Hypoxia-inducible factor-1 alpha in the heart: a double agent?
Hypoxia-inducible factor (HIF) is a set of transcription factors that regulate the cellular response to hypoxia. There is a great body of evidence supporting the protective role of HIF-1α in cardiovascular pathophysiology, however, newer studies are hinting at a maladaptive and deleterious role of this transcription factor that merits further investigation. There is a general agreement, however, that HIF-mediated responses appear to differ under conditions of acute and chronic oxygen deprivation. The intensity and sustainability of HIF-1α activation are major determinants of whether the responses are pathological or beneficial. HIF activation is seen to be beneficial in the setting of acute myocardial ischemia and deleterious in chronic conditions. In this review, we will focus on recent insights into the role of HIF-1α in the heart and especially in the setting of ischemic heart disease.


Local tumour ablative therapies: opportunities for maximising immune engagement and activation.
The relationship between cancer and the immune system is a complex one. The immune system can prevent tumour growth by eliminating cancer cells but this editing process ultimately results in poorly immunogenic cells remaining allowing for unchallenged tumour growth. In light of this, the focus of cancer treatment should be to maximise cancer elimination and the prevention of escape mechanisms. In this review we will examine current and emerging ablative treatment modalities that induce Immunogenic Cell Death (ICD), a special type of cell death that allows for immune cell involvement and the generation of an anti-tumour specific immune response. When paired with immune modulating agents, capable of potentiating the immune response and reversing the immune-suppressive environment created by tumours, we may be looking at the future of anti-cancer therapy.


Repeated automatic versus ambulatory blood pressure measurement: the effects of age and sex in a normal ageing population.
To study blood pressure adaptation in relation to age and sex. In a subsample, laboratory blood pressure measurements were compared with ambulatory daytime blood pressure measurements to determine the degree of agreement between the two methods. The night-time blood pressure reduction was analysed as a function of blood pressure status, age and sex. A cross-sectional study in 469 healthy volunteers, aged 23-82 years, stratified for age, sex and educational level. Laboratory blood pressure was measured automatically (Dinamap 8100) five times during a 20 min recording session. Cardiovascular events in the medical history were identified in order to treat the cardiovascular event-free group separately in subsequent analyses. Within 3 weeks after laboratory blood pressure measurement, ambulatory blood pressure was measured for 24 h in 135 volunteers from the main study. Both diastolic and systolic blood pressure varied markedly in a single measurement session as a function of age, independent of mean pressure level. After 15 min no further blood pressure decrease was observed. On the basis of the average of the final two blood pressure measurements, 18.8% of the subjects were in the hypertensive range (WHO/ISH guidelines). Ambulatory blood pressure measurements were in accord with earlier findings and correlated 0.74 and 0.73 with laboratory diastolic and systolic blood pressure, respectively, but weighted kappa values indicated only moderate agreement (0.42 and 0.51). Women showed a more profound reduction in cnight-time blood pressure than did men. There is a substantial change in blood pressure during a single measurement session which is greater in older age groups. The moderate agreement between the two methods of blood pressure measurement supports the notion that blood pressure measured in a single session has limited generalizability to average daytime levels in a population sample.


Versatile strategies for adult neurogenesis: avenues to repair the injured brain.
Brain injuries due to trauma or stroke are major causes of adult death and disability. Unfortunately, few interventions are effective for post-injury repair of brain tissue. After a long debate on whether endogenous neurogenesis actually happens in the adult human brain, there is now substantial evidence to support its occurrence. Although neurogenesis is usually significantly stimulated by injury, the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient. Alternatively, exogenous stem cell transplantation has shown promising results in animal models, but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use. Recently, a high focus was placed on glia-to-neuron conversion under single-factor regulation. Despite some inspiring results, the validity of this strategy is still controversial. In this review, we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury. We also discuss their advantages and drawbacks, as to provide a comprehensive account of their potentials for further studies.


Methods for the solubilisation of membrane proteins: the micelle-aneous world of membrane protein solubilisation.
The solubilisation of membrane proteins (MPs) necessitates the overlap of two contradictory events; the extraction of MPs from their native lipid membranes and their subsequent stabilisation in aqueous environments. Whilst the current myriad of membrane mimetic systems provide a range of modus operandi, there are no golden rules for selecting the optimal pipeline for solubilisation of a specific MP hence a miscellaneous approach must be employed balancing both solubilisation efficiency and protein stability. In recent years, numerous diverse lipid membrane mimetic systems have been developed, expanding the pool of available solubilisation strategies. This review provides an overview of recent developments in the membrane mimetic field, with particular emphasis placed upon detergents, polymer-based nanodiscs and amphipols, highlighting the latest reagents to enter the toolbox of MP research.


Etoposide sensitivity and topoisomerase II activity in Chinese hamster V79 monolayers and small spheroids.
Chinese hamster V79 cells grown in suspension culture as spheroids are more resistant than monolayers to killing and mutation by ionizing radiation. A change in DNA conformation appears to accompany this increase in radiation resistance. We were therefore interested in whether the activity of topoisomerase II, a nuclear enzyme involved in DNA conformational changes and possibly in DNA repair, might differ in monolayers and small spheroids. One-day-old spheroid cells were more resistant than monolayer cells to the toxic effects of etoposide, a topoisomerase II inhibitor. Fewer strand breaks were induced by etoposide in spheroid DNA than monolayer DNA, as measured by the DNA precipitation and alkali unwinding assays, although identical amounts of damage were produced in monolayers and spheroids by the topoisomerase I inhibitor camptothecin, and the cell cycle specific agent, 5-fluorouracil. There was no evidence of a subpopulation of spheroid cells which were more resistant to etoposide, and no change in the rate of incorporation or DNA chain elongation in spheroids compared to monolayers. Topoisomerase II activity in 1-day-old spheroids, measured by decatenation of trypanosome kinetoplast DNA, was reduced to 68% of the monolayer value; in 3-4-day-old spheroids the level was 32.5%. These results indicate that topoisomerase II activity and sensitivity to a topoisomerase II inhibitor are reduced in 1-day-old spheroid cells. We suggest that the decrease in the activity of this enzyme may be linked to the change in DNA conformation in spheroids and the decrease in their radiation sensitivity.


A first-principles study of NO adsorption and oxidation on Au(111) surface.
Density functional theory and slab models are employed to study NO molecule adsorption and reaction on clean and atomic oxygen precovered Au(111) surfaces. While clean Au(111) surface is catalytically inert and can only weakly adsorb NO, an atomic oxygen precovered Au(111) surface is found to be very active to NO. On the clean surface, NO prefers to bond at the onefold on-top surface site with a tilted geometry. On 0.33 ML (monolayer) oxygen precovered surface NO reacts with chemisorbed oxygen to form chemisorbed NO(2) by conquering a small energy barrier about 0.18 eV, and the desorption energy of NO(2) is 0.64 eV. On 1.0 ML oxygen coverage surface, no barrier is found while NO reacts with precovered oxygen. The desorption energy of NO(2) is 0.03 eV. The desorption of NO(2) is the rate determining step on both surfaces and the overall reaction barriers are 0.64 and 0.03 eV, respectively. The activation energies depend on the initial coverage of oxygen, which compare favorably with experiments on Au surface with different oxygen coverages.


Transverse coupling property of beam from ECR ion sources.
Experimental evidence of the property of transverse coupling of beam from Electron Cyclotron Resonance (ECR) ion source is presented. It is especially of interest for an ECR ion source, where the cross section of extracted beam is not round along transport path due to the magnetic confinement configuration. When the ions are extracted and accelerated through the descending axial magnetic field at the extraction region, the horizontal and vertical phase space strongly coupled. In this study, the coupling configuration between the transverse phase spaces of the beam from ECR ion source is achieved by beam back-tracking simulation based on the measurements. The reasonability of this coupling configuration has been proven by a series of subsequent simulations.


Substantial detrusor overactivity in conscious spontaneously hypertensive rats with hyperactive behaviour.
The spontaneously hypertensive rat (SHR) is a useful model for studying the mechanisms of detrusor overactivity (DO). However, owing to their confounding phenotypic characteristics of hyperactive behaviour, there could be some problems with the interpretation of cystometric data, which is significantly confused by abdominal straining (AS), causing changes in intravesical pressure (IVP). IVP and intra-abdominal pressure (IAP) were recorded simultaneously to evaluate true DO in conscious healthy male SHRs and Wistar/ST (Wistar) rats. Intravesical pressure rises (IVPRs), defined as increments that exceeded 2 cmH(2)O from baseline, were counted, and those that were caused by AS or DO were determined according to the presence of simultaneous changes in IAP. Compared with Wistar rats, SHRs had a shorter filling phase (p<0.01) and greater frequency of IVPRs (p<0.01). SHRs, but not Wistar rats, showed DO. The substantial DO represented up to 76% of total IVPRs, with the remainder caused by AS. The amplitude (p<0.05) but not the frequency of AS (p>0.05), was higher in SHR than Wistar rats. In conscious SHRs, variations in IAP due to hyperactive behaviour may cause misinterpretation of pressure parameters and result in false reports of DO. Thus, simultaneous registration of IAP and IVP is needed for accurate recording of substantial DO in these animals.


Cytoprotective effects of essential oil of Pinus halepensis L. against aspirin-induced toxicity in IEC-6 cells.
Essential oils from Pinus species have been reported to have various therapeutic properties. This study was undertaken to identify the chemical composition and cytoprotective effects of the essential oil of Pinus halepensis L. against aspirin-induced damage in cells in vitro. The cytoprotection of the oil against toxicity of aspirin on the small intestine epithelial cells IEC-6 was tested. The obtained results have shown that 35 different compounds were identified. Aspirin induced a decrease in cell viability, and exhibited significant damage to their morphology and an increase in superoxide dismutase (SOD) and catalase (CAT) activities. However, the co-treatment of aspirin with the essential oil of Pinus induced a significant increase in cell viability and a decrease in SOD and CAT activities. Overall, these finding suggest that the essential oil of Pinus halepensis L. has potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.


