Characterization and functional role of the QH site of bo-type ubiquinol oxidase from Escherichia coli.
Cytochrome bo is a four-subunit terminal ubiquinol oxidase in the aerobic respiratory chain of Escherichia coli that vectorially translocates protons not only via directed protolytic reactions but also via proton pumping. Previously, we postulated that a bound quinone in the high-affinity quinone binding site (QH) mediates electron transfer from the low-affinity quinol oxidation site (QL) in subunit II to low-spin heme b in subunit I as an electron gate and a transient electron reservoir [Sato-Watanabe, M., Mogi, T., Ogura, T., Kitagawa, T., Miyoshi, H., Iwamura, H., and Anraku, Y. (1994b) J. Biol. Chem. 269, 28908-28912]. In the present study, we carried out screening of ubiquinone analogues using a bound ubiquinone-free enzyme (DeltaUbiA1) that has been isolated from a ubiquinone biosynthesis mutant, and identified PC24 (2-chloro-4, 6-dinitrophenol), PC32 (2,6-dibromo-4-cyanophenol), and PC52 (2-isopropyl-5-methyl-4,6-dinitrophenol) as potent QH site inhibitors. PC15 (2,6-dichloro-4-nitrophenol) and PC16 (2, 6-dichloro-4-dicyanovinylphenol), potent QL site inhibitors, did not exhibit such a selective inhibition of the QH site. Binding studies using the air-oxidized DeltaUbiA enzyme showed that PC32 and PC52 have 4- to 7-fold higher affinity than ubiquinone-1. Reconstitution of the QH site with PC32 and PC52 resulted in a decrease of the apparent Vmax value to 1/7 and 1/3, respectively, of the control activity. These findings suggest that structural features of the QL and QH sites are different, and provide further support for the involvement of the QH site in intramolecular electron transfer and facile oxidation of quinols at the QL site.


Uptake of heterologous DNA by Haemophilus influenzae.
With the use of highly competent Haemophilus influenzae cells, it was possible to demonstrate the uptake of heterologous DNAs. However, these DNAs, as expected, were only 1% or less as effective when competing for uptake with Haemophilus DNA. Escherichia coli DNA was removed from solution by competent cells to the extent expected if all the E. coli DNA particles contained at least one uptake recognition signal. The data were consistent with a model in which there was one uptake signal per 20 X 10(6) to 30 X 10(6) daltons of E. coli DNA. Since H. influenzae DNA has many more recognition signals, approximately one per 2 X 10(6) daltons (Danner et al., Gene 77:311-318, 1980; K. Vogt and S. H. Goodgal, submitted for publication), it has been suggested that the slower rate of E. coli DNA binding and the so-called specificity of Haemophilus DNA binding are due to the number of recognition signals per molecule of DNA as well as the nature of the DNA receptor (Vogt and Goodgal, submitted for publication). The specificity of native H. influenzae DNA binding does not apply to the uptake of denatured DNA in the transforming system (low pH) for denatured DNA.


Currarino syndrome: repair of the dysraphic anomalies and resection of the presacral mass in a combined neurosurgical and general surgical approach.
OBJECTIVEIt is well established that Currarino syndrome (CS) may be associated with spinal dysraphism. Here, the authors report on 10 CS patients with dysraphic anomalies who had undergone a combined neurosurgical and general surgical approach to repair the dysraphic anomalies and resect the presacral mass in a single operation. They discuss the spectrum of spinal dysraphism that may coexist in CS in the context of its developmental etiology.METHODSChildren with a confirmed CS diagnosis who had undergone the combined operative approach were identified from a departmental database. Presenting features were recorded and preoperative imaging was analyzed to record features of the presacral mass and the dysraphic anomalies. The histopathological nature of the resected presacral mass and the outcomes postoperatively and at the last follow-up were reviewed.RESULTSBetween 2008 and 2015, 10 patients presented with CS, 9 with constipation. Median age at the time of surgery was 1.3 years. Six of the 10 patients had anorectal malformation consisting of anal stenosis, rectal stenosis, or imperforate anus. Spinal anomalies included anterior meningocele (5 cases), low-lying conus (8), terminal syrinx (4), fatty filum (5), caudal lipoma (3), and intraspinal cyst (1). In all cases, the lumbosacral spinal canal was accessed via a midline approach with laminoplasty, allowing spinal cord untethering and repair of the dysraphic anomalies. Following dural closure, the incision was extended inferiorly to incorporate a posterior sagittal approach to resect the presacral mass. The histopathological nature of the mass was mature teratoma (8 cases), complex hamartomatous malformation (1), or neurenteric cyst (1). There were no new instances of neurological deterioration, with most instances of persisting morbidity related to constipation (6 cases) or neurogenic bladder dysfunction (8). There were no infective complications, no instances of cerebrospinal fluid fistula, no recurrences of the presacral mass, and no cases of retethering of the spinal cord.CONCLUSIONSAlthough not part of the original triad, spinal dysraphic anomalies are common in CS and in keeping with a disorder of secondary neurulation. Lumbosacral MRI is an essential investigation when CS is suspected. Children are at risk of sphincter impairment due to the anorectal malformation; however, both spinal cord tethering and compression from the presacral mass may further compromise long-term continence. A combined operative approach to repair the dysraphic anomalies and resect the presacral mass is described with good postoperative and long-term outcomes.


Morphine, opioid peptides, and pancreatic islet function.
Since the isolation of enkephalins 7 yr ago, there has been an explosive increase in knowledge and an enormous interest in the action of both exogenous and endogenous opiates. This review deals with the interaction of opiates with the endocrine pancreas. The results of animal studies performed in vitro do not allow any conclusion to be drawn, because the effects of opioid peptides on pancreatic hormone release seem dependent on many variables, including the agent investigated, dose administered, concentration of glucose in the medium, and experimental procedure used. The results of in vivo animal studies suggest that central administration of opiates and opioid peptides acts indirectly via the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion, while peripheral administration tends to stimulate insulin and glucagon secretion. This last statement seems also to be true for studies performed in human beings. The narcotic addict offers a model to evaluate the hormonal and metabolic effects of a chronically administered agent that binds and activates endogenous receptors. In these subjects, it is possible to find increased concentrations of glycosylated hemoglobin A1 and a marked reduction of the acute insulin response to intravenous glucose, but not to arginine, which suggests a state of defective glucose recognition by pancreatic beta-cells during narcotic addiction. Thus, the heroin addict, like patients with non-insulin-dependent diabetes, does not respond appropriately to glucose signals.(ABSTRACT TRUNCATED AT 250 WORDS)


Ultraviolet-visible imaging acousto-optic tunable filters in KDP.
There is a need to develop large-aperture acousto-optic tunable filters (AOTFs) in the UV region for applications in astronomy, environmental sciences, biology, etc. We have developed a high-quality noncollinear AOTF cell that uses a single crystal of KDP that has nearly a four times larger acousto-optic figure of merit, M2, than quartz. The linear and angular apertures of this cell are 1.5 cm x 1.5 cm and 1.2 degrees, respectively. The spectral range is 220-480 nm, with 160-cm(-1) spectral resolution and high transmission in the UV. We present an analysis of the design and describe the characterization results.


Occupational health in India.
The population of India has crossed the billion mark; only one other country (China) shares this distinction. A declining female population and low literacy are negatives in an otherwise vibrant country. The empowerment of females and their role in society has become a point of debate, and radical economic changes are likely, to allow India to join the global economy. Problems in occupational health and safety (OHS) include: OHS legislation that covers only a minority of the working population; child labour; a physician-driven OHS model; little attention to industrial hygiene; poor surveillance of occupational diseases (making it impossible to gauge the burden of illness due to occupational exposures); and a fragile OHS academic base. A silver lining comprises the inclusion of OHS in national health policy and the decision by the Indian Medical Association to educate its members in occupational health. India urgently requires modern OHS legislation with adequate enforcement machinery, and establishment of centres of excellence in occupational medicine, to catch up with the rest of the world.


Structural Insights Into the Effects of Interactions With Iron and Copper Ions on Ferritin From the Blood Clam Tegillarca granosa.
In addition to its role as an iron storage protein, ferritin can function as a major detoxification component in the innate immune defense, and Cu2+ ions can also play crucial antibacterial roles in the blood clam, Tegillarca granosa. However, the mechanism of interaction between iron and copper in recombinant Tegillarca granosa ferritin (TgFer) remains to be investigated. In this study, we investigated the crystal structure of TgFer and examined the effects of Fe2+ and Cu2+ ions on the TgFer structure and catalytic activity. The crystal structure revealed that TgFer presented a typically 4-3-2 symmetry in a cage-like, spherical shell composed of 24 identical subunits, featuring highly conserved organization in both the ferroxidase center and the 3-fold channel. Structural and biochemical analyses indicated that the 4-fold channel of TgFer could be serviced as potential binding sites of metal ions. Cu2+ ions appear to bind preferentially with the 3-fold channel as well as ferroxidase site over Fe2+ ions, possibly inhibiting the ferroxidase activity of TgFer. Our results present a structural and functional characterization of TgFer, providing mechanistic insight into the interactions between TgFer and both Fe2+ and Cu2+ ions.


Effects of recombinant human activated protein C in human models of endotoxin administration.
Alterations in the generation of activated protein C (APC) as well as in the interactions of APC with the endothelial protein C receptor are present in severe sepsis and acute lung injury. Administration of recombinant human activated protein C (rhAPC) improves the survival of critically ill patients with sepsis, but the mechanisms by which rhAPC produces benefit are not well defined. Human models of systemic and pulmonary endotoxin exposure may provide important insights into the mechanisms of action of rhAPC in critical illness. In volunteers given systemic endotoxin, rhAPC had minimal effects on physiologic parameters, including blood pressure, markers of inflammation, and measures of sepsis-induced coagulopathy. In contrast, in the setting of pulmonary endotoxin exposure, rhAPC decreased neutrophil migration into the airspaces and also diminished neutrophil chemotaxis. Administration of rhAPC did not affect other parameters of neutrophil function, including kinase activation, production of proinflammatory cytokines, or apoptosis. Such results indicate that the effects of rhAPC in inhibiting the infiltration of neutrophils into the lungs and other inflammatory sites may contribute to its beneficial effects in sepsis.


