biosynthesis, and thus the enhanced DOPAC response in the chronically stressed rats suggests an increase in NE synthesis. In order to investigate this possibility, two further methods of assessing NE biosynthesis were employed. Tyrosine hydroxylase (TH) activity was assayed in vitro in the presence of saturating concentrations of cofactor. No change in maximal TH activity could be detected in hippocampus of chronically cold-stressed rats. In addition, the in vivo rate of tyrosine hydroxylation in cold-stressed rats was measured by the accumulation of 3,4-dihydroxyphenylalanine in tissue following inhibition of aromatic amino acid decarboxylase. It was found that, whereas basal synthesis was the same in both groups of rats, synthesis accompanying a novel stressor was increased to a greater extent in the chronically stressed rats.


Assessment of the level of the actual and desirable levels of computer literacy, usage and expected knowledge of undergraduate students of nursing.
The aim of the study was to determine the perceptions of students entering nursing at the bachelors level, of their actual and desirable knowledge about computers and their applications relevant to nursing and health care. Within the health care system the use of computerized systems is increasing rapidly. In Australia, the NSW Health Department's Information Management Resource Consortium pilot project--to introduce the First Data Hospital Information System into NSW public hospitals--is a significant example of this trend. While the importance of computerized systems is fairly well recognized for the areas of management and research, they are becoming increasingly significant in the delivery of clinical care and quality assurance. It is important that nurses during their undergraduate education develop the computer literacy and awareness that will allow them access to the both the information and its management. To achieve this effectively it is essential to determine both the entry knowledge of students and what skills and knowledge are essential and desirable for their future roles as nurses. The research undertaken replicated an American study [2] and used their validated questionnaire. Both pre-registration(n=20) and post-registration (n=24) undergraduate students responded to a 21 item questionnaire. The issues addressed related to computer literacy, usage, and knowledge of clinical applications. Both groups desired more "hands on" experience and knowledge in the nurse's role in developing applications and using computers to help care for patients. These results were consistent with the Parks et. al. study. The significance of comparing actual and desirable levels of computer knowledge and awareness is in assisting educators to shape curriculum and course content to more effectively meet the educational needs of these groups in terms of Health Informatics.


A global multinational survey of cefotaxime-resistant coliforms in urban wastewater treatment plants.
The World Health Organization Global Action Plan recommends integrated surveillance programs as crucial strategies for monitoring antibiotic resistance. Although several national surveillance programs are in place for clinical and veterinary settings, no such schemes exist for monitoring antibiotic-resistant bacteria in the environment. In this transnational study, we developed, validated, and tested a low-cost surveillance and easy to implement approach to evaluate antibiotic resistance in wastewater treatment plants (WWTPs) by targeting cefotaxime-resistant (CTX-R) coliforms as indicators. The rationale for this approach was: i) coliform quantification methods are internationally accepted as indicators of fecal contamination in recreational waters and are therefore routinely applied in analytical labs; ii) CTX-R coliforms are clinically relevant, associated with extended-spectrum β-lactamases (ESBLs), and are rare in pristine environments. We analyzed 57 WWTPs in 22 countries across Europe, Asia, Africa, Australia, and North America. CTX-R coliforms were ubiquitous in raw sewage and their relative abundance varied significantly (<0.1% to 38.3%), being positively correlated (p < 0.001) with regional atmospheric temperatures. Although most WWTPs removed large proportions of CTX-R coliforms, loads over 103 colony-forming units per mL were occasionally observed in final effluents. We demonstrate that CTX-R coliform monitoring is a feasible and affordable approach to assess wastewater antibiotic resistance status.