A new method for broadening the detection range of immunoassay and its application in β-hCG quantitative detection.
Early pregnancy prediction requires very high β-hCG detection sensitivity, while embryonic development monitoring and trophoblastic disease detection require a wider detection range. In this study, based on light-initiated chemiluminescence assay (LICA), one high-affinity mAb and one low-affinity mAb were selected and coated on chemibeads with a larger coating area in different ratios to immobilize the antibodies. The two immobilized mAbs were mixed with different concentrations to detect β-hCG. When the high-affinity mAb-coated chemibeads and low-affinity mAb-coated chemibeads were used at working concentrations of 0.100 mg mL-1 and 0.014 mg mL-1, respectively, the sensitivity and detection range were maximized. The assay was precise for measuring β-hCG with repeatability and intermediate precision of <5% CV. The assay has a high sensitivity with a limit of quantification (LoQ) of 0.49 IU L-1, which is lower than that of most β-hCG detection kits. Over the range of 1 IU L-1 to 16 000 IU L-1, the assay had a proper linearity (r = 0.9995). No false negative results due to the hook effect were observed at β-hCG concentrations up to 225 000 IU L-1. The assay showed a good correlation with the Abbott assay (r = 0.9910). LICA combined with immobilized mAbs with different affinities ensures the sensitivity of β-hCG detection and broadens the detection range.


Toxicity assessment of effluent from flash light manufacturing industry by bioassay tests in Trigonella foenumgracum.
A rapid bioassay test was conducted to study heavy metal accumulation and biochemical changes in Trigonella foenumgracum (methi) irrigated with 25, 50, 75 and 100% of effluent from flash light manufacturing industry at 60 days after sowing. Total metal concentration in effluent samples was: Cr = 0.12 < Cd = 0.18 < Pb = 0.24 < Cu = 2.68 mg l(-1) whereas, metals were not detected in control. An increase in photosynthetic pigments of exposed plant was noticed up to 50% concentrations of the effluent followed by a decrease at higher concentration as compared to their respective control.An enhanced lipid peroxidation in the treated plants was observed, which was evident by increased level of antioxidants: proline, cysteine, malondialdehyde and ascorbic acid content. The treated plants accumulated metals in the following order: Cu > Pb > Cr > Cd in the roots and shoots.


[Plants, medicine and genetics, which applications for tomorrow?].
From 60,000 B.C. to the 19th century, plants were the main source for human drugs. Plant-derived pharmaceuticals were partly supplanted by drugs produced by the industrial methods of chemical synthesis at the beginning of the 19th century. However, 50% of small molecules used for cancer therapy or the most efficient drugs for flu or paludism treatment are still extracted or derived from plants. Furthermore, strategies which aim at improving plant expression systems for biopharmaceutical production are currently making them safe and extremely cost-effective alternatives to microbial and mammalian cell cultures for the production of either simple or highly complex recombinant therapeutic proteins.


Fifty-four-month survival in a 3-year-old child presenting with an aggressive metastatic dedifferentiated clival chordoma.
Dedifferentiated chordoma is a rare, aggressive, chemoresistant and radioresistant malignancy arising from notochord remnants that can occur anywhere along the spine. Incidence in patients under 20 years of age is 1 per 250 million. We report a case of dedifferentiated clival chordoma presenting in a 3-year-old boy with pulmonary metastasis, which responded unusually well to chemotherapy, achieving complete metastatic clearance and debulking of the primary tumour. Proton beam therapy achieved further tumour control, with excellent quality of life for multiple years. On disease relapse, an atypical lateral transcondylar surgical approach achieved complete macroscopic clearance but there was cutaneous seeding. This, and continued primary site activity, failed to be controlled with targeted therapy, traditional chemotherapy and photon radiation, resulting in gradual neurological decline and death. Intensive management resulted in above-average survival despite diagnosis late in the disease course, which may be of value directing investigation into optimal management.


Effect of taxifolin and epigallocatechin-3-gallate on biomineralization potential of stem cells from dental apical papilla.
Considering the variety of pharmacological activities and the potential to mediate biomineralization, the flavonoids taxifolin and epigallocatechin-3-gallate (EGCG) could be explored as biomolecules in scaffolds for regenerative endodontic procedures. The aim of this study was to evaluate the effect of taxifolin and EGCG on the cell viability, differentiation, and expression of biomineralization markers in stem cells from the apical papilla. Stem cells from the apical papilla were exposed to single or continuous treatments with taxifolin at 200, 100 and 50 µM and EGCG at 50, 25 and 12.5 µM for 48 h, 8 and 14 days, in regular or mineralizing media. Cell viability, alkaline phosphatase activity and calcium deposition were analyzed using resazurin, p-nitrophenylphosphate and alizarin-based assays. None of the flavonoid groups affected cell viability at 48 h, however at 8 and 14 days, Taxifolin 200 µM and EGCG 50 µM were cytotoxic. Cells did not express alkaline phosphatase activity when grown in regular medium, even in the presence of flavonoids. Alkaline phosphatase activity and biomineralization potential were higher in cells treated with Taxifolin 50 µM and EGCG 12.5 µM. Taxifolin and EGCG exhibited a concentration, time, and therapeutic mode dependent bioactivity on stem cells from the apical papilla. Both flavonoids at the lower concentrations tested exhibited cytocompatibility and increased expression of mineralization markers in the presence of mineralizing agents.


The range of intrinsic frequencies represented by medial entorhinal cortex stellate cells extends with age.
In both humans and rodents, the external environment is encoded in the form of cognitive maps. Neurons in the medial entorhinal cortex (mEC) represent spatial locations in a sequence of grid-like patterns scaled along the dorsal-ventral axis. The grid spacing correlates with the intrinsic resonance frequencies of stellate cells in layer II of mEC. We investigated the development of frequency preferences in these cells from weaning to adulthood using patch-clamp and sharp microelectrode recordings. We found that the dorsal-ventral gradient of stellate cell properties and frequency preferences exists before animals are able to actively explore their environment. In the transition to adulthood, cells respond faster and become less excitable, and the range of intrinsic resonance frequencies in the population expands in the dorsal direction. This is likely to reflect both the growth of the brain and the expansion of the internal representation caused by new exploratory experience.


[The progress of Chinese surgery in 2017].
The article outlined the speeches of Surgeon Branch during the Annual Scientific Conference of Chinese Medical Association in 2018.From the perspectives of inheritance, innovation, standardization and improvement, it summarizes the major progress of Chinese surgery in 2017 and introduces the objectives and action plans of Chinese Medical Association Branch of Surgery this year.


Demystifying behaviour and dental anxiety in schoolchildren during endodontic treatment for primary teeth-controlled clinical trial.
Behaviour and anxiety of children are predictors of effective dental treatment. Compare the behaviour and anxiety during preventive care, endodontic treatment, and dental extraction. Controlled clinical trial was conducted with 99 children aged 6-9 years. The children were distributed among three groups: G1 (control)-prophylaxis and topical fluoride; G2 (intervention)-endodontic treatment; and G3 (intervention)-tooth extraction. Behaviour was measured using the Frankl scale. Dental anxiety was assessed using the modified Venham Picture Test and measured at three moments: before, during, and after the procedure. Caregivers answered a questionnaire addressing the child's previous dental experience. Clinical examinations were performed by a calibrated examiner (Kappa > 0.70) for the identification of dental caries (d-dmft/D-DMFT). Statistical analysis involved repeated-measures Poisson regression, with level of significance was P < 0.05. Neither negative behaviour nor anxiety was associated with the type of procedure. Negative behaviour was associated with the need for restraint during a previous dental appointment (P = 0.012). Dental anxiety was associated with age (P = 0.037), previous difficult behaviour (P < 0.001), moment of measurement (P < 0.001), and dental caries on permanent teeth (P = 0.001). Negative behaviour and dental anxiety in children were not associated with the type of treatment performed.


Decreased mitochondrial nitric oxide synthase activity and hydrogen peroxide relate persistent tumoral proliferation to embryonic behavior.
Differential expression and activity of constitutive mitochondrial nitric oxide synthase (mtNOS) in the mitochondrial compartment is followed by significant variations in matrix nitric oxide (NO) steady-state concentration. The mitochondrial utilization of NO involves the production of superoxide anion and H(2)O(2), a species freely diffusible outside the mitochondria that participates in the modulation of cell proliferation and apoptosis and in cell transformation and cancer. On these bases, we analyzed the modulation of mtNOS in the frame of cellular redox state in M3, MM3, and P07 murine tumors and their respective cell lines, as compared with normal proliferating and quiescent tissues. The results showed that: (a) tumoral and proliferating mitochondria only retain 10-50% of the activity of complexes I, II-III, and IV and Mn-SOD of quiescent tissues; (b) normal proliferating tissues, like embryonic liver or pregnant mammary gland, have 10-20% of mtNOS expression and activity and mitochondrial H(2)O(2) yield than quiescent nonproliferating tissues; (c) similarly but irrespective of mtNOS expression, tumoral mitochondria have no >5% of mtNOS activity and H(2)O(2) yield of mature tissues; and (d) in opposition to stable tissues, both tumoral and normal proliferating cells exhibit high cyclin D1 expression and low pro-apoptotic p38mitogen-activated protein kinase activity. Dually, H(2)O(2) stimulated tumor cell proliferation (<10 microM) or markedly inhibited it (>10 microM) with parallel variations of cyclin D1, phospho-extracellular-regulated kinase1/2, and phospho-p38mitogen-activated protein kinase. It is surmised that decreased oxidative phosphorylation, defective tumoral mtNOS, and low mitochondrial NO-dependent H(2)O(2) may be a platform to link persistent tumoral growth to embryonic behavior.


Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology.
Physical fatigability and avoidance of physically demanding tasks in chronic fatigue syndrome (CFS) were assessed by the achievement or nonachievement of 85% of age-predicted maximal heart rate (target heart rate, THR) during incremental exercise. The association with functional status impairment, somatization, and psychopathology was examined. A statistically significant association was demonstrated between this physical fatigability variable and impairment, and a trend was found for an association with somatization. No association was demonstrated with psychopathology. These results are in accordance with the cognitive-behavioral model of CFS, suggesting a major contribution of avoidance behavior to functional status impairment; however, neither anxiety nor depression seem to be involved in the avoidance behavior. Aerobic work capacity was compared between CFS and healthy controls achieving THR. Physical deconditioning with early involvement of anaerobic metabolism was demonstrated in this CFS subgroup. Half of the CFS patients who did not achieve THR did not reach the anaerobic threshold. This finding argues against an association in CFS between avoidance of physically demanding tasks and early anaerobic metabolism during effort.