EELS investigations of different niobium oxide phases.
Electron energy loss spectra in conjunction with near-edge fine structures of purely stoichiometric niobium monoxide (NbO) and niobium pentoxide (Nb2O5) reference materials were recorded. The structures of the niobium oxide reference materials were checked by selected area electron diffraction to ensure a proper assignment of the fine structures. NbO and Nb2O5 show clearly different energy loss near-edge fine structures of the Nb-M4,5 and -M2,3 edges and of the O-K edge, reflecting the specific local environments of the ionized atoms. To distinguish the two oxides in a quantitative manner, the intensities under the Nb-M4,5 as well as Nb-M2,3 edges and the O-K edge were measured and their ratios calculated. k-factors were also derived from these measurements.


Curing of symbiotic plasmid of Mesorhizobium huakuii subsp. rengei isolated from Astragalus sinicus.
Astragalus sinicus (Chinese Milk vetch), a green manure leguminous plant, harbors Mesorhizobium huakuii subsp. rengei strain B3 in the root nodules. The visualization of symbiotic plasmid of strain B3 showed the presence of one sym plasmid of about 425 kbp. Curing of sym plasmid by temperature and acrydine orange was studied. Growing rhizobial cells at high temperature (37 degrees C) or treating the cells with acrydine orange at 50 mg/l eliminated sym plasmid of M. huakuii strain B3, which was confirmed by sym plasmid visualization and plant infection test of cured strains.


Relative specificity as an important consideration in the big data era.
Technological breakthroughs such as high-throughput methods, genomics, single-cell studies, and machine learning have fundamentally transformed research and ushered in the big data era of biology. Nevertheless, current data collections, analyses, and modeling frequently overlook relative specificity, a crucial property of molecular interactions in biochemical systems. Relative specificity describes how, for example, an enzyme reacts with its many substrates at different rates, and how this discriminatory action alone is sufficient to modulate the substrates and downstream events. As a corollary, it is not only important to comprehensively identify an enzyme's substrates, but also critical to quantitatively determine how the enzyme interacts with the substrates and to evaluate how it shapes subsequent biological outcomes. Genomics and high-throughput techniques have greatly facilitated the studies of relative specificity in the 21st century, and its functional significance has been demonstrated in complex biochemical systems including transcription, translation, protein kinases, RNA-binding proteins, and animal microRNAs (miRNAs), although it remains ignored in most work. Here we analyze recent findings in big data and relative specificity studies and explain how the incorporation of relative specificity concept might enhance our mechanistic understanding of gene functions, biological phenomena, and human diseases.


Effects of chronic exposure to triclosan on reproductive and thyroid endpoints in the adult Wistar female rat.
Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. Previously, subchronic TCS treatment to female rats was found to advance puberty and potentiate the effect of ethinyl estradiol (EE) on uterine growth when EE and TCS were co-administered prior to weaning. In the pubertal study, a decrease in serum thyroxine (T4) concentrations with no significant change in serum thyroid-stimulating hormone (TSH) was also observed. The purpose of the present study was to further characterize the influence of TCS on the reproductive and thyroid axes of the female rat using a chronic exposure regimen. Female Wistar rats were exposed by oral gavage to vehicle control, EE (1 μg/kg), or TCS (2.35, 4.69, 9.375 or 37.5 mg/kg) for 8 months and estrous cyclicity monitored. Although a divergent pattern of reproductive senescence appeared to emerge from 5 to 11 months of age between controls and EE-treated females, no significant difference in cyclicity was noted between TCS-treated and control females. A higher % control females displayed persistent diestrus (PD) by the end of the study, whereas animals administered with positive control (EE) were predominately persistent estrus (PE). Thyroxine concentration was significantly decreased in TCS-administered 9.375 and 37.5 mg/kg groups, with no marked effects on TSH levels, thyroid tissue weight, or histology. Results demonstrate that a long-term exposure to TCS did not significantly alter estrous cyclicity or timing of reproductive senescence in females but suppressed T4 levels at a lower dose than previously observed.


Treatment of lower extremity long bone nonunion with expandable intramedullary nailing and autologous bone grafting.
Nonunion of long bones in lower limbs is a common complication of orthopedic trauma that can be extremely debilitating. This retrospective study describes our experience using expandable intramedullary nails and autologous bone grafting in treating lower limb long bone nonunion with bone defects. Nineteen patients (mean age 38.9 years, range 18-61) with lower limb long bone nonunion and defects caused by femoral or tibial fracture types were as follows: A2 (3 femoral, 1 tibial), A3 (1 femoral, 2 tibial), B2 (3 femoral, 4 tibial), and B3 (1 femoral, 4 tibial). Expandable intramedullary nailing and autologous bone (iliac and/or fibular) grafting were used for the treatment. Postoperative bone healing as determined by analysis of standard anteroposterior and lateral X-ray films every 4 weeks. Complications were noted. The average number of previous surgeries was 1.9 (range 1-4). The mean duration from original injury to treatment was 17.6 months (range 9-40 months). Femoral shaft nonunion healed on average of 26.5 weeks (range 16-60 weeks) after surgery, while tibial shaft nonunion healed on average of 23.6 weeks (range 12-40 weeks) after surgery. Class I healing occurred in all but two patients who experienced chronic postoperative osteomyelitis and delayed wound healing, respectively. Two patients complained of postoperative donor site pain. The use of expandable intramedullary nails and autologous bone grafts was an effective method for repair of nonunion of lower limb fractures combining with bone defects with minimal complications.


[The application of microwave energy in preparing medicinal plant drugs. 1].
Using a specially constructed microwave device, containing a steady-state-broadcasting magnetron that is infinitely adjustable within a range of 100 to 1200 W, the applicability of microwave energy for drying medicinal plants was investigated. When optimising the drying parameters (e.g. microwave power, time of irradiation, mass of plant material, thickness of layer) most of the obtained leave, flower, herb and root drugs showed a significant better appearance (colour) than the air dried drugs.


[A rare cause of acute abdomen in childhood: primary omental torsion].
We examined the fact that 12 years old obese girl who applied to our clinic with acute abdomen symptoms and we determined primer omental torsion (POT) at laparotomy in this case. This disease is rare in childhood and imitates the signs of acute appendicitis. Obesity and anatomic variations ofthe omentum are predisposingfactorsfor POI ln this study we wanted to share our experiences in diagnosis and treatment ofPOI


Induction and augmentation of labor: basis and methods for current practice.
Medical control of labor is often necessary in modern obstetrics. The status of the cervix may dictate the method of induction and influence its success. Four milligrams of prostaglandin (PGE2) gel applied intravaginally has been shown to be a safe, efficacious, and extremely well-tolerated agent to promote cervical ripening. The patient should be monitored before and at least 4 hours after PGE2 gel application, since the incidence of uterine activity is high after this treatment and many of these pregnancies are at risk. The rare case of hyperstimulation may be treated with a tocolytic agent. The start of oxytocin may be individually tailored, but we do not recommend its use in less than 4 hours after gel insertion. Oxytocin should be used with great caution if the patient continues to have uterine activity from the PGE2 gel. Because, in part, the use of the PGE2 gel for cervical ripening is not approved by the Food and Drug Administration in the United States, it is prudent to discuss its use with the patient, document carefully, and use this medication only if there is clear indication. Protocols for the use of oxytocin currently used in many hospitals seem to be based on outdated pharmacologic data. Relatively new information on the pharmacology and clinical effects of oxytocin are reviewed to provide a rational approach to its clinical use in accordance with recently published guidelines from the American College of Obstetricians and Gynecologists (ACOG). The current data overwhelmingly indicate that oxytocin should be started at a low dose (0.5-1 mU/min) with a slow, arithmetical increase every 30 to 60 minutes. Previous reports of a high incidence of fetal distress, uterine dysfunction, and hyperstimulation in induced labor may be related to use of oxytocin at doses higher than currently appear appropriate. The risks of induction and augmentation can be reduced by careful patient selection and preparation. Oxytocin is safe and effective with expert medical management which provides careful monitoring, controlled infusion, persistence, and the knowledge of when to stop.


Bacterial pleomorphism and competition in a relative humidity gradient.
The response of different bacterial species to reduced water availability was studied using a simple relative humidity gradient technique. Interestingly, distinct differences in morphology and growth patterns were observed between populations of the same species growing at different relative humidity. Gram-positive cocci increased in cell size as they approached humidity growth limits and staphylococcal species started growing in tetrad/cubical formations instead of their normal grape-like structures. Gram-negative rods displayed wave-like patterns, forming larger waves as they became increasingly filamentous at low humidity. In contrast, cells of the Gram-positive bacterium Bacillus subtilis became shorter, curved, and eventually almost coccoid. Moreover, B. subtilis started to sporulate at low humidity. The altered morphology and/or growth patterns of bacteria growing at low humidity might be more ecologically relevant than their textbook appearance at high humidity since their natural habitats are often dry. Transmission electron microscopic analyses revealed that staphylococci grown at low humidity have significantly thickened cell walls, which may explain why these cells displayed increased resistance to vancomycin. We conclude that our relative humidity gradient technique is widely applicable for investigating effects of relative humidity on microbial survival, growth and competitive success at solid-air interfaces, making it a versatile tool in microbial ecology.


Progression through meiosis I and meiosis II in Arabidopsis anthers is regulated by an A-type cyclin predominately expressed in prophase I.
Meiosis is often described as a special case of cell division since it differs from mitosis in having two nuclear divisions without an intervening S-phase. It will be of great interest to uncover what molecular mechanisms underlie these special features of meiosis. We previously reported that the tardy asynchronous meiosis (tam) mutant of Arabidopsis (Arabidopsis thaliana) is slower in cell cycle progression in male meiosis. Here we report that TAM encodes the A-type cyclin, CYCA1;2. The point mutation in tam replaced a conserved threonine with an isoleucine in the linker region between the alpha4 and alpha5 helices of the first cyclin fold. By studying the dynamics of a CYCA1;2-green fluorescent protein fusion protein under the control of the CYCA1;2 promoter, we found that the fusion protein was most abundant at pachytene, but was undetectable from late prophase I until telophase II. Nonetheless, cell cycle progression in tam was delayed in both pachytene and meiosis II. We conclude either that the CYCA1;2 produced in prophase I indirectly regulates meiosis II progression, or that a very low level of CYCA1;2 directly regulates meiosis II progression. Either of these scenarios is a deviation from the typical mode of action of mitotic cyclins in mitosis and meiosis I, in which each nuclear division is coupled with a peak of expression of mitotic cyclins.


