Temporal trends in adolescent pregnancies in Lombardy, Italy: 1996-2010.
Data from southern European countries concerning teenage pregnancy have not been properly analysed so far. We provide the temporal trend of adolescent pregnancy rates in Lombardy, Northern Italy. Using the hospital discharge register (1996-2010), teenage pregnancy-related admission rates per 1000 girls aged 13 to 19 years, residing in Lombardy, were computed. Miscarriage-, induced abortion-, and delivery ratios/100 pregnancies, and caesarean section ratio/100 deliveries, were calculated. The pregnancy rate increased from 9.07 in 1996-2000 to 10.20 in 2001-2005, and remained at that level (10.27) in 2006-2010. However, the rates by country of birth (native Italian and non-native Italian) showed a steady decline in 2003-2010, when data about residents in Lombardy, categorised by sex, age and country of birth, were available. The induced abortion rate rose from 5.38/1000 to 5.55/1000, then decreased slightly in 2006-2010. The abortion ratio/100 pregnancies diminished from 59.3 in 1996-2000 to 50.3 in 2006-2010. Between 1996 and 2010, the overall teenage pregnancy rate has risen in Lombardy. When the rates were calculated separately for adolescents born in Italy and immigrants, the trends reverted in the period 2003-2010: in both groups pregnancy- and birth rates steadily declined. Pregnancy-, abortion-, and birth rates in non-native Italians, after having dropped, are all still much higher than those among native Italians. Because the number of non-native Italian adolescent girls markedly increased over the last two decades, their group--with decreasing, but still higher, birth- and abortion rates--has caused the observed rise in those rates when all adolescents residing in Lombardy are considered indistinctly.


Reversible EOL-indicator: a new cause for low pacemaker rate.
A case is presented in which a new cause for decrease in pacemaker rate was encountered: six months after implantation of a Medtronic 5967 pacemaker, the first routine check-up revealed a rate of 62.5 ppm instead of 70 ppm. After application of a magnet, all measurements returned to normal. The cause for this phenomenon, which could not be attributed to battery depletion or oversensing, was probably a change of state of the flip-flop which is responsible for the sudden rate drop of 10% which serves as the end-of-life (EOL)-indicator in this pacemaker. This change of state may result from a very short decrease of power supply voltage during shipment or at the time of implant, and is fully and permanently reversible by performance of the magnet test. In order to prevent unnecessary pacemaker explants, future pacemaker circuits should be redesigned to eliminate the effect of very short voltage changes. Meanwhile, a routine magnet test should be performed immediately after implantation.


Poliovirus and vesicular stomatitis virus replication in the presence of 6-diazo-5-oxo-L-norleucine or 2-deoxy-D-glucose.
The effects of 6-diazo-5-oxo-L-norleucine (DON), 2-deoxy-D-glucose (DOG), and tunicamycin (TM) on the replication of poliovirus (PV) and vesicular stomatitis virus (VSV) were examined. During a 48-hr replication period, TM, DON, and DOG inhibit VSV plaque formation in HEp-2 cells by 99.9%, 99.8%, and 99.9% respectively. Inhibition of VSV by DON is reversed with glutamine. Although all three agents are known to affect glycoprotein synthesis, DON and DOG also inhibit plaque formation of viruses devoid of structural glycoproteins. Thus, plaque formation of PV types 1 and 3 and Coxsackie B3 virus is delayed in HEp-2 and Buffalo green monkey kidney cells during exposure to these agents. Since these viruses do not contain glycoproteins and since concentrations up to 10 micrograms TM/ml cause no significant inhibition of PV, DON and DOG are affecting another viral or cellular process. Inhibition of PV replication by DON is reversed by addition of 25 mM glutamine or marginally by exposure to a combination of 5 mM concentrations of cytidine, uridine, adenosine monophosphate, and guanosine monophosphate. Inhibition of PV replication by DOG is reversed with 5 mM uridine alone. During DON exposure of HEp-2 cells infected with PV, the amount of 3H-uridine incorporation at 5.5 hr postinfection (pi) is reduced to 53% of untreated controls, an amount 11% greater than incorporation in cultures infected with PV but not treated with DON. These data indicate that the inhibition of PV replication by DON or DOG occurs at the level of viral RNA synthesis, while the primary target of these agents during VSV replication is probably glycosylation.


Evidence that blood vessels in guinea-pig lung are supplied by both noradrenergic and dopaminergic axons.
Assay of catecholamines in guinea-pig lung showed that the amount of dopamine in this tissue is 3-4 times greater than that predicted to be associated only with noradrenergic nerves, and is depleted by animal treatment with 6-hydroxydopamine. Fluorescence microscopy after formaldehyde condensation did not reveal any non-neuronal stores of catecholamines within the lung. The pulmonary and bronchial arterial vessels are accompanied by numerous fine nerve fibres that exhibit immunoreactivity for tyrosine hydroxylase, and are therefore presumed to be catecholaminergic. A small proportion of these fibres are also immunoreactive for DOPA decarboxylase. The results are consistent with innervation of pulmonary and bronchial resistance vessels by dopaminergic as well as noradrenergic sympathetic axons.


Regulatory efficacy of fermented plant extract on the intestinal microflora and lipid profile in mildly hypercholesterolemic individuals.
In recent years, the use of fermented plant products to protect against various metabolic syndromes has been increasing enormously. The objective of this study was to check the regulatory efficacy of fermented plant extract (FPE) on intestinal microflora, lipid profile, and antioxidant status in mildly hypercholesterolemic volunteers. Forty-four mildly hypercholesterolemic individuals (cholesterol 180-220 mg/dL) were recruited and assigned to two groups: experimental or placebo. Volunteers were requested to drink either 60 mL of FPE or placebo for 8 weeks. Anthropometric measurements were done in the initial, 4th, 8th, and 10th weeks. The anthropometric parameters such as body weight, body fat, and body mass index were markedly lowered (p<0.05) on FPE intervention participants. Moreover, the total antioxidant capacity and total phenolics in plasma were considerably increased along with a reduction (p<0.05) in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) after FPE supplementation. Participants who drank FPE showed a pronounced increase (p<0.05) in the number of beneficial bacteria such as Bifidobacterium spp. and Lactobacillus spp., whereas the number of harmful bacteria such as Escherichia coli and Clostridium perfringens (p<0.05) were concomitantly reduced. Furthermore, the lag time of LDL oxidation was substantially ameliorated in FPE-administered group, thus indicating its antioxidative and cardioprotective properties. Treatment with FPE substantially improved the intestinal microflora and thereby positively regulated various physiological functions by lowering the anthropometric parameters, TC, and LDL-c, and remarkably elevated the antioxidant capacity and lag time of LDL oxidation. Therefore, we recommended FPE beverage for combating hypercholesterolemia.


SYCAMORE--a systems biology computational analysis and modeling research environment.
SYCAMORE is a browser-based application that facilitates construction, simulation and analysis of kinetic models in systems biology. Thus, it allows e.g. database supported modelling, basic model checking and the estimation of unknown kinetic parameters based on protein structures. In addition, it offers some guidance in order to allow non-expert users to perform basic computational modelling tasks. SYCAMORE is freely available for academic use at http://sycamore.eml.org. Commercial users may acquire a license. firstname.lastname@example.com.


Peroxisome proliferator-activated receptor (PPAR) expression in cultured bovine endometrial cells and response to omega-3 fatty acid, growth hormone and agonist stimulation in relation to series 2 prostaglandin production.
The peroxisome proliferator-activated receptors (PPARs) are a family of nuclear transcription factors thought to act as receptors for polyunsaturated fatty acids and to reduce production of series 2 prostaglandins (PG). The objectives of the current study were to characterize PPAR expression and the prostaglandin synthetic activity of cultured bovine endometrial cells in response to known PPAR ligands, as well as to key stimulators and inhibitors of series 2 prostaglandin secretion. PPARalpha and PPARdelta, but not PPARgamma, mRNAs are expressed in the BEND cell line regardless of treatment. Under resting conditions, PPARalpha mRNA levels increase in response to growth hormone (P < 0.05). In cells stimulated with PdBu, growth hormone depresses PPARalpha mRNA levels, regardless of whether cells also are treated with IFNtau. In contrast, PPARdelta mRNA levels are increased by exposure to PdBu, eicosapentanoic acid and IFNtau, and these effects are additive. PPAR mRNA levels are not predictive of prostaglandin accumulation. Agonist activation of PPARalpha, PPARdelta or PPARgamma augments PdBu-induced increases in prostaglandin H synthase-2 mRNA and media accumulation of prostaglandins F2alpha and E2. Treatment with the PPARalpha/delta agonist carbaprostacyclin, but not the PPARalpha agonist Wy14643 or PPARgamma agonist ciglitazone, completely reverses the IFNtau suppression of prostaglandin synthesis. In conclusion, PPARalpha and PPARdelta function in the response of bovine endometrium to growth hormone and long chain omega-3 polyunsaturated fatty acids.


Temporal bone CT-based anatomical parameters associated with the development of cholesteatoma.
Cholesteatoma is caused by disorders of the middle ear ventilation that trigger a progressive series of events responsible for its formation. The aim of this study was to identify possible radiological CT-derived parameters predisposing to ventilation disorders and cholesteatoma. In this retrospective study, patients diagnosed with cholesteatomatous chronic otitis media who underwent temporal bone CT and open tympanoplasty surgery have been included, as well as control patients with clinical examination negative for organic otological pathology who underwent temporal bone CT for other reasons. For each patient, the following parameters have been extracted from CT volumes: degree of mastoid pneumatization, prominence of the cog, patency of the Eustachian tube, antrum width, aditus width, anterior and posterior epitympanic widths, and epitympanic height. Sixty patients have been included, thirty of whom belonged to the group of patients with cholesteatoma and the remaining part to the group of patients without organic otological pathology. The prevalence of a low degree of mastoid pneumatization was significantly higher among patients with cholesteatoma, as well as for the prevalence of cog prominence (p < 0.001). All the continuous variables were found to have statistical significance (p < 0.05) in the comparison between groups except for the width of the antrum. Mastoid pneumatization degree, prominence of the cog and epitympanic measures based on temporal bone CT could be good radiological correlates of the ventilatory capabilities of the epitympanum which, if compromised, can facilitate the development of cholesteatoma.


An increase in in vitro fertilization ability of low-density human sperm capacitated by multiple-tube swim-up.
Comparison was made of the efficacy of multiple-tube swim-up (MT-SU) and single-tube swim-up (ST-SU) preparations on inducing human sperm fertilization ability in semen samples of less than 60 million motile sperm/ml. Two parallel groups of in vitro fertilization (IVF) patients possessing sperm density of this category had their sperm capacitated by MT-SU or ST-SU. The MT-SU patients' sperm fertilized 71 +/- 6.0% of eggs retrieved in comparison to 39 +/- 7.9% in the parallel ST-SU patients (P less than 0.001). Similarly, MT-SU increased the rate of human sperm penetration into zona-free hamster eggs. The increased fertilization rate of MT-SU sperm was not from acceleration of the acrosome reaction, but may be attributed to the higher efficiency of MT-SU in removing antifertility factors present in the seminal plasma from sperm.