The Schöttle Point Is Consistently Located Distal to the Medial Femoral Physis in Pediatric Patients: A Digitally Reconstructed Radiographic Study.
Significant controversy surrounds ideal tunnel position for medial patellofemoral ligament (MPFL) reconstruction (MPFLR) in the pediatric setting. The start point for femoral tunnel positioning (the Schöttle point) relative to the distal medial femoral physis is not well defined. Previous studies provide conflicting data regarding position of the MPFL origin and the Schöttle point relative to the distal femoral physis. The Schöttle point would be consistently distal to the distal medial femoral physis. Descriptive laboratory study. The institutional picture archiving and communication system was queried for computed tomography (CT) imaging studies of pediatric knees. Data were imported to an open-source image computing platform. True lateral digitally reconstructed radiographs and 3-dimensional (3D) renderings were generated, and the Schöttle point was registered in 3D space. Then, 3D distance measurements were obtained from the Schöttle point to the distal medial femoral physis. A total of 49 pediatric knee CT scans were included. Mean age was 13.0 ± 2.3 years. Mean minimum distance from the medial physis to the Schöttle point was 9.9 ± 3.0 mm (range, 3.4-16.1 mm). In 49 of 49 cases (100%), the Schöttle point was distal to the physis. Using a 6-mm reaming diameter would result in 3 of 49 (6%) femurs having violation of the distal medial femoral physis. Moving the start point 3 mm distally would result in 0 of 49 (0%) sustaining physeal injury. The Schöttle point is consistently distal to the distal medial femoral physis. The mean minimum distance from the Schöttle point to the physis on the medial cortex is 9.9 mm. The Schöttle point provides a safe and reliable radiographic landmark for pediatric MPFLR, although reaming diameter should be considered.


Plantlets from aspen tissue cultures.
After 2 weeks in the dark, leafy shoots were initiated on subcultured callus tissue of triploid quaking aspen on Wolter's medium without auxin and with 6-benzylaminopurine at 0.05, 0.10., 0.15, or 0.20 milligram per liter substituted for kinetin. Shoots transferred to Wolter's medium under light (323 milliphots) grew large roots and were isolated as plantlets.


Anthropogenic-driven rapid shifts in tree distribution lead to increased dominance of broadleaf species.
Over the past century, major shifts in the geographic distribution of tree species have occurred in response to changes in land use and climate. We analyse species distribution and abundance from about 33 000 forest inventory plots in Spain sampled twice over a period of 10-12 years. We show a dominance of range contraction (extinction), and demographic decline over range expansion (colonization), with seven of 11 species exhibiting extinction downhill of their distribution. Contrary to expectations, these dynamics are not always consistent with climate warming over the study period, but result from legacies in forest structure due to past land use change and fire occurrence. We find that these changes have led to the expansion of broadleaf species (i.e. family Fagaceae) over areas formerly dominated by conifer species (i.e. family Pinaceae), due to the greater capacity of the former to respond to most disturbances and their higher competitive ability. This recent and rapid transition from conifers to broadleaves has important implications in forest dynamics and ecosystem services they provide. The finding raises the question as to whether the increasing dominance of relatively drought-sensitive broadleaf species will diminish resilience of Mediterranean forests to very likely drier conditions in the future.


Amniotic fluid cortisol and alpha-fetoprotein in normal and aneuploid pregnancies.
Cortisol and alpha-fetoprotein (AFP) levels were measured in amniotic fluid (AF) samples at 15-20 weeks of gestation from 125 normal pregnancies and 29 pregnancies affected by aneuploidy. The normal pregnancy group was further subdivided into 'low' AF-AFP (less than 0.6 MOM, n = 60) and 'normal' AF-AFP (0.6 less than AFP less than 1.4 MOM, n = 65). A significant, inverse, linear correlation was found between cortisol and AF-AFP for both normal AFP and low AFP groups (r = -0.26, and r = -0.4, respectively, p less than 0.05). Gestational age was significantly correlated with both cortisol and AFP levels in the normal pregnancy groups. No difference was found when cortisol levels were compared between the low and normal AFP groups. The correlation between cortisol and AFP in aneuploid pregnancies was not significant (p = 0.37). The strong association between cortisol or AFP and gestational age in normal pregnancy (p less than 0.00001) was lost in trisomic gestation. We conclude that higher cortisol levels do not seem to be the cause of low AFP in normal or aneuploid pregnancies.


Management of posterior reversible syndrome in preeclamptic women.
Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome associated with a number of conditions including preeclampsia. It is characterized by seizures, alteration of consciousness, visual disturbances, and symmetric white matter abnormalities, typically in the posterior parietooccipital regions of the cerebral hemispheres, at computed tomography (CT) and magnetic resonance (MRI). We report three new cases of PRES in preeclamptic patients and describe the management of these patients. We present a brief review of other cases in the literature, with particular attention to the anesthetic management.


Risk of prostate cancer for men with prior negative biopsies undergoing magnetic resonance imaging compared with biopsy-naive men: A prospective evaluation of the PLUM cohort.
Men with prior negative prostate biopsies have a lower risk of being diagnosed with prostate cancer in comparison with biopsy-naive men. However, the relative clinical utility of identified lesions on multiparametric magnetic resonance imaging (mpMRI) is uncertain between the 2 settings. Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015 to June 2020) were examined. The detection of any prostate cancer and clinically significant prostate cancer (Gleason score ≥ 3 + 4) was stratified by Prostate Imaging-Reporting and Data System (PI-RADS) scores in the prior negative and biopsy-naive settings. Multivariable logistic regression models (PLUM models) assessed predictors, and decision curve analyses were used to estimate the clinical utility of PI-RADS cutoffs relative to the models. Nine hundred men (420 prior negative patients and 480 biopsy-naive patients) were included. Prior negative patients had lower risks of any prostate cancer (27.9% vs 54.4%) and clinically significant prostate cancer (20.0% vs 38.3%) in comparison with biopsy-naive patients, and this persisted when they were stratified by PI-RADS (eg, PI-RADS 3: 13.6% vs 27.4% [any prostate cancer] and 5.2% vs 15.4% [clinically significant prostate cancer]). The rate of detection of clinically significant prostate cancer was 5.3% among men with prior negative biopsy and PI-RADS ≤ 3. Family history and Asian ancestry were significant predictors among biopsy-naive patients. PLUM models demonstrated a greater net benefit and reduction in biopsies (45.8%) without missing clinically significant cancer in comparison with PI-RADS cutoffs (PI-RADS 4: 34.0%). Patients with prior negative biopsies had lower prostate cancer detection by PI-RADS score category in comparison with biopsy-naive men. Decision curve analyses suggested that many biopsies could be avoided by the use of the PLUM models or a PI-RADS 4 cutoff without any clinically significant cancer being missed. Men with a prior negative prostate biopsy had a lower risk of harboring prostate cancer in comparison with those who never had a biopsy. This was true even when patients in each group had similar multiparametric magnetic resonance imaging (mpMRI) findings in terms of Prostate Imaging-Reporting and Data System (PI-RADS)-graded lesions. Decision curve analyses showed that many biopsies could be avoided by the use of the Prospective Loyola University mpMRI prediction models or a PI-RADS 4 cutoff for patients with prior negative biopsies.


Selective inhibition of trypanosomal glyceraldehyde-3-phosphate dehydrogenase by protein structure-based design: toward new drugs for the treatment of sleeping sickness.
Within the framework of a project aimed at rational design of drugs against diseases caused by trypanosomes and related hemoflagellate parasites, selective inhibitors of trypanosomal glycolysis were designed, synthesized, and tested. The design was based upon the crystallographically determined structures of the NAD:glyceraldehyde-3-phosphate dehydrogenase complexes of humans and Trypanosoma brucei, the causative agent of sleeping sickness. After one design cycle, using the adenosine part of the NAD cofactor as a lead, the following encouraging results were obtained: (1) a 2-methyl substitution, targeted at a small pocket near Val 36, improves inhibition of the parasite enzyme 12.5-fold; (2) an 8-(thien-2-yl) substitution, aimed at Leu 112 of the parasite enzyme, where the equivalent residue in the mammalian enzyme is Val 100, results in a 167-fold better inhibition of the trypanosomal enzyme, while the inhibition of the human enzyme is improved only 13-fold; (3) exploitation of a "selectivity cleft" created by a unique backbone conformation in the trypanosomal enzyme near the adenosine ribose yields a considerable improvement in selectivity: 2'-deoxy-2'-(3-methoxybenzamido)adenosine inhibits the human enzyme only marginally but enhances inhibition of the parasite enzyme 45-fold when compared with adenosine. The designed inhibitors are not only better inhibitors of T. brucei GAPDH but also of the enzyme from Leishmania mexicana.


Phosphorylation of histones in cells treated with hypertonic and acidic media.
Factors in the extracellular environment, specifically hypertonic or acidic growth media, are shown to alter the modification of histones in several cell lines. For histone 2A, changes in modification were visible in the mass pattern and were found to be primarily changes in phosphorylation. The increased modification of the core histones was quickly reversed when cells were returned to normal medium.


miR-200b and miR-200c co-contribute to the cisplatin sensitivity of ovarian cancer cells by targeting DNA methyltransferases.
Cisplatin is a first-line chemotherapy drug that is commonly used in the treatment of epithelial ovarian cancer (EOC). However, insensitivity to cisplatin markedly influences the outcomes of chemotherapy. MicroRNAs (miRNAs/miRs) have been demonstrated to modulate drug resistance in a number of types of cancer. The aim of the present study was to investigate the key miRNAs involved in modulating drug resistance in ovarian cancer cells. miR-200b and miR-200c were identified to be frequently deregulated in ovarian cancer. Upregulation of miR-200b and miR-200c promoted EOC cell death in the presence of cisplatin. Upregulation of miR-125b-5p significantly decreased tumor growth in combination with cisplatin in a mouse model. Significantly, miR-200b and miR-200c reversed cisplatin resistance by targeting DNA methyltransferases (DNMTs) (directly targeting DNMT3A/DNMT3B and indirectly targeting DNMT1 via specificity protein 1). These results indicate that miR-200b- and miR-200c-mediated regulation of DNMTs serves a crucial function in the cellular response to cisplatin. miR-200b- and miR-200c-mediated downregulation of DNMTs may improve chemotherapeutic efficacy by increasing the sensitivity of cancer cells and thus may have an impact on ovarian cancer therapy.