Selectivity and control of Euphorbia heterophylla in sugarcane by herbicide in post-emergence.
To obtain good control of wild poinsettia (Euphorbia heterophylla) in post-emergence in sugarcane crop, we evaluate the herbicides association on post-emergence of E. heterophylla and the ratoon cane selectivity. The experimental scheme was in randomized blocks with 6 treatments and 4 replications. The treatments were: control; ametryn + mesotrione + sulfentrazone (1,500 + 144 + 800 g i.a ha-1); ametryn + mesotrione + diclosulan (1,500 + 144 + 200 g i.a ha-1); ametryn + mesotrione (2,500 + 144 g i.a ha-1: Highest dose); ametryn + mesotrione (2,000 + 144 g i.a ha-1: Lowest dose) and ametryn + mesotrione + diuron (1,000 + 144 + 1,250 g i.a ha-1). The percentage of control, dry mass, height and percentage of germination of E. heterophylla and injury level, yield and technological quality of sugarcane were evaluated. The best control of E. heterophylla was: ametryn + mesotrione +sulfentrazone; ametryn + mesotrione + diclosulan and ametryn + mesotrione (Lowest dose). As for the ratoon cane selectivity the best yield was achieved with the association ametryn + mesotrione +diclosulan. An appropriate association of herbicide molecules provides successful control of E. heterophylla, especially the association of sulfentrazone or diclosulan together with ametryn and mesotrione.


Liquid proteins--a new frontier for biomolecule-based nanoscience.
Solid, liquid, or gas? The physical states adopted by nano-objects such as proteins are critically dependent on the size and range of the intermolecular attractive forces, and as a consequence, pure liquids comprising solventless melts of structurally intact, discrete functional nanoconstructs are conspicuously absent. Here we describe how globular proteins can be surface-engineered such that anhydrous powders of these nanoscale objects melt at close to room temperature to produce solvent-free liquids comprising exceedingly high concentrations of structurally and functionally intact biomolecules. These liquids offer unprecedented opportunities in bionanomaterials research, represent a new phase for protein chemistry, and challenge the existing paradigm on the role of water molecules in protein folding and function.


Evaluation of sorghum flour functionality and quality characteristics of gluten-free bread and cake as influenced by ozone treatment.
Commercially milled food-grade sorghum flour was subjected to ozone at the rate of 0.06 L/min for 15, 30, and 45 min. The pH of ozone-treated flour decreased as exposure time increased. The L* (lightness) values of sorghum flour significantly increased (p < 0.05), while the b* (yellowness) values significantly decreased as ozone exposure time increased. Peak viscosity significantly increased as time of ozonation increased from 0 to 45 min. Results showed that gluten-free cake volume significantly increased as ozonation time increased. Additionally, longer ozonation exposure times increased cells per slice area, lightness, and slice brightness values in gluten-free cakes while reducing crumb firmness. Despite improving lightness and slice brightness values, ozonation did not significantly increase the specific volume of gluten-free batter-based bread. While ozonation improved the volume and texture in cakes, it did not have the same positive effects on gluten-free bread. Bread made from ozonated sorghum flour had an open ragged structure with equivalent volume to the control flour. In both applications, the increased brightness and lightness values due to ozone exposure is recommended to increase the acceptability of sorghum products.


Screening of specific nucleic acid aptamers binding tumor markers in the serum of the lung cancer patients and identification of their activities.
Lung cancer is by far the leading cause of cancer death in the world. Despite the improvements in diagnostic methods, the status of early detection was not achieved. So, a new diagnostic method is needed. The aim of this study is to obtain the highly specific nucleic acid aptamers with strong affinity to tumor markers in the serum of the lung cancer patients for targeting the serum. Aptamers specifically binding to tumor markers in the serum of the lung cancer patients were screened from the random single-stranded DNA library with agarose beads as supports and the serum as a target by target-substituting subtractive SELEX technique and real-time quantitative polymerase chain reaction technique. Subsequently, the secondary single-stranded DNA library obtained by 10 rounds of screening was amplified to double-stranded DNA, followed by high-throughput genome sequence analysis to screen aptamers with specific affinity to tumor markers in the serum of the lung cancer patients. Finally, six aptamers obtained by 10 rounds of screening were identified with high specific affinity to tumor markers in the serum of the lung cancer patients. Compared with other five aptamers, the aptamer 43 was identified both with the highest specificity to bind target molecule and without any obvious affinity to non-specific proteins. The screened aptamers have relatively high specificity to combine tumor markers in the serum of the lung cancer patients, which provides breakthrough points for early diagnosis and treatment of lung cancer.


Artificial Intelligence in the Advanced Diagnosis of Bladder Cancer-Comprehensive Literature Review and Future Advancement.
Artificial intelligence is highly regarded as the most promising future technology that will have a great impact on healthcare across all specialties. Its subsets, machine learning, deep learning, and artificial neural networks, are able to automatically learn from massive amounts of data and can improve the prediction algorithms to enhance their performance. This area is still under development, but the latest evidence shows great potential in the diagnosis, prognosis, and treatment of urological diseases, including bladder cancer, which are currently using old prediction tools and historical nomograms. This review focuses on highly significant and comprehensive literature evidence of artificial intelligence in the management of bladder cancer and investigates the near introduction in clinical practice.


Evaluation of the process performance of a down-flow hanging sponge reactor for direct treatment of domestic wastewater in Bangkok, Thailand.
This study assesses the performance of an aerobic trickling filter, down-flow hanging sponge (DHS) reactor, as a decentralized domestic wastewater treatment technology. Also, the characteristic eukaryotic community structure in DHS reactor was investigated. Long-term operation of a DHS reactor for direct treatment of domestic wastewater (COD = 150-170 mg/L and BOD = 60-90 mg/L) was performed under the average ambient temperature ranged from 28°C to 31°C in Bangkok, Thailand. Throughout the evaluation period of 550 days, the DHS reactor at a hydraulic retention time of 3 h showed better performance than the existing oxidation ditch process in the removal of organic carbon (COD removal rate = 80-83% and BOD removal rate = 91%), nitrogen compounds (total nitrogen removal rate = 45-51% and NH4+-N removal rate = 95-98%), and low excess sludge production (0.04 gTS/gCOD removed). The clone library based on the 18S ribosomal ribonucleic acid gene sequence revealed that phylogenetic diversity of 18S rRNA gene in the DHS reactor was higher than that of the present oxidation ditch process. Furthermore, the DHS reactor also demonstrated sufficient COD and NH4+-N removal efficiency under flow rate fluctuation conditions that simulates a small-scale treatment facility. The results show that a DHS reactor could be applied as a decentralized domestic wastewater treatment technology in tropical regions such as Bangkok, Thailand.


Active specific immunotherapy potential for the treatment of large bowel cancer.
Active specific immunotherapy, harnessing the strength and specificity of the host immune response to destroy neoplastic cells, may offer an ideal surgical adjuvant treatment modality for human colon cancer. Unfortunately, achievement of this goal has been obscured by 1) the effect of excess residual disease to interfere with the host's destructive response, 2) the weak nature of tumor resistance, 3) the potential adverse effect of concomitant treatments such as chemotherapy, and 4) the present limitation of poorly defined immunogens to induce, as well as insensitive assay systems to detect, host sensitizaion. Recent immunologic and chemical research revealing distinctive surface membrane structures on colon cancer cells suggests that a controlled trial of irradiated, autochtonous cell vaccines (without mycobacterial adjuvants) may provide a new therapeutic tool for Dukes B2 and C stages of human colon cancer.


Effect of patient decision aids on choice between sugammadex and neostigmine in surgeries under general anesthesia: a multicenter randomized controlled trial.
Shared decision making using patient decision aids (PtDAs) was established over a decade ago, but few studies have evaluated its efficacy in Asian countries. We therefore evaluated the application of PtDAs in a decision conflict between two muscle relaxant reversal agents, neostigmine and sugammadex, and sequentially analyzed the regional differences and operating room turnover rates. This multicenter, outcome-assessor-blind, randomized controlled trial included 3,132 surgical patients from two medical centers admitted between March 2020 and August 2020. The patients were randomly divided into the classical and PtDA groups for pre-anesthesia consultations. Their clinicodemographic characteristics were analyzed to identify variables influencing the choice of reversal agent. On the day of the pre-anesthesia consultation, the patients completed the four SURE scale (sure of myself, understand information, risk-benefit ratio, encouragement) screening items. The operating turnover rates were also evaluated using anesthesia records. Compared with the classical group, the PtDA group felt more confident about receiving sufficient medical information (P < 0.001), felt better informed about the advantages and disadvantages of the medications (P < 0.001), exhibited a superior understanding of the benefits and risks of their options (P < 0.001), and felt surer about their choice (P < 0.001). Moreover, the PtDA group had a significantly greater tendency to choose sugammadex over neostigmine (P < 0.001). PtDA interventions in pre-anesthesia consultations provided surgical patients with clear knowledge and better support. PtDAs should be made available in other medical fields to enhance shared clinical decision-making.