Single-molecule methylation profiles of cell-free DNA in cancer with nanopore sequencing.
Epigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for detecting and characterizing diseases such as cancer. We developed a strategy using nanopore-based single-molecule sequencing to measure cfDNA methylomes. This approach generated up to 200 million reads for a single cfDNA sample from cancer patients, an order of magnitude improvement over existing nanopore sequencing methods. We developed a single-molecule classifier to determine whether individual reads originated from a tumor or immune cells. Leveraging methylomes of matched tumors and immune cells, we characterized cfDNA methylomes of cancer patients for longitudinal monitoring during treatment.


Citizen scientist monitoring accurately reveals nutrient pollution dynamics in Lake Tanganyika coastal waters.
Several studies in Lake Tanganyika have effectively employed traditional methods to explore changes in water quality in open waters; however, coastal monitoring has been restricted and sporadic, relying on costly sample and analytical methods that require skilled technical staff. This study aims in validating citizen science water quality collected data (nitrate, phosphate and turbidity) with those collected and measured by professional scientists in the laboratory. A second objective of the study is to use citizen scientist data to identify the patterns of seasonal and spatial variations in nutrient conditions and forecast potential changes based on expected changes in population and climate (to 2050). The results showed that the concentrations of nitrate and phosphate measured by citizen scientists nearly matched those established by professional scientists, with overall accuracy of 91% and 74%, respectively. For total suspended solids measured by professional and turbidity measured by citizen scientists, results show that, using 14 NTU as a cut-off, citizen scientist measurements of Secchi tube depth to identify lake TSS below 7.0 mg/L showed an accuracy of 88%. In both laboratory and citizen scientist-based studies, all measured water quality variables were significantly higher during the wet season compared to the dry season. Climate factors were discovered to have a major impact on the likelihood of exceeding water quality restrictions in the next decades (2050), which could deteriorate lake conditions. Upscaling citizen science to more communities on the lake and other African Great Lakes would raise environmental awareness, inform management and mitigation activities, and aid long-term decision-making.


Modulation of the mechanosensing of mesenchymal stem cells by laser-induced patterning for the acceleration of tissue reconstruction through the Wnt/β-catenin signaling pathway activation.
Growing evidence suggests that the physical microenvironment can guide cell fate. However, cells sense cues from the adjacent physical microenvironment over a limited distance. In the present study, murine mesenchymal stem cells (MSCs) and murine preosteoblastic cells (MC3T3-E1) behaviors are regulated by the cell-material interface using ordered-micro and disordered-nano patterned structures on Ti implants. The optimal bone formation structure is a stable wave (horizontal direction: ridge, 2.7 µm; grooves, 5.3 µm; and vertical direction: distance, 700 µm) with the appropriate density of nano-branches (6.0 per µm2). The repeated waves provide cells with directional guidance, and the disordered branches influence cell geometry by providing different spacing and density nanostructure. And micro-nano patterned structure can provide biophysical cues to direct cell phenotype development, including cell size, shape, and orientation, to influence cellular processes including survival, growth, and differentiation. Thus, the overlaid isotropic and anisotropic cues, ordered-micro and disordered-nano patterned structures, could transfer further and alter cell shape and induce nuclear orientation by activating Wnt/β-catenin signaling to promote integrin α5, integrin β1, cadherin 2, Runx2, Opn, and Ocn. That canonical Wnt signaling inhibitor dickkopf1 further demonstrates osteogenic differentiation induced by ordered-micro and disordered-nano patterned structures, which is related to Wnt/β-catenin signaling. Our findings show the role of ordered microstructures and disordered nanostructures in modulating stem cell differentiation with potential medical applications. STATEMENT OF SIGNIFICANCE: It remains a challenge to modify poor osteogenic and osteoconductive properties of titanium alloy bases on the inherent poverty of titanium. We demonstrate that ordered microtopography and disordered nano topography pattern structure could lead to osteogenic differentiation in vitro and bone regeneration in vivo. Furthermore, the pattern structure is created through selective laser melting and alkali heat. And the structure only takes advantage of titanium itself and does not bring in active film, such as hydroxyapatite. On the other hand, we find that cell shape and orientation show angle-orientation tendency due to the polarity, which involves with mechanical signal created via patterned structure. Meanwhile, the Wnt/Ca2+ signaling pathway is activated.


Telomeric 3' overhangs in chronic HBV-related hepatitis and hepatocellular carcinoma.
Telomeric 3' overhang is a key component of telomere structure, but little is known about its role in hepatocarcinogenesis. We examined the 3' overhang and telomere length, mRNA levels of hTERT, POT1, TRF1 and cytokeratin 19 (CK19) in 41 hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) and adjacent non-HCCs of B viral chronic hepatitis/cirrhosis. 3' overhang length was positively correlated with telomere length (p < 0.001). In non-HCCs, the 3' overhang shortened with increasing age (p = 0.043). Twenty-six HCCs had shorter and 15 HCCs had longer 3' overhangs than the adjacent non-HCCs. The mRNA levels of hTERT, POT1 and TRF1 were upregulated in HCCs than in non-HCCs. HCCs with lengthened 3' overhangs expressed higher hTERT mRNA levels than those with shortened 3' overhangs, when compared to 3' overhangs in non-HCCs (p = 0.044). POT1 and TRF1 showed no significant difference according to the 3' overhangs. HCCs with long 3' overhangs had higher mitosis (p = 0.046) and more frequent multipolar mitosis compared to those with short 3' overhangs (p = 0.034). HCCs with high cytokeratin 19 mRNA levels, a marker for hepatic progenitor cells, had longer 3' overhangs than HCCs with low cytokeratin 19 mRNA levels (p= 0.019). In conclusion, the 3' overhang erosion might be closely related to the number of cell divisions in telomerase-negative hepatocytes of chronic hepatitis/cirrhosis. In telomerase-positive HCCs, an altered 3' overhang are involved in HBV-related hepatocarcinogenesis and hTERT might be involved in regulation of 3' overhang.


Evaluation of single and joint toxicity of perfluorooctane sulfonate and zinc to Limnodrilus hoffmeisteri: Acute toxicity, bioaccumulation and oxidative stress.
Perfluorooctane sulfonate (PFOS) and zinc have been detected in aquatic environment widely. In order to study the combined effects of PFOS and Zn, a series of experiments was conducted to explore the acute mortality, bioaccumulation and antioxidant status of Limnodrilus hoffmeisteri. The acute toxicity was evaluated by calculating 24h-EC50 values, and it was observed that 24h-EC50 values in single and joint treatments decreased with decreasing pH value or increasing exposure concentration. Toxic unit analysis suggested that the combined effects of the PFOS+Zn binary mixture were mostly simple addition, with 8 groups showing synergism and only one group showing antagonism. The analysis of internal Zn and PFOS concentration showed that the possible interaction between Zn and PFOS can affect the bioaccumulation of the two chemicals in L. hoffmeisteri. In addition, oxidative stress status was assessed by measuring oxidation-related biochemical parameters such as superoxide dismutase, glutathione peroxidase and malondialdehyde, and the integrated biomarker response index was estimated to rank the toxicity order. Exposures to Zn and PFOS were found to evoke some changes in the antioxidant defense system, and a strong self-adaptive ability was noticed for L. hoffmeisteri after 10 d exposure.


Not there yet: using data-driven methods to predict who becomes costly among low-cost patients with type 2 diabetes.
Diabetes is a leading cause of Medicare spending; predicting which individuals are likely to be costly is essential for targeting interventions. Current approaches generally focus on composite measures, short time-horizons, or patients who are already high utilizers, whose costs may be harder to modify. Thus, we used data-driven methods to classify unique clusters in Medicare claims who were initially low utilizers by their diabetes spending patterns in subsequent years and used machine learning to predict these patterns. We identified beneficiaries with type 2 diabetes whose spending was in the bottom 90% of diabetes care spending in a one-year baseline period in Medicare fee-for-service data. We used group-based trajectory modeling to classify unique clusters of patients by diabetes-related spending patterns over a two-year follow-up. Prediction models were estimated with generalized boosted regression, a machine learning method, using sets of all baseline predictors, diabetes predictors, and predictors that are potentially-modifiable through interventions. Each model was evaluated through C-statistics and 5-fold cross-validation. Among 33,789 beneficiaries (baseline median diabetes spending: $4153), we identified 5 distinct spending patterns that could largely be predicted; of these, 68.1% of patients had consistent spending, 25.3% had spending that rose quickly, and 6.6% of patients had spending that rose progressively. The ability to predict these groups was moderate (validated C-statistics: 0.63 to 0.87). The most influential factors for those with progressively rising spending were age, generosity of coverage, prior spending, and medication adherence. Patients with type 2 diabetes who were initially low spenders exhibit distinct subsequent long-term patterns of diabetes spending; membership in these patterns can be largely predicted with data-driven methods. These findings as well as applications of the overall approach could potentially inform the design and timing of diabetes or cost-containment interventions, such as medication adherence or interventions that enhance access to care, among patients with type 2 diabetes.


A case study of aggregation behaviors of titanium dioxide nanoparticles in the presence of dodecylbenzene sulfonate in natural water.
The present work aims to ascertain the mechanisms of surfactant (dodecylbenzene sulfonate; DBS) effects on the aggregation behaviors of TiO2 nanoparticles (TiO2-NPs) in natural water samples. Aggregation experiments were conducted at a TiO2-NPs concentration of 10mg/L in deionized water and in natural water samples via dynamic light scattering and Zeta potential determination. Average attachment efficiency was calculated to compare the aggregation behaviors of nanoparticles in the two aqueous media. Results showed that the effects of DBS on aggregation could be interpreted by both Derjaguin-Landau-Verwey-Overbeek (DLVO) and non-DLVO mechanisms. In natural water samples, aggregation did not occur rapidly and was able to develop slowly under all conditions, and the roles of DBS were obvious at high DBS concentration owing to the impacts of inherent components of natural water samples, such as colloids and natural organic compounds. Future aggregation studies should concentrate on multi-factor, multi-colloidal and dynamic aspects under similar environmental conditions.