Stimulation of postsynaptic alpha1b- and alpha2-adrenergic receptors amplifies dopamine-mediated locomotor activity in both rats and mice.
Recent experiments have shown that mice lacking the alpha1b-adrenergic receptor (alpha1b-AR KO) are less responsive to the locomotor hyperactivity induced by psychostimulants, such as D-amphetamine or cocaine, than their wild-type littermates (WT). These findings suggested that psychostimulants induce locomotor hyperactivity not only because they increase dopamine (DA) transmission, but also because they release norepinephrine (NE). To test whether NE release could increase DA-mediated locomotor hyperactivity, rats were treated with GBR 12783 (10 mg/kg), a specific inhibitor of the DA transporter, and NE release was enhanced with dexefaroxan (0.63-10 mg/kg), a potent and specific antagonist at alpha2-adrenergic receptors. Dexefaroxan increased the GBR 12783-mediated locomotor response by almost 8-fold. The role of alpha1b-ARs in this effect was then verified in alpha1b-AR KO mice: whereas dexefaroxan (1 mg/kg) doubled locomotor hyperactivity induced by GBR 12783 (14 mg/kg) in WT mice, it decreased it by 43% in alpha1b-AR KO mice. Finally, to test whether this latter inhibition was related to the occupation of alpha2-adrenergic autoreceptors or of alpha2-ARs not located on noradrenergic neurons, effects of dexefaroxan on locomotor hyperactivity induced by D-amphetamine (0.75 mg/kg) were monitored in rats depleted in ascending noradrenergic neurons. In these animals dexefaroxan inhibited by 25-70% D-amphetamine-induced locomotor hyperactivity. These data indicate not only that the stimulation of alpha1b-ARs increases DA-mediated locomotor response, but also suggest a significant implication of postsynaptic alpha2-ARs. Involvement of these adrenergic receptor mechanisms may be exploited in the therapy of Parkinson's disease.


Risk of neurodegenerative disease or dementia in adults with attention-deficit/hyperactivity disorder: a systematic review.
Several psychiatric disorders have been associated with an increased risk of developing a neurodegenerative disease and/or dementia. Attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder, has been understudied in relation to dementia risk. We summarized existing literature investigating the risk of incident neurodegenerative disease or dementia associated with ADHD. We searched five databases for cohort, case-control, and clinical trial studies investigating associations between ADHD and neurodegenerative diseases/dementia in May 2023. Study characteristics were extracted by two independent raters, and risk of bias was assessed using the Newcastle Ottawa Scale. Search terms yielded 2,137 articles, and seven studies (five cohort and two case-control studies) ultimately met inclusion criteria. Studies examined the following types of neurodegeneration: all-cause dementia, Alzheimer's disease, Parkinson's and Lewy body diseases, vascular dementia, and mild cognitive impairment. Heterogeneity in study methodology, particularly covariates used in analyses and types of ratios for risk reported, prevented a meta-analysis and data were therefore summarized as a narrative synthesis. The majority of studies (4/7) demonstrated an overall low risk of bias. The current literature on risk of developing a neurodegenerative disease in ADHD is limited. Although the studies identified present evidence for a link between ADHD and subsequent development of dementia, the magnitude of the direct effect of ADHD on neurodegeneration is yet to be determined and better empirically designed studies are first needed. Furthermore, the mechanism of how or why ADHD is associated with an increased risk of developing a neurocognitive disorder is still unclear and should be explored in future studies. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022348976, the PROSPERO number is CRD42022348976.


Short-term effects of a revegetation program on the Orthopteran diversity in oak forests of the southern Iberian Peninsula.
Orthopterans are insects closely linked to vegetation as primary consumers as well as for other biological processes such as oviposition and development. This research aims to assess the effect of a revegetation program that began in 2007 in the compensation area linked to the construction of the Breña II dam on Orthopteran diversity within several different human-created and natural habitats (forest-islands, hedges, and river-copses). We assessed vegetation and orthopteran communities during monthly sampling performed during March through September 2011. For the Orthopterans, two replicates per habitat type were sampled in each of the eight selected sampling plots, providing 48 observations per environment per month. To characterize the structure of communities, diversity, dominance, and evenness were calculated, and posterior comparisons were made using bootstrapping analysis. Additionally, rarefaction curves were obtained. We found large between-habitat differences in plant abundance but smaller differences in diversity. The high degree of vegetational homogeneity likely explains the structural similarity among the Orthopteran communities in the different habitats. Although Caelifera were more abundant and diverse in unmanaged biotopes, Ensifera seem to be favored in revegetated areas. Because accurate management requires documenting diversity at the field scale, work like that presented here should increase the efficiency of future assessments of Orthopteran habitat suitability for diversity conservation.


Analysis of recorded biomedical book and journal use in the Yale Medical Library. II. Subject and user relations.
Cancelled charge slips collected over a one-year period supply the data for this analysis of circulation in the Yale Medical Library. Full-time teaching faculty are the heaviest users of journal literature, and students, of monograph literature. Faculties of Medical School departments are compared in terms of their use of material in individual subjects. Subject literatures are analyzed in terms of groups of users borrowing from them. The extent to which journal titles used by medical students are also used by Medical School faculty is examined. One of the products of the study is a rank list of journal titles used in the Library. Results are presented in several tables.


Evaluation of EED Inhibitors as a Class of PRC2-Targeted Small Molecules for HIV Latency Reversal.
A hallmark of human immunodeficiency type-1 (HIV) infection is the integration of the viral genome into host chromatin, resulting in a latent reservoir that persists despite antiviral therapy or immune response. Thus, key priorities toward eradication of HIV infection are to understand the mechanisms that allow HIV latency and to develop latency reversal agents (LRAs) that can facilitate the clearance of latently infected cells. The repressive H3K27me3 histone mark, catalyzed by the PRC2 complex, plays a pivotal role in transcriptional repression at the viral promoter in both cell line and primary CD4+ T cell models of latency. EZH2 inhibitors which block H3K27 methylation have been shown to act as LRAs, suggesting other PRC2 components could also be potential targets for latency reversal. EED, a core component of PRC2, ensures the propagation of H3K27me3 by allosterically activating EZH2 methyltransferase activity. Therefore, we sought to investigate if inhibition of EED would also reverse latency. Inhibitors of EED, EED226 and A-395, demonstrated latency reversal activity as single agents, and this activity was further enhanced when used in combination with other known LRAs. Loss of H3K27me3 following EED inhibition significantly increased the levels of H3K27 acetylation globally and at the HIV LTR. These results further confirm that PRC2 mediated repression plays a significant role in the maintenance of HIV latency and suggest that EED may serve as a promising new target for LRA development.


The Case of Billy Best: 25 Years Later.
Billy Best was diagnosed with Hodgkin lymphoma in 1994 at age 16 and became well-known when he ran away from home to avoid receiving further chemotherapy. His story became national news when, with the support of his adopted parents, he returned home and opted to use complementary and alternative medicine (CAM) instead of standard chemotherapy and radiation for his cancer treatment. Now 25 years since Billy Best entered the public eye, his story is one that is frequently referenced in pediatrics, bioethics, and other related fields. Here, the authors examine the evolution of various features of this case, including treatment of Hodgkin lymphoma, the interplay between medicine and the media, the role of CAM in pediatric care, navigating entrenched disagreements and how best to integrate adolescents into health care decision-making, and the role of narrative in medical practice. The authors explore the unique role of each of these facets of Billy Best's case, describing how each has or has not changed in the quarter century since that time amid the changing landscape of pediatric health care. Ultimately, although many advances have occurred since Billy Best's time, significant work remains. Additional effort will be required in the future to optimize communication, improve treatment toxicities from Hodgkin lymphoma without decreasing survival, integrate the voice and perspective of adolescents into their treatment decisions, and navigate the roles of CAM and the media in pediatric health care.


[Lung cancer screening in urban Beijing from 2014 to 2019].
Objective: To analyze the current status of lung cancer screening among residents in Urban Beijing Cancer Screening Program, 2014-2019. Methods: Based on an on-going cancer screening program launched by the National Urban Cancer Screening Program, residents aged 40 to 69 were recruited from 80 streets in six districts of Beijing (Dongcheng, Xicheng, Chaoyang, Haidian, Fengtai, and Shijingshan District) by using a cluster sampling method. Subjects who were evaluated as high-risk individuals by using the questionnaire received Low-Dose spiral Computed Tomography (LDCT) screening in designated hospitals. All participants were followed up annually using active and passive follow-up methods to obtain their health outcomes (diagnosed with lung cancer or not). The proportion of high-risk cases evaluated by using the questionnaire, clinical recall rate for receiving LDCT screening, the proportion of cases with positive pulmonary node, incidence rate, cumulative incidence rate, and the proportion of patients with stage 0 or Ⅰ were calculated. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (95%CI) among individuals who experienced different screening scenarios. Results: A total of 88 044 residents with the age of (57.4±7.4) with completed high-risk assessment were included in the analysis. 23.14% of participants were evaluated as high-risk individuals by using the questionnaire. The clinical recall rate was 52.26% among the high-risk individuals. The positive rate of pulmonary node detected by LDCT was 10.99%. The incidence rate of lung cancer among males and females aged 40-69 years were 172.82/100 000 person-years and 133.52/100 000 person-years, respectively after 3 years follow-up. The incidence rates increased with age (Ptrend<0.001). The incidence rate of lung cancer among high-risk individuals was 259.22/100 000 person-years, with the HR (95%CI) about 2.27 (1.83-2.81) when compared with that among low-risk individuals. The incidence rate and cumulative incidence rate of lung cancer among individuals with positive pulmonary node detected by LDCT were 1 825.03/100 000 person-years and 4 615.38/100 000, respectively, with the HR (95%CI) about 13.80 (8.91-21.36) when compared with that among individuals with no or negative pulmonary node. The early diagnosis rate among individuals who received LDCT screening was 70.21%, which was higher than that among individuals with no LDCT screening (45.45%). Conclusion: Individuals with a high risk of lung cancer in Beijing have a better recall rate of receiving LDCT screening. Using LDCT screening among high-risk individuals is an effective strategy to detect lung cancer cases and improve the early detection rates of lung cancer in Beijing, China.


Computed tomography findings of testicular adrenal rest tumors resulted from 21-hydroxylase deficiency.
21-hydroxylase deficiency is a rare kind of autosomal recessive disorders, which can result in congenital adrenal hyperplasia and/or testicular adrenal rest tumors. 21-hydroxylase deficiency with TARTs is prone to be misdiagnosed as Leydig cell tumors. Although the sonographic characteristics of TARTs have been summarized in previous reports, its features in computed tomography images were rarely reported. In this study, we presented and summarized the clinical and imaging data of a special case suffering this disease, aiming to improve the imaging diagnosis performance.


