Comprehensive Thermochemical Benchmark Set of Realistic Closed-Shell Metal Organic Reactions.
We introduce the new MOR41 benchmark set consisting of 41 closed-shell organometallic reactions resembling many important chemical transformations commonly used in transition metal chemistry and catalysis. It includes significantly larger molecules than presented in other transition metal test sets and covers a broad range of bonding motifs. Recent progress in linear-scaling coupled cluster theory allowed for the calculation of accurate DLPNO-CCSD(T)/CBS(def2-TZVPP/def2-QZVPP) reference energies for 3d,4d,5d-transition metal compounds with up to 120 atoms. Furthermore, 41 density functionals, including seven GGAs, three meta-GGAs, 14 hybrid functionals, and 17 double-hybrid functionals combined with two different London dispersion corrections, are benchmarked with respect to their performance for the newly compiled MOR41 reaction energies. A few wave function-based post-HF methods as, e.g., MP2 or RPA with similar computational demands are also tested and in total, 90 methods were considered. The double-hybrid functional PWPB95-D3(BJ) outperformed all other assessed methods with an MAD of 1.9 kcal/mol, followed by the hybrids ωB97X-V (2.2 kcal/mol) and mPW1B95-D3(BJ) (2.4 kcal/mol). The popular PBE0-D3(BJ) hybrid also performs well (2.8 kcal/mol). Within the meta-GGA class, the recently published SCAN-D3(BJ) functional as well as TPSS-D3(BJ) perform best (MAD of 3.2 and 3.3 kcal/mol, respectively). Many popular methods like BP86-D3(BJ) (4.9 kcal/mol) or B3LYP-D3(BJ) (4.9 kcal/mol) provide significantly worse reaction energies and are not recommended for organometallic thermochemistry considering the availability of better methods with the same computational cost. The results regarding the performance of different functional approximations are consistent with conclusions from previous main-group thermochemistry benchmark studies.


Internal quality control in point-of-care testing: where's the evidence?
ISO 22870 standards require protocols for performance of internal quality control for all point-of-care testing devices and training of users in its theory and practice. However, the unique setting of point-of-care testing (i.e. processes conducted by non-scientific users) means that laboratory internal quality control programmes do not easily translate to point-of-care testing. In addition, while the evidence base for internal quality control within the laboratory has been increasing, the equivalent literature surrounding point-of-care testing is very limited. This has led to wide variation in what is considered acceptable practice for internal quality control at the point of care. Indeed, it has been demonstrated that internal quality control is an area of deficiency in point-of-care testing. Internal quality control protocols used at point-of-care testing should be defined based on risk management. The protocol will therefore be dependent on analyser complexity and availability of inbuilt system checks, the risk associated with release of an incorrect patient result as well as frequency of use. The emphasis should be on designing an effective internal quality control protocol as opposed to the inherent tendency of introducing high-frequency quality control. Typically a simple pass or fail criterion is used for internal quality control in point-of-care testing based on whether internal quality control results fall within assigned ranges. While simply taught, such criteria can require broad internal quality control ranges to decrease the probability of false rejection (also reducing the probability of error detection). Customized internal quality control ranges, two-tier acceptance systems and assay-specific internal quality control can be used to improve error detection rates.


Circular RNA circMAN2B2 facilitates lung cancer cell proliferation and invasion via miR-1275/FOXK1 axis.
Lung cancer remains a leading cause of cancer-related deaths worldwide. In the past years, increasing reports indicate that circular RNAs (circRNAs) exert a great important role in human cancers, including lung cancer. However, the knowledge about circRNA in lung cancer remains very little so far. In the present study, we screened out a highly expressed novel circRNA named circMAN2B2 in lung cancer tissues. We investigated the function of circMAN2B2 and found that circMAN2B2 knockdown significantly inhibited cell proliferation and invasion in both H1299 and A549 lung cancer cells. Mechanistically, we found that circMAN2B2 could sponge miR-1275 to inhibit its level. Through a series of functional experiments, we dissected the role of miR-1275 in lung cancer and proved the anti-tumor role of miR-1275. Furthermore, we found that miR-1275 exerted its role in lung cancer by regulating FOXK1 expression. In addition, we demonstrated that restoration of FOXK1 could rescue circMAN2B2 knockdown-induced repression of cell proliferation and invasion. Taken together, our study demonstrated that circMAN2B2 acts as an oncogenic role in lung cancer through promoting FOXK1 expression by sponging miR-1275.


Mitochondrial paracrystalline inclusions in the peroneus brevis muscle of patients with peripheral neuropathy.
In a series of 50 consecutive biopsies of peroneus brevis muscle (PBm) taken from patients with ascertained or suspected polyneuropathy in the course of sural nerve biopsy, we found a high incidence (26%) of intramitochondrial paracrystalline inclusions (MPI). Five out of these 13 patients were also submitted to an additional biopsy of a proximal muscle, which in no case confirmed the finding of MPI. Six out of the 13 patients with MPI were affected by diseases with a presumably important ischemic component. The mean age of patients with MPI was quite elevated (60.7), and the difference in distribution of age between patients with and without MPI was statistically significant. No significant difference in histochemical changes was found between the group of MPI patients and a control group of age-matched patients without MPI, thus excluding that MPI in the PBm are specifically associated with other neurogenic or myopathic aspects. We conclude that aging and, probably, ischemia are largely responsible for the frequent presence of MPI in the PBm. In addition, factors intrinsic to the muscle itself, possibly related to morphological, physiological, or biochemical peculiarities, may also influence the development of MPI.