Metrics of care and cardiovascular outcomes in patients with ST-elevation myocardial infarction treated with pharmacoinvasive strategy: a decade-long network in a populous city in Brazil.
Pharmacoinvasive strategy is an effective myocardial reperfusion therapy when primary percutaneous coronary intervention (p-PCI) cannot be performed in a timely manner. Authors sought to evaluate metrics of care and cardiovascular outcomes in a decade-long registry of a pharmacoinvasive strategy network for the treatment of ST-elevation myocardial infarction (STEMI). Data from a local network including patients undergoing fibrinolysis in county hospitals and systematically transferred to the tertiary center were accessed from March 2010 to September 2020. Numerical variables were described as median and interquartile range. Area under the curve (AUC-ROC) was used to analyze the predictive value of TIMI and GRACE scores for in-hospital mortality. A total of 2,710 consecutive STEMI patients aged 59 [51-66] years, 815 women (30.1%) and 837 individuals with diabetes (30.9%) were analyzed. The time from symptom onset to first-medical-contact was 120 [60-210] minutes and the door-to-needle time was 70 [43-115] minutes. Rescue-PCI was required in 929 patients (34.3%), in whom the fibrinolytic-catheterization time was 7.2 [4.9-11.8] hours, compared to 15.7 [6.8-22,7] hours in those who had successful lytic reperfusion. All cause in-hospital mortality occurred in 151 (5.6%) patients, reinfarction in 47 (1.7%) and ischemic stroke in 33 (1.2%). Major bleeding occurred in 73 (2.7%) patients, including 19 (0.7%) cases of intracranial bleeding. C-statistic confirmed that both scores had high predictive values for in-hospital mortality, demonstrated by TIMI AUC-ROC of 0.80 [0,77-0.84] and GRACE AUC-ROC of 0.86 [0.83-0.89]. In a real world registry of a decade-long network for the treatment of ST-elevation myocardial infarction based on the pharmacoinvasive strategy, low rates of in-hospital mortality and cardiovascular outcomes were observed, despite prolonged time metrics for both fibrinolytic therapy and rescue-PCI. Register Clinicaltrials.gov NCT02090712 date of first registration 18/03/2014.


Magnetic frustration of graphite oxide.
Delocalized π electrons in aromatic ring structures generally induce diamagnetism. In graphite oxide, however, π electrons develop ferromagnetism due to the unique structure of the material. The π electrons are only mobile in the graphitic regions of graphite oxide, which are dispersed and surrounded by sp3-hybridized carbon atoms. The spin-glass behavior of graphite oxide is corroborated by the frequency dependence of its AC susceptibility. The magnetic susceptibility data exhibit a negative Curie temperature, field irreversibility, and slow relaxation. The overall results indicate that magnetic moments in graphite oxide slowly interact and develop magnetic frustration.


RELATIONSHIP BETWEEN THE USE OF KANGAROO POSITION ON PRETERM BABIES AND MOTHER-CHILD INTERACTION UPON DISCHARGE.
To analyze the influence of the Kangaroo Position duration in the initial interactions between mothers and preterm infants. This is an exploratory prospective observational study that analyzed the mother-infant interaction during breastfeeding, before hospital discharge. All eligible newborns, with a gestational age of 28-32 weeks and a birth weight of 1,000-1,800 g from June 11 to September 31, 2014 were included. The films of the interaction were evaluated by the "Mother-Baby Interaction Protocol 0-6 months" tool. The duration of the Kangaroo Position during all the hospitalization period was correlated with the interaction between mother and preterm infant. The longer the dyad spent time in the Kangaroo Position, the more the newborns made physical contact attempts with their mothers during breastfeeding (r=0.37; p=0.03); and the longer the time in the Kangaroo Position, the less the mothers talked to their children (r=-0.47; p=0.006). Longer periods in the Kangaroo Position stimulates the initial exchanges of contact between preterm infant with his mother, which suggests a higher alert status of the newborn and a better availability for interactions with the mother during breastfeeding.


Induction of 27-kDa heat shock protein following cerebral ischemia in a rat model of ischemic tolerance.
Preconditioning the brain with sublethal cerebral ischemia induces tolerance to subsequent lethal periods of ischemia (ischemic tolerance). The purpose of this study is to investigate the role of low-molecular weight stress proteins, 27-kDa heat shock protein (HSP27) and alpha B crystallin, in ischemic tolerance. We measured the content of these proteins with enzyme immunoassay in the rat hippocampus and cerebral cortex following 6 min of ischemia with and without preconditioning with 3 min of ischemia and 3 days of reperfusion. We also visualized the localization of HSP27 immunohistochemically in comparison with that of HSP70. A 3-min period of ischemia caused a 2.4-fold increase in HSP27 content in the hippocampus after 3 days. Immunohistochemical localization of HSP27 was found in glial cells in all subregions of the hippocampus, whereas HSP70 immunostaining was seen only in CA1 pyramidal neurons. HSP27 content in the hippocampus decreased 2 h after 6 min of ischemia. HSP27 content progressively increased in the unpreconditioned hippocampus after 1 and 3 days, but returned to preischemic levels in the preconditioned hippocampus. HSP27 and HSP70 immunostaining was seen in CA1 pyramidal neurons after 1 day both with and without preconditioning. After 3 and 7 days, an intense HSP27 staining was observed in reactive glial cells in the CA1 without preconditioning, whereas the staining decreased in the preconditioned hippocampus. HSP70 staining was seen only in neurons at these time points. We observed no significant changes in HSP27 content in the cerebral cortex although neurons in the third and fifth layers were immunostained after 1 and 3 days. We observed no alterations in alpha B crystallin content after ischemia both in the hippocampus and the cortex. The present study demonstrated that cerebral ischemia induces HSP27 expression but not alpha B crystallin. Both HSP27 and HSP70 induction had a good temporal correlation with the induction of ischemic tolerance. However, different sites of action were suggested because the localization and cell types of HSP27 induction were quite different from those of HSP70 induction. The result suggests that it is unlikely that HSP27 is directly involved in the protection afforded by ischemic preconditioning.


Differential staining of the X-chromosome during meiosis of orthoptera by a silver impregnation procedure.
Differential staining of the X chromosome of Orthoptera, which normally cannot be distinguished from the autosomes during the more condensed stages of meiosis, has been achieved by a silver impregnation procedure involving a pretreatment with 2 x SSC at 60 degrees C. The results suggest that the saline citrate solution preferentially extracts proteins from the X chromosome. This method may be useful for distinguishing chromosome regions composed of facultative heterochromatin in Orthoptera.


Screening and isolation of antibiotic resistance inhibitors from herb materials-resistance inhibition of volatile components of Korean aromatic herbs.
The resistance inhibitory activities of 54 odorant mixtures (essential oil) from 41 Korean aromatic herbs were tested against multi-drug resistant Staphylococcus aureus SA2, which has resistances to 10 usual antibiotics including chloramphenicol. As results, combinations of 28 kinds of samples from 21 herbs and chloramphenicol have resistance inhibitory activities in dose dependent manner.


Anti-apoptotic and anti-oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A-induced nephropathy.
Although the pathogenesis of cyclosporine (CsA) nephropathy is not completely understood, it is attributed to oxidative damage and apoptosis. Grape seed proanthocyanidin extract (GSPE) is a molecule with anti-oxidant and anti-apoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing CsA nephropathy. Twenty-four Sprague-Dawley rats were divided into four groups. The control, GSPE, CsA and CsA+GSPE groups were given 1 mL olive oil, 100 mg/kg GSPE, 25 mg/kg CsA and 100 mg/kg GSPE+25 mg/kg CsA, respectively. On day 21, blood samples were taken for blood urea nitrogen (BUN), creatinine and CsA levels, and renal tissue was used for total oxidant system (TOS), total anti-oxidant system (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) measurements. In addition to renal histopathology, apoptosis staining was performed on renal tissue. The BUN, creatinine, TOS, OSI, MDA, histopathological score, and apoptotic index exhibited increases in the CsA group. In the CsA+GSPE group, however, BUN, creatinine, OSI, MDA, renal histopathological score and apoptotic index (AI) decreased and TAS levels increased. In addition, there was no difference between the CsA and CsA+GSPE groups with regard to CsA levels. We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.


Physical activity and metabolic syndrome: A population base study (forest and tree model algorithms).
Lifestyle changes, prominently low mobility in recent years, have increased the prevalence of metabolic syndrome (MetS), and cardiovascular disease risk. This study aimed to determine the relationship between physical activity and MetS using modern statistical methods in a population-based study. The target population included 10,663 people aged 40-70 years in phase 1 of the Persian Kharameh cohort study conducted in 2017. The data used in this study had questions about physical activity, demographic, anthropometrics, blood pressure, and biochemical data. Participants who their activity was within the fourth quarter were 36% less likely to develop MetS than the participants in the first quarter. In the decision-Tree algorithm with all variables, physical activity was significant after gender and comorbidity. With a lack of comorbidities and physical activity less than 2338 Metabolic Equivalent of Task (MET) and age greater than 53 years, the probability was 26.7% for the male population. For the female population, if associated with comorbidities, a history of diabetes in first-degree relatives, or both, the chance of developing MetS was estimated to be 70.4%. In the decision-tree algorithm, 56.0% of the predictions for MetS were due to gender. After gender, the presence of comorbidities, age, occupation, family history of diabetes, place of residence, and physical activity was discovered as the essential variables in predicting and identifying factors associated with MetS, respectively. Modern statistical methods can be used in similar research due to better presentation of results in applied clinical laws. An essential approach for treating the syndrome and preventing its complications is a lifestyle change, including educating about physical activity and promoting it.


Trypanosoma evansi: recent outbreaks in Europe.
Here, two recent outbreaks of Trypanosoma evansi infection in mainland France and Spain associated with the importation of dromedary camels from the Canary Islands, are reported. The disease is well-known on the Archipelago since 1997 and many efforts have been made towards control and eventual eradication, but some areas still remain affected. Both mainland outbreaks were controlled by means of massive treatments and monthly serological, parasitological and molecular (PCR) evaluations carried out by Valencian Regional Animal Health laboratory and by CIRAD, Montpellier, respectively. Possible causes for the persistence of the parasite in a small area of the Canaries are discussed. T. evansi must be included among the animal health conditions for international trade within the European Union as well as many other countries. Moreover, procedures including diagnosis, curative or preventive treatment and quarantine should be established to insure the status of the animals moving from a country to another.