Identification of histone 3 variant 2 interacting factors.
The epigenome is defined as a type of information that can be transmitted independently of the DNA sequence, at the chromatin level, through post-translational modifications present on histone tails. Recent advances in the identification of histone 3 variants suggest a new model of information transmission through deposition of specific histone variants. To date, several non-centromeric histone 3 variants have been identified in mammals. Despite protein sequence similarity, specific deposition complexes have been characterized for both histone 3.1 (H3.1) and histone 3.3 (H3.3), whereas no deposition complex for histone 3.2 (H3.2) has been identified to date. Here, we identified human H3.2 partners by immunopurification of nuclear H3.2 complexes followed by mass spectrometry analysis. Further biochemical analyses highlighted two major complexes associated with H3.2, one containing chromatin associated factor-1 subunits and the other consisting of a subcomplex of mini chromosome maintenance helicases, together with Asf1. The purified complexes could associate with a DNA template in vitro.


A Rapid and Efficient Method to Dissect Pupal Wings of Drosophila Suitable for Immunodetections or PCR Assays.
Wing development in Drosophila melanogaster is an ideal model for studying morphogenesis at tissue level. These appendages develop from a group of cells named wing imaginal discs formed during embryonic development. In the larval stages the imaginal discs grow, increasing its number of cells and forming monolayered epithelial structures. Inside the pupal case, the imaginal discs bud out and fold into bilayers along a line that becomes the future margin of the wing. During this process, the longitudinal primodia veins originate vein cells on the prospective dorsal and ventral surfaces of the wing. During the pupal stage the stripes of vein cells of each surface communicate in order to generate tight tubes; at the same time, the cross-veins begin their formation. With the help of appropriate molecular markers, it is possible to identify the major elements composing the wing during its development. For this reason, the ability to accurately detect transcripts or proteins in this structure is critical for studying their abundance and localization related to the development process of the wing. The procedure described here focuses on manipulating pupal wings, providing detailed instructions on how to dissect the wing during the pupal stage. The dissection of pupal tissue is more difficult to perform than their counterparts in third instar larvae. This is why this approach was developed, to obtain rapid and efficient high quality samples. Details of how to immunostain and mount these wing samples, to allow the visualization of proteins or cell components, are provided in the protocol. With little expertise it is possible to collect 8-10 high quality pupal wings in a short amount of time.


p21((WAF1))-mediated transcriptional targeting of inducible nitric oxide synthase gene therapy sensitizes tumours to fractionated radiotherapy.
Cancer gene therapy that utilizes toxic transgene products requires strict transcriptional targeting to prevent adverse normal tissue effects. We report on the use of a promoter derived from the cyclin dependent kinase inhibitor, p21((WAF1)), to control transgene expression. We demonstrate that this promoter is relatively silent in normal cells (L132, FSK, HMEC-1) compared to the almost constitutive expression obtained in tumour cells (DU145, LNCaP, HT29 and MCF-7) of varying p53 status, a characteristic that will be important in gene therapy protocols. In addition, we found that the p21((WAF1)) promoter could be further induced by both external beam radiation (up to eight-fold in DU145 cells), intracellular-concentrated radionuclides ([(211)At]MABG) (up to 3.5-fold in SK-N-BE(2c) cells) and hypoxia (up to four-fold in DU145 cells). We have previously achieved significant radiosensitization of tumour cells both in vitro and in vivo by using inducible nitric oxide synthase (iNOS) gene therapy to generate the potent radiosensitizer, nitric oxide (NO(.-)). Here, we report that a clinically relevant schedule of p21((WAF1))-driven iNOS gene therapy significantly sensitized both p53 wild-type RIF-1 tumours and p53 mutant HT29 tumours to fractionated radiotherapy. Our data highlight the utility of this p21((WAF1))/iNOS-targeted approach.


Climate change in Australian tropical rainforests: an impending environmental catastrophe.
It is now widely accepted that global climate change is affecting many ecosystems around the globe and that its impact is increasing rapidly. Many studies predict that impacts will consist largely of shifts in latitudinal and altitudinal distributions. However, we demonstrate that the impacts of global climate change in the tropical rainforests of northeastern Australia have the potential to result in many extinctions. We develop bioclimatic models of spatial distribution for the regionally endemic rainforest vertebrates and use these models to predict the effects of climate warming on species distributions. Increasing temperature is predicted to result in significant reduction or complete loss of the core environment of all regionally endemic vertebrates. Extinction rates caused by the complete loss of core environments are likely to be severe, nonlinear, with losses increasing rapidly beyond an increase of 2 degrees C, and compounded by other climate-related impacts. Mountain ecosystems around the world, such as the Australian Wet Tropics bioregion, are very diverse, often with high levels of restricted endemism, and are therefore important areas of biodiversity. The results presented here suggest that these systems are severely threatened by climate change.


Platonic love, transference love, and love in real life.
Plato and Freud transformed our way of looking at love. In Plato's Dialogues one can trace the transition and transformation of the mythical view on love into philosophical conceptualizations. The waning of the mythical point of view created the demand for man to know himself, and love became a puzzle. Plato was the first to propose that erotic impulses can undergo sublimation to higher and desexualized aims. Freud was not a Platonist, but if we trace the history of certain ideas it becomes evident that Plato's influence on Freud went further and deeper than was assumed by previous psychoanalytic writers. Freud's conceptualization of the libido can be seen as a Latinized version of Plato's Eros. Some of the difficulties associated with the psychoanalytic use of the term sublimation go back to the Platonic origin of the term. Freud's conviction that tender and aim-inhibited love was a later transformation of sexual impulses also went back to Plato, as did his belief that aim-inhibited love endures longer than sexual love. Because erotic love impulses can be sublimated, transference love can be harnessed in the service of cure based on insight. Erotized transference is not based on the refinding of an early love object and therefore is less capable of yielding the therapeutic climate required for psychoanalytic treatment. Freud's treatment procedure confirms Plato's belief in the plasticity of Eros.


Ultrasonography of adrenal lesions.
A total of 98 adrenal glands in 49 patients were prospectively investigated by ultrasonography (US). The US had a sensitivity of 76.7%, a specificity of 92.7%, and an accuracy of 85.7%. It is mainly the smaller lesions (0.5 to 2.8 cm, mean 1.2) which decrease the sensitivity of US. Large tumors in or near the glands and anatomical variants may decrease the accuracy of US as well. The ultrasound detection of a large and solid adrenal tumor, especially one with irregular border, or a tumor with invasion to the inferior vena cava, suggests the high possibility of malignancy. While a tumor with central necrosis may be suggestive of pheochromocytoma, despite its large size. US is a good primary screening modality for patients with suspected adrenal lesions; and it may help to differentiate malignant from benign tumors of the adrenal.


Induction of angiogenesis by platelet-activating factor in the rat striatum.
Angiogenesis, the formation of new blood vessels, has been studied following injection of platelet-activating factor into the rat striatum. Immunohistochemical analysis for laminin showed that platelet-activating factor induced significant neovascularization in the striatum. A dose-dependent loss of striatal neurons accompanied this angiogenic activity. The platelet-activating factor-induced neovascularization and neurodegeneration were attenuated by the platelet-activating factor receptor antagonist, BN52021, or the inducible nitric oxide synthase inhibitor, aminoguanidine. Additionally, these agents significantly reduced levels of the angiogenic agent vascular endothelial growth factor, which was markedly enhanced in platelet-activating factor-injected striatum. Double immunofluorescence staining demonstrated that expression of vascular endothelial growth factor and inducible nitric oxide synthase were predominantly localized to microglia, suggesting that inflammatory responses mediated by activated microglia could contribute to platelet-activating factor-induced angiogenesis and neuronal loss.


Improved photocatalytic hydrogen evolution driven by chloro(terpyridine)platinum(ii) derivatives tethered to a single pendant viologen acceptor.
Three chloro(4'-(N-methylpyridinium)-2,2':6',2''-terpyridine)platinum(ii) (abbreviated as ) derivatives tethered to a single alkyl viologen unit (-(CH2)n-CH2-N(+)C5H4-C5H4N(+)-CH3; abbreviated as -, where n = 1, 3, and 4), i.e., , have been synthesized and investigated in detail. It is shown that the turnover number (TON) for the photocatalytic H2 evolution from water in the presence of a sacrificial electron donor EDTA (ethylenediaminetetraacetic acid disodium salt) is dramatically improved by the attachment of a single alkyl unit (TON = 21.5-25.2, 12 h). Spectrophotometric studies reveal that the photoirradiation of in the presence of EDTA initially leads to the formation of a 1-electron-reduced species, and then to a 2-electron-reduced species, where reductive quenching of a photoexcited species is a major path to the reduced photoproduct in each step. Electrochemical studies show that two consecutive 1-electron reductions at the unit are nearly overlapped with the corresponding reductions at the unit. The 1-electron-reduced species can be thus expressed as either or , while the 2-electron-reduced one as . Moreover, the latter products behave as stacked species involving three types of π-dimer sites, ()2, ()2, and ()(), and do not drive thermal H2 evolution according to the reaction: + 2H(+) → + H2. The H2 evolution from water photocatalyzed by has been found to occur via formation of 3-electron-reduced species; + EDTA + hν → (or ) + EDTA(ox), and (or ) + 2H(+) → (or ) + H2.


Is starvation a cause of overmortality of the Mediterranean sardine?
Animal mortality is difficult to observe in marine systems, preventing a mechanistic understanding of major drivers of fish population dynamics. In particular, starvation is known to be a major cause of mortality at larval stages, but adult mortality is often unknown. In this study, we used a laboratory food-deprivation experiment, on wild caught sardine Sardina pilchardus from the Gulf of Lions. This population is interesting because mean individual phenotype shifted around 2008, becoming dominated by small, young individuals in poor body condition, a phenomenon that may result from declines in energy availability. Continuous monitoring of body mass loss and metabolic rate in 78 captive food-deprived individuals revealed that sardines could survive for up to 57 days on body reserves. Sardines submitted to long-term caloric restriction prior to food-deprivation displayed adaptive phenotypic plasticity, reducing metabolic energy expenditure and enduring starvation for longer than sardines that had not been calorie-restricted. Overall, entry into critical fasting phase 3 occurred at a body condition of 0.72. Such a degree of leanness has rarely been observed over 34 years of wild population monitoring. Still, the proportion of sardines below this threshold has doubled since 2008 and is maximal in January and February (the peak of the reproductive season), now reaching almost 10 % of the population at that time. These results indicate that the demographic changes observed in the wild may result in part from starvation-related adult mortality at the end of the winter reproductive period, despite adaptive plastic responses.