Correlations between sleep patterns and cardiovascular diseases in a Chinese middle-aged population.
Epidemiological and animal studies have suggested an association between habitual sleep patterns and cardiovascular (CV) disease, but the results are still controversial. Therefore, the aims of this study are to investigate the relationships between habitual sleep patterns and CV disease based on Prospective Urban Rural Epidemiology (PURE) China study. PURE China study recruited 46 285 participants, aged 35-70, from 12 provinces and 115 communities in China. Habitual sleep patterns and CV disease were self-reported. Multilevel logistic regression was used in our analysis. In this study, 39 515 participants were eligible in our analysis, including 23 345 (59.1%) women and 16 170 (40.9%) men. Sleeping ≥9 h per day was associated with increased odds of CV disease (OR = 1.16, 95% CI: 1.01-1.32, p = 0.033) compared with sleeping 7-8 h per day. Taking daytime naps was also associated with an increased odds of CV disease, and the CV odds increased with increasing napping duration (p for trend < 0.001). For the sleeping < 6 h per day, we only found an association with coronary artery disease (CAD) (OR = 1.58, 95% CI: 1.01-2.48, p = 0.046). Participants with only 7-8 h sleep per night had lowest prevalence of CV disease (OR = 0.77, 95% CI: 0.65-0.90, p = 0.001) compared with other sleep patterns. Napping, long and short duration of habitual sleep may increase the odds of CV disease. Only participants sleeping 7-8 hours at night are recommended in this study, and large longitudinal studies are needed to confirm these results.


The Role of Dimensionality in Understanding Granuloma Formation.
Within the first 2-3 months of a Mycobacterium tuberculosis (Mtb) infection, 2-4 mm spherical structures called granulomas develop in the lungs of the infected hosts. These are the hallmark of tuberculosis (TB) infection in humans and non-human primates. A cascade of immunological events occurs in the first 3 months of granuloma formation that likely shapes the outcome of the infection. Understanding the main mechanisms driving granuloma development and function is key to generating treatments and vaccines. In vitro, in vivo, and in silico studies have been performed in the past decades to address the complexity of granuloma dynamics. This study builds on our previous 2D spatio-temporal hybrid computational model of granuloma formation in TB (GranSim) and presents for the first time a more realistic 3D implementation. We use uncertainty and sensitivity analysis techniques to calibrate the new 3D resolution to non-human primate (NHP) experimental data on bacterial levels per granuloma during the first 100 days post infection. Due to the large computational cost associated with running a 3D agent-based model, our major goal is to assess to what extent 2D and 3D simulations differ in predictions for TB granulomas and what can be learned in the context of 3D that is missed in 2D. Our findings suggest that in terms of major mechanisms driving bacterial burden, 2D and 3D models return very similar results. For example, Mtb growth rates and molecular regulation mechanisms are very important both in 2D and 3D, as are cellular movement and modulation of cell recruitment. The main difference we found was that the 3D model is less affected by crowding when cellular recruitment and movement of cells are increased. Overall, we conclude that the use of a 2D resolution in GranSim is warranted when large scale pilot runs are to be performed and if the goal is to determine major mechanisms driving infection outcome (e.g., bacterial load). To comprehensively compare the roles of model dimensionality, further tests and experimental data will be needed to expand our conclusions to molecular scale dynamics and multi-scale resolutions.


Maintenance Therapy in Colorectal Cancer: Moving the Artillery Down While Keeping an Eye on the Enemy.
The survival improvement in metastatic colorectal cancer, achieved with more intensive chemotherapy regimens, has recently led clinicians to question the optimal duration of therapies and to consider the role of maintenance. Indeed, patients whose disease is controlled after induction chemotherapy may benefit from continuing a less intensive regimen in order to reinforce the results achieved with up-front treatment. In addition, the more favorable toxicity profile of maintenance approaches would ensure a better quality of life. After discussing the rationale and the difference of pursuing a maintenance strategy with chemotherapeutic and/or biologic agents, we present significant available data from the literature and comment on the current implications and future directions of maintenance therapy. The current roles of depotentiated treatment schedules, antiangiogenic compounds, epidermal growth factor receptor inhibitors, and novel targeted therapies are also reviewed. Finally, we address elements that may foster clinical and social debate on this topic, suggesting potential aspects that need to be further investigated.


The effects of higenamine on LPS-induced experimental disseminated intravascular coagulation (DIC) in rats.
The effect of higenamine, a benzyl-tetrahydroisoquinoline alkaloid of the roots of Aconitum spp. (Ranunculaceae), on disseminated intravascular coagulation (DIC), was investigated using an experimental DIC rat model. The oral administration of higenamine (10 mg/kg or 50 mg/kg), significantly ameliorated the decrease of fibrinogen level in plasma, the increase of fibrinogen/fibrin degradation product (FDP) level, and the prolongation of prothrombin time (PT) induced by the i. v. infusion of lipopolysaccharide (LPS). The prolongation of activated partial thrombin time (aPTT) and the decrease of platelet count were suppressed. The increase in serum aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were also significantly prevented with higenamine. The above results are suggestive that higenamine has therapeutic potential for DIC and/or accompanying multiple organ failure (MOF).


Enhancing bioavailability and hepatoprotective activity of andrographolide from Andrographis paniculata, a well-known medicinal food, through its herbosome.
Andrographis paniculata is a health food used extensively in Southeast Asia, India and China and contains the pharmacologically important phytochemical andrographolide. Although andrographolide has antihepatotoxic activity, its bioavailability from A. paniculata is restricted by its rapid clearance and high plasma protein binding. The aim of this study was to formulate a herbosome of andrographolide with a naturally occurring phospholipid in order to enhance the bioavailability and hepatoprotective activity of andrographolide in rats. Andrographolide herbosome equivalent to 25 and 50 mg kg(-1) andrographolide significantly protected the liver of rats, restoring hepatic enzyme activities with respect to carbon tetrachloride-treated animals (P < 0.05 and P < 0.01 respectively). The rat plasma concentration of andrographolide obtained from the complex equivalent to 25 mg kg(-1) andrographolide (C(max) = 9.64 microg mL(-1)) was higher than that obtained from 25 mg kg(-1) andrographolide (C(max) = 6.79 microg mL(-1)), and the complex maintained its effective plasma concentration for a longer period of time. The results proved that the andrographolide complex produced by this method has better bioavailability and hence improved hepatoprotective activity compared with andrographolide at the same dose. Andrographolide complexation is therefore helpful in solving the problem of rapid clearance and low elimination half-life associated with andrographolide from A. paniculata.