Antiepileptic drug poisoning: Three-year experience.
Antiepileptic drugs, which are also called anticonvulsants, are used in the therapy and prophylaxis of epileptic seizures. The purpose of this paper was to investigate the relevant epidemiological data and to determine which of these drugs was the most frequent cause of intoxication. Another purpose of this study was to determine the neurological, cardiac, and biochemical problems caused by antiepileptics. This retrospective study included 95 consecutive patients under 18 years of age with antiepileptic intoxication, presenting to and being followed-up in, the Toxicology Unit between January 2010 and February 2013. The data were obtained by screening the patient files. Of the cases, 67 (70.5%) were self-poisoned by first generation antiepileptics (FGAEs) and 28 (29.5%) by second generation antiepileptics (SGAEs). The Glasgow Coma Scale (GCS) scores and the serum lactate levels of the patients poisoned by FGAEs and SGAEs on admission to emergency department were 15 (25th: 12; 75th: 15; 95th: 15; IQR: 3) and 1.9 (25th: 1.4; 75th: 3.1; 95th: 5.6; IQR: 1.7), and 15 (25th: 14.3; 75th: 15; 95th: 15; IQR: 0.75) and 1.07 (25th: 0.9; 75th: 1.6; 95th: 5.5; IQR: 0.71), respectively. The serum lactate levels of patients poisoned by FGAEs were significantly higher (p < 0.001). Among the cases poisoned by carbamazepine, the most frequent cause of intoxication, the GCS score was significantly lower and serum lactate level was significantly higher in the group with high serum levels of carbamazepine (p = 0.004 and p < 0.001, respectively). In cases poisoned by valproic acid (VPA), the second frequent cause of intoxication, there was neither a significant association between the serum VPA level and the GCS score, nor between the serum lactate level and the systolic blood pressure (p = 0.470, p = 0.897, and p = 0.088, respectively). However, there was a positive correlation between the serum VPA level and the serum ammonia level (kk = 0.742, p < 0.001). First generation antiepileptics are more toxic than SGAEs. In patients with serum carbamazepine level, particularly those over 30 mg/L, serious disorders of consciousness, cardiovascular toxicity, and metabolic disorders may occur. In VPA intoxication, there is a positive correlation between the serum VPA levels and ammonia levels. On account of this finding, one should be more careful about hyperammonemic hepatic encephalopathy as the serum VPA level rises.


A preliminary investigation of serum folate concentrations in sows during pregnancy and at weaning.
The mean serum folate concentrations of Large White sows were compared between one group of 13 animals, 43-80 days pregnant and another group of 9 animals at weaning when the litters were 28-30 days old. The mean concentration was higher in sows at weaning (p<0.05) and the lowest levels were found in sows no more than 51 days pregnant (p<0.05).


Blocking effect of diltiazem in the isolated rat phrenic hemidiaphragm.
The effects of diltiazem on indirectly and directly elicited twitch were studied in the isolated rat phrenic hemidiaphragm preparation. Diltiazem (30-500 microM) blocked the indirectly elicited twitch response and this effect was not affected by reducing the extracellular calcium from 2.5 to 1.25 mM. An effect on the directly elicited twitch was also observed (100-300 microM). Diltiazem (30-300 microM) blocked the peak tetanic tension and tetanic fade was present. The results were consistent with an action of diltiazem on the nicotinic receptor-ion channel complex.


Lymphomatoid papulosis. Case report providing evidence for a monocyte-macrophage origin of the atypical cells.
A patient with "classical" lymphomatoid papulosis is described in whom self-healing tumorous lesions occurred. Histologic, immunologic, enzyme histochemical and ultrastructural studies were performed. The atypical cells were found to be of monocyte-macrophage origin. The infiltrate also contained a variable number of suppressor-cytotoxic T-lymphocytes, depending on the stage of the tumorous lesions. The number of IgA positive B-lymphocytes in the peripheral blood was increased. The findings indicate that "classical" lymphomatoid papulosis is not a cutaneous T-cell lymphoma, but is the expression of an abnormal, immune reaction in the skin.


Two distinct TL-like molecular subsets defined by monoclonal antibodies on the surface of human thymocytes with different expression on leukemia lines.
Monoclonal antibodies reacting with TL-like class I antigens expressed on the surface of human thymocytes and some T leukemia lines were found to define three independent epitopic clusters, two of which could be shown to reside on serologically distinct molecular subsets by a solid-phase radioimmunoassay as well as by sequential immunoprecipitation. Both molecular subsets consist of a 49-K heavy chain associated with a beta-2 microglobulin light chain. Thymocytes expressed similar amounts of the two molecular subsets, while on T leukemia lines the amount of these two molecular subsets varied from line to line.


Dose-response relationship and reproducibility of urinary salbutamol excretion during the first 30 min after an inhalation.
To determine the reproducibility and dose-response relationship for urinary salbutamol excretion post inhalation. Fifteen volunteers inhaled either one, two, three, four or five doses of 100 micro g salbutamol on separate days and then seven of these also repeated each of the one, three and five doses on five occasions. After each study dose urine was collected 30 min post inhalation. The mean (SD) 30 min urinary salbutamol after one, two, three, four and five doses was 2.61 (1.0.), 5.47 (1.59), 8.68 (2.73), 12.34 (3.96) and 15.99 (4.50) micro g, respectively. Statistical analysis revealed a linear relationship (P < 0.001). Mean (SD) coefficient of variation after one, three and five doses was 10.5 (3.6), 10.1 (2.7) and 9.4 (2.3)%. The 30 min salbutamol urinary excretion post inhalation pharmacokinetic method, to compare inhaled products, is linear with inhaled dose and reproducible.


Cannabinoid CB1 receptor-mediated modulation of evoked dopamine release and of adenylyl cyclase activity in the human neocortex.
1. The present study investigated the binding characteristics of various ligands to cannabinoid CB(1) receptors in human neocortex and amygdala. In addition, the functionality of CB(1) receptors in the human neocortex was assessed by examining the effects of CB(1) receptor ligands on evoked [(3)H]-dopamine (DA) release in superfused brain slices and on synaptosomal cAMP accumulation. 2. Saturation-binding assays in human neocortical and amygdala synaptosomes using a radiolabelled cannabinoid receptor agonist ([(3)H]-CP55.940) revealed pK(d) values of 8.96 and 8.63, respectively. The numbers of binding sites (B(max)) were 3.99 and 2.67 pmol (mg protein)(-1), respectively. 3. Various cannabinoid receptor ligands inhibited [(3)H]-CP55.940 binding with rank order potencies corresponding to those of previous studies in animal tissues. 4. Electrically evoked [(3)H]-DA release from human neocortical slices was inhibited by CP55.940 (IC(50) 6.76 nm, I(max) 65%) and strongly enhanced by the cannabinoid receptor antagonist AM251. However, [(3)H]-DA release was not influenced in rat neocortex. In human tissue, the estimated endocannabinoid concentration in the biophase of the release-modulating CB(1) receptors was 1.07 nm, expressed in CP55.940 units. 5. K(+)-evoked [(3)H]-DA release in the presence of tetrodotoxin (TTX) was strongly inhibited by CP55.940 in humans, but not in rats. 6. In human tissue, CP55.940 inhibited forskolin-stimulated cAMP accumulation (IC(50) 20.89 nm, I(max) 35%). AM251 blocked this effect and per se increased forskolin-stimulated cAMP accumulation by approximately 20%. 7. In conclusion, cannabinoids modulate [(3)H]-DA release and adenylyl cyclase activity in the human neocortex. CB(1) receptors are located on dopaminergic nerve terminals and seem to be tonically activated by endocannabinoids.


Number of Drinks to "Feel a Buzz" by HIV Status and Viral Load in Men.
The impact of HIV and its treatment on the effects of alcohol remain unclear. Blood alcohol concentrations have been noted to be higher in HIV infected individuals prior to antiretroviral initiation. Our goal was to compare number of drinks to "feel a buzz or high" among HIV infected and uninfected men, stratified by viral load (VL) suppression. Data includes 1478 HIV infected and 1170 uninfected men in the veterans aging cohort study who endorsed current drinking. Mean (SD) number of drinks to feel a buzz was 3.1 (1.7) overall. In multivariable analyses, HIV infected men reported a lower mean number of drinks to feel a buzz compared to uninfected men (coef = -14 for VL < 500; -34 for VL ≥ 500; p ≤ .05). Men with HIV, especially those with a detectable VL, reported fewer drinks to feel a buzz. Future research on the relationship between alcohol and HIV should consider the role of VL suppression.


Predictive Nomogram for Unfavorable Outcome of Spontaneous Intracerebral Hemorrhage.
The goal of this retrospective study was to evaluate the effect of surgical timing on patient outcomes after spontaneous intracerebral hemorrhage (ICH). We also identified risk factors associated with poor prognosis. We reviewed all patients who underwent surgery for ICH between January 2014 and January 2021. The outcome was measured using the modified Rankin Scale (mRS) score at 6 months after the surgery. Patients with mRS 0-2 were considered having favorable outcomes, and those with mRS 3-5 were considered having unfavorable outcomes. The relationships of surgical timing with the risk of unfavorable outcomes were identified using the interaction and stratified analyses, and generalized additive and logistic regression models. A nomogram was established and evaluated using a receiver operating characteristic curve analysis, plotted decision curve, and calibration curve. We identified 53 patients with favorable outcomes and 144 with unfavorable outcomes. The number of cases who underwent surgery at >12 hours and <36 hours in the favorable outcome group was more than that in the unfavorable outcome group (P < 0.001). When the time to operating room (TOR) was less than 21 hours, a shorter TOR was associated with unfavorable outcomes, using the smoothing spline analysis (odds ratio = 0.8, P < 0.001). Finally, we developed a nomogram using systolic blood pressure, Glasgow Coma Scale, midline shift, hematoma volume, and TOR for predicting the unfavorable outcome. The area under the curve, accuracy, specificity, and sensitivity of nomogram were 0.90, 0.87, 0.72, and 0.93, respectively. Surgical timing between 12 and 26 hours after ICH was associated with favorable outcomes. The nomogram including systolic blood pressure, Glasgow Coma Scale, midline shift, hematoma volume, and TOR was reliable for predicting the ICH outcome.


19F: A small probe for a giant protein.
Herein we describe a method for the efficient production (∼90% fluorination) of 5-F-Trp human H ferritin via the selective incorporation of 19F into the side chain of W93 using 5-fluoroindole as the fluorinated precursor of the amino acid. Human H ferritin is a nanocage composed of 24 identical subunits, each containing a single Trp belonging to a loop exposed on the external surface of the protein nanocage. This makes 5-F-Trp a potential probe for the study of intermolecular interactions in solution by exploiting its intrinsic fluorescence. More interestingly, albeit the large size of the cage (12 nm external diameter, ∼500 kDa molecular mass) we observe a broad but well defined NMR 19F resonance that can be used for the dual purpose of detecting solution intermolecular interactions via chemical shift perturbation mapping and monitoring the uptake of ferritin by cells treated with ferritin-based drug carriers, the latter being an application area of increasing importance.


Time to acute general surgical review: a retrospective study in a tertiary referral centre.
The Acute Surgical Unit (ASU) is a busy service receiving Emergency Department (ED) referrals for adult and paediatric general surgery care alongside trauma. The ASU model deviates from the traditional on-call model and has been shown to improve efficiency and patient outcomes. The primary aim was to evaluate time to surgical review ED presentation and general surgical referral. Secondary aims were to assess referral numbers, pathology and demographics at our institution. A retrospective observational analysis was conducted on all referral times from the ED to the ASU between 1 April and 30 September 2022. Patient demographics, triage and referral times, and diagnoses were collected from the electronic medical record. Time between referral, review and surgical admission were calculated. A total of 2044 referrals were collected during the study period, and 1951 (95.45%) were included for analysis. Average time from ED presentation to surgical referral was 4 hours and 54 min with average time to surgical review from referral taking 40 min. On average, total time from ED presentation to surgical admission was 5 h and 34 min. Trauma Responds took 6 min to review. Colorectal pathology was the most commonly referred disease type. The ASU model is efficient and effective within our health service. Overall delays in surgical care may be external to the general surgery unit, or before the patient is made known to the surgical team. Analysis of time to surgical review is a key statistic in the delivery of acute surgical care.