The interaction of outgoing echolocation pulses and echoes in the false killer whale's auditory system: evoked-potential study.
Brain auditory evoked potentials (AEP) associated with echolocation were recorded in a false killer whale Pseudorca crassidens trained to accept suction-cup EEG electrodes and to detect targets by echolocation. AEP collection was triggered by echolocation pulses transmitted by the animal. The target was a hollow aluminum cylinder of strength of -22 dB at a distance from 1 to 8 m. Each AEP record was obtained by averaging more than 1000 individual records. All the records contained two AEP sets: the first one of a constant latency and a second one with a delay proportional to the distance. The timing of these two AEP sets was interpreted as responses to the transmitted echolocation pulse and echo, respectively. The echo-related AEP, although slightly smaller, was comparable to the outgoing click-related AEP in amplitude, even though at a target distance as far as 8 m the echo intensity was as low as -64 dB relative to the transmitted pulse in front of the head. The amplitude of the echo-related AEP was almost independent of distance, even though variation of target distance from 1 to 8 m influenced the echo intensity by as much as 36 dB.


[Sex hormones and adipocytokines in postmenopausal women].
Visceral fat accumulation occuring in postmenopausal women is connected with hypoestrogenism, decreased production of sex-hormone binding globuline (SHBG) and with rise in free testosterone. They have been identified as risk factors for cardiovascular diseases. The exact mechanisms mediating relationships between the excess of visceral adiposity, hormonal variations after menopause and metabolic disturbances, remain unknown. We speculate that adipocytokines produced by adipose tissue: adiponectin, leptin and resistin, might play a role. Adiponectin is a hormone which plays a role in insulin sensitivity and lipid oxidation, and possesses anti-inflammatory properties. Increased levels of androgens post menopause and low SHBG are connected with decreased production of adiponectin. Leptin is another of the adipocytokines which has been shown to be linked to insulin resistance, increased pressure and hypertriglyceridaemia. Sex steroids have effect on leptin secretion but the associations between leptin and menopause are controversial. Recently it was found that resistin, another bioactive substance produced by adipose tissue may related to insulin resistance. Studies on animals indicate that ovariectomy and testosterone significantly increased resistin expression. It seems that adipocytokines may be a link connecting postmenopasual hormonal changes, the excess of visceral fat and increased risk of cardiovascular diseases.


Stigma, Emotion Appraisal, and the Family Environment as Predictors of Carer Burden for Relatives of Individuals Who Meet the Diagnostic Criteria for Borderline Personality Disorder.
There is some research exploring carers' experiences within the National Health Service in the UK, but only one has focused on carers of individuals with borderline personality disorder (BPD). Ninety-eight carers completed a questionnaire-based study; 57 carers of individuals who meet the diagnostic criteria for BPD were compared to 41 carers of individuals with other mental health problems. The study aimed to investigate whether perceived stigma, perceived threat of strong emotions, and expressed emotion (EE) within the family environment predicted carer burden. The results showed that carers of those who met the diagnosis for BPD experienced higher levels of carer burden, stigma, EE, emotional over involvement (EOI), criticism (CC), and perceived threat of strong emotions than carers of individuals with other mental health difficulties. EOI, CC, carer group (BPD and mental health), and gender of participant were predictors of carer burden, with EOI explaining the most variance of burden.


In vitro effects of ozone on human erythrocyte membranes: an EPR study.
The effects of ozone at different concentrations (10, 30, 45 g/m3) on fluidity and thermotropic properties of erythrocyte membranes were investigated by EPR using two spin probes: 5-doxylstearic acid (5-DSA) and 16-doxylstearic acid (16-DSA). The effect of ozone on the erythrocyte membrane fluidity was a dose-dependent process. The ozone at concentration of 10 g/m3 caused rigidization of the membrane while at concentration of 45 g/m3 increased fluidity both on the surface and in the deeper hydrocarbon region of the membrane. Temperature transitions close to the polar heads region (monitored by 5-DSA) were not sensitive to an increase in ozone concentration. In the case of 16-DSA, low temperature thermotropic transition (around 20 degrees C) gradually decreased with the increase of ozone concentration. High temperature transition (around 40 degrees C) significantly differed at the ozone concentration of 10 g/m3 and 45 g/m3, being higher and lower, respectively, as compared to untreated cells. For the ozone concentration of 45 g/m3 the disappearance of the low temperature break and the appearance of two breaks at 37 degrees C and 16 degrees C were observed.


Guanidyl-Rich Poly(β Amino Ester)s for Universal Functional Cytosolic Protein Delivery and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 Ribonucleoprotein Based Gene Editing.
Protein therapeutics are highly promising for complex disease treatment. However, the lack of ideal delivery vectors impedes their clinical use, especially the carriers for in vivo delivery of functional cytosolic protein. In this study, we modified poly(β amino ester)s (PAEs) with a phenyl guanidine (PG) group to enhance their suitability for cytosolic protein delivery. The effects of the PG group on protein binding, cell internalization, protein function protection, and endo/lysosomal escape were systematically evaluated. Compared to the unmodified PAEs (L3), guanidyl rich PAEs (L3PG) presented superior efficiency of protein binding and protein internalization, mainly via clathrin-mediated endocytosis. In addition, both PAEs showed robust capabilities to deliver cytosolic proteins with different molecular weight (ranging from 30 to 464 kDa) and isoelectric points (ranging from 4.3 to 9), which were significantly improved in comparison with the commercial reagents of PULsin and Pierce Protein Transection Reagent. Moreover, L3PG successfully delivered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 ribonucleoprotein (RNP) into HeLa cells expressing green fluorescent protein (GFP) and achieved more than 80% GFP expression knockout. These results demonstrated that guanidyl modification on PAEs can enhance its capabilities for intracellular delivery of cytosolic functional proteins and CRISPR/Cas9 ribonucleoprotein. The guanidyl-rich PAEs are promising nonviral vectors for functional protein delivery and potential use in protein and nuclease-based gene editing therapies.


Neuroectodermal and neuroendocrine tumors principally seen in children.
Neuroectodermal tumors comprise a large proportion of childhood neoplasms. Neuroblastic tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma, are the most frequent extracranial solid cancers of childhood, occurring primarily in infants and toddlers. Primitive neuroectodermal tumors, including Ewing sarcoma and peripheral neuroepitheliomas, occur most frequently in older children and adolescents, and as pediatric sarcomas are second in frequency only to rhabdomyosarcomas. Rarer neuroectodermal tumors include desmoplastic small cell tumors, esthesioneuroblastomas, and melanotic neuroectodermal tumors, the first two entities occurring as rather site-specific lesions in the abdomen and nose, respectively. Diagnosis can be difficult due to the undifferentiated nature of many of these cancers, but ancillary studies, including electron microscopy, immunohistochemistry, cytogenetics, and molecular genetics, enhance their recognition. The molecular nature of childhood neuroectodermal tumors is as diverse as their histology, ranging from the fusion genes characterizing the Ewing sarcoma family of tumors to the proto-oncogene amplification seen in aggressive neuroblastomas.


Monoclonal antibody against alpha(1----3) dextran transfers suppression of the immune response to the acetylcholine receptor.
Previous studies have demonstrated that immunization of BALB/c mice with alpha(1----3) dextran (Dex) is accompanied by a reduction in the subsequent immune response to the acetylcholine receptor (AChR), depending on the timing of the Dex administration relative to AChR challenge. Here, we report that suppression of the anti-AChR response can be transferred by a monoclonal antibody, known as DX2, which is specific for Dex. Serum transfer experiments have also supported the notion that antibody is important for this effect. In addition, two new idiotypic markers have been defined that are expressed mainly by antibodies against Dex, including DX2. The anti-idiotypic reagents (Sh135 and EB5) are derived from the immune response to the AChR. A human monoclonal antibody which binds to Dex (SR 11) resembles the BALB/c antibodies that are involved in the suppression of the anti-AChR response. These findings emphasize the functional relevance of the AChR-Dex network not only for the BALB/c immune response to the AChR, but also for humans with the autoimmune disease, myasthenia gravis.


Degenerative pontine lesions in patients with familial narcolepsy.
Narcolepsy is characterized by chronic excessive daytime sleepiness with episodic sleep attacks. There are several associated symptoms of narcolepsy: cataplexy (bilateral muscle weakness without loss of consciousness provoked by an emotional trigger, e.g. laughter), sleep paralysis and hypnagogic-hypnopompic hallucinations. Most cases are sporadic; familial narcolepsy contributes to only 1-5% of all cases. While most cases of narcolepsy are idiopathic and are not associated with clinical or radiographic evidence of brain pathology, symptomatic or secondary narcolepsy may occur occasionally in association with lesions caused by tumours, demyelination or strokes of the diencephalon, midbrain, and pons. There are some examples of non-specific brainstem lesions found in magnetic resonance imaging (MRI) in patients with idiopathic narcolepsy. The authors present eleven patients from a five-generation family with many members who suffer from episodic excessive daytime sleepiness. Narcolepsy was diagnosed in 9 patients. Sleepiness was frequently associated with cataplexy, hypnagogic-hypnopompic hallucinations and sleep paralysis. Improvement in their clinical state was observed during the treatment with modafinil. All probands had MRI of the brain, routine blood tests, EEG, polysomnography, examination of the level of hypocretin in cerebrospinal fluid and evaluation by means of Epworth and Stanford Sleepiness Scales. In 9 patients with narcolepsy, decreased thickness of the substantia nigra was found and in six of them degenerative lesions in the pontine substantia nigra were also noticed. The significance of these changes remains unclear. No data have been published until now concerning the presence of any brain lesions in patients with familial narcolepsy.


Characteristics of US public schools with reported cases of novel influenza A (H1N1).
The 2009 pandemic of influenza A (H1N1) has disproportionately affected children and young adults, resulting in attention by public health officials and the news media on schools as important settings for disease transmission and spread. We aimed to characterize US schools affected by novel influenza A (H1N1) relative to other schools in the same communities. A database of US school-related cases was obtained by electronic news media monitoring for early reports of novel H1N1 influenza between April 23 and June 8, 2009. We performed a matched case-control study of 32 public primary and secondary schools that had one or more confirmed cases of H1N1 influenza and 6815 control schools located in the same 23 counties as case schools. Compared with controls from the same county, schools with reports of confirmed cases of H1N1 influenza were less likely to have a high proportion of economically disadvantaged students (adjusted odds ratio (aOR) 0.385; 95% confidence interval (CI) 0.166-0.894) and less likely to have older students (aOR 0.792; 95% CI 0.670-0.938). We conclude that public schools with younger, more affluent students may be considered sentinels of the epidemic and may have played a role in its initial spread.