Long-acting reversible contraceptive use in urban women from a title X-supported Boston community health center.
Unintended and adolescent pregnancy disproportionately affects minority populations, but the effect of age, race and ethnicity on the use of long-acting reversible contraception (LARC) has not been well studied. The objective of this pilot study was to examine LARC use over a 5-year period among women receiving care at a Boston community health center. Retrospective cohort study of LARC method use among black, Hispanic, and white women receiving care at the Dimock Center from 2006 to 2010. This study included 276 women (60.1% black, 18.5% Hispanic, and 9.1% white). LARC was not used as a first-line method in the majority (96.0%), regardless of age, race, and ethnicity; yet nearly half identified a long-acting contraceptive as their method of choice. The findings of this pilot study reveal opportunities to reduce unintended pregnancy through increased LARC use, which may be accomplished by provider and patient education.


DNA-binding properties of amidine-substituted spiropyran photoswitches.
Two amidine-substituted spiropyran derivatives have been characterized with respect to the DNA-binding properties over a broad pH interval. The two derivatives differ in the number of positive charges. By varying the pH, the protonation state of the derivatives is also changed, allowing for additional variations in the charge distribution. We show that the closed spiro isomer does not bind for either of the two derivatives, whereas the open merocyanine forms bind both in the protonated and in the nonprotonated state, but with dramatically different binding constants. Flow-oriented linear dichroism (LD) measurements also show that there are differences in the binding modes between the various forms. We rationalize these differences in terms of structure and charge distribution.


[Professional practice: yesterday and today].
Past and present in professional activity. In times of crisis the author looks back to pose the professional activity problems, not only for dentists but in general, the university graduated, based on ethics, which is apparently disappearing nowadays.


Further evidence of differences in substance use and dependence between Australia and the United States.
The current study compared the prevalence of substance use and DSM-IV dependence in the USA and Australia. Participants aged 18-54 were selected from two cross-sectional nationally representative Australian (National Survey on Mental Health and Well-Being - NSMHWB, 1997, n=7570) and American (National Epidemiologic Survey on Alcohol and Related Conditions - NESARC, 2001-2002, n=29,673) household surveys. The NSMHWB utilised the Composite International Diagnostic Interview, whereas the NESARC used the Alcohol Use Disorder and Associated Disabilities Interview Schedule. The 12-month prevalence of alcohol use was lower in the USA (56.5%) than in Australia (77.2%), although the rates of alcohol dependence were similar in both countries. The USA had higher rates of alcohol dependence conditional on use (9.0%) compared to Australia (6.8%). Australians had higher levels of drug use, dependence, and conditional dependence than Americans (except for sedatives and opioids). The absence of significant interactions between country of interview and the common correlates of substance use disorders indicated that the influence of these factors was similar in the USA and Australia. In conclusion, the current investigation revealed striking differences in the rates of conditional drug dependence between Australia and the USA. The cross-national generalizability of the relationships between the common correlates and prevalence of substance use and dependence indicates that a similar process of vulnerability to dependence may be operating in the USA and Australia. In the future, these cross-national differences could be used to help better understand the factors that influence drug use and the development of dependence.


Effect of the lipidosterolic extract of Serenoa repens (Permixon) and its major components on basic fibroblast growth factor-induced proliferation of cultures of human prostate biopsies.
To assess the effect of the lipidosterolic extract of Serenoa repens (LSESr) on in vitro cell proliferation in biopsies of human prostate Cell proliferation was assessed by incorporation of [3H]thymidine followed by historadiography. Basic fibroblast growth factor (b-FGF) induced a considerable increase in human prostate cell proliferation (from +100 to +250%); the glandular epithelium was mainly affected, minimal labeling being recorded in the other regions of the prostate. Similar results were observed with epidermal growth factor (EGF), although the increase in cell proliferation was not recorded in some cases. Lovastatin, an inhibitor of hydroxymethylglutaryl coenzyme A, antagonized both the basal proliferation and the growth factor-stimulated proliferation of human prostate epithelium (EGF, mean inhibition approximately 80-95%; b-FGF, mean inhibition approximately 40-90%). Geraniol, a precursor of both farnesyl pyrophosphate and geranylgeranyl pyrophosphate, and farnesol, the precursor of farnesyl pyrophosphate, increased cell proliferation only in some prostate specimens, this effect being antagonized by lovastatin. LSESr did not affect basal prostate cell proliferation, with the exception of two prostate specimens in which a significant inhibition of basal proliferation was observed with the highest concentration of LSESr (30 micrograms/ ml). In contrast, LSESr inhibited b-FGF-induced proliferation of human prostate cell cultures; this effect was significant for the highest concentration of LSESr (30 micrograms/ml). In some prostate samples, a similar inhibition was also noted with lower concentrations. Unsaturated fatty acids (UFA), in the range 1-30 ng/ml), did not affect the basal prostate cell proliferation, only a slight increase in cell proliferation was noted in 1 prostate specimen. UFA (1, 10 or 30 micrograms/ml) markedly inhibited the b-FGF-induced cell proliferation down to the basal value. Lupenone, hexacosanol and the unsaponified fraction of LSESr markedly inhibited the b-FGF-induced cell proliferation, whereas a minimal effect on basal cell proliferation was noted. Despite the large variability in the response of the prostate samples to b-FGF, these results indicate that LSESr and its components affect the proliferative response of prostate cells to b-FGF more than their basal proliferation.


Structural and Optical Properties of Metal-Nitrosyl Complexes.
The electronic, structural and optical properties (including Spin-Orbit Coupling) of metal nitrosyl complexes [M(CN)5(NO)]2- (M = Fe, Ru or Os) are investigated by means of Density Functional Theory, TD-DFT and MS-CASPT2 based on an RASSCF wavefunction. The energy profiles connecting the N-bound (η1-N), O-bound (η1-O) and side-on (η2-NO) conformations have been computed at DFT level for the closed shell singlet electronic state. For each structure, the lowest singlet and triplet states have been optimized in order to gain insight into the energy profiles describing the conformational isomerism in excited states. The energetics of the three complexes are similar-with the N-bound structure being the most stable-with one exception, namely the triplet ground state of the O-bound isomer for the iron complex. The conformation isomerism is highly unfavorable in the S0 electronic state with the occurrence of two energy barriers higher than 2 eV. The lowest bands of the spectra are assigned to MLCTNO/LLCTNO transitions, with an increasing MLCT character going from iron to osmium. Two low-lying triplet states, T1 (MLCTNO/LLCTNO) and T2 (MLCTNO/ILNO), seem to control the lowest energy profile of the excited-state conformational isomerism.