Evaluation of an expanded two-ELISA approach for confirmation of reactive serum samples in an HIV-screening programme for pregnant women.
Serum specimens were collected from 31,232 pregnant women in Amsterdam between 1988 and 1995 in a screening programme for human deficiency virus (HIV) infection. The sera of 56 (0.179%) women tested were confirmed as positive for HIV. A total of 67 sera reacted positive or borderline by the screening enzyme-linked immunosorbent assay (ELISA) and indeterminate or negative by HIV-1 Western blot; 42 of these specimens were available for evaluation of the strategy for diagnosis of HIV infection. A two-ELISA approach with the second ELISA based on a principle different from that of the screening ELISA, expanded with the use of a membrane immunoassay based on two synthetic peptides specific for HIV-1 gp41 and HIV-2 gp36 envelope proteins, was compared with the Western blot analysis. Indeterminate results were resolved with a nucleic acid sequence-based amplification assay (NASBA) for HIV-1 RNA and a strip immunoassay (SIA) for the simultaneous detection of antibodies to HIV-1 or HIV-2 and HIV-1 p24 antigen. Eleven samples were weakly or borderline positive by the screening test and gave indeterminate results by Western blot. The expanded two-ELISA approach designated these sera as HIV-negative, and confirmed negative by NASBA and the SIA. Twenty-one samples showed borderline or positive results on the screening test and negative results by Western blot. Again, these sera were characterised as HIV-negative by the expanded two-ELISA procedure, and this characterisation was confirmed by both NASBA and the SIA. Five HIV-2-positive serum samples were recognised by the expanded two-ELISA approach and the SIA; these sera were negative by NASBA. Finally, another five serum samples were weakly or borderline positive by both ELISAs and positive by the membrane immunoassay; of these five, two sera generated positive patterns and the other three indeterminate patterns on Western blots, and four were positive by the NASBA assay. Follow-up serum specimens from these five women were negative and the reactivity of the initial specimens was thus likely to have been the result of cross-contamination. Our results demonstrate the effectiveness of a simple confirmation approach of two HIV ELISAs expanded with a membrane spot assay to discriminate between infection with HIV-1 or HIV-2. The data also indicate the importance of retesting individuals with indeterminate or positive confirmational results to exclude the possibility of contamination as the cause of reactivity of the original specimen.


Intracellular Voyeurism: Examining the Modulation of Host Cell Activities bySalmonella enterica Serovar Typhimurium.
Salmonella spp. can infect host cells by gaining entry through phagocytosis or by inducing host cell membrane ruffling that facilitates bacterial uptake. With its wide host range, Salmonella enterica serovar Typhimurium has proven to be an important model organism for studying intracellular bacterial pathogenesis. Upon entry into host cells, serovar Typhimurium typically resides within a membrane-bound compartment termed the Salmonella-containing vacuole (SCV). From the SCV, serovar Typhimurium can inject several effector proteins that subvert many normal host cell systems, including endocytic trafficking, cytoskeletal rearrangements, lipid signaling and distribution, and innate and adaptive host defenses. The study of these intracellular events has been made possible through the use of various imaging techniques, ranging from classic methods of transmission electron microscopy to advanced livecell fluorescence confocal microscopy. In addition, DNA microarrays have now been used to provide a "snapshot" of global gene expression in serovar Typhimurium residing within the infected host cell. This review describes key aspects of Salmonella-induced subversion of host cell activities, providing examples of imaging that have been used to elucidate these events. Serovar Typhimurium engages specific host cell machinery from initial contact with the host cell to replication within the SCV. This continuous interaction with the host cell has likely contributed to the extensive arsenal that serovar Typhimurium now possesses, including two type III secretion systems, a range of ammunition in the form of TTSS effectors, and a complex genetic regulatory network that coordinates the expression of hundreds of virulence factors.


pS2 Gene expression in HepG2 cells: complex regulation through crosstalk between the estrogen receptor alpha, an estrogen-responsive element, and the activator protein 1 response element.
The pS2 promoter is complex with binding sites for a number of protein factors that may participate in modulating its activity. The pS2 gene was transcriptionally activated by estrogens in HepG2 cells transformed (HepER3) to express the estrogen receptor alpha (ERalpha). The phorbol ester phorbol 12-myristate 13-acetate (PMA) stimulated pS2 expression in both HepER3 and the parental, non-ER-expressing HepG2 cells, although its activity was substantially less in HepG2 cells. The use of selective protein kinase inhibitors suggested that the MAPK pathway contributes substantially to estrogen stimulation of the pS2 promoter. The activator protein 1 (AP1) site at -332 to -338 in the pS2 promoter had a dominant role in the response to both estrogens and PMA, although the estrogen response element at -393 to -405 was essential to mediate the response to estrogen. The potentiation of pS2 promoter activity by the AP1 motif in response to estrogen was dependent on the ligand binding domain of ERalpha. Furthermore, the presence of an intact AP1 element in the pS2 promoter sustained suppression of pS2 promoter activity by an LXXLL peptide. In summary, the data suggest that the effect of estrogen is mediated through a cross-talk between the estrogen-responsive element and the AP1 response element and that ERalpha plays a crucial role in mediating the effect of both estrogen and PMA.


Omental Infarction In A Child.
Omental infarction is a rare cause of acute abdomen in children. Typical findings on imaging establish the diagnosis. We present case of a 7 years old boy who presented with acute right iliac fossa pain with diagnosis of omental infarction on imaging and findings confirmed on laparotomy. Sound knowledge regarding this infrequent cause of acute abdomen in children is necessary for timely diagnosis.


Preparation of novel N-doped biochar and its high adsorption capacity for atrazine based on π-π electron donor-acceptor interaction.
Novel nitrogen (N)-doped cellulose biochar (NC1000-10) with large adsorption capacity (103.59 mg g-1) for atrazine (ATZ) was synthesized through the one-pot method. It has the best adsorption efficiency than N-doped biochars prepared from hemicellulose and lignin. The adsorption behaviors of ATZ by N-doped biochars with different N doping ratios (NC1000-5, NC1000-10, NC1000-20 and NC1000-30) were significantly different, which was attributed to the difference of sp2 conjugate C (ID/IG = 0.99-1.18) and doped heteroatom N (pyridinic N, pyrrolic N and graphitic N). Adsorption performance of ATZ on NC1000-10 conformed to the pseudo-second-order kinetic and Langmuir adsorption isotherm model. Thermodynamic calculations showed that adsorption performance was favorable. Besides, wide pH adaptability (pH = 2-10), good resistance to ionic strength and excellent recycling efficiency make it have extensive practical application potential. Further material characterizations and the density functional theory (DFT) calculations indicated that good adsorption performance of NC1000-10 for ATZ mainly depended on chemisorption, and π-π electron donor-acceptor (EDA) interaction contributed the most due to high graphitization degree. Specifically, pyridinic N and graphitic N further promoted adsorption performance by hydrophobic effect and π-π EDA interaction between ATZ and NC1000-10, respectively. Pyrrolic N and other surface functional groups (-COOH, -OH) facilitated the hydrogen bond effect.


Temporal coherence after multiple forward scattering through random three-dimensional inhomogeneities in an ocean waveguide.
An analytical expression is derived for the temporal coherence of an acoustic field after multiple forward scattering through random three-dimensional (3D) inhomogeneities in an ocean waveguide. This expression makes it possible to predict the coherence time scale of field fluctuations in ocean-acoustic measurements from knowledge of the oceanography. It is used to explain the time scale of acoustic field fluctuations observed at megameter ranges in various deep ocean-acoustic transmission experiments. It is shown that this time scale is nonlinearly related to the much longer coherence time scale of deep ocean internal waves through a multiple forward scattering process. It is also shown that 3D scattering effects become pronounced when the acoustic Fresnel width exceeds the cross-range coherence length of the deep ocean internal waves, which lead to frequency and range-dependent power losses in the forward field that may help to explain historic long range measurements.


Social determinants of health in selected slum areas in Jordan: challenges and policy directions.
The unplanned urbanization in Jordan has over time created many informal settlements "slums" around big cities as Amman, Zerka and Aqaba. The purpose of this study was to highlight the most common challenges related to social determinants of health in two selected slum areas in Amman and Aqaba and suggest policy directions and interventions to meet these challenges. In addition to a prestructured interview with all household heads living in the two slum sites, focus group meetings with a purposefully selected sample of 12 slum dwellers in each site were used to assess the structural and intermediary determinants of health as perceived by slum residents in the two study locations. The study found that slum residents in the two locations suffer from many challenges as severe poverty; unemployment; illiteracy and low education attainments; gender discrimination; insufficient and poor diet; social and official exclusion; unhealthy environment; lack of water supply, electricity and basic sanitation facilities; high prevalence of diseases; and insufficient and inappropriate health services. Specific policy directions to meet these challenges were recommended and grouped into three main clusters: social protection, social inclusion and empowerment. New plans and tools should be developed by local authorities in Jordan to understand, protect, include and empower those vulnerable people who are forced to live in these unhealthy and inhuman environments.


[Retroperitoneal ganglioneuroma in the infancy].
Specific management guides for suprarenal incidentalomas detected after birth do not exist for children, but due to the high proportion of malignant tumors, surgical resection is recommended. We present the case of a 7-year-old patient with a non-functioning left suprarenal incidentaloma. Surgical resection and subsequent anatomopathologic analysis of the mass confirmed the diagnosis of ganglioneuroma in process of maturation. Most ganglioneuromas are incidental and have a good prognosis due to their benign behaviour, even though malignant transformation has also been described, for which reason postoperative controls to detect local recurrence and occurrence of new foci are recommended.


Cationic albumin-conjugated pegylated nanoparticles allow gene delivery into brain tumors via intravenous administration.
Patients with malignant gliomas have a poor prognosis because these tumors do not respond well to conventional treatments. Studies of glioma xenografts suggest that they may be amenable to gene therapy with cytotoxic genes, such as the proapoptotic Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL). Gene therapy of gliomas ideally employs i.v. given vectors, thus excluding viral vectors as they cannot cross the brain microvascular endothelium or blood-brain barrier. Recently, we reported the synthesis of cationic albumin-conjugated pegylated nanoparticles (CBSA-NP) and showed their accumulation in mouse brain cells upon i.v. administration. In this study, plasmid pORF-hTRAIL (pDNA) was incorporated into CBSA-NP, and the resulting CBSA-NP-hTRAIL was evaluated as a nonviral vector for gene therapy of gliomas. Thirty minutes after transfection of C6 glioma cells, CBSA-NP-hTRAIL was internalized and mostly located in the cytoplasm, whereas NP-hTRAIL was entrapped in the endolysosomal compartment. At 6 and 48 hours after transfection, respectively, released pDNA was present in the nuclei and induced apoptosis. At 30 minutes after i.v. administration of CBSA-NP-hTRAIL to BALB/c mice bearing i.c. C6 gliomas, CBSA-NP-hTRAIL colocalized with glycoproteins in brain and tumor microvasculature and, via absorptive-mediated transcytosis, accumulated in tumor cells. At 24 and 48 hours after i.v. administration of CBSA-NP-hTRAIL, respectively, hTRAIL mRNA and protein were detected in normal brain and tumors. Furthermore, repeated i.v. injections of CBSA-NP-hTRAIL induced apoptosis in vivo and significantly delayed tumor growth. In summary, this study indicates that CBSA-NP-hTRAIL is a promising candidate for noninvasive gene therapy of malignant glioma.