Aging Effect on Categorical Perception of Mandarin Tones 2 and 3 and Thresholds of Pitch Contour Discrimination.
The purpose of the study was to examine the aging effect on the categorical perception of Mandarin Chinese Tone 2 (rising F0 pitch contour) and Tone 3 (falling-then-rising F0 pitch contour) as well as on the thresholds of pitch contour discrimination. Three experiments of Mandarin tone perception were conducted for younger and older listeners with Mandarin Chinese as the native language. The first 2 experiments were in the categorical perception paradigm: tone identification and tone discrimination for a series of stimuli, the F0 contour of which systematically varied from Tone 2 to Tone 3. In the third experiment, the just-noticeable differences of pitch contour discrimination were measured for both groups. In the measures of categorical perception, older listeners showed significantly shallower slopes in the tone identification function and significantly smaller peakedness in the tone discrimination function compared with younger listeners. Moreover, the thresholds of pitch contour discrimination were significantly higher for older listeners than for younger listeners. These results suggest that aging reduced the categoricality of Mandarin tone perception and worsened the psychoacoustic capacity to discriminate pitch contour changes, thereby possibly leading to older listeners' difficulty in identifying Tones 2 and 3.


Surgical approach to tumors arising from the posterior two thirds of the nasal septum.
A surgical approach to tumors of the septum is discussed. Two patients who had tumors in the posterior two thirds of the septum are shown in this paper. One had a benign mixed tumor and the other had an extramedullary plasmacytoma in the posterior two thirds of the septum. They underwent resection of the tumors with the septum by lateral rhinotomy. The first case additionally underwent an oval-shape resection of the palate. The postoperative profiles of the nose are good.


Genotype and variations in core promoter and pre-core regions are related to progression of disease in HBV-infected patients from Northern Vietnam.
Vietnam is one of the countries with a high rate of hepatitis B virus (HBV) infection, but there are only a few reports about relation of HBV genotypes and mutations to clinical course in Northern Vietnam. The characteristics of HBV and its relationship to clinical outcome in patients from Northern Vietnam were analyzed. Serum samples were collected from 183 HBV-infected Vietnamese patients. They were clinically categorized into 4 groups: hepatocellular carcinoma (HCC), liver cirrhosis (LC), chronic hepatitis (CH), and asymptomatic carriers (ASC). HBV serology, alpha-fetoprotein, HBV genotypes, HBV-DNA level and mutations in the core promoter and pre-core regions of HBV-DNA were examined. The majority of sera contained HBV genotype B (67.8%) and C (27.9%). The median age was matched between genotype B and C (38.2 vs. 42.9 years). The rates of HBeAg seroconversion and G1896A for genotype B were significantly higher than those for genotype C (P<0.05). Genotype C had a higher HBV-DNA level than genotype B. C1858 was frequent, especially in genotype C (62.7%). The most prevalent genotype in ASC and CH was genotype B. The presence of the mutation A1762T/G1764A correlated with disease progression. The triple mutation T1753C/A1762T/ G1764A was quite common and was more prevalent in LC and HCC than in CH and ASC. In Northern Vietnamese, HBV genotypes B and C were prevalent. Genotype C and mutations in the core promoter region were associated with progressive, severe liver diseases.


Aggregation-induced emission and aggregation-promoted photochromism of bis(diphenylmethylene)dihydroacenes.
Reported herein is a new class of pure polycyclic hydrocarbon molecules, designed through a novel aggregation-induced emission (AIE) strategy, with unexpected photochromic properties. The restriction of intramolecular motion was found as a comprehensive mechanism for the AIE effect. The photochromism mechanism study revealed that the photocyclization reaction of cis-stilbene, the molecular conformation in the single crystal and the tetracene backbone should contribute to the unique photo behavior. In particular, the fast responsive, photo-reversible and thermo-irreversible photochromic effect facilitated in the solid state opens a new field of aggregation-promoted photochromism.


[The effect of scalp infiltration with bupivacaine on blood coagulability and fibrinolysis in neurovascular surgery].
We investigated the effect of scalp infiltration with bupivacaine on blood coagulability and fibrinolysis in neurovascular surgery. Patients were randomly divided into two groups: scalp infiltration group (who received scalp infiltration with 0.5% bupivacaine prior to surgical incision, n = 7) and control group (n = 6). The blood coagulability and fibrinolysis were measured before and after surgical incision using a thromboelastogram (Thromboelastograph C-3000, Haemoscope). In the control group, the reaction and coagulation times were significantly shortened (30% and 23%, respectively, P < 0.05) and the maximum amplitude, which reflects coagulability, increased significantly (21%, P < 0.01) compared to each presurgical value. The scalp infiltration prior to the surgical incision prevented these reactions (P < 0.05). The fibrinolytic rate did not change in either group. We conclude that scalp infiltration prior to surgical incision is beneficial for attenuating an increase in blood coagulability, which could induce perioperative complications due to associated systemic diseases (i.e. hypertension, diabetes, ischemic heart disease, etc.).


Blockchain and Machine Learning Inspired Secure Smart Home Communication Network.
With the increasing growth rate of smart home devices and their interconnectivity via the Internet of Things (IoT), security threats to the communication network have become a concern. This paper proposes a learning engine for a smart home communication network that utilizes blockchain-based secure communication and a cloud-based data evaluation layer to segregate and rank data on the basis of three broad categories of Transactions (T), namely Smart T, Mod T, and Avoid T. The learning engine utilizes a neural network for the training and classification of the categories that helps the blockchain layer with improvisation in the decision-making process. The contributions of this paper include the application of a secure blockchain layer for user authentication and the generation of a ledger for the communication network; the utilization of the cloud-based data evaluation layer; the enhancement of an SI-based algorithm for training; and the utilization of a neural engine for the precise training and classification of categories. The proposed algorithm outperformed the Fused Real-Time Sequential Deep Extreme Learning Machine (RTS-DELM) system, the data fusion technique, and artificial intelligence Internet of Things technology in providing electronic information engineering and analyzing optimization schemes in terms of the computation complexity, false authentication rate, and qualitative parameters with a lower average computation complexity; in addition, it ensures a secure, efficient smart home communication network to enhance the lifestyle of human beings.


Transcatheter Treatment of Apicoaortic Conduit Dysfunction.
We report a 77-year-old male patient with a history of aortic valve bypass with an apicoaortic conduit 11 years ago for severe aortic stenosis, presenting with acute decompensated congestive heart failure. Severe conduit valve regurgitation and was successfully treated with transcatheter aortic valve replacement (TAVR) of the native aortic valve using a self-expanding bioprosthesis followed by transcatheter closure of the apicoaortic conduit.


Primary desmoplastic small-round-cell tumor of the ovary.
Desmoplastic small-round-cell tumor (DSRCT) is an extremely rare and highly aggressive malignancy. It is of yet unclear origin, but it is assumed to be of a mesothelial origin based on its tendency for widespread metastasis in serosal linings. In this report, we describe a young female who presented with bilateral ovarian masses that mimicked the classic clinical picture of ovarian cancer. The patient had a cytoreductive surgery done in the form of total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic peritonectomy, low para-aortic and bilateral iliac lymphadenectomy. Postoperative course was smooth with no adverse events. The final pathology report revealed desmoplastic small-round-cell tumor. Afterwards, the patient was referred to medical oncologist to receive her adjuvant therapy. DSRCT is still an unknown disease to us given the limited number of cases and poor survival. Given the lack of clear guidelines, treatment is offered based on the best available evidence and the collaborative effort of a multi-disciplinary team.


Prevalence and nature of hyperamylasemia in acute alcoholism.
Determination of serum amylase activity in 100 consecutive patients admitted to an alcohol detoxification unit revealed hyperamylasemia in 39 cases. Further clinical evaluation of 15 of the 39 alcoholic patients with hyperamylasemia was unremarkable except for bilateral enlargement of the parotid glands in two cases. Nine of the 15 patients demonstrated markedly low amylase to creatinine clearance ratio; however, macroamylase complexes were not detected in the sera of any patients. Serum isoamylase separation revealed that the mean salivary isoamylase for the 15 alcoholic patients was significantly (P less than 0.05) elevated as compared to the control values. Individually, the salivary-type isoamylase was clearly elevated in ten patients while pancreatic type isoamylase was elevated in four. These data indicate that elevated serum amylase activity occurs frequently in alcoholic patients. Hyperamylasemia in a large number of alcoholic patients is nonpancreatic in origin and may be related to the injurious effect of ethanol on salivary glands and other tissues.


[Neuroendocrine carcinoma of the prostate].
Small cell of undifferenciated tumors are present in almost all organs, and it impose the need of performing a differential diagnosis between undifferenciated tumors with residual differentiation according to the type of organ, and the carcinoma of small cells of neuroendocrine origin. The concept of neuroendocrine differentiation (NED) in the prostatic adenocarcinoma has reached considerable attention due to its prognostic and therapeutic implies. Here it is presented a new neuroendocrine prostatic carcinoma case taking care of its hystopathologic diagnosis and evolution.


Prospects for gene therapy in hearing loss.
Deafness is the most common form of sensory impairment in humans. Depending on the age of onset, hearing impairment can affect oral language acquisition, cognitive development and psychosocial development. Here, we cover the latest advances in gene therapy for alleviating or preventing hearing loss. This review is not meant to be comprehensive, but to highlight some of the most recent developments in the field. Several recent reviews have described potential therapeutic approaches.