Using weighted linear spatial decomposition to investigate brain activity through a set of fixed current dipoles.
We developed a method with the aim of decorrelating scalp EEG based on a set of spatial constraints. We assume that the scalp EEG can be modelled by a small number of current dipoles of fixed location and orientation, placed at regions of interest. The algorithm is based on weighted linear spatial decomposition in order to obtain a weighted solution to the inverse problem. An EEG data matrix is first weighted in favour of a single dipole in the set. The dipole moment is then calculated from the weighted EEG by the pseudo-inverse method. This is repeated for each dipole. Six seizures were processed from 4 patients using the standard least-squares solution and our weighted version. The average cross-correlation between channels was calculated for each case. The first method resulted in a mean drop in cross-correlation of 16.5% from that of the scalp. Our method resulted in a reduction of 34.5%. Our method gives a more spatially decorrelated signal in regions of interest (although it is not intended as an accurate localization tool). Subsequent analysis is more robust and less likely to be dependent on specific recording montages. This is more than could be obtained using a standard least-squares solution using the same model.


Computational simulation-assisted design and experimental verification of molecularly imprinted polymers for selective extraction of chlorogenic acid.
Chlorogenic acid (CGA) is an active ingredient in honeysuckle with a broad-spectrum of antibacterial activity, suppressing tumor growth and other pharmacological effects. However, it is susceptible to damage during traditional extraction and separation processes. Therefore, developing selective and efficient extraction methods of CGA is essential. Based on computational molecular simulations, a reliable and efficient molecularly imprinted polymers (MIPs) were successfully developed for selective extraction of CGA. MIPs and non-molecularly imprinted polymers (NIPs) were synthesized using a precipitation polymerization method, employing three different functional monomers: [methacrylic acid (MAA), 4-vinylpyridine (4-VP), and methyl methacrylate (MMA)], with CGA serving as the template molecule. To simulate the polymers and predict the optimal ratio between the template and functional monomer, the computational studies and adsorption performance experiments were carried out. The adsorption characteristics and thermal stability of polymers were evaluated by isothermal adsorption, adsorption kinetics, selective adsorption and thermogravimetric analysis, aiming to obtain the MIPs with specific recognition and selectivity for CGA. When the molar ratio of template CGA to functional monomer 4-VP was 1:8, the prepared MIPs was found to have the maximum adsorption capacity (14.85 mg g-1) and the highest imprinting factor (1.74) at the CGA concentration of 100 mg L-1. These results were consistent with those obtained by computational molecular simulation. This study not only provides good guidance for developing separation materials for extracting CGA from natural plants but also inspires the application of computer simulation and molecular docking techniques in the preparation of specific MIPs materials.


Regenerative therapies in young hearts with structural or congenital heart disease.
Pediatric heart failure (HF) is rare. The prognosis is generally poor. HF is most frequently related to cardiomyopathy or congenital heart disease (CHD). Associated phenotypes are HF with preserved (HFpEF) or reduced ejection fraction (HFrEF); both in children with biventricular or univentricular circulation. Cardiac growth, differentiation, proliferation and consecutively regenerative and repair mechanisms are inversely related to the patient's age; edaphic and circulating cardiac progenitor cells as well; in sum, there are enormous endogenous potentials repairing a diseased heart in particular in young children. Efforts supporting pediatric cardiac regeneration are clearly justified; cell-based therapies have been addressed in small series of children with end-stage HF of either the left or right ventricle, more recently in randomized clinical trials. Different cell populations like autologous bone marrow mononuclear cells, progenitor cells or cardiac derived cells have been injected into coronaries or directly into the myocardium. Beneficial at least transient improvement of cardiac function was observed in patients with dilative cardiomyopathy and CHD, mainly hypoplastic left heart syndrome (HLHS). Cellular repopulation and possibly more crucial, paracrine effects contributed in slowing down progression of pediatric end-stage HF. Our review summarizes the current knowledge in different scenarios of HF by cell-based cardiac therapies in critically ill children. Based on the actual clinical experience future work to distinguish responders from non-responders among other refinements will lead to individualized precision treatment of HF in children, what means a lot to a child on a long list waiting for heart transplantation (HTX).