Anatomic and clinical pathology of cognitive impairment and dementia.
Progressive cognitive impairment and its clinical culmination in dementia loom as a major public health problem in the coming generation of older adults, and this fact compels investigation to develop interventions that prevent, delay, or cure. The tools of anatomic pathology have provided key insights into the complex convergence of multiple diseases that commonly contribute to the dementia syndrome and its prodrome in the community setting, and they have suggested some exposures that may modulate disease burden. The tools of clinical pathology, in combination with neuroimaging, have revolutionized the approach to clinical investigation of Alzheimer's disease and are now doing the same with Lewy body disease and vascular brain injury. The tools of anatomic and clinical pathology will continue to contribute to our understanding of these diseases as we advance toward effective interventions for the diseases that commonly cause cognitive impairment and dementia in older adults.


Trauma specific versus generic measurement of distress and the validity of self-reported symptoms in sexually abused children.
This study examined two issues in the assessment of child sexual abuse victims: sensitivity to trauma-related symptoms and validity of self-reports. The Trauma Symptom Checklist for Children (TSCC) and Personality Inventory for Youth (PIY) were completed by 41 sexually abused children. Parents and children completed diagnostic interviews for PTSD. We predicted that TSCC validity scales would be moderately correlated with PIY scales measuring similar constructs, and that TSCC clinical scales would be more sensitive to PTSD status than the PIY clinical scales. Results supported both hypotheses. TSCC validity scales appeared to be less likely to identify clinical cases, however. Clinical and research implications are discussed.


Glucosinolate Accumulation and Hydrolysis in Leafy Brassica Vegetables Are Influenced by Leaf Age.
The health-beneficial effects of Brassica vegetables are mainly attributed to their high contents of glucosinolates and the products of their hydrolysis, especially isothiocyanates. Distribution of glucosinolates across plant organs can strongly vary. Here, we investigated the effect of leaf age on glucosinolate accumulation and hydrolysis in two leafy Brassica vegetables, pak choi and giant red mustard. We also evaluated the activity of the hydrolyzing enzyme myrosinase across the leaves. Finally, we assessed whether glucosinolates are transported from older leaves to younger leaves. Young leaves of both species contained more than 3-fold more glucosinolates than older ones. Accordingly, more isothiocyanates were released in the young leaves. Myrosinases fully hydrolyzed all of the amounts of glucosinolates regardless of the leaf age. Moreover, older leaves were observed to supply younger leaves with glucosinolates. Thus, this study suggests that consumers can improve the nutritional value of food by incorporating young leaves of leafy Brassicas in their diet.


IL-5 Promoter Polymorphism Enhances IgE Responses to Staphylococcal Superantigens in Adult Asthmatics.
Interleukin 5 (IL-5) is a key cytokine involved in the induction of T-helper type 2 (Th2) responses in the asthmatic airway. We investigated IL-5 genetic polymorphisms associated with asthma phenotypes, including IgE responses to staphylococcal enterotoxins A and B (SEA and SEB, respectively), in asthmatics. Adult asthmatics (n=310) and normal controls (n=160) were enrolled in the present study. Serum total and specific IgE to SEA and SEB were measured. Two IL-5 polymorphisms, -746A>G and +4499T>G, were genotyped using the primer-extension method. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the two groups. Asthmatics carrying the AG/GG genotype at -746A>G had a significantly higher prevalence of serum specific IgE to SEA (P=0.008), higher total IgE levels (P=0.014), and lower PC20 methacholine levels (P=0.002) compared to those with the AA genotype. These findings suggest that the IL-5 promoter polymorphism at -746A>G enhances serum total and specific IgE responses to SEA, which may augment airway hyperresponsiveness in adult asthmatics.


Heating-enabled formation of droplet interface bilayers using Escherichia coli total lipid extract.
Droplet interface bilayers (DIBs) serve as a convenient platform to study interactions between synthetic lipid membranes and proteins. However, a majority of DIBs have been assembled using a single lipid type, diphytanoylphosphatidylcholine (DPhPC). The work described herein establishes a new method to assemble DIBs using total lipid extract from Escherichia coli (eTLE); it is found that incubating oil-submerged aqueous droplets containing eTLE liposomes at a temperature above the gel-fluid phase transition temperature (Tg) promotes monolayer self-assembly that does not occur below Tg. Once monolayers are properly assembled via heating, droplets can be directly connected or cooled below Tg and then connected to initiate bilayer formation. This outcome contrasts immediate droplet coalescence observed upon contact between nonheated eTLE-infused droplets. Specific capacitance measurements confirm that the interface between droplets containing eTLE lipids is a lipid bilayer with thickness of 29.6 Å at 25 °C in hexadecane. We observe that bilayers formed from eTLE or DPhPC survive cooling and heating between 25 and 50 °C and demonstrate gigaohm (GΩ) membrane resistances at all temperatures tested. Additionally, we study the insertion of alamethicin peptides into both eTLE and DPhPC membranes to understand how lipid composition, temperature, and membrane phase influence ion channel formation. Like in DPhPC bilayers, alamethicin peptides in eTLE exhibit discrete, voltage-dependent gating characterized by multiple open channel conductance levels, though at significantly lower applied voltages. Cyclic voltammetry measurements of macroscopic channel currents confirm that the voltage-dependent conductance of alamethicin channels in eTLE bilayers occurs at lower voltages than in DPhPC bilayers at equivalent peptide concentrations. This result suggests that eTLE membranes, via composition, fluidity, or the presence of subdomains, offer an environment that enhances alamethicin insertion. For both membrane compositions, increasing temperature reduces the lifetimes of single channel gating events and increases the voltage required to cause an exponential increase in channel current. However, the fact that alamethicin insertion in eTLE exhibits significantly greater sensitivity to temperature changes through its Tg suggests that membrane phase plays an important role in channel formation. These effects are much less severe in DPhPC, where heating from 25 to 50 °C does not induce a phase change. The described technique for heating-assisted monolayer formation permits the use of other high transition temperature lipids in aqueous droplets for DIB formation, thereby increasing the types of lipids that can be considered for assembling model membranes.


Pd-Catalyzed γ-C(sp3)-H Fluorination of Free Amines.
The first example of free amine γ-C(sp3)-H fluorination is realized using 2-hydroxynicotinaldehyde as the transient directing group. A wide range of cyclohexyl and linear aliphatic amines could be fluorinated selectively at the γ-methyl and methylene positions. Electron withdrawing 3,5-disubstituted pyridone ligands were identified to facilitate this reaction. Computational studies suggest that the turnover determining step is likely the oxidative addition step for methylene fluorination, while it is likely the C-H activation step for methyl fluorination. The explicit participation of Ag results in a lower energetic span for methylene fluorination and a higher energetic span for methyl fluorination, which is consistent with the experimental observation that the addition of silver salt is desirable for methylene but not for methyl fluorination. Kinetic studies on methyl fluorination suggest that the substrate and PdL are involved in the rate-determining step, indicating that the C-H activation step may be partially rate-determining. Importantly, an energetically preferred pathway has identified an interesting pyridone-assisted bimetallic transition state for the oxidative addition step in methylene fluorination, thus uncovering a potential new role of the pyridone ligand.


Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to antibiotic- and nonantibiotic-related pressure.
Tuberculosis (TB) is a global health problem estimated to kill 1.4 million people per year. Recent advances in the genomics of the causative agents of TB, bacteria known as the Mycobacterium tuberculosis complex (MTBC), have allowed a better comprehension of its population structure and provided the foundation for molecular evolution analyses. These studies are crucial for a better understanding of TB, including the variation of vaccine efficacy and disease outcome, together with the emergence of drug resistance. Starting from the analysis of 73 publicly available genomes from all the main MTBC lineages, we have screened for evidences of positive selection, a set of 576 genes previously associated with drug resistance or encoding membrane proteins. As expected, because antibiotics constitute strong selective pressure, some of the codons identified correspond to the position of confirmed drug-resistance-associated substitutions in the genes embB, rpoB, and katG. Furthermore, we identified diversifying selection in specific codons of the genes Rv0176 and Rv1872c coding for MCE1-associated transmembrane protein and a putative l-lactate dehydrogenase, respectively. Amino acid sequence analyses showed that in Rv0176, sites undergoing diversifying selection were in a predicted antigen region that varies between "modern" lineages and "ancient" MTBC/BCG strains. In Rv1872c, some of the sites under selection are predicted to impact protein function and thus might result from metabolic adaptation. These results illustrate that diversifying selection in MTBC is happening as a consequence of both antibiotic treatment and other evolutionary pressures.


Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings.
Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.