Eight Weeks of Physical Training Decreases 2 Years of DNA Methylation Age of Sedentary Women.
Purpose: The acceleration of epigenetic age is a predictor of mortality and contributes to the increase in chronic diseases. Adherence to a healthy lifestyle is a strategy to reduce epigenetic age. The present study aimed to determine whether eight weeks of combined (aerobic and strength) training (CT) can influence the epigenetic age of women between 50 and 70 years old and the differences in sites and methylated regions. Methods: Eighteen women (AARLow: lower age acceleration residual, n = 10; AARHigh: higher age acceleration residual, n = 8) participated in a combined exercise training program (60 minutes, 3× a week) for eight weeks. DNA was extracted from whole blood using the salting out technique. DNA methylation was performed using the array technique (Illumina's Infinium Methylation BeadChip 850k). We used the DNA Methylation Age Calculator platform to calculate the biological epigenetic age. Two-way ANOVA followed by FISHER LSD posthoc was Applied, adopting p < .05. Results: After eight weeks of CT, there were no changes to the epigenetic age acceleration for the AARLow group (PRE: -2.3 ± 3.2 to POST: -2.3 ± 3.6). However, the AARHigh group significantly decreased the age acceleration (PRE: 3.6 ± 2.6 to POST: 2.2 ± 2.7) (group effect, p = .01; time effect, p = .31; group vs. time effect, p = .005). Conclusion: CT for eight weeks benefits the epigenetic clock of women with the most accelerated age.


Massive Hemorrhage from the Posterior Ethmoidal Artery during Transsphenoidal Surgery: Report of 2 Cases.
Nasal bleeding is a major complication that can occur during and after transsphenoidal surgery (TSS) for intra- and suprasellar tumors. In most cases, the cause of this bleeding can be attributed to a branch of the maxillary artery called the sphenopalatine artery, injury to which can lead to life-threatening situations. Upon exposure of the suprasellar region and planum sphenoidale during surgery, it is also important to avoid damaging the posterior ethmoidal artery (PEA), a branch of the ophthalmic artery. While recent advancement in endoscopic techniques enables the performance of extended TSS, the chances of PEA injury seem to be increasing. In the current report, we present two cases that showed massive PEA bleeding during regular (not extended) TSS. The total blood loss was 2280 ml and 2150 ml, and endoscopic views disturbed by the massive hemorrhages remarkably delayed accurate stanching of the responsive artery. Therefore, anatomical recognition of the PEA is required to avoid fatal hemorrhaging during even regular TSS, especially for the beginners of this surgery.


Bentall procedure for an adult patient with supravalvular aortic stenosis and coronary aneurysms.
We describe the surgical management of a 35-year-old male with multiple coronary aneurysms and a diffuse form of supravalvular aortic stenosis who presented with acute myocardial infarction and left ventricular dysfunction. The patient underwent a Bentall procedure with left internal mammary artery to left anterior descending artery bypass grafting with the use of cardiopulmonary bypass utilizing the right axillary artery for arterial cannulation.


DNA methylation is a common molecular alteration in colorectal cancer cells and culture method has no influence on DNA methylation.
The present study aimed to explore whether culture method had an influence on DNA methylation in colorectal cancer (CRC). In the present study, CRC cells were cultured in two-dimensional (2D), three-dimensional (3D) and mouse orthotopic transplantation (Tis) cultures. Principal component analysis (PCA) was used for global visualization of the three samples. A Venn diagram was applied for intersection and union analysis for different comparisons. The methylation condition of 5'-C-phosphate-G-3' (CpG) location was determined using unsupervised clustering analysis. Scatter plots and histograms of the mean β values between 3D vs. 2D, 3D vs. Tis and Tis vs. 2D were constructed. In order to explore the biological function of the genes, gene ontology and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analyses were utilized. To explore the influence of culture condition on genes, quantitative methylation specific polymerase chain reaction (QMSP) was performed. The three samples connected with each other closely, as demonstrated by PCA. Venn diagram analysis indicated that some differential methylation positions were commonly shared in the three groups of samples and 16 CpG positions appeared hypermethylated in the three samples. The methylation patterns between the 3D and 2D cultures were more similar than those of 3D and Tis, and Tis and 2D. Results of gene ontology demonstrated that differentially expressed genes were involved in molecular function, cellular components and biological function. KEGG analysis indicated that genes were enriched in 13 pathways, of which four pathways were the most evident. These pathways were pathways in cancer, mitogen-activated protein kinase signaling, axon guidance and insulin signaling. Furthermore, QMSP demonstrated that methylation of mutL homolog, phosphatase and tensin homolog, runt-related transcription factor, Ras association family member, cadherin-1, O-6-methylguanine-DNA-methyltransferase and P16 genes had no obvious difference in 2D, 3D and Tis culture conditions. In conclusion, the culture method had no influence on DNA methylation in CRC cells.


Engineering stability in NADPH oxidases: A common strategy for enzyme production.
NADPH oxidases (NOXs) are membrane enzymes whose sole function is the generation of reactive oxygen species. Humans have seven NOX isoenzymes that feature distinct functions in immune response and cell signaling but share the same catalytic core comprising a FAD-binding dehydrogenase domain and a heme-binding transmembrane domain. We previously described a mutation that stabilizes the dehydrogenase domain of a prokaryotic homolog of human NOX5. The thermostable mutant exhibited a large 19 °C increase in the apparent melting temperature (app Tm) and a much tighter binding of the FAD cofactor, which allowed the crystallization and structure determination of the domain holo-form. Here, we analyze the transferability of this mutation onto prokaryotic and eukaryotic full-length NOX enzymes. We found that the mutation exerts a significative stabilizing effect on the full-length NOX5 from both Cylindrospermum stagnale (app Tm increase of 8 °C) and Homo sapiens (app ΔTm of 2 °C). Enhanced thermal stability resulted in more homogeneous preparations of the bacterial NOX5 with less aggregation problems. Moreover, we also found that the mutation increases the overall expression of recombinant human NOX4 and NOX5 in mammalian cells. Such a 2-5-fold increase is mainly due to the lowered cell toxicity, which leads to higher biomasses. Because of the high sequence identity of the catalytic core within this family of enzymes, this strategy can be a general tool to boost the production of all NOXs.


LINC00460 Facilitates Cell Proliferation and Inhibits Ferroptosis in Breast Cancer Through the miR-320a/MAL2 Axis.
Background: Emerging evidence suggests that long noncoding RNAs (lncRNAs) play an important role in the progression of multiple human cancers including breast cancer. In this study, we aimed to research novel functions of long intergenic noncoding RNA 460 (LINC00460) on cell proliferation and ferroptosis in breast cancer. Method: UALCAN, TANRIC, and GSE16446 data were used to analyze the expression of LINC00460 in breast cancer tissues. Furthermore, real-time quantitative PCR, western blot, cell proliferation assay, iron assay, and malondialdehyde (MDA) assay were applied to detect the function and mechanism of particular molecules. Results: The LINC00460 expression was significantly increased in breast cancer tissues compared with normal tissues. Importantly, patients with high LINC00460 expression showed a longer overall survival rate. LINC00460 knockdown markedly suppressed the proliferation of breast cancer cells and promoted ferroptosis. Mechanistic analysis revealed that LINC00460 promoted myelin and lymphocyte protein 2 (MAL2) expression by sponging miR-320a. Moreover, both miR-320a knockdown and MAL2 overexpression could reverse the effects of LINC00460 silencing on cell proliferation and ferroptosis. Conclusions: In summary, our results reveal an alternative mechanism by which breast cancer cells can acquire resistance to ferroptosis via the LINC00460/miR-320a/MAL2 axis.


Synthesis of carbazole-based polymers with 1,3,4-oxadiazole pendant group and their application in organic light-emitting diodes.
Structurally well-defined copolymers with high solubility were prepared via palladium-catalyzed polycondensation of N-(2-ethylhexyl)-3,6-dibromocarbazole with 2-aryl-5-(4-aminophenyl)-1,3,4-oxadiazole (aryl = phenyl, p-methylphenyl, p-methoxyphenyl). Copolymers consisted of alkylcarbazole groups in the main chain and 1,3,4-oxadiazole pendants in the side chain. The influence of their aryl substituents on physical, optical, band gaps and electroluminescent characteristics of the copolymers was investigated. Both UV-Visible absorption and photoluminescence emission peaks of the copolymers were similar to each other. The band gap energy of the polymers was measured in the range of 2.84 to approximately 2.88 eV, and HOMO energy in the range of -5.13 to approximately -5.18 eV. These copolymers were used as hole-transporting layers (HTL) in the light-emitting diodes with Alq3 as an emitting layer. Compared to devices with P-H and P-OCH3 used as HTL, it should be noted that device with P-CH3 used as HTL showed higher luminescence. Maximum luminescence of devices was measured to be 276 cd/m2 at 14 V with P-H, 625 cd/m2 at 15 V with P-CH3, and 471 cd/m2 at 14 V with P-OCH3. This might be due to effect of subtle changes in HOMO energy level of polymers with changing substituent groups. Phosphorescent polymer light emitting diodes were also fabricated with an emitting layer consisting of P-CH3 matrix and a red phosphorescent dopant (lr-PIQCH).


Mass spectrometry and characterization of Aedes aegypti trypsin modulating oostatic factor (TMOF) and its analogs.
Trypsin modulating oostatic factor (TMOF), a decapeptide that directly inhibits the biosynthesis of trypsin- and chymotrypsin-like enzymes in epithelial cells of mosquito midgut and indirectly inhibits vitellogenesis in anautogenous females, has been sequenced by Fourier transform mass spectrometry analysis. The peptide has a primary amino acid sequence of NH2-Tyr-Asp-Pro-Ala-(Pro)6-COOH and probably exhibits left-handed helical conformation as was shown by computer stereoview simulation. The factor is metabolized very rapidly (half-life of 1.6 h) in intact mosquitoes when injected after the blood meal. Inhibition of trypsin biosynthesis was followed in ligated abdomens, which synthesize trypsin but do not metabolise TMOF. At concentrations of 3 x 10(-9) M and 6.8 x 10(-6) M, TMOF inhibited 50 and 90% of trypsin-like enzyme biosynthesis, respectively. Several analogs of varying chain lengths were synthesized and evaluated for biological activity using dose-response curves. Switching the positions of Tyr and Asp at the N-terminus reduced the activity of the hormone, indicating that the N-terminus is important for biological activity. Removal of two to five prolines at the C-terminus also reduced activity, indicating that both the N- and C-termini are important. Synthesis of trypsin-like isozyme was followed in several insect species using [1,3-3H]diisopropyl-fluorophosphate (DFP) in the presence of tosylamide-2-phenylethyl chloromethyl ketone. Marked reduction of [1,3-3H]diisopropyl-phosphoryl-trypsin-like derivatives was noted after TMOF treatment, as assessed by polyacrylamide gel electrophoresis. These results indicate that the biosynthesis of trypsin-like enzyme in mosquitoes and other insects may be regulated by sequence-related TMOFs.