[Differential diagnosis of certain knee joint tumours and casuistry].
The subject of this information is the case of 33-year old male patient with tumefactive lesions of knee joint. It became an inspiration for this study due to diagnostic difficulties. The article covers the differential diagnosis of such pathologies as: synovial sarcoma, chondromatosis, tuberculosis and knee joint synovitis.


Characterization of the mycoplasma membrane proteins. V. Release and localization of membrane-bound enzymes in Acholeplasma laidlawii.
The peripheral membrane protein fraction released by washing Acholeplasma laidlawii membranes with low-ionic strength buffers contained about 50% of the total membrane-bound ribonuclease and deoxyribonuclease activities. The ATPase, NADH oxidase and p-nitrophenylphosphatase activities remained bound to the membrane even when EDTA was added to the wash fluids, and thus appear to belong to the integral membrane protein group. Serving as a marker for peripheral membrane proteins, the membrane-bound ribonuclease activity was solubilized by bile salts much more effectively than the integral membrane-bound enzymes. On the other hand, the solubilized ribonuclease showed a much lower capacity to reaggregate with other solubilized membrane components to membranous structures. Yet, most of the ribonuclease molecules which were bound to the reaggregated membranes could not be released by low-ionic strength buffer. The reaggregated membranes differed from the native membranes in the absence of particles on their fracture faces obtained by freeze cleaving, and by their much higher labeling by the [125-I]lactoperoxidase iodination system. These results suggest that most of the proteins are exposed on the reaggregated membrane surfaces, with very little, if any, protein embedded in its lipid bilayer core. Enzyme disposition in the A. laidlawii membrane was studied by comparing the activity of isolated membranes with that of membranes of intact cells after treatment with pronase or with an antiserum to membranes. The data indicate the asymmetrical disposition of these activities, the ATPase and NADH oxidase being localized on the inner membrane surface, while the nucleases are exposed on the external membrane surface.


Phenylalanine-binding RNAs and genetic code evolution.
We isolated RNAs by selection-amplification, selecting for affinity to Phe-Sepharose and elution with free l-phenylalanine. Constant sequences did not contain Phe condons or anticodons, to avoid any possible confounding influence on initially randomized sequences. We examined the eight most frequent Phe-binding RNAs for inclusion of coding triplets. Binding sites were defined by nucleotide conservation, protection, and interference data. Together these RNAs comprise 70% of the 105 sequenced RNAs. The KD for the strongest sites is approximately 50 microM free amino acid, with strong stereoselectivity. One site strongly distinguishes free Phe from Trp and Tyr, a specificity not observed previously. In these eight Phe-binding RNAs, Phe codons are not significantly associated with Phe binding sites. However, among 21 characterized RNAs binding Phe, Tyr, Arg, and Ile, containing 1342 total nucleotides, codons are 2.7-fold more frequent within binding sites than in surrounding sequences in the same molecules. If triplets were not specifically related to binding sites, the probability of this distribution would be 4.8 x 10(-11). Therefore, triplet concentration within amino acid binding sites taken together is highly likely. In binding sites for Arg, Tyr, and Ile cognate codons are overrepresented. Thus Arg, Tyr, and Ile may be amino acids whose codons were assigned during an era of direct RNA-amino acid affinity. In contrast, Phe codons arguably were assigned by another criterion, perhaps during later code evolution.


Outcomes following cyst curettage and bone grafting for the management of periprosthetic cystic evolution after AES total ankle replacement.
We present a prospective series of 50 AES total ankle replacements performed between 2003 and 2006. The present report concerns medium-term results of cyst curettage-grafting. Twenty total ankle replacements underwent revision: 6 by tibiotalocalcaneal arthrodesis and 14 by cyst curettage-grafting. With 79% and 92% rates of unimproved or worsened functional and radiological status respectively, our results in cyst grafting are poor. No previous series of curettage-graft in evolutive periprosthetic total ankle replacement cyst have been reported. In periprosthetic cyst, we recommend annual radiological surveillance, with CT in case of cyst enlargement and/or increased pain, to allow implant removal and reconstruction-arthrodesis before collapse.


Overcoming Tumor Resistance to Oncolyticvaccinia Virus with Anti-PD-1-Based Combination Therapy by Inducing Antitumor Immunity in the Tumor Microenvironment.
The tumor microenvironment (TME) comprises different types of immune cells, which limit the therapeutic efficacy of most drugs. Although oncolytic virotherapy (OVT) boosts antitumor immunity via enhanced infiltration of tumor-infiltrated lymphocytes (TILs), immune checkpoints on the surface of tumors and TILs protect tumor cells from TIL recognition and apoptosis. OVT and immune checkpoint blockade (ICB)-based combination therapy might overcome this issue. Therefore, combination immunotherapies to modify the immunosuppressive nature of TME and block immune checkpoints of immune cells and tumors are considered. In this study, cancer-favoring oncolytic vaccinia virus (CVV) and anti-programmed cell death protein-1 (anti-PD-1) were used to treat mouse colorectal cancer. Weekly-based intratumoral CVV and intraperitoneal anti-PD-1 injections were performed on Balb/c mice with subcutaneous CT26 tumors. Tumor volume, survival curve, and immunohistochemistry-based analysis demonstrated the benefit of co-treatment, especially simultaneous treatment with CVV and anti-PD-1. Infiltration of CD8+PD-1+ T-cells showed correlation with these results. Splenocytes enumeration also suggested CD4+ and CD8+ T-cell upregulation. In addition, upregulated CD8, PD-1, and CD86 messenger RNA expression was observed in this combination therapy. Therefore, CVV+anti-PD-1 combination therapy induces antitumor immunity in the TME, overcoming the rigidity and resistance of the TME in refractory cancers.


In-situ monitoring of breast cancer cell (MCF-7) growth and quantification of the cytotoxicity of anticancer drugs fluorouracil and cisplatin.
A wireless sensing device was developed for the in-situ monitoring of the growth of human breast cancer cells (MCF-7) and evaluation of the cytotoxicity of the anticancer drugs fluorouracil and cisplatin. The sensor is fabricated by coating a magnetoelastic ribbon-like sensor with a layer of polyurethane that protects the iron-rich sensor from oxidation and provides a cell-compatible surface. In response to a time-varying magnetic field, the magnetoelastic sensor longitudinally vibrates, emitting magnetic flux that can be remotely detected by a pick-up coil. No physical connections between the sensor and the detection system are required. The wireless property facilitates aseptic biological operation, especially in cell culture as illustrated in this work. The adhesion of cells on the sensor surface results in a decrease in the resonance amplitude, which is proportional to the cell concentration. A linear response was obtained in cell concentrations of 5 x 10(4) to 1 x 10(6)cells ml(-1), with a detection limit of 1.2 x 10(4) cells ml(-1). The adhesion strength of cells on the sensor is qualitatively evaluated by increasing the amplitude of the magnetic excitation field. And the cytotoxicity of the anticancer drugs fluorouracil and cisplatin is evaluated by the magnetoelastic biosensor. The cytostatic curve is related with the quantity of cytostatic drug. The lethal concentration (LC50) for cells incubated in the presence of drugs for 20 h is calculated to be 19.9 microM for fluorouracil and 13.1 microM for cisplatin.


Investigations on the polymorphism of sperm diaphorase in man. Evidence for a third common allele, SD.
The polymorphism of sperm diaphorase (SD) was investigated in 141 unrelated persons from Hessen, Germany, by high voltage thin-layer agarose gel electrophoresis (Age) and thin-layer isoelectric focusing on polyacrylamide gel (Pagif). In addition to the three known common phenotypes SD 1, 2-1, and 2, two further phenotypes with the preliminary designation SD 3-1 and SD 3-2 were discovered. This polymorphism can thus be explained in terms of three alleles, SD1, SD2, and SD3 segregating at an autosomal locus. The allele frequencies calculated from the five different phenotypes SD 1, 2, 2-1, 3-1, and 3-2 are: SD1 = 0.7553, SD2 = 0.2234, and SD3 = 0.0213. As we also found SD activity in female reproductive tract tissues (ovaries, oviducts, uterus), the term 'gonadal diaphorase' (GD) appears to be applicable.


Differential effects of cisplatin in proximal and distal renal tubule epithelial cell lines.
Pathological studies suggest that cisplatin injures different portions of the nephron to different extents. To investigate this issue further, we examined the cytotoxicity and uptake of cisplatin in cell lines derived from S1 and S3 proximal tubule and distal convoluted tubule segments isolated from a mouse carrying the SV40 large T-antigen transgene. S1 cells displayed the highest sensitivity to cisplatin cytotoxicity, followed by S3 and distal convoluted tubule (DCT) cells. These differences in cytotoxicity did not correlate with differences in cisplatin uptake. Cytotoxic concentrations of cisplatin triggered apoptosis in all three cell lines. Although BAX and BCL-2 expression was similar among the three cell lines, the expression of the anti-apoptotic protein, BCL-X(L), was significantly lower in S1 cells than in S3 and DCT cells, and this may have contributed to the heightened sensitivity of S1 cells. Cisplatin transport characteristics demonstrated a saturable component of cisplatin uptake and differences in apparent K(M) and Vmax values among the three cell lines. The three cell lines were 43- to 176-fold more sensitive to cisplatin than to carboplatin. This distinction between the two drugs could not be fully explained by differences in the uptake rates of carboplatin and cisplatin. We conclude that cells from different portions of the nephron display different sensitivities to cisplatin, different transport characteristics for cisplatin and different levels of expression of BCL-X(L). In addition, the relative resistance of renal cells to carboplatin vs cisplatin is mostly due to the differential effects that follow internalization.