Expressions of insulin-like growth factor receptor-1 and cezanne-1 in lung adenocarcinoma.
IGF1R (insulin-like growth factor receptor-1) was confirmed to play a significant role in the development of cancer. Cezanne-1 overexpression was considered to be associated with enhancement of EGFR signaling pathway and reduced degeneration of EGFR. There was a close relationship between EGFR and IGFR as previous study showed. Dynamic balance between receptor ubiquitination and deubiquitination was critical in the process of termination of IGF signaling pathway. So we conducted an IHC staining to initially prove the correlation. Cezanne-1 and IGF1R expressions were evaluated in 103 patients with lung adenocarcinoma using immunohistochemical (IHC) analysis. The relationship between expressions of cezanne-1 and IGF1R were analyzed by χ2 test. Kaplan-Meier method was used to generate the survival curve, and the statistical difference was calculated by log-rank test. We also used data in R2 system to verify the relationship between IGF1R and cezanne-1. R2 system showed there was a close correlation between IGF1R and cezanne-1. Positive expression of cezanne-1 was detected in 64.1% patients. A significant association was shown between cezanne-1 and IGF1R expression (p < 0.001). Multivariate analysis confirmed that both cezanne-1 and IGF1R expressions were independent prognostic factors for OS. (HR 2.96, 95% CI 1.090-8.060, p = 0.033; HR 2.273, 95% CI 1.016-5.085, p = 0.046, respectively). Our findings indicated both cezanne-1 and IGF1R expressions were negative independent predictive factors for the prognosis of lung adenocarcinoma, respectively. There was a close positive interrelationship between cezanne-1 and IGF1R expression.


Complement activation and its relationship to adult respiratory distress syndrome. An experimental study in pigs.
Pulmonary leucostasis induced by complement activation has been considered an important pathogenic factor in adult respiratory distress syndrome (ARDS). To determine whether complement activation per se could evoke pulmonary dysfunction similar to ARDS, pigs were repeatedly infused with complement-activated plasma (CAP). Complement activation was produced by incubation of plasma with zymosan. Three groups of animals were investigated. Control animals received non-activated plasma. Nine animals (Group II) were given four infusions of CAP at a rate of 7 ml X min-1, and another nine animals (Group III) received two CAP infusions at a rate of 7 ml X min-1 followed by two at a rate of 14 ml X min-1. In the control animals there were no changes in gas exchange or haemodynamic variables and the leucocyte counts gradually increased. Infusion of CAP resulted in transient peripheral leucopenia and a dose-rate-dependent reversible increase in pulmonary vascular resistance in all animals. In one animal of Group II and in six of Group III there was a significant infusion-related decrease in Pao2 due to increased venous admixture. These animals were characterized by an enhanced pulmonary vascular tone before the start of the first CAP infusion. They also displayed a more pronounced pulmonary vascular response to infusion of CAP. The changes in gas exchange variables and pulmonary haemodynamics showed no relation to the degree of leucopenia or decrease in platelet count. The increased venous admixture was caused by "dry" ventilation/perfusion mismatching and not by oedema. These results suggest that additional factors besides complement activation and pulmonary leucostasis are required for the development of increased microvascular permeability and the pulmonary oedema characterizing ARDS.


[Platelet Metabolism in Clopidogrel Resistant and Sensitive Patients With Ischemic Heart Disease].
to investigate relationship between activity of platelet nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) dependent dehydrogenases in patients with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG) and their sensitivity to clopidogrel. We studied 51 male patients with chronic IHD before and after CABG. Control group comprised 35 healthy men. In IHD patients spontaneous and induced platelet aggregation was measured by aggregometry before CABG (in 2 weeks after cessation of antiplatelet drugs), after CABG during therapy with clopidogrel (75 mg/day), and in 6 months after surgery. Patients were classified as clopidogrel sensitive or resistant using cutoff of 50% inhibition of initial ADP (5 M) induced platelet aggregation after 2 weeks of treatment with clopidogrel. Activity of platelet NAD and NADP dependent dehydrogenases was measured by bioluminescent method. There were 41 clopidogrel sensitive and 10 clopidogrel resistant patients. Irrespective of sensitivity to clopidogrel platelet metabolism in IHD patients was characterized by reduced activity of anaerobic energetics, glutathione-dependent antioxidant system, reactions that transport products of lipid catabolism on glycolysis, and NADPH-dependent transfer of substrates from citric acid cycle to amino acid metabolism. Metabolic features of platelets characteristic of clopidogrel resistance were low activity of the key reaction of pentose phosphate cycle reflecting state of plastic metabolism, and substrate flow in the tricarbonic acid cycle - determinant of intensity of aerobic energy. Clopidogrel-sensitive patients had increased platelets NADP-malate dehydrogenase activity (the key reaction of lipid anabolism).


[Health criteria and scope of workers' periodic health check-ups for selected types of work and exposure factors - Nofer Institute of Occupational Medicine guidelines].
Workers' medical prophylactic examinations referred to in the Labor Code are one of the tasks of the occupational medicine services. They are regulated by law which has been in force for more than 20 years in unchanged form. During this period, new harmful, burdensome or dangerous to health factors appeared in the workplaces, for which no preventive health check-up standard was defined. In the meantime, the health criteria for drivers and persons applying for driving licenses have also been significantly liberalized. The above changes, the authors' own experience, comments and problems reported by physicians who provide workers' prophylactic health care and employers as well as analysis of literature related to workers' health care in other countries have created the need to harmonize and update guidelines on health requirements for selected types of work. In addition the scope and frequency of prophylactic examinations for exposures, which are not included in applicable legal acts, has been developed. Med Pr. 2019;70(1):125-37.


Activation of NOD1 and NOD2 in the development of liver injury and cancer.
Hepatocytes and liver-resident antigen-presenting cells are exposed to microbe-associated molecular patterns (MAMPs) and microbial metabolites, which reach the liver from the gut via the portal vein. MAMPs induce innate immune responses via the activation of pattern recognition receptors (PRRs), such as toll-like receptors (TLRs), nucleotide-binding oligomerization domain 1 (NOD1), and NOD2. Such proinflammatory cytokine responses mediated by PRRs likely contribute to the development of chronic liver diseases and hepatocellular carcinoma (HCC), as shown by the fact that activation of TLRs and subsequent production of IL-6 and TNF-α is required for the generation of chronic fibroinflammatory responses and hepatocarcinogenesis. Similar to TLRs, NOD1 and NOD2 recognize MAMPs derived from the intestinal bacteria. The association between the activation of NOD1/NOD2 and chronic liver diseases is poorly understood. Given that NOD1 and NOD2 can regulate proinflammatory cytokine responses mediated by TLRs both positively and negatively, it is likely that sensing of MAMPs by NOD1 and NOD2 affects the development of chronic liver diseases, including HCC. Indeed, recent studies have highlighted the importance of NOD1 and NOD2 activation in chronic liver disorders. Here, we summarize the roles of NOD1 and NOD2 in hepatocarcinogenesis and liver injury.


Coxsackievirus-induced myocarditis is dependent on distinct immunopathogenic responses in different strains of mice.
Myocarditis is defined as an inflammation of the heart muscle and often follows enterovirus infections. Frequently, patients surviving the acute inflammatory stage undergo complete recovery, but myocarditis can result in dilated cardiomyopathy. A murine model of myocarditis has been developed that uses cardiotropic variants of coxsackievirus Group B. Type 3 (CVB3), and either BALB/c (H-2d), MRL+/+ (H-2k), or DBA/2 (H-2d) male mice. Infection of all three mouse strains results in equivalent levels of myocardial inflammation 7 days later. IgG antibodies are detected by immunofluorescent staining in DBA/2 but not BALB/c or MRL+/+ myocardium and correlate with the detection of anti-heart antibodies in the sera of DBA/2 mice by immunofluorescence. CD4+ cell depletion of DBA/2 and MRL+/+ mice prevents myocarditis, but both CD4+ and CD8+ T cells cause cardiac inflammation in BALB/c mice, although CD8+ cells are substantially more pathogenic than CD4+ cells in this strain. No or few CD8+ T cells infiltrate the myocardium of either DBA/2- or MRL+/(+)-infected animals, although this is the predominant T-cell population in BALB/c mice. Apoptosis was measured by terminal deoxynucleotidyl transferase-staining of myocardial sections. No apoptosis was observed in inflamed DBA/2 hearts. Apoptosis was restricted to inflammatory cell infiltrates of infected MRL+/+ hearts, but apoptosis was wide-spread in both the inflammatory cell infiltrates and in myocytes outside inflammatory lesions in BALB/c mice. Atria natriuretic factor (ANF) mRNA expression was only elevated in the left ventricles of BALB/c mice. CD8+ T-cell depletion abrogated the appearance of apoptotic myocytes and ANF mRNA expression. The fact that ventricular ANF production often occurs during cardiac failure suggests that myocardial stress is substantially greater in BALB/c mice than in other strains despite equivalent amounts of cardiac inflammation.


RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle.
The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences < ~200 bases) were sequenced, 52 million reads were mapped, and 24,616 known transcripts were quantified according to the bovine reference genome. A comparison of the high- and low-RFI groups revealed 70 and 19 significantly DEGs in Holstein and Jersey cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP's and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins.


Metallosphaera tengchongensis sp. nov., an acidothermophilic archaeon isolated from a hot spring.
Two novel acidothermophilic archaea, strains Ric-A(T) and Ric-F, were isolated from muddy water samples of a sulfuric hot spring located in Tengchong County, Yunnan Province, PR China. The strains were aerobic and facultatively chemolithoautotrophic. Both strains could oxidize S(0) and K2S4O6 for autotrophic growth, and could use organic materials for heterotrophic growth. Growth was observed at 55-75 °C and pH 1.5-6.5. The strains could oxidize metal sulfide ores, showing their potential in bioleaching. The DNA G+C contents of strains Ric-A(T) and Ric-F were 41.8 and 41.6 mol%, respectively. Analysis of 16S rRNA gene sequences showed that the two strains shared 99.8 % sequence similarity to each other, but <97 % to other known species of the genus Metallosphaera. DNA-DNA hybridization indicated that the isolates were different strains of a novel species of the genus Metallosphaera. Strains Ric-A(T) and Ric-F also shared a number of physiological and biochemical characteristics that distinguished them from recognized species of the genus Metallosphaera. On the basis of phenotypic, chemotaxonomic and phylogenetic comparisons with their closest relatives, it was concluded that strains Ric-A(T) and Ric-F represent a novel species of the genus Metallosphaera, for which the name Metallosphaera tengchongensis sp. nov. is proposed. The type strain is Ric-A(T) ( = NBRC 109472(T) = CGMCC 1.12287(T)).