Brucellosis in India: results of a collaborative workshop to define One Health priorities.
Brucellosis is an important zoonosis worldwide. In livestock, it frequently causes chronic disease with reproductive failures that contribute to production losses, and in humans, it causes an often-chronic febrile illness that is frequently underdiagnosed in many low- and middle-income countries, including India. India has one of the largest ruminant populations in the world, and brucellosis is endemic in the country in both humans and animals. In November 2017, the International Livestock Research Institute invited experts from government, national research institutes, universities, and different international organizations to a one-day meeting to set priorities towards a "One Health" control strategy for brucellosis in India. Using a risk prioritization exercise followed by discussions, the meeting agreed on the following priorities: collaboration (transboundary and transdisciplinary); collection of more epidemiological evidence in humans, cattle, and in small ruminants (which have been neglected in past research); Economic impact studies, including cost effectiveness of control programmes; livestock vaccination, including national facilities for securing vaccines for the cattle population; management of infected animals (with the ban on bovine slaughter, alternatives such as sanctuaries must be explored); laboratory capacities and diagnostics (quality must be assured and better rapid tests developed); and increased awareness, making farmers, health workers, and the general public more aware of risks of brucellosis and zoonoses in general. Overall, the meeting participants agreed that brucellosis control will be challenging in India, but with collaboration to address the priority areas listed here, it could be possible.


Multivariate temporal pattern analysis applied to the study of rat behavior in the elevated plus maze: methodological and conceptual highlights.
Aim of this article is to illustrate the application of a multivariate approach known as t-pattern analysis in the study of rat behavior in elevated plus maze. By means of this multivariate approach, significant relationships among behavioral events in the course of time can be described. Both quantitative and t-pattern analyses were utilized to analyze data obtained from fifteen male Wistar rats following a trial 1-trial 2 protocol. In trial 2, in comparison with the initial exposure, mean occurrences of behavioral elements performed in protected zones of the maze showed a significant increase counterbalanced by a significant decrease of mean occurrences of behavioral elements in unprotected zones. Multivariate t-pattern analysis, in trial 1, revealed the presence of 134 t-patterns of different composition. In trial 2, the temporal structure of behavior become more simple, being present only 32 different t-patterns. Behavioral strings and stripes (i.e. graphical representation of each t-pattern onset) of all t-patterns were presented both for trial 1 and trial 2 as well. Finally, percent distributions in the three zones of the maze show a clear-cut increase of t-patterns in closed arm and a significant reduction in the remaining zones. Results show that previous experience deeply modifies the temporal structure of rat behavior in the elevated plus maze. In addition, this article, by highlighting several conceptual, methodological and illustrative aspects on the utilization of t-pattern analysis, could represent a useful background to employ such a refined approach in the study of rat behavior in elevated plus maze.


COVID-19 and regional differences in the timeliness of hip-fracture surgery: an interrupted time-series analysis.
It is of great importance to examine the impact of the healthcare reorganization adopted to confront the COVID-19 pandemic on the quality of care provided to non-COVID-19 patients. The aim of this study is to assess the impact of the COVID-19 national lockdown (March 9, 2020) on the quality of care provided to patients with hip fracture (HF) in Piedmont and Emilia-Romagna, two large regions of northern Italy severely hit by the pandemic. We calculated the percentage of HF patients undergoing surgery within 2 days of hospital admission. An interrupted time-series analysis was performed on weekly data from December 11, 2019 to June 9, 2020 (≈6 months), interrupting the series in the 2nd week of March. The same data observed the year before were included as a control time series with no "intervention" (lockdown) in the middle of the observation period. Before the lockdown, 2-day surgery was 69.9% in Piedmont and 79.2% in Emilia-Romagna; after the lockdown, these proportions were equal to 69.8% (-0.1%) and 69.3% (-9.9%), respectively. While Piedmont did not experience any drop in the amount of surgery, Emilia-Romagna exhibited a significant decline at a weekly rate of -1.29% (95% CI [-1.71 to -0.88]). Divergent trend patterns in the two study regions reflect local differences in pandemic timing as well as in healthcare services capacity, management, and emergency preparedness.