Association of maternal obesity with preterm birth phenotype and mediation effects of gestational diabetes mellitus and preeclampsia: a prospective cohort study.
The association between maternal obesity and preterm birth remains controversial and inconclusive, and the effects of gestational diabetes mellitus (GDM) and preeclampsia (PE) on the relationship between obesity and preterm birth have not been studied. We aimed to clarify the relationship between prepregnancy body mass index (BMI) and the phenotypes of preterm birth and evaluate the mediation effects of GDM and PE on the relationship between prepregnancy BMI and preterm birth. We conducted a prospective cohort study of 43,056 women with live singleton births from 2017 through 2019. According to the WHO International Classification, BMI was classified as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-25 kg/m2), overweight (BMI 25-30 kg/m2) and obese (BMI ≥30 kg/m2). Preterm birth was defined as gestational age less than 37 weeks (extremely, < 28 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). The clinical phenotypes of preterm birth included spontaneous preterm birth (spontaneous preterm labor and premature rupture of the membranes) and medically indicated preterm birth. We further analyzed preterm births with GDM or PE. Multivariable logistic regression analysis and causal mediation analysis were performed. Risks of extremely, very, and moderately preterm birth increased with BMI, and the highest risk was observed for obese women with extremely preterm birth (OR 3.43, 95% CI 1.07-10.97). Maternal obesity was significantly associated with spontaneous preterm labor (OR 1.98; 95% CI 1.13-3.47), premature rupture of the membranes (OR 2.04; 95% CI 1.08-3.86) and medically indicated preterm birth (OR 2.05; 95% CI 1.25-3.37). GDM and PE mediated 13.41 and 36.66% of the effect of obesity on preterm birth, respectively. GDM mediated 32.80% of the effect of obesity on spontaneous preterm labor and PE mediated 64.31% of the effect of obesity on medically indicated preterm birth. Maternal prepregnancy obesity was associated with all phenotypes of preterm birth, and the highest risks were extremely preterm birth and medically indicated preterm birth. GDM and PE partially mediated the association between obesity and preterm birth.


The acceptability among young Hindus and Muslims of actively ending the lives of newborns with genetic defects.
To explore the views in non-Western cultures about ending the lives of damaged newborns. 254 university students from India and 150 from Kuwait rated the acceptability of ending the lives of newborns with genetic defects in 54 vignettes consisting of all combinations of four factors: gestational age (term or 7 months); severity of genetic defect (trisomy 21 alone, trisomy 21 with serious morphological abnormalities or trisomy 13 with impending death); the parents' attitude about prolonging care (unknown, in favour or opposed); and the procedure used (withholding treatment, withdrawing it or injecting a lethal substance). Four clusters were identified by cluster analysis and subjected to analysis of variance. Cluster I, labelled 'Never Acceptable', included 4% of the Indians and 59% of the Kuwaitis. Cluster II, 'No Firm Opinion', had little variation in rating from one scenario to the next; it included 38% of the Indians and 18% of the Kuwaitis. In Cluster III, 'Parents' Attitude+Severity+Procedure', all three factors affected the ratings; it was composed of 18% of the Indians and 16% of the Kuwaitis. Cluster IV was called 'Severity+Parents' Attitude' because these had the strongest impact; it was composed of 40% of the Indians and 7% of the Kuwaitis. In accordance with the teachings of Islam versus Hinduism, Kuwaiti students were more likely to oppose ending a newborn's life under all conditions, Indian students more likely to favour it and to judge its acceptability in light of the different circumstances.


Neurochemical coding and projection patterns of gastrin-releasing peptide-immunoreactive myenteric neurone subpopulations in the guinea-pig gastric fundus.
The aim of this study was to characterise the projection and neurochemical coding patterns of gastrin-releasing peptide (GRP)-containing subpopulations of myenteric neurones in the guinea-pig gastric fundus. For this purpose, we used retrograde tracing with the dye DiI and immunohistochemistry against GRP, choline acetyltransferase (ChAT), enkephalin (ENK), substance P (SP) and neuropeptide Y (NPY). Cell counts revealed that 44% of the myenteric neurones were GRP-positive. Of the GRP-positive neurones, 92% were ChAT-positive and, hence, 8% were presumptively nitric oxide synthase positive (NOS). The GRP-positive subpopulations were ChAT/GRP (40% of all GRP neurones), ChAT/NPY/GRP (25%), ChAT/SP/GRP/+/-ENK (20%), ChAT/ENK/GRP (8%), NOS/NPY/GRP/+/-ENK (5%) and NOS/GRP (3%). The tracing experiments revealed the relative contributions of the various GRP-positive subpopulations to the innervation of the circular muscle and the mucosa. GRP immunoreactivity was detected in 46 and 38% of the DiI-labelled muscle and mucosa neurones, respectively. GRP was almost exclusively found in ascending ChAT-positive mucosa and muscle neurones. The populations encoded ChAT/SP/GRP/+/-ENK and ChAT/ENK/GRP projected predominantly to the circular muscle, whereas the ChAT/NPY/GRP and ChAT/GRP populations had primarily projections to the mucosa. GRP was colocalised with ChAT, ENK and/or SP in varicose nerve fibres innervating the circular muscle and the muscularis mucosae, whereas in the mucosal epithelium GRP was mainly present in nerve fibres containing ChAT and NPY. The data suggest that in the guinea-pig gastric fundus, the ChAT/SP/GRP/+/-ENK and ChAT/ENK/GRP neurones are ascending excitatory muscle motor neurones, whereas the ChAT/NPY/GRP and ChAT/GRP neurones are very likely involved in the regulation of mucosal functions.


Changes in the diversity and composition of gut microbiota in pigeon squabs infected with Trichomonas gallinae.
Pigeons, as the only altricial birds in poultry, are the primary Trichomonas gallinae (T. gallinae) host. To study the effects of T. gallinae infection on gut microbiota, we compared the microbiota diversity and composition in gastrointestinal (GI) tracts of pigeons at the age of 14 and 21 day with different degrees of T. gallinae infection. Thirty-six nestling pigeons were divided into three groups: the healthy group, low-grade and high-grade trichomonosis group. Then, the crop, small intestine and rectum contents were obtained for sequencing of the 16S rRNA gene V3-V4 hypervariable region. The results showed that the microbiota diversity was higher in crop than in small intestine and rectum, and the abundance of Lactobacillus genus was dominant in small intestine and rectum of healthy pigeons at 21 days. T. gallinae infection decreased the microbiota richness in crop at 14 days. The abundance of the Firmicutes phylum and Lactobacillus genus in small intestine of birds at 21 days were decreased by infection, however the abundances of Proteobacteria phylum and Enterococcus, Atopobium, Roseburia, Aeriscardovia and Peptostreptococcus genus increased. The above results indicated that crop had the highest microbiota diversity among GI tract of pigeons, and the gut microbiota diversity and composition of pigeon squabs were altered by T. gallinae infection.


Stable antiferromagnetic property and tunable electronic structure of two-dimensional MnPX3(X = S and Se) from pristine structure to Janus phase.
Transition-metal phosphorus trichalcogenides have been considered as very promising two-dimensional (2D) magnetic candidates up-to-date. We performed a systematical first-principles study on the electronic structures and magnetic properties of pristine MnPX3(X = S and Se) and Janus Mn2P2S3Se3monolayers. All monolayers behave as a direct-band-gap semiconductor in antiferromagnetic ground state which is caused by strong direct and indirect exchange interactions. It is found that the electronic structures and magnetic properties can be manipulated by Janus phase. The calculated band gap is 2.44 eV, 1.80 eV and 1.86 eV for MnPS3, MnPSe3and Mn2P2S3Se3with a valley polarization with consideration of spin-orbital coupling (SOC), respectively. In particular, significant energy-splittings emerge in the SOC-band structures of Janus Mn2P2S3Se3due to its broken-inversion-symmetry. Estimated by Monte Carlo simulations, the Néel temperature is 96 K, 71 K and 79 K based on Ising model while halved down to 41 K, 33 K and 36 K on the basis ofXYmodel for MnPS3, MnPSe3and Mn2P2S3Se3, respectively, indicating theXYmodel should be more reliable to describe the spin dynamics. Our research offers an insight into the magnetic mechanism and paves a feasible path to modulate the magnetism for 2D magnets in realistic applications on spintronics.


Synthesis of double perovskite and quadruple perovskite nanocrystals through post-synthetic transformation reactions.
Lead-free halide perovskite nanocrystals (NCs) represent a group of emerging materials which hold promise for various optical and optoelectronic applications. Exploring facile synthetic methods for such materials has been of great interest to not only fundamental research but also technological implementations. Herein, we report a fundamentally new method to access lead-free Bi-based double perovskite (DP) and quadruple perovskite (or layered double perovskite, LDP) NCs based on a post-synthetic transformation reaction of Cs3BiX6 (X = Cl, Br) zero-dimensional (0D) perovskite NCs under mild conditions. The produced NCs show good particle uniformity, high crystallinity, and comparable optical properties to the directly synthesized NCs. The relatively slow kinetics and stop-on-demand feature of the transformation reaction allow real-time composition-structure-property investigations of the reaction, thus elucidating a cation-alloyed intermediate-assisted transformation mechanism. Our study presented here demonstrates for the first time that post-synthetic transformation of 0D perovskite NCs can serve as a new route towards the synthesis of high-quality lead-free perovskite NCs, and provides valuable insights into the crystal structures, excitonic properties and their relationships of perovskite NCs.


Initial clinical experience with a new low-profile thoracic endograft.
The Zenith Alpha thoracic endograft (William Cook Europe, ApS, Bjaeverskov, Denmark) is a new low-profile thoracic endograft that has recently become commercially available in Europe. The reduced profile offers potential benefits and extended applicability, especially in patients with small or diseased iliofemoral vessels. The aim of this study was to evaluate the safety and efficacy of thoracic endovascular aortic repair performed with the new Zenith Alpha thoracic endograft. From November 2013 to the present, Zenith Alpha thoracic stent grafts have been employed to treat 42 patients (31 men; median age, 71 years; range, 54-83 years) suffering from descending thoracic aortic disease: 34 degenerative aneurysms, 4 aortic ulcers, 2 false aneurysms following prior thoracic open repair, and 2 traumatic blunt injuries. The mean proximal neck length was 25 mm (range, 17-40 mm), with a mean access vessel diameter of 6.7 mm (range, 6-11 mm). In 11 cases, aortoiliac occlusive disease (TransAtlantic Inter-Society Consensus type B and C lesions) was present. The proximal landing was in zone 1 in 2 cases, in zone 2 in 25 cases, in zone 3 in 11 cases, and in zone 4 in 4 cases. Fifty-one endografts (45 proximal components and 6 distal components) were deployed in 42 patients. The endografts were deployed safely and effectively from one surgical femoral access site in all cases. In patients with associated aortoiliac disease, no adjunctive procedures for device insertion, except for predilation with balloon angioplasty in two cases, were required. No major complications related to the devices were observed in any of the patients during the postoperative course, and there was no perioperative mortality, paraparesis, or paraplegia. At 30 days, morbid events included one case of major stroke, two cases of transient acute renal failure, and one case of postimplantation syndrome. No access-related complications were recorded. Computed tomography performed within 6 months was obtained in 39 patients and confirmed 100% clinical success without device-related complications. No type I endoleaks or bird's beak effects were documented. Our early experience shows that deployment of the new Zenith Alpha endograft from a surgical femoral access is safe and effective in treating thoracic aortic aneurysms, aortic ulcers, and traumatic blunt injuries, even in patients with small or diseased access vessels. Endograft conformance to the aorta and exclusion of the aneurysm were satisfactory. Long-term durability remains to be evaluated.