Patterns of morphological integration between parietal and temporal areas in the human skull.
Modern humans have evolved bulging parietal areas and large, projecting temporal lobes. Both changes, largely due to a longitudinal expansion of these cranial and cerebral elements, were hypothesized to be the result of brain evolution and cognitive variations. Nonetheless, the independence of these two morphological characters has not been evaluated. Because of structural and functional integration among cranial elements, changes in the position of the temporal poles can be a secondary consequence of parietal bulging and reorientation of the head axis. In this study, we use geometric morphometrics to test the correlation between parietal shape and the morphology of the endocranial base in a sample of adult modern humans. Our results suggest that parietal proportions show no correlation with the relative position of the temporal poles within the spatial organization of the endocranial base. The vault and endocranial base are likely to be involved in distinct morphogenetic processes, with scarce or no integration between these two districts. Therefore, the current evidence rejects the hypothesis of reciprocal morphological influences between parietal and temporal morphology, suggesting that evolutionary spatial changes in these two areas may have been independent. However, parietal bulging exerts a visible effect on the rotation of the cranial base, influencing head position and orientation. This change can have had a major relevance in the reorganization of the head functional axis.


Pharmacist-led academic detailing intervention in primary care: a mixed methods feasibility study.
Background Academic detailing is a form of continuing medical education in which a trained health professional such as a physician or pharmacist visits prescribers in their practice to provide evidence-based information. While academic detailing has been adopted in other countries, this strategy is not routinely used in Ireland. Objective The aim of this study was to assess the feasibility and acceptability to General Practitioners (GPs) of a pharmacist-led academic detailing intervention in Ireland. Setting General Practice in County Cork, Ireland. Method A mixed methods feasibility study comprising a pharmacist-led academic detailing intervention on urinary incontinence in older people, quantitative data from patient medical records, and qualitative data from focus groups with GPs. The medical records for all patients aged ≥ 65 years who were attending a participating GP with a diagnosis of urinary incontinence were analysed using a before-after approach. The measures of prescribing assessed before and after the intervention were: LUTS-FORTA criteria, Drug Burden Index, and the Anticholinergic Cognitive Burden scale. Focus groups were carried out with GPs who participated in the academic detailing intervention. Main outcome measure The quantitative prescribing patterns of the GPs and their qualitative responses from the focus groups. Results Twenty-three GPs participated in the academic detailing intervention from a selection of different types of general practice. The medical records of 154 patients were analysed. There was minimal or no change in any of the prescribing measures used. Fourteen GPs attended focus groups. GPs considered the topic of urinary incontinence as relevant to general practice. Participants appreciated the succinct nature of the information in the educational materials but expressed a preference for a more easily retrievable format, such as an online version rather than paper-based. Conclusion This study demonstrated that a pharmacist-led academic detailing intervention was acceptable to GPs in Ireland. Further research is needed in a larger population evaluating the impact and cost effectiveness of academic detailing to optimise patient care.


Structural diversity in copper-sulfur chemistry: synthesis of novel Cu/S clusters through metathesis reactions.
With the ultimate goal of understanding the Cu(4)S cluster in nitrous oxide reductase, studies of the fundamental chemistry of nitrogen-donor ligand-supported copper-sulfur species have been pursued. Reactions of Cu(II)X(2) (X = Cl(-) or CF(3)SO(3)(-)), N,N,N',N'-tetramethyl-trans-(1R,2R)-diaminocyclohexane, and Li(2)S or Na(2)S(2) yielded clusters that contain [Cu(2)(micro-S(2))(2)](2+), [Cu(3)(micro-S)(2)](3+), [Cu(4)(micro-S(2))(2)](4+), and/or [Cu(6)(micro-S(2))(4)](4+) cores, depending on the specific reaction conditions, notably the nature of X and the sulfur source used. Copper(II) and/or Copper(III) and variable sulfur oxidation levels, including S(2-), S(2)(2-), and S(2)(-*), were identified by X-ray crystallography and spectroscopy.


Finite element stress analysis of a class I amalgam restoration subjected to setting and thermal expansion.
Stress analyses are presented for a second mandibular premolar with a class 1 amalgam restoration. The effects of amalgam setting and thermal expansions are examined. An axisymmetric representation of the structure is used and the analyses are carried out by the finite element method. Lined and unlined restorations are compared with regard to the principal stresses set up in the composite structures and also the patterns of deformation incurred. The effects of various enamel and dentin stiffness combinations are also considered.


Wireless Networks under a Backoff Attack: A Game Theoretical Perspective.
We study a wireless sensor network using CSMA/CA in the MAC layer under a backoff attack: some of the sensors of the network are malicious and deviate from the defined contention mechanism. We use Bianchi's network model to study the impact of the malicious sensors on the total network throughput, showing that it causes the throughput to be unfairly distributed among sensors. We model this conflict using game theory tools, where each sensor is a player. We obtain analytical solutions and propose an algorithm, based on Regret Matching, to learn the equilibrium of the game with an arbitrary number of players. Our approach is validated via simulations, showing that our theoretical predictions adjust to reality.


Alabama hospitals reduce infections by 19%.
By using an automated system which quickly points out which patients have developed infections, hospitals in Alabama have been able to reduce the nosocomial infection rate by 19% and save millions of dollars in treatment costs. Not only are hospitals responding to individual infections faster, they are also using the system to analyze trends and implement performance improvements to prevent infections from happening in the first place.