Feeding lactose increases ruminal butyrate and plasma beta-hydroxybutyrate in lactating dairy cows.
Ruminal fermentation of lactose increases molar proportions of butyrate, which is metabolized by the ruminal epithelium to beta-hydroxybutyrate (BHBA). To determine the effects of dietary whey, and specifically lactose, on concentrations of ruminal and blood volatile fatty acids (VFA) and blood BHBA, 8 Holstein and 4 Brown Swiss multiparous cows (210 +/- 33 d in milk) were blocked by breed and randomly assigned to one of three 4 x 4 Latin squares. Treatments were control (CON; 7.1% of dietary dry matter [DM] as cornstarch), liquid whey (WHEY; 9.4% of diet DM) containing 70% lactose on a DM basis, low lactose (LOLAC; 7.1% lactose), or high lactose (HILAC; 14.3% lactose). Diets contained 53% forage as corn silage, alfalfa hay, and grass hay (DM basis) and a corn and soybean meal-based concentrate. Average dietary percentage of crude protein and energy density (Mcal/kg net energy for lactation) were 16.8 and 1.47, respectively. Feeding lactose increased DM intake. Milk production and composition were not affected by diet with the exception of decreased urea nitrogen in milk from cows fed lactose. Greater proportions of ruminal propionate were observed in cows fed CON relative to those fed WHEY and LOLAC. Increasing dietary lactose increased proportions of ruminal butyrate and decreased acetate and branched-chain VFA. Concurrent with the increase in ruminal butyrate concentrations, there was an increase in plasma BHBA as lactose in the diet increased. Concentrations of VFA in plasma were not affected by diet with the exception of the branched-chain VFA, which were increased in cows fed LOLAC compared with WHEY. These data indicate lactose fermentation increases proportions of ruminal butyrate and plasma BHBA in lactating dairy cows; however, the observed increase in plasma BHBA is not sufficient to subject cows to ketosis.


An intelligent system for improving adherence to guidelines on acute stroke.
A timely, accurate assessment and decision-making process is essential for the diagnosis and treatment of the acute stroke, which is the world's third leading cause of death. This process is often performed using the traditional method that increases the complexity, duration, and medical errors. The present study aimed to design and evaluate an intelligent system for improving adherence to the guidelines on the assessment and treatment of acute stroke patients. Decision-making rules and data elements were used to predict the severity and to treat patients according to the specialists' opinions and guidelines. A system was then developed based on the intelligent decision-making algorithms. The system was finally evaluated by measuring the accuracy, sensitivity, specificity, applicability, performance, esthetics, information quality, and completeness and rates of medical errors. The segmented regression model was used to evaluate the effect of systems on the level and the trend of guideline adherence for the assessment and treatment of acute stroke. Fifty-three data elements were identified and used in the data collection and comprehensive decision-making rules. The rules were organized in a decision tree. In our analysis, 150 patients were included. The system accuracy was 98.30%. Evaluation results indicated an error rate of 1.69% by traditional methods. Documentation quality (completeness) increased from 78.66% to 100%. The average score of system quality was 4.60 indicating an acceptable range. After the system intervention, the mean of the adherence to the guideline significantly increased from 65% to 99.5% (P < 0.0008). The designed system was accurate and can improve adherence to the guideline for the severity assessment and the determination of a therapeutic trend for acute stroke patients. It leads to physicians' empowerment, significantly reduces medical errors, and improves the documentation quality.


An adaptive semiparametric and context-based approach to unsupervised change detection in multitemporal remote-sensing images.
In this paper, a novel automatic approach to the unsupervised identification of changes in multitemporal remote-sensing images is proposed. This approach, unlike classical ones, is based on the formulation of the unsupervised change-detection problem in terms of the Bayesian decision theory. In this context, an adaptive semiparametric technique for the unsupervised estimation of the statistical terms associated with the gray levels of changed and unchanged pixels in a difference image is presented. Such a technique exploits the effectivenesses of two theoretically well-founded estimation procedures: the reduced Parzen estimate (RPE) procedure and the expectation-maximization (EM) algorithm. Then, thanks to the resulting estimates and to a Markov random field (MRF) approach used to model the spatial-contextual information contained in the multitemporal images considered, a change detection map is generated. The adaptive semiparametric nature of the proposed technique allows its application to different kinds of remote-sensing images. Experimental results, obtained on two sets of multitemporal remote-sensing images acquired by two different sensors, confirm the validity of the proposed approach.