Iridoid and phenylethanoid glycosides from Phlomis longifolia var. longifolia.
From the aerial parts of Phlomis longifolia var. longifolia four iridoid glucosides, shanzhiside methyl ester (1), 5-deoxypulchelloside I (2), lamalbide (3), phlomiol (4) and three phenylethanoid glycosides, verbascoside (5), forsythoside B (6), leucosceptoside A (7) along with the caffeic acid ester, chlorogenic acid (8) were isolated. The structures of the isolated compounds were established by spectroscopic (UV, IR, 1D- and 2D-NMR, FABMS) and chemical evidence. The structure elucidation of the iridoid compounds 2 and 3 are discussed in detail.


Radiogenomics in Clear Cell Renal Cell Carcinoma: A Review of the Current Status and Future Directions.
Radiogenomics is a field of translational radiology that aims to associate a disease's radiologic phenotype with its underlying genotype, thus offering a novel class of non-invasive biomarkers with diagnostic, prognostic, and therapeutic potential. We herein review current radiogenomics literature in clear cell renal cell carcinoma (ccRCC), the most common renal malignancy. A literature review was performed by querying PubMed, Medline, Cochrane Library, Google Scholar, and Web of Science databases, identifying all relevant articles using the following search terms: "radiogenomics", "renal cell carcinoma", and "clear cell renal cell carcinoma". Articles included were limited to the English language and published between 2009-2021. Of 141 retrieved articles, 16 fit our inclusion criteria. Most studies used computed tomography (CT) images from open-source and institutional databases to extract radiomic features that were then modeled against common genomic mutations in ccRCC using a variety of machine learning algorithms. In more recent studies, we noted a shift towards the prediction of transcriptomic and/or epigenetic disease profiles, as well as downstream clinical outcomes. Radiogenomics offers a platform for the development of non-invasive biomarkers for ccRCC, with promising results in small-scale retrospective studies. However, more research is needed to identify and validate robust radiogenomic biomarkers before integration into clinical practice.


Effectiveness and Safety of P2Y12 Inhibitors Pretreatment in Primary Percutaneous Coronary Intervention with Long Transfer Times.
Early initiation of a new P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients prior to primary percutaneous coronary intervention (PCI) is recommended over clopidogrel. However, comparative data remain limited, especially in semi-rural regions with subsequent longer transfer times. We aimed to assess the determinants, effectiveness, and safety of pretreatment with new P2Y12 inhibitors compared with clopidogrel in a primary PCI regional network. Outcomes of 1235 primary PCI patients pretreated with new P2Y12 inhibitors (n = 1050) or clopidogrel (n = 185) were evaluated using a prospective registry. Primary effectiveness endpoint was the composite of death, recurrent myocardial infarction, stroke, or new revascularization. Serious bleedings were defined as Bleeding Academic Research Consortium ≥ 2. Clopidogrel was more likely to be used in older and female patients with more comorbidities. Mean transfer time was longer in the clopidogrel group (123.3 ± 67.3 vs. 102.3 ± 57.2 min; p < 0.01). The primary endpoint was less frequent with new P2Y12 inhibitors compared with clopidogrel (14.9 vs. 30.3%; odds ratio 0.58, 95% confidence interval [CI] 0.39-0.87; p < 0.01), mostly driven by a reduced rate of death (4.5 vs. 26% respectively; hazard ratio 0.25, 95% CI 0.16-0.38; p < 0.01). Bleeding rates did not differ between groups (1 vs. 0.5%, respectively; p = 0.96). Compared with clopidogrel, pretreatment with new P2Y12 inhibitors seems to be associated with lower risks of mortality and ischemic outcomes, and similar risks of bleeding in a real-world registry. Our results are in line with the guidelines recommending the preferential pre-PCI administration of new P2Y12 inhibitors in STEMI patients referred for primary PCI.


Efficient removal of organic compounds from shale gas wastewater by coupled ozonation and moving-bed-biofilm submerged membrane bioreactor.
Shale gas wastewater (SGW) with complex composition and high salinity needs an economical and efficient method of treatment with the main goal to remove organics. In this study, a coupled system consisting of ozonation and moving-bed-biofilm submerged membrane bioreactor (MBBF-SMBR) was comprehensively evaluated for SGW treatment and compared with a similar train comprising ozonation and submerged membrane bioreactor (SMBR) without addition of carriers attaching biofilm. The average removal rates of MBBF-SMBR were 77.8% for dissolved organic carbon (DOC) and 37.0% for total nitrogen (TN), higher than those observed in SMBR, namely, 73.9% for DOC and 18.6% for TN. The final total membrane resistance in SMBR was 40.1% higher than that in MBBF-SMBR. Some genera that specifically contribute to organic removal were identified. Enhanced gene allocation for membrane transport and nitrogen metabolism was found in MBBF-SMBR biofilm, implying that this system has significant industrial application potential for organics removal from SGW.


Structural properties and bonding characteristics of honeycomb structure of composite ZnMnO2 and activated carbon.
Structural properties and chemical bonding of new composites (ZnMnO2 and activated carbon) with honeycomb structure have been studied by using X-ray diffraction and Fourier transform infrared. The composition of the powder of ZnMnO2 has been studied by X-ray fluorescence in waste derived from a conventional battery. X-ray diffraction data show that the average crystallite size and the dislocation density for the composite are 90.17 nm and 12.30 × 1013 m-2, respectively. The C-O and C=O bonding for composites seen shifted to the lower wave number of pure ZnMnO2 and activated carbon indicated size reduction as an effect of Zn or Mn in the site of activated carbon. In addition, the reflection loss was analyzed by vector network analyzer and shows reflection loss of about -21.72 dB, the frequency range being 4.40-4.59 GHz for a thickness of 6 nm. The honeycomb structure of composite ZnMnO2-AC in this study promises new types of composite materials for various applications.


Application of a validated LC-MS/MS method for JWH-073 and its metabolites in blood and urine in real forensic cases.
Synthetic cannabinoids, which were synthesized to improve the therapeutic effects of cannabis, have become a major issue when they are abused. They have different chemical structures from tetrahydrocannabinol (THC) but similar effects on endocannabinoid receptors. "Spice" named products have more serious side effects than cannabis and can even cause death. These mixtures are prepared by spraying chemicals onto small pieces of herbs and are being dishonestly sold as "natural" and "legal" products over the internet. Their popularity is continuously increasing. Studies on detecting synthetic cannabinoids in biological samples as well as pharmacology and toxicology studies of these chemicals are very limited. A fast, specific and robust method for the detection and quantification of JWH-073, JWH-073 N-butanoic acid, and JWH-073 N-(4-hydroxybutyl) in blood and urine has been developed that uses solid-phase extraction (SPE) followed by UPLC-MS/MS analysis. This method has been validated in terms of its linearity (0.1-50 ng/mL), selectivity, intra-assay and inter-assay accuracy and precision (CV<10%), recovery (75-95%), limits of detection (LODs) (0.08-0.13 ng/mL), and limits of quantification (LOQs) (0.11-0.17 ng/mL). Matrix effects, stability, and process efficiency parameters of this method have also been assessed. This method was applied to 2596 authentic samples received by the Department of Toxicology (Istanbul) in the Presidency of Council of Forensic Medicine (Turkey) between September 1, 2012, and February 28, 2015.


Interleukin-2 and the septohippocampal system: intrinsic actions and autoimmune processes relevant to neuropsychiatric disorders.
The effects of IL-2 on brain development, function, and disease are the result of IL-2's actions in the peripheral immune system and its intrinsic actions in the central nervous system (CNS). Determining whether, and under what circumstances (e.g., development, acute injury), these different actions of IL-2 are operative in the brain is essential to make significant advances in understanding the multifaceted affects of IL-2 on CNS function and disease, including psychiatric disorders. For several decades, there has been a great deal of speculation about the role of autoimmunity in brain disease. More recently, we have learned a great deal about the role of cytokines on neurobiological processes, and there have been many studies that have found peripheral immune alterations in patients with neurological and neuropsychiatric diseases. Despite a plethora of published literature, almost all of this data in humans is correlative and much of the basic research has understandably relied on simpler models (e.g., in vitro models). Good animal models such as our IL-2 knockout mouse model could provide valuable new insight into understanding how the complex biology of a cytokine such as IL-2 can have simultaneous, dynamic effects on multiple systems (e.g., regulating homeostasis in the brain and immune system, autoimmunity that can affect both systems). Animal models can also provide much needed new data elucidating neuroimmunological and autoimmune processes involved in brain development and disease. Such information may ultimately provide critical new insight into the role of brain cytokines and autoimmunity in prominent neurological and neuropsychiatric diseases (e.g., Alzheimer's disease, autism, multiple sclerosis, schizophrenia).


Epidemiology and nomogram for predicting the cancer-specific survival of ovarian granulosa cell tumor: A seer database study.
ovarian granulosa cell tumor (OGCT) is a kind of infrequent ovarian malignant tumor with limited epidemiological data available. we established a predictive nomograph to verify the clinical prognosis. 1005 diagnosed with ovarian granulosa cell tumor (OGCT) were extracted from Surveillance, Epidemiology, and End Results (SEER) public database from 2000-2018. Kaplan-Meier analysis was applied to distinguish risk factors, univariate and multivariate Cox analyses were used to determine the independent prognostic factors for cancer-specific survival (CSS) of OGCT patients. The obtained prognostic variables were combined to construct a nomogram model for predicting CSS in OGCT patients. Model performance was detected and evaluated with ROC curves and calibration plots. Data collected from 1005 patients were divided into two groups: training cohort(n=703,70%) and validation cohort(n=302,30%). The multivariate Cox model identified five covariates including age, marital status, AJCC stages, surgery and chemotherapy as independent interfering factors of CSS. The nomogram has shown a promising and excellent accuracy in evaluating 3 -, 5 -, 8-year CSS in OGCT patients. In terms of the CSS of the training cohort, the AUC values of the 3 -, 5 -, 8-year ROC curves were 0.819,0.8,0.819, while in terms of the CSS of the validation cohort, the AUC values of the validation cohort were 0.822,0.84,0.823, respectively. All the calibration curves showed pleasant consistency between predicted and actual survival rates. The nomogram model established in the study can improve the veracity of prognosis prediction, thereby improving the accuracy of individualized survival risk assessment, and providing targeted and constructive recommendations for specific treatment options. Age, advanced clinical stage, widower and without surgery therapy are independent risk factors for poor prognosis and the nomogram we constructed can help clinicians efficiently recognize high-risk OGCT patients to guide targeted therapies and improve their outcomes.