[Social consequences of breast cancer in women suffering from the disease].
The opinion poll was carried out among 350 patients suffering from the breast cancer who had been treated in 1995 in the Autonomous Public Oncological Health Centre in Lublin. Out of this group 155 women filled in their questionnaires correctly and the data included in them underwent the statistic analysis whose aim was to determine the consequences of the breast cancer detection for women and their families as well as to evaluate the influence of the disease on the social situation of the subjects. The average age of the subjects was 56.7 and the largest group consisted of women at the age of 60 to 88 (41.9%). In the majority of cases (85.2%) the detection took place by means of self-examination, 88.4% of the women primarily underwent surgical treatment, the remaining 11.6% had no chance for radical treatment. Metastases were recorded in 13.5% of the cases in the period of 5 years after the application of treatment. The neoplasm triggered serious outcomes in the mental sphere of the women's lives. Feelings of fear (56.8%) and sadness (56.1%) were dominating. The sense of low self-esteem occurred in 19.4% of the subjects. In 41.9% of the women increased irritability and nervous excitability were observed which resulted in a more frequent usage of the tranquilizers (by 32.3% of them). The disease caused changes also in the economical and professional spheres of the women's lives. 57.4% of the women claimed that their family income had become lower which was the result of their retirement and ceasing their professional careers in 49% of the cases. Only 16.1% of the women did not observe any impact of the disease on their professional work. The changes which appeared in their lives in connection with the disease created the need for support and help from the side of the medical staff (47.1%) as well as the need for contacts and exchange of experience with women in a similar situation (40%). At the same time only a small percentage of women (16.8%) had an access to the Amazons' clubs and wanted to benefit from their aid.


Quality of reproductive healthcare for adolescents: A nationally representative survey of providers in Mexico.
Adolescents need sexual and reproductive health services but little is known about quality-of-care in lower- and middle-income countries where most of the world's adolescents reside. Quality-of-care has important implications as lower quality may be linked to higher unplanned pregnancy and sexually transmitted infection rates. This study sought to generate evidence about quality-of-care in public sexual and reproductive health services for adolescents. This cross-sectional study had a complex, probabilistic, stratified sampling design, representative at the national, regional and rural/urban level in Mexico, collecting provider questionnaires at 505 primary care units in 2012. A sexual and reproductive quality-of-healthcare index was defined and multinomial logistic regression was utilized in 2015. At the national level 13.9% (95%CI: 6.9-26.0) of healthcare units provide low quality, 68.6% (95%CI: 58.4-77.3) medium quality and 17.5% (95%CI: 11.9-25.0) high quality reproductive healthcare services to adolescents. Urban or metropolitan primary care units were at least 10 times more likely to provide high quality care than those in rural areas. Units with a space specifically for counseling adolescents were at least 8 times more likely to provide high quality care. Ministry of Health clinics provided the lowest quality of service, while those from Social Security for the Underserved provided the best. The study indicates higher quality sexual and reproductive healthcare services are needed. In Mexico and other middle- to low-income countries where quality-of-care has been shown to be a problem, incorporating adolescent-friendly, gender-equity and rights-based perspectives could contribute to improvement. Setting and disseminating standards for care in guidelines and providing tools such as algorithms could help healthcare personnel provide higher quality care.


The effect of mesna on plasma total homocysteine concentration in hemodialysis patients.
Plasma total homocysteine (tHcy) level is an independent risk factor for the development of atherosclerosis. The degree of risk in most of the population is decreased by using dietary vitamin supplementation; however, more than 90% of patients with end-stage renal disease have increased tHcy levels despite supplementation. Only a small fraction of tHcy is removed by hemodialysis because of extensive disulfide bonding to albumin. The objective of this study is to determine whether a single intravenous dose of mesna, a thiol-containing drug analogue of taurine, facilitates tHcy clearance during hemodialysis. Initial in vitro thiol exchange tests were performed with mesna in plasma from dialysis patients. Mesna, 300 micromol/L (49.2 mg/L), was incubated with plasma at 37 degrees C, and free homocysteine was measured at various times. In vivo, mesna activity was tested in 10 hemodialysis patients by administering 2.5 or 5.0 mg/kg of mesna intravenously at the beginning of a treatment cycle. Blood samples were drawn throughout dialysis, and plasma tHcy levels were compared with those obtained from a previous dialysis session in which mesna was not administered. In vitro, mesna liberated 36.5% +/- 2.5% of protein-bound homocysteine in 30 minutes. In vivo, a single 2.5-mg/kg dose of mesna was ineffective; however, at 5.0 mg/kg, it caused a 55.2% +/- 3.9% decrease in plasma tHcy levels postdialysis compared with a 34.2% +/- 5.3% decrease with dialysis alone (P < 0.001). Intravenous mesna causes a rapid decrease in plasma tHcy levels during hemodialysis.


The extraction, characterization and in vitro translation of RNA from adult Schistosoma mansoni.
We have extracted RNA from Schistosoma mansoni using the lithium chloride-urea method which gives good yields of undegraded RNA. The results of agarose gel electrophoresis of RNA extracted by this procedure suggest that S. mansoni has an in vivo nick in the large rRNA sub-unit. Translation of the RNA in a rabbit reticulocyte lysate gave significant incorporation of [35S]methionine into synthesized proteins. Immunoprecipitation of these translation products using a hyperimmune monkey serum sedimented between 5 and 8% of the radioactivity, which appeared to be present in approximately 13 proteins of molecular weights 18, 20, 21, 22, 23, 35, 40, 54, 60, 70, 74, 78 and 105 K Daltons.


The effects of intensity on the detection of interaural differences of time in high-frequency trains of clicks.
Threshold values of interaural differences of time (delta IDTs ) were measured for trains of dichotic clicks whose levels were 20, 40, or 60 dB SPL. All clicks were bandpass filtered at 4 kHz, and the number of clicks in the train (n) was 1, 2, 4, 8, 16, or 32. The interclick interval (ICI) was 5, 2, or 1 ms. Performance was compared to that of an ideal integrator of information, which produces slopes of - 0.5 when log delta IDT versus log n is plotted. The results showed that increases in level had no effect on the slopes of the log-log functions regardless of the ICI but did decrease the intercepts. Shortening the ICI caused the slopes to go from nearly - 0.5 towards 0.0. The improvement with level could be explained by either a decrease in the temporal variability of neural discharges, or by an increase in the number of samples of IDT at higher intensities brought on by increased firing rates or the activation of more auditory units. A review of the physiological literature found the most parsimonious explanation to be that the decline in threshold IDT was mediated by an increase in the number of active units, each possessing the same degree of adaptation.