The influence of verification jig on framework fit for nonsegmented fixed implant-supported complete denture.
The purpose of this retrospective study was to assess if there was a difference in the likelihood of achieving passive fit when an implant-supported full-arch prosthesis framework is fabricated with or without the aid of a verification jig. This investigation was approved by the University of Rochester Research Subject Review Board (protocol #RSRB00038482). Thirty edentulous patients, 49 to 73 years old (mean 61 years old), rehabilitated with a nonsegmented fixed implant-supported complete denture were included in the study. During the restorative process, final impressions were made using the pickup impression technique and elastomeric impression materials. For 16 patients, a verification jig was made (group J), while for the remaining 14 patients, a verification jig was not used (group NJ) and the framework was fabricated directly on the master cast. During the framework try-in appointment, the fit was assessed by clinical (Sheffield test) and radiographic inspection and recorded as passive or nonpassive. When a verification jig was used (group J, n = 16), all frameworks exhibited clinically passive fit, while when a verification jig was not used (group NJ, n = 14), only two frameworks fit. This difference was statistically significant (p < .001). Within the limitations of this retrospective study, the fabrication of a verification jig ensured clinically passive fit of metal frameworks in nonsegmented fixed implant-supported complete denture.


Diversity and distribution of the bmp gene cluster and its Polybrominated products in the genus Pseudoalteromonas.
The production of pentabromopseudilin and related brominated compounds by Pseudoalteromonas spp. has recently been linked to the bmp biosynthetic gene cluster. This study explored the distribution and evolutionary history of this gene cluster in the genus Pseudoalteromonas. A phylogeny of the genus revealed numerous clades that do not contain type strains, suggesting considerable species level diversity has yet to be described. Comparative genomics revealed four distinct versions of the gene cluster distributed among 19 of the 101 Pseudoalteromonas genomes examined. These were largely localized to the least inclusive clades containing the Pseudoalteromonas luteoviolacea and Pseudoalteromonas phenolica type strains and show clear evidence of gene and gene cluster loss in certain lineages. Bmp gene phylogeny is largely congruent with the Pseudoalteromonas species phylogeny, suggesting vertical inheritance within the genus. However, the gene cluster is found in three different genomic environments suggesting either chromosomal rearrangement or multiple acquisition events. Bmp conservation within certain lineages suggests the encoded products are highly relevant to the ecology of these bacteria.


Oral administration of paeoniflorin attenuates allergic contact dermatitis by inhibiting dendritic cell migration and Th1 and Th17 differentiation in a mouse model.
Allergic contact dermatitis (ACD) is a hapten-specific CD4(+) T-cells mediated inflammatory response of the skin. Its pathomechanism involves 2 phases, an induction phase and an elicitation phase. Langerhans cells (LCs) and dendritic cells (DCs) in the skin play key roles in presenting low molecular weight chemicals (haptens) to the lymph nodes. Therefore, inhibition of the migration of LCs or DCs and T-cell proliferation is each expected to control ACD disease. To explore the effectiveness of paeoniflorin (PF) on the migration of LCs and T-cell proliferation in vivo, we establish a murine model of ACD, promoted by repeated exposure to an allergen (specifically 1-Chloro-2,4-dinitrobenzene (DNCB)). Administration of PF inhibits DC migration in this DNCB-induced model in the induction phase. As a result, epidermal LC density in the elicitation phase increased in PF-treated mice when compared to PF-untreated mice. At the same time, PF reduced IFN-γ(+)CD4(+) and IL-17(+)CD4(+) T cells proliferation (but not IL-4(+)CD4(+) T cells proliferation), leading to an attenuated cutaneous inflammatory response. Consistent with this T-cell proliferation profile, secretions of IFN-γ and IL-17 were reduced and IL-10 secretion increased in PF-treated mice, but production of IL-4 and IL-5 remained unchanged in the skin and blood samples. These results suggest that oral administration of PF can treat and prevent ACD effectively through inhibition of DC migration, and thus decrease the capacity of DCs to stimulate Th1 and Th17 cell differentiation and cytokine production.