Finding the Next Deep-Ultraviolet Nonlinear Optical Material: NH4B4O6F.
Nonlinear optical materials are essential for the development of solid-state lasers. KBe2BO3F2 (KBBF) is a unique nonlinear optical material for generation of deep-ultraviolet coherent light; however, its industrial application is limited. Here, we report a new material NH4B4O6F, which exhibits a wide deep-ultraviolet transparent range and suitable birefringence that enables frequency doubling below 200 nm. NH4B4O6F possesses large nonlinear coefficients about 2.5 times that of KBBF. In addition, it is easy to grow bulk crystals and does not contain toxic elements.


An evaluation of HIV RNA and CD4 cell count as surrogates for clinical outcome. Delta Coordinating Committee and Virology Group.
To evaluate the role of viral load, as measured by HIV-1 RNA, and CD4 cell counts as surrogates for clinical outcome using the data from the Delta trial. A total of 1280 participants (40% of the 3207 participants in the Delta trial) with baseline and at least one other serum sample stored at -70 degrees C were included in the extended virology study, of whom 411 were allocated to zidovudine (ZDV) alone, 439 to ZDV plus didanosine (ddl) and 430 to ZDV plus zalcitabine (ddC). The extent to which changes in HIV or CD4 cell levels up to week 32 can explain the benefit of combination therapy was investigated by fitting these marker levels in addition to allocated treatment to Cox proportional hazards models for time to death and to disease progression. RNA at baseline and changes at weeks 8, 16 and 32 were independent and highly significant predictors of disease progression or death. The hazard of progression was increased fourfold (P < 0.0004) for each log10 higher baseline RNA and was reduced by 43% (P = 0.004) and by 38% (P = 0.002) for each log10 reduction at weeks 8 and 16, respectively. Compared with ZDV monotherapy, the progression rate was reduced by 43% (P = 0.0001) by ZDV plus ddl and by 36% (P = 0.001) by ZDV plus ddC. After adjusting for RNA up to week 16, however, there was a highly significant treatment effect favouring ZDV monotherapy, which was not explained by RNA: the adjusted progression rates were 66% higher (P = 0.005) for ZDV plus ddl and 67% higher (P = 0.004) for ZDV plus ddC compared with ZDV alone. In contrast, after adjusting for CD4 to week 16 there remained a significant treatment effect favouring combination therapy: compared with ZDV monotherapy, the progression rate was reduced by 29% (P < 0.0001) by ZDV plus ddl and 12% (P = 0.1) by ZDV plus ddC. Adjustment for both RNA and CD4 to week 16 resulted in a relative increase in the hazard of progression (49% (P = 0.04) for ZDV plus ddl and 37% (P = 0.09) for ZDV plus ddC) not explained by the two markers combined. Clinical benefit from combinations of ZDV plus ddl or ZDV plus ddC was underestimated by CD4 cell counts and overestimated by RNA levels and by the two markers combined. Neither HIV RNA levels nor CD4 cell counts appear to be complete surrogates for clinical outcome.


Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a global public health emergency, and new therapeutics are needed. This article reports the potential drug target and mechanism of action of Arbidol (umifenovir) to treat coronavirus disease 2019 (COVID-19). Molecular dynamics and structural analysis were used to show how Arbidol targets the SARS-CoV-2 spike glycoprotein and impedes its trimerization, which is key for host cell adhesion and hijacking, indicating the potential of Arbidol to treat COVID-19. It is hoped that knowledge of the potential drug target and mechanism of action of Arbidol will help in the development of new therapeutics for SARS-CoV-2.


Impact of the learning curve on the outcome of domino liver transplantation.
Domino liver transplantation (DLT) is a strategy used to increase the number of available grafts. In this procedure, the transplant recipient is a living donor of her own liver. It is mandatory that the graft should be fully functional and the genetic defect should recur with sufficient latency period in the new recipient. Corino-Andrade disease, or familial amyloidotic polyneuropathy (FAP), satisfies these conditions. We retrospectively reviewed our prospective database of DLT. From July 2004 to April 2013, we performed 12 DLTs. We assessed age, sex, real Model for End-Stage Liver Disease (MELD) score, waiting list time, cold and warm ischemia times, intraoperative transfusion requirements, hospital stay, early peritransplantation morbidity (post-reperfusion syndrome, intraoperative cardiac arrest, post-transplantation thrombotic events, and biliary morbidity), acute cellular rejection, retransplantation, mortality, patient and graft survivals. With the intention to study the effect of the learning curve in the global survival results (including both donors and recipients of livers with FAP), we divided our series into 2 periods: the early period (from 2004 to 2008) and the present period (from 2009 to 2013). The crude mortality was 40% vs 0% (P = .042) in the early and present periods, respectively. The cumulative patient survival was also significantly in favor of the present period (P = .049). The graft loss prevalence was 60% vs 7.1% (P = .019) in the early and present periods, respectively. The cumulative graft survival was also significantly in favor of the present period (P = .030; Fig 2). In conclusion, we consider DLT to be a complex procedure, whose initial results are conditioned by the learning curve.


Oogenesis: chromatin and microtubule dynamics during meiotic prophase.
Changes in the organization of germinal vesicle chromatin in mouse oocytes have been analyzed by fluorescence microscopy with respect to progressive stages of follicular development and the disposition of oocyte cytoplasmic microtubules. Four discrete patterns of chromatin organization exist in germinal vesicle (GV)-stage oocytes isolated from the ovaries of 21-25-day-old gonadotropin-primed mice. Analysis of ovarian cryosections stained with the DNA-binding fluorochrome Hoechst 33258 indicates that sequential changes in GV chromatin occur during folliculogenesis that result in the formation of a continuous perinucleolar chromatin sheath at the time of antrum formation. Specific alterations in the cytoplasmic microtubule complex of GV-stage oocytes were observed that correlate with chromatin patterns. The extensive cytoplasmic microtubule complex seen in oocytes of preantral follicles initially localizes to perinuclear areas of the ooplasm. This is followed by a progressive reduction in cytoplasmic microtubules and the appearance of prominent microtubule-organizing centers at the nuclear periphery. Coordinated nuclear and microtubular alterations also occur under in vitro conditions prior to progression of meiosis to prometaphase-1. The results are discussed with respect to the ongoing differentiation of the oocyte nucleus and the microtubule cytoskeleton during folliculogenesis in preparation for the resumption of meiosis.


Profiling the expression of genes controlling rice grain quality.
Rice provides a staple source of energy, protein and other nutrients to half of the world population. Over 90 of the rice seeds consists of starch and protein by dry weight. The quantity and property of starch and protein thus play a dominant role in the yield and quality of rice. The amylase content of starch is a determining factor in the eating and cooking quality while the amount and essential amino acids balance of storage proteins affect the nutritional quality of rice. In China, the super-hybrid rice currently under the last phase of development has a 35 yield advantage over the best inbred rice varieties. However, its grain quality needs further improvement. This study reported the expression patterns of 44 genes participating in starch, storage protein, and lysine synthesis in the developing rice grain. Field grown rice cultivar 9311, the paternal line of an elite super-hybrid rice LYP9 with its draft genomic sequence released, was used as plant material. Results revealed diverse yet coordinated expression profiles of the genes involved in the three pathways which lead to the final composition and property of starch, protein and lysine that determine the quality of rice, providing useful information for rice quality improvement.


ArF 193 nm excimer laser corneal surgery as a possible risk factor in cataractogenesis.
It was evaluated whether ArF 193 nm excimer laser corneal surgery represents a risk factor in cataractogenesis. For this purpose, 20 male albino rabbits underwent a photorefractive keratectomy and biochemical analyses on aqueous humour (hydrogen peroxide, ascorbic acid, and reduced and oxidized glutathione) and on lens (malondialdehyde, reduced and oxidized glutathione) were performed. In the aqueous humour of all treated animals a significant increase in hydrogen peroxide and in oxidized glutathione and a concomitant decrease in ascorbic acid and reduced glutathione concentration were observed. Moreover, all these variations were significantly correlated with the cumulative UV dose used. In the lens, after excimer laser corneal surgery, there was a dramatic loss of reduced glutathione and a parallel increase in oxidized glutathione levels. Malondialdehyde concentration was also increased, but only at the highest UV exposure. Moreover, all these variations were significantly correlated with the cumulative UV dose used. These findings demonstrate that the exposure of aqueous humour and lens to the secondary radiation generated after ArF 193 nm excimer laser corneal photoablative keratectomy induces biochemical modifications which are known to be markers of cataractogenesis.


Association Between Cardiovascular Disease and Cognitive Dysfunction in Breast Cancer Survivors.
Breast cancer survivors (BCSs) may have a greater risk for cardiovascular disease (congestive heart failure and hypertension), which in turn, can affect cognitive dysfunction, a frequent, bothersome, and potentially debilitating symptom. The purpose of this study was to examine the relationship of cardiovascular disease on cognitive function in BCSs. Baseline data from a double-blind randomized controlled trial for cognitive training of BCSs were examined. Early-stage BCS (stages I-IIIA) who were 21 years or older, completed adjuvant therapy (≥6 months), and reported cognitive concerns completed questionnaires and a brief neuropsychological assessment, including tests of memory, attention and working memory, speed of processing, and verbal fluency. Descriptive statistics, Pearson correlation coefficient, and separate linear regression models for each cognitive domain were conducted. Forty-seven BCSs, who were on average 57.3 (SD, 8.1) years old, were 58% White, and had some college education (75%), completed the study. Furthermore, 44.7% of the BCS had cardiovascular disease (congestive heart failure or hypertension). In linear regression models, cardiovascular disease was significantly related to immediate and delayed memory and attention and working memory ( P < .01-.05). Breast cancer survivors who have cardiovascular disease may also be at a greater risk for cognitive dysfunction post treatment. Results from this study inform both clinical practice and future research, specifically by examining the intersection between cancer, cardiovascular disease (cardiotoxicity), and cognition. Nurses should be aware that BCSs with co-occurring cardiovascular disease are at a higher risk for cognitive dysfunction and work within the multidisciplinary team to optimize BCS health and function.