SERR-spectroelectrochemical study of a cbb3 oxygen reductase in a biomimetic construct.
The cbb3 oxygen reductase from Bradyrhizobium japonicum was immobilized on nanostructured silver electrodes by anchoring the enzyme via a His-tag to a Ni-NTA coating, followed by reconstitution of a lipid bilayer. The immobilized enzyme retains the native structure and catalytic activity as judged by in situ surface-enhanced vibrational spectroscopy and cyclic voltammetry, respectively. Spectroelectrochemical titrations followed by SERR spectroscopy of the integral enzyme and its monohemic (fixO) and dihemic subunits (fixP), allowed the determination of the reduction potentials for the different heme c groups. Both in the isolated subunits and in the integral enzyme the Met/His-coordinated hemes from the two subunits present identical reduction potentials of 180 mV, whereas for the bis-His heme from fixP the value is ca. 400 mV. The determination of reduction potentials of the individual hemes c reported in this work provides the basis for further exploring the mechanism of electroprotonic energy transduction of this complex enzyme.


Modulating airway defenses against microbes.
Prevention and treatment of respiratory infections remain an important health care challenge as the US population ages, contains more susceptible or high-risk people, and encounters new pathogens or antibiotic resistant bacteria. Reasonably protective vaccines against very common microbes are available for childhood and adult immunization, but, generally, these are underutilized. A broader definition of higher risk individuals is evolving, which will include more for immunization. Different approaches to vaccine development through design of new component vaccines are necessary. This review has updated host defense mechanisms at three levels in the human respiratory tract: naso-oropharynx (upper airways), conducting airways, and alveolar space. Examples of representative pathogenic microbes have been inserted at the respective airway segment where they may colonize or create infection (influenza, measles virus, Porphyromonas gingivalis causing periodontitis, Bordetella pertussis, Chlamydia pneumoniae, Streptococcus pneumoniae, and Bacillus anthracis ). Hopefully, microbe-host interactions will suggest new approaches for preventing these kinds of infections.


Subcritical Fluid Extraction of Chinese Quince Seed: Optimization and Product Characterization.
Chinese quince seed (CQS) is an underutilized oil source and a potential source of unsaturated fatty acids and α-tocopherol-rich oil. Subcritical fluid (SCF) extraction is executed at lower pressures and temperatures than the pressures and temperatures used in supercritical fluid extraction. However, no studies on the SCF extraction of CQS oil are reported. Therefore, the objective of this study was to evaluate the use of SCF for the extraction of CQS oil and to compare the use of SCF with the classical Soxhlet (CS) and supercritical CO₂ (SC-CO₂) extraction methods. Response surface methodology (RSM) was used to investigate the extraction conditions: temperature (45-65 °C), time (30-50 min), and solvent/solid ratio (5-15 mL/g). The optimization results showed that the highest yield (27.78%) was obtained at 56.18 °C, 40.20 min, and 12.57 mL/g. The oil extracted by SCF had a higher unsaturated fatty acid content (86.37%-86.75%), higher α-tocopherol content (576.0-847.6 mg/kg), lower acid value (3.97 mg/g), and lower peroxide value (0.02 meq O₂/kg) than extractions using CS and SC-CO2 methods. The SCF-defatted meal of oilseed exhibited the highest nitrogen solubility index (49.64%) and protein dispersibility index (50.80%), demonstrating that SCF extraction was a promising and efficient technique as an alternative to CS and SC-CO2 methods, as very mild operating conditions and an eco-friendly solvent can be used in the process with maximum preservation of the quality of the meal.


Habitat type drives the spatial distribution of Australian fish chorus diversitya).
Fish vocalize in association with life functions with many species calling en masse to produce choruses. Monitoring the distribution and behavior of fish choruses provides high-resolution data on fish distribution, habitat use, spawning behavior, and in some circumstances, local abundance. The purpose of this study was to use long-term passive acoustic recordings to obtain a greater understanding of the patterns and drivers of Australian fish chorus diversity at a national scale. This study detected 133 fish choruses from year-long recordings taken at 29 Australian locations with the highest fish chorus diversity identified at a site in the country's northern, tropical waters. A linear model fitted with a generalized least squares regression identified geomorphic feature type, benthic substrate type, and northness (of slope) as explanatory variables of fish chorus diversity. Geomorphic feature type was identified as the significant driver of fish chorus diversity. These results align with broad-scale patterns reported previously in fish biodiversity, fish assemblages, and fish acoustic diversity. This study has highlighted that passive acoustic monitoring of fish chorus diversity has the potential to be used as an indicator of fish biodiversity and to highlight habitats of ecological importance.


Multicenter Retrospective Analysis of Second-Line Therapy after Gemcitabine Plus Nab-Paclitaxel in Advanced Pancreatic Cancer Patients.
Pancreatic cancer is one of the most lethal solid tumors. In many European countries gemcitabine plus nab-paclitaxel is the preferred first-line treatment. An increasing number of patients are eligible for second-line therapy, but the best regimen is still controversial. This study aimed to evaluate the efficacy of oxaliplatin-based compared to irinotecan-based therapies in this setting. 181 advanced pancreatic cancer patients consecutively treated in three centers with a second-line therapy progressed on gemcitabine plus nab-paclitaxel were retrospectively enrolled. OS and PFS were calculated using the Kaplan-Meier method and survival of the two groups was compared using the log-rank test. The median PFS and OS were respectively 3.5 (95%CI 3.2-3.8) and 8.8 months (95%CI 7.9-9.8) from second-line therapy in the overall population. The median PFS and OS were respectively 3.3 (95%CI 3.1-3.5) and 8.2 months (95%CI 7.24-9.34) with an irinotecan-based combination compared to 4.0 (95%CI 2.4-5.7) and 10.3 months (95%CI 8.62-12.02) in patients receiving an oxaliplatin-based combination. We observed a clear trend for longer survival outcomes with platinum-based doublet compared to regimens including irinotecan or nal-IRI. Head-to-head trials are still lacking. The neutrophil-to-lymphocyte ratio and the presence of liver metastases could drive physicians in tailoring the treatment strategy.