ZO-1 expression and phosphorylation in diabetic nephropathy.
Cellular mechanisms responsible for the loss of capillary wall permselectivity in diabetic nephropathy are not well characterized. ZO-1 is a junctional protein involved in the assembly and proper function of a number of tight junctions and is also expressed at the junction of podocytes with the slit diaphragm. We investigated the effect of diabetes and high glucose concentration on the expression of ZO-1 in animal models of both type 1 and 2 diabetes and in rat glomerular epithelial cells. In diabetic animals, immunohistochemistry and Western blotting showed decreased expression of ZO-1 in glomeruli. Immunogold electron microscopy revealed redistribution of ZO-1 from the podocyte membrane to the cytoplasm in the diabetic animals. Exposure of rat glomerular epithelial cells to high glucose resulted in a decrease in the intensity of ZO-1 staining and redistribution of ZO-1 from the membrane to the cytoplasm, changes that are attenuated by blockade of the angiotensin II type 1 receptor. ZO-1 protein expression and serine and tyrosine phosphorylation of ZO-1 were also decreased in cells exposed to high glucose. These findings suggest that alterations in the content and localization of ZO-1 may be relevant to the pathogenesis of proteinuria in diabetes.


The conditions required to isolate and maintain viable cotton (Gossypium hirsutum L.) microspores.
Cultural systems developed for the successful production of haploid plants from anther and microspore culture of a number of species are lethal to cotton microspores. Components of these systems were examined individually and in simple combinations to determine their specific effect on cotton microspore viability during isolation and culture. An organically buffered pH of 7.0 was critical for survival. The addition of potassium salts, near standard concentrations used for other species, enhanced survival and the cytoplasmic appearance of isolated microspores. Severe toxicity resulted from ammonium, calcium and magnesium salts, and these ions were tolerated only at very low concentrations. Iron, glutamine, serine, inositol, vitamins, and trace minerals were generally not detrimental to microspores at standard concentrations. An isolation and cultural maintenance system was developed that yields large quantities of healthy, viable cotton microspores. This initial step allows for further research in inducing cotton microspores to divide and undergo embryogenesis.


Nanoghosts: Harnessing Mesenchymal Stem Cell Membrane for Construction of Drug Delivery Platforms Via Optimized Biomimetics.
Mesenchymal stem cells (MSCs) are becoming hotspots for application in disease therapies recently, combining with biomaterials and drug delivery system. A major advantage of MSCs applied in drug delivery system is that these cells enable specific targeting and releasing of cargos to the disease sites. However, the potential tumor tropic effects of MSCs raised concerns on biosafety. To solve this problem, there are emerging methods of isolating cell membranes and developing nanoformulations to perform drug delivery, which avoids concerns on biosafety without disturbing the membrane functions of specific polarizing and locating. These cargoes are so called "nanoghosts." This review article summarizes the current applications of nanoghosts, the promising potential of MSCs to be applied in membrane isolation and nanoghost construction, and possible approaches to develop better drug delivery system harnessing from MSC ghost cell membranes.


Diffusivity and quantitative T1 profile of human visual white matter tracts after retinal ganglion cell damage.
In patients with retinal ganglion cell diseases, recent diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts such as the optic tract, and optic radiation. However, the microstructural origin of these diffusivity changes is unknown as DTI metrics involve multiple biological factors and do not correlate directly with specific microstructural properties. In contrast, recent quantitative T1 (qT1) mapping methods provide tissue property measurements relatively specific to myelin volume fractions in white matter. This study aims to improve our understanding of microstructural changes in visual white matter tracts following retinal ganglion cell damage in Leber's hereditary optic neuropathy (LHON) patients by combining DTI and qT1 measurements. We collected these measurements from seven LHON patients and twenty age-matched control subjects. For all individuals, we identified the optic tract and the optic radiation using probabilistic tractography, and evaluated diffusivity and qT1 profiles along them. Both diffusivity and qT1 measurements in the optic tract differed significantly between LHON patients and controls. In the optic radiation, these changes were observed in diffusivity but were not evident in qT1 measurements. This suggests that myelin loss may not explain trans-synaptic diffusivity changes in the optic radiation as a consequence of retinal ganglion cell disease.