Hospital closure: a review of current and proposed research.
This paper reviews available data describing issues and research findings with implications for hospital closings. Factors contributing to fiscal problems of hospitals (e.g., inadequate reimbursement, inflation, management problems, organizational structure, societal factors) are discussed. Selected studies offering examples of hospital and community characteristics associated with closure are presented. This review suggests that future directions for research should focus not only on hospital cost control but also on insuring equity in the distribution of hospital services. Specifically, research is needed that further describes the hospital closure phenomenon, the effects of closure, and the policy choices that might be pursued to insure equity in the continuation of hospital services to disadvantaged populations.


Testing the fading affect bias for healthy coping in the context of death.
Affect fades faster for unpleasant events than for pleasant events (e.g., Walker, Vogl, & Thompson, 1997 ), which is referred to as the fading affect bias (FAB; Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003 ). Although research has generally shown that the FAB is a healthy coping mechanism, this same finding has not been demonstrated at a specific level of analysis accounting for particular event types and related individual differences (e.g., Gibbons et al., 2013 ). Given the strong unpleasant emotions associated with death (Rask, Kaunonen, & Paunonen-Ilmonen, 2002 ), the current study examined FAB in the context of death events and participant attitudes toward death. General healthy coping was shown by robust FAB across death and control (i.e., everyday) events and by a negative correlation between negative religious coping and FAB. Although healthy coping at a specific level of analysis was supported by increased FAB for participants who held accepting attitudes toward death when they recalled everyday events, it was not supported by decreased FAB for the same participants when they recalled death events. This effect was mediated by rehearsal ratings, not depression. Implications are discussed.


Oral Manifestations of Menopause: An Interprofessional Intervention for Dental Hygiene and Physician Assistant Students.
Purpose: Interprofessional education (IPE) is a means of fostering integration and collaboration between health care professions. The purpose of this study was to evaluate the effect of an IPE educational module on dental hygiene (DH) and physician assistants (PA) students' knowledge of the oral manifestations of menopause and overall confidence in treating these conditions.Methods: A convenience sample of DH and PA students was used for this mixed-method study. Quantitative data was collected with pre- and post-tests using a modified Readiness for Interprofessional Learning Survey (RIPLS) and a principle investigator (PI)-designed knowledge of menopause test, to determine the students' attitudes and learning levels. Students participated in a one-time workshop that included an educational presentation on the oral manifestations of menopause and a case study exercise using a pseudo-standardized patient. Students from both disciplines, worked in preselected groups to create a patient care plan addressing the oral manifestations of menopause. Qualitative data was collected from student comments.Results: Study results indicate an increase in participants' knowledge of the oral manifestations of menopause (p<0.05). Results also suggest improved attitudes toward interprofessional teamwork and collaboration (p<0.05), positive professional identity (p<0.05), roles and responsibilities (p<0.05) for IPEC core competencies RR1, RR2, RR3, RR4, interprofessional communication (p<0.05) for IPEC core competencies CC3, CC4, CC 6. Qualitative data from interprofessional care plan formulation and debriefing demonstrated facilitation of gained confidence in applying new skills related to the oral manifestations of menopause.Conclusion: Patients experiencing menopause are susceptible to oral manifestations. Implementation of an IPE intervention demonstrated correlation between an IPE experience and participants' knowledge, attitudes and confidence. Preparing students to meet the needs of menopausal women may ultimately decrease oral discomfort and improve overall quality of life.


Construction of modern Australian first trimester ultrasound dating and growth charts.
Accurate pregnancy dating is vital to obstetric management. However, first trimester fetal charts commonly used in Australia rely on data reported more than three decades ago. This study reports first trimester dating and growth charts for crown-rump length between 5 and 14 weeks of gestation and biparietal diameter between 9 and 14 weeks of gestation on an Australia population using modern real-time ultrasound equipment. All consenting eligible women attending a large Sydney clinic for first trimester ultrasound between March 2005 and December 2006 were recruited. Measurements were carried out to Australasian Society for Ultrasound in Medicine standard protocols. Statistical analyses were undertaken using polynomial regression models and thorough diagnostic checks made. Overall 396 eligible women consented to the study, with 268 between 9 and 14 weeks of gestation. The average participant age was 34 years (range 22-45 years), 371 and all yielded valid biometry measurements. Equations, means and 90% reference intervals for crown-rump length measurements and biparietal diameter measurements were derived using polynomial regression models. Thorough residual and diagnostic checks were made. Once validated by others, we believe they will warrant consideration for use by Australasian Society for Ultrasound in Medicine.


The contribution of local thyroxine monodeiodination to intracellular 3,5, 3'-triiodothyronine in several tissues of hyperthyroid rats at isotopic equilibrium.
The local conversion of T4 as a source of intracellular T3 in several organs of both hypothyroid and euthyroid rats has recently been recognized to be an important phenomenon. In the present study the source and quantity of T3 in various peripheral tissues of hyperthyroid rats were investigated. Athyreotic rats received a continuous iv infusion of 3.5 micrograms T4/100 g BW X day over a prolonged period in order to attain hyperthyroid conditions. At the same time, the animals also received a continuous iv infusion of [125I]T4 and [131I]T3 until isotopic equilibrium was achieved. After the animals were bled and perfused, the source and quantity of T3 in various tissue homogenates and subcellular preparations of liver, kidney, and the anterior pituitary gland were analyzed. In spite of the elevated plasma T3 and T4 levels, the concentration of T3 in the cerebral cortex and cerebellum was within the normal range. The contribution of T3 derived from local T4 to T3 conversion [Lc T3(T4)] was rather low in both parts of the brain (cerebral cortex, 26%; cerebellum, 15%) when compared with values previously determined for euthyroid rats (cerebral cortex, 67%; cerebellum, 50%). It is concluded that in the cerebral cortex and cerebellum of hyperthyroid rats normal T3 concentrations were maintained by a compensatory decrease in the degree of Lc T3(T4). Whereas previous studies revealed that Lc T3(T4) contributes significantly to the T3 in the pituitary glands of both hypothyroid and euthyroid rats, this was not the case for the hyperthyroid animals; virtually all T3 was derived from plasma. The elevated plasma T3 levels caused an increased T3 content in both the homogenate and the nuclear fraction, leading to plasma TSH levels which were below the detection limit. It was found that the T3 in muscle was derived exclusively from plasma. Both the liver and kidney showed high concentrations of T3. Whereas Lc T3(T4) was the main source of T3 in the liver, it contributed only a minor fraction of the total T3 content in the kidney. In the liver Lc T3(T4) accounted for 50-53% of the T3 content in the mitochondrial and cytosolic fractions and about 64% in the microsomal fraction. In the kidney there was a small, but significant, amount of Lc T3(T4) in these subcellular fractions. In contrast, in the hepatic nuclei only 13% of the T3 was attributable to Lc T3(T4), whereas no Lc T3(T4) could be detected in the renal nuclei.


Sediment microbes mediate the impact of nutrient loading on blue carbon sequestration by mixed seagrass meadows.
Recent studies have reported significant variability in sediment organic carbon (SOC) storage capacity among seagrass species, but the factors driving this variability are poorly understood, limiting our ability to make informed decisions about which seagrass types are optimal for carbon offsetting and why. Here we show that differences in SOC storage capacity among species within the same geomorphic environment can be explained (in part) by below-ground processes in response to nutrient load; specifically, differences in the activity of microbes harboured by morphologically-different seagrass species. We found that increasing nutrient load enhanced the relative contribution of seagrass and algal sources to SOC pools, boosting sediment microbial biomass and extracellular enzyme activity within mixed seagrass meadows composed of Thalassia hemprichii and Enhalus acoroides, and thus possibly weaken the seagrass blue carbon sequestration capacity. The relative contribution of seagrass plant material to sediment bacterial organic carbon (BOC) and the influencing SOC-decomposing enzymes in E. acoroides meadows were half that of T. hemprichii meadows living side-by-side, even though the mixed seagrass meadows received SOC from the same sources. Overall this research suggests that microbial activity can vary significantly among seagrass species, thereby causing fine-scale (within-meadow) variability in SOC sequestration capacity in response to nutrient load.


[RNA transport from isolated nuclei of cultured Djungarian hamster cells].
The in vitro system of RNA transport containing isolated nuclei of Djungarian hamster cells transformed by SV-40 virus was studied. A functional test for cytoplasmic contaminations of the nuclei was proposed. The release of the newly synthesized RNA was found to be dependent on the duration of incubation, temperature and pH of the incubation medium as well as on the presence of spermine, spermidine, dithiothreitol, Mg2+, EDTA, exogenous RNA, nucleoside triphosphates and cytosol. The results obtained indicate that RNA release is an active process with activation energy of 12 kcal/mol. ATP, GTP, CTP and UTP have equal ability to serve as energy sources for the release of RNA. The nucleoside triphosphatase activity of the nuclei was the same in the presence of these four nucleoside triphosphates.


Enhancing topology adaptation in information-sharing social networks.
The advent of the Internet and World Wide Web has led to unprecedent growth of the information available. People usually face the information overload by following a limited number of sources which best fit their interests. It has thus become important to address issues like who gets followed and how to allow people to discover new and better information sources. In this paper we conduct an empirical analysis of different online social networking sites and draw inspiration from its results to present different source selection strategies in an adaptive model for social recommendation. We show that local search rules which enhance the typical topological features of real social communities give rise to network configurations that are globally optimal. These rules create networks which are effective in information diffusion and resemble structures resulting from real social systems.


Type II intramolecular [5+2] cycloaddition: facile synthesis of highly functionalized bridged ring systems.
A type II intramolecular oxidopyrylium-mediated [5+2] cycloaddition reaction allows the efficient and diastereoselective formation of various highly functionalized and synthetically challenging bridged seven-membered ring systems (such as bicyclo[4.4.1]undecane, bicyclo[4.3.1]decane, bicyclo[5.4.1]dodecane, and bicyclo[6.4.1]]tridecane). This simple, thermal, direct transformation has a broad substrate scope and is high yielding, with high functional-group tolerance and unique endo selectivity. The highly strained tricyclic cores of ingenol mebutate (picato) and cyclocitrinol are synthesized efficiently and diastereoselectively using this methodology.