The Cancer Microbiome: Recent Highlights and Knowledge Gaps.
Knowledge of the human microbiome, which is likely a critical factor in the initiation, progression, and prognosis of multiple forms of cancer, is rapidly expanding. In this review, we focus on recent investigations to discern putative, causative microbial species and the microbiome composition and structure currently associated with procarcinogenesis and tumorigenesis at select body sites. We specifically highlight forms of cancer, gastrointestinal and nongastrointestinal, that have significant bacterial associations and well-defined experimental evidence with the aim of generating directions for future experimental and translational investigations to develop a clearer understanding of the multifaceted mechanisms by which microbiota affect cancer formation. SIGNIFICANCE: Emerging and, for some cancers, strong experimental and translational data support the contribution of the microbiome to cancer biology and disease progression. Disrupting microbiome features and pathways contributing to cancer may provide new approaches to improving cancer outcomes in patients.


Detecting malnutrition's warning signs with simple screening tools.
Nutrition problems of aging adults can be prevented, controlled, or treated, but the warning signs of malnutrition are often overlooked. Untreated malnutrition can lead to a spiral of infection, further malnutrition, and death. Simple assessment tools developed and distributed by the Nutrition Screening Initiative (NSI) can be used during an office visit to identify risk factors for poor nutritional status. These include advanced age, depression, social isolation, physical or cognitive impairment, and low income. Patients who are identified as being at high risk require immediate intervention, including medical and psychological evaluations. Often, an older adult without cognitive impairment can resume independent function when proper support is provided to correct the causes of malnutrition.


Air-stable and freestanding lithium alloy/graphene foil as an alternative to lithium metal anodes.
Developing high-capacity anodes is a must to improve the energy density of lithium batteries for electric vehicle applications. Alloy anodes are one promising option, but without pre-stored lithium, the overall energy density is limited by the low-capacity lithium metal oxide cathodes. Recently, lithium metal has been revived as a high-capacity anode, but faces several challenges owing to its high reactivity and uncontrolled dendrite growth. Here, we show a series of Li-containing foils inheriting the desirable properties of alloy anodes and pure metal anodes. They consist of densely packed LixM (M = Si, Sn, or Al) nanoparticles encapsulated by large graphene sheets. With the protection of graphene sheets, the large and freestanding LixM/graphene foils are stable in different air conditions. With fully expanded LixSi confined in the highly conductive and chemically stable graphene matrix, this LixSi/graphene foil maintains a stable structure and cyclability in half cells (400 cycles with 98% capacity retention). This foil is also paired with high-capacity Li-free V2O5 and sulfur cathodes to achieve stable full-cell cycling.


[Lipocalin and kidney transplant].
Kidney transplantation is frequently complicated by delayed graft function (DGF). DGF is associated with more frequent rejection episodes, increased need of post-transplantation biopsies, dialysis sessions and prolonged hospitalization. These complications may have negative impact on long-term survival of transplanted kidney.Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is regarded as acute kidney injury marker.This preliminary study aimed at evaluating whether uNGAL may be early predictor of DGF in kidney transplanted patients. Urine samples were collected from renal transplant recipients on day 1 post-transplantation to determine 24/h urinary NGAL and creatinine excretion. On same day, routine blood chemistry was assessed. N. 20 renal transplant recipients were evaluated. DGF was observed in n. 6 patients (DGF-patients). In DGF-patients compared to NO-DGF-patients, mean age was higher (586 Vs 5111, p=0.001), while 24/h urine output (5735 Vs 4150 2230 ml/24h; p=0.001) and urinary creatinine excretion (191184 Vs 683660 mg/24h; p=0.001) were lower. No difference was found between DGF- and NO-DGF-patients in 24/h urinary NGAL excretion (1,202,20 Vs 2,444,0 mg/24h; p<0.20). In univariate analysis, DGF was inversely associated to 24/h urine output (r2=-0.795, p=0.001) and urinary creatinine excretion (r2=-0.480, p=0.037) and positively to age (r2=0.446, p=0.049). In multivariate analysis 24/h urine output (p=0.014) and 24/h urinary creatinine excretion (p=0.039) were associated to DGF. This preliminary study suggests that 24/h urinary NGAL excretion, measured 1 day after kidney transplantation, is not a reliable predictor of DGF. Larger study with longer observation period is mandatory.


Effects of soft denture liners on L929 fibroblasts, HaCaT keratinocytes, and RAW 264.7 macrophages.
The effects of six soft liners (Ufi Gel P (UG), Sofreliner S (SR), Durabase Soft (D), Trusoft (T), Coe Comfort (CC), and Softone (ST)) on L929, HaCat, and RAW 264.7 cells were investigated. Eluates (24 and 48 h) from the materials were applied on the cells and the viability, type of cell death, and morphology were evaluated. Cells were also seeded on the specimens' surfaces (direct contact) and incubated (24 or 48 h), and viability was analyzed. Controls were cells in culture medium without eluates or specimens. For cell viability, no significant differences were found among materials or between extraction periods, and the liners were noncytotoxic or slightly cytotoxic. Morphology of RAW 264.7 cells was altered by the 24 h eluates from CC and D and the 48 h eluates from SR, CC, and D. The 24 and 48 h eluates from all materials (except T) increased the percentages of L929 necrotic cells. For direct contact tests, the lowest cytotoxicity was observed for UG and SR. Although eluates did not reduce viability, morphology alterations and increase in necrosis were seen. Moreover, in the direct contact, effects on viability were more pronounced, particularly for D, T, CC and ST. Thus, the use of UG and SR might reduce the risk of adverse effects.