Expression of VCAM-1, ICAM-1, E- and P-selectin and tumour-associated macrophages in renal cell carcinoma.
Neoangiogenesis is accompanied by an increase in endothelial surface, which can support infiltration by immune cells depending on adhesion molecule expression. Therefore, the expression of cell adhesion molecules on microvessels and epithelial cells was analysed in renal cell carcinomas as compared to tumour-free tissue. PECAM-1, CD34, ICAM-1, VCAM-1, VLA-4, P- and E-selectin, the macrophage antigens Ki-M1P and Mac-1, and lymphocyte function antigen LFA-1 were identified immunohistochemically. VCAM-1, ICAM-1, and E-selectin were equally or less expressed, whereas P-selectin was increased on microvessels in tumour tissue. The density of VCAM-1-positive tumour microvessels correlated positively with an advanced tumour stage and E- and P-selectin-positive tumour microvessels with the amount of associated macrophages. The expression of ICAM-1 and VCAM-1 on neoplastic epithelia correlated with an increased density of macrophages and a minor degree of tumour differentiation. The positive correlation of macrophage infiltration and expression of cell adhesion molecules on tumour microvessels and epithelia with minor tumour differentiation and an advanced stage indicates that adhesion molecule expression is not associated with an effective antitumour function of macrophages


Preparative enantiomeric separation of new aromatase inhibitors by HPLC on polysaccharide-based chiral stationary phases: Determination of enantiomeric purity and assignment of absolute stereochemistry by X-ray structure analysis.
The development of high-performance liquid chromatography methods on polysaccharide-based stationary phases (cellulose or amylose derivatives) has permitted preparative enantioseparations of various 6-[1(imidazol-1-yl)-1-phenylmethyl]-3-methyl-1,3-benzoxazol-2(3H)-one and 6-[1(imidazol-1-yl)-1-phenylmethyl]-3-methyl-1,3-benzothiazol-2(3H)-one, aromatase inhibitors, with satisfactory yields. Analytical enantioseparation methods using both UV and evaporative light-scattering detection (ELSD) were validated to determine the enantiomeric purity of these compounds. Using UV detection, linear calibration curves in the range from 4 x 10(-6) to 4.8 x 10(-4) M range were obtained; repeatability, limits of detection (LD), and quantification (LQ) were determined: LD varied, for the various solutes, from 1 to 80 microg/l and from 2.05 to 10.05 mg/l with UV detection and ELSD, respectively. Single-crystal X-ray analysis was successful in determining the absolute configuration of the individual enantiomers. The relationship between retention order and absolute configuration of the enantiomers was established.


Premonitory Urge and Tic Severity, Comorbidities, and Quality of Life in Chronic Tic Disorders.
Tics are intimately associated with premonitory urges (PU) but knowledge about urges is still limited, with small sample sizes often limiting the generalizability of findings. This study addressed the following open questions: (1) is tic severity associated with urge severity, (2) how common is relief, (3) which comorbidities are associated with urges, (4) are urges, tics, and comorbidities associated with lower quality of life, and (5) can complex and simple, motor and vocal tics be differentiated based on PU? N = 291 patients who reported a confirmed diagnosis of chronic primary tic disorder (age = 18-65, 24% female) filled out an online survey assessing demographic data, comorbid conditions, location, quality and intensity of PU, as well as quality of life. Every tic was recorded, and whether the patient experienced a PU, the frequency, intensity, and quality of that urge. PU and tic severity were significantly associated, and 85% of urge-related tics were followed by relief. A diagnosis of attention deficit/hyperactivity disorder (ADHD) or depression, female gender, and older age increased the likelihood of experiencing PU, while more obsessive compulsive (OCD) symptoms and younger age were associated with higher urge intensities. PU, complex vocal tics, ADHD, OCD, anxiety, and depression were related to lower quality of life. Motor and vocal, complex and simple tics did not differ regarding PU intensity, frequency, and quality, or relief. The results shed light on the relationship between PU, tics, comorbidities, age, gender, and quality of life in tic disorders.


Experimental autoimmune encephalomyelitis as a model of immune-mediated CNS disease.
Experimental autoimmune encephalomyelitis models are used to analyze the generation and organization of the myelin-specific autoimmune repertoire, and potential immunoregulatory loops preventing spontaneous activation of encephalitogenic T cells. These lymphocytes are profoundly modulated by infectious agents, which may trigger, or more commonly, prevent experimental autoimmune encephalomyelitis. The development and resolution of the pathogenic central nervous system infiltrations is controlled by locally produced cytokines that cause recruitment of infiltrate cells, and their disappearance. Several of the new findings seem now to be applicable for therapeutic strategies, especially with the aim of interfering with immunospecific recognition steps involved in disease generation.


Laparoscopic radical prostatectomy--an analysis of factors affecting operating time.
Although laparoscopic radical prostatectomy (LRP) is accomplished within 2 to 3 hours by experienced surgeons, less is known about the operating times (OTs) for recently trained surgeons or the influence of additional factors. As of November 2001 at our institution, two senior surgeons had each performed more than 100 cases of LRP and two junior surgeons had each performed fewer than 30. We prospectively studied the next 100 consecutive LRPs to assess the factors influencing the OT. Transperitoneal LRPs were performed by two senior (n = 62) and two junior surgeons (n = 38) with random case assignment. We assessed body mass index, prostate size, prior abdominal surgery, androgen deprivation, surgeon experience, procedures in addition to LRP, lymph node dissection, nerve sparing, and sural nerve grafting as potential predictors of the OT. Prostate weight, androgen deprivation, and prior abdominal surgery did not significantly affect the OT, but grade 1 obesity increased the OT by an average of 38 minutes. The mean OT by surgeon experience was 214 minutes for seniors and 347 minutes for juniors (P <0.001). By procedure type, the OT ranged from 180 minutes for LRP only by seniors to 459 minutes for LRP plus lymph node dissection plus sural nerve grafting by juniors. Lymph node dissection and sural nerve grafting significantly increased the OT by 46 and 101 minutes, respectively, and nerve sparing did not. For each combination of procedures, seniors averaged significantly shorter times than did juniors. A multiple regression model with stepwise selection showed that prostate weight, sural nerve grafting, pelvic lymph node dissection, use of a surgical robot, and surgeon experience significantly affected the OT. The results of this prospective study of 100 cases of LRP showed that the OT for senior surgeons averaged 2 to 3 hours, but less experienced surgeons, and additional procedures, add significantly to the OT.


Carbon dioxide fluxes over a grazed prairie and seeded pasture in the Northern Great Plains.
Temperate grasslands are vast terrestrial ecosystems that may be an important component of the global carbon (C) cycle; however, annual C flux data for these grasslands are limited. The Bowen ratio/energy balance (BREB) technique was used to measure CO2 fluxes over a grazed mixed-grass prairie and a seeded western wheatgrass [Pascopyrum smithii (Rybd) Löve] site at Mandan, ND from 24 April to 26 October in 1996, 1997, and 1998. Above-ground biomass and leaf area index (LAI) were measured about every 21 days throughout the season. Root biomass and soil organic C and N content were determined to 110 cm depth in selected increments about mid-July each year. Peak above-ground biomass and LAI coincided with peak fluxes and occurred between mid-July to early August. Biomass averaged 1227 and 1726 kg ha(-1) and LAI 0.44 and 0.59, for prairie and western wheatgrass, respectively. Average CO2 flux for the growing season was 279 g CO2 m(-2) for prairie and 218 g CO2 m(-2) for western wheatgrass (positive flux is CO2 uptake and negative flux is CO2 loss to the atmosphere). Using prior measured dormant season CO2 fluxes from the prairie sites gave annual flux estimates that ranged from -131 to 128 g CO2 m(-2) for western wheatgrass and from -70 to 189 g CO2 m(-2) for the prairie. This wide range in calculated annual fluxes suggests that additional research is required concerning dormant season flux measurements to obtain accurate estimates of annual CO2 fluxes. These results suggest Northern Great Plains mixed-grass prairie grasslands can either be a sink or a source for atmospheric CO2 or near equilibrium, depending on the magnitude of the dormant season flux.


When Science Becomes Embroiled in Conflict: Recognizing the Public's Need for Debate while Combating Conspiracies and Misinformation.
Most democracies seek input from scientists to inform policies. This can put scientists in a position of intense scrutiny. Here we focus on situations in which scientific evidence conflicts with people's worldviews, preferences, or vested interests. These conflicts frequently play out through systematic dissemination of disinformation or the spreading of conspiracy theories, which may undermine the public's trust in the work of scientists, muddy the waters of what constitutes truth, and may prevent policy from being informed by the best available evidence. However, there are also instances in which public opposition arises from legitimate value judgments and lived experiences. In this article, we analyze the differences between politically-motivated science denial on the one hand, and justifiable public opposition on the other. We conclude with a set of recommendations on tackling misinformation and understanding the public's lived experiences to preserve legitimate democratic debate of policy.


Ruthenium(II) polypyridyl complexes as carriers for DNA delivery.
Two novel water soluble ruthenium(II) complexes [Ru(bpy)(2)(bqbg)](2+) and [Ru(phen)(2)(bqbg)](2+) have been structurally characterized and their DNA condensation activity, cytotoxicity, and cellular uptake studies of DNA condensates as potential non-viral DNA carriers were evaluated.


[Arteriovenous fistulas complicating in situ venous femoropopliteal bypass. A sample case].
Arteriovenous communications are a rare but specific complication of in situ saphenous vein arterial bypass. In this bypass procedure, some collaterals of the saphenous vein may remain patent. In this report, a characteristic example illustrates this complication. Local and general manifestations secondary to the development of these fistulas must be prevented by complementary surgical or radiological obliteration.


Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats.
In addition to their antimicrobial activity, antibiotics modulate cellular host defence. Granulocyte-colony stimulating factor (G-CSF) is also a well known immunomodulator; however little is known about the interactions of G-CSF with antibiotics. We investigated in septic rats the effects of two antibiotic combinations with G-CSF. In two clinic modelling randomised trials (CMRTs), male Wistar rats were anesthetized, given antibiotic prophylaxis, had a laparotomy with peritoneal contamination and infection (PCI), and were randomly assigned (n = 18 rats/group) to: 1) PCI only; 2) PCI+antibiotic; and, 3) PCI+antibiotic+G-CSF prophylaxis (20 mug/kg, three times). This sequence was conducted first with 10 mg/kg coamoxiclav, and then with ceftriaxone/metronidazole (Cef/met, 10/3 mg/kg). In additional animals, the blood cell count, migration and superoxide production of PMNs, systemic TNF-alpha and liver cytokine mRNA expression levels were determined. Only the combination coamoxiclav plus G-CSF improved the survival rate (82 vs. 44%, p < 0.001). Improved survival with this combination was accompanied by normalised antimicrobial PMN migratory activity and superoxide production, along with normalised systemic TNF-alpha levels and a reduced expression of TNF-alpha and IL-1 in the liver. There are substantial differences in the interaction of antibiotics with G-CSF. Therefore, the selection of the antibiotic for combination with G-CSF in sepsis treatment should be guided not only by the bacteria to be eliminated, but also by the effects on antimicrobial functions of PMNs and the cytokine response.