[Wulst Activation in Pied Flycatcher Nestlings in Feeding Behavior Induced by Patterned Visual Stimulus].
Immunohistochemical detection of c-Fos was used to study the transcriptional activation in two higher visual centers (Wulst area and Entopallium) of 12-day-old pied flycatcher (Ficedula hypoleuca) during the realization of feeding behavior guided by patterned visual stimulus, simulating the species-specific one. Activation was compared in 4 groups of nestlings. Control group was not subjected to any experimental influence. In binocular, right-field (deprivation of the left eye) and left-filed (deprivation of the right eye) groups the vision feeding responses were provoked, reinforced and evaluated. It was shown that the visual afferentation from the right eye was more significant for the organization of early feeding behavior guided by a moving patterned visual stimulus as compared with the afferentation from the left eye. Feeding behavior induced activation of c-Fos expression only in neurons of the higher center of thalamofugal system--Wulst area. The comparison of transcriptional activation in different groups revealed the significant increase of c-Fos induction related with feeding behavior only in the left hemisphere and only in binocular and right-field groups.


Regulation of nuclear factor-kappaB (NF-kappaB) activity and apoptosis by estradiol in bovine granulosa cells.
Although atresia of bovine follicles is associated with apoptosis of granulosa cells, the signals initiating this cell death have not been resolved. NF-kappaB has been implicated as an important regulator of genes controlling apoptosis, and previous studies indicate that estradiol may modulate NF-kappaB activation. We hypothesized that estradiol activates NF-kappaB, and thus, inhibits apoptosis in granulosa cells of dominant follicles. Dominant follicles were collected on Days 4, 6, and 8 of the first follicular wave following ovulation and assayed for NF-kappaB activity. Concentrations of estradiol in follicular fluid decreased on Day 6 compared to Day 4 of the wave. NF-kappaB activity in granulosa cells was lower on Day 8 compared to Days 4 and 6. In vitro, NF-kappaB activity and minimal incidence of apoptosis (<4%), as measured by Annexin V and TUNEL assays, were associated with production of estradiol. However, inhibition of NF-kappaB in vitro led to a suppression of apoptosis. These results indicate that follicular NF-kappaB activation is associated with estradiol production. However, whether NF-kappaB is playing a pro- or anti-apoptotic role in granulosa cells of the dominant bovine follicle remains to be elucidated.


Opiates and thermoregulation in mice. I. Agonists.
These studies were undertaken to determine the effects of morphine and other opiate and opioid agonists on body temperature in the mouse. Mice were lightly restrained, and rectal temperatures were monitored after injection of opiate analgesics at each of three ambient temperatures. The drugs tested were pure agonists representing eight different chemical classes. At 20 degrees C, morphine, hydromorphone, levorphanol, oxymorphone, methadone, etonitazene, fentanyl, etorphine and meperidine produced hyperthermia in low doses and hypothermia as the doses were raised. Codeine produced only hypothermia at 20 degrees C in the doses studied. At 25 degrees C, the hypothermic responses were greatly reduced in magnitude, and most drugs produced biphasic or only hyperthermic responses. At 30 degrees C, dose-related hyperthermia was the usual response with the exception of meperidine which produced only hypothermia, although a temperature increase was observed after anileridine, a closely related phenylpiperidine. There is good correlation between the relative potencies of the agonists with respect to their hypothermic effects in mice and their relative potencies as analgesics in mice. The temperature effects of morphine are complex but appear to be characteristic of opiate agonists as a class. The magnitude and the direction of the temperature responses to opiates are dose-dependent and profoundly influenced by the environmental temperature.


Increases in job strain are associated with incident hypertension in the CARDIA Study.
Job strain, defined as high job demands and low decision latitude, has been associated with increased blood pressure levels in some studies, but most of these studies have been cross-sectional. We sought to determine whether changes in job strain during young adulthood were associated with the development of hypertension, using the Coronary Artery Risk Development in Young Adults cohort. A total of 3,200 employed, initially normotensive participants, aged 20 to 32 in 1987-1988, were followed for 8 years; the Job Content Questionnaire was completed twice: initially and 8 years later. Hypertension at follow-up was defined as systolic blood pressure (SBP) of 160 or higher and diastolic blood pressure of 95 mmHg or higher, or reporting being on antihypertensive medication. Job strain (based on job demands above the median and decision latitude below the median of the sample) was associated with hypertension incidence (ps <.05) for the entire cohort and among White women and men. Adjustment for baseline SBP, education, body mass index (BMI), change in BMI, and age did not alter these relations. The ratio of increasing demands relative to decreasing decision latitude was also associated with greater incidence of hypertension in the entire cohort in the multivariate model (odds ratio = 2.06, 95% confidence interval = 1.01-4.26). An increase in job strain is associated with incident hypertension, particularly among Whites.


Modeling aerobic biotransformation of vinyl chloride by vinyl chloride-assimilating bacteria, methanotrophs and ethenotrophs.
Recent studies have investigated the potential of enhanced groundwater Vinyl Chloride (VC) remediation in the presence of methane and ethene through the interactions of VC-assimilating bacteria, methanotrophs and ethenotrophs. In this study, a mathematical model was developed to describe aerobic biotransformation of VC in the presence of methane and ethene for the first time. It examines the metabolism of VC by VC-assimilating bacteria as well as cometabolism of VC by both methanotrophs and ethenotrophs, using methane and ethene respectively, under aerobic conditions. The developed model was successfully calibrated and validated using experimental data from microcosms with different experimental conditions. The model satisfactorily describes VC, methane and ethene dynamics in all microcosms tested. Modeling results describe that methanotrophic cometabolism of ethene promotes ethenotrophic VC cometabolism, which significantly enhances aerobic VC degradation in the presence of methane and ethene. This model is expected to be a useful tool to support effective and efficient processes for groundwater VC remediation.


Association of sexual dysfunction according to DSM-5 diagnostic criteria with avoidance of and discomfort during sex in a population-based sample.
Sexual dysfunction frequencies and diagnostic indicators among older populations are relevant for public health measures, but evidence from large population-based studies is still scarce. To determine sexual dysfunction frequencies for women and men according to the Diagnostic and Statistical Manual of Mental Disorders (fifth edition; DSM-5) among 45- to 74-year-old participants of the population-based Hamburg City Health Study and the factors associated with sexual dysfunction diagnoses. We determined sexual dysfunction frequencies according to the DSM-5 and the factors associated with sexual dysfunction diagnoses (quality/avoidance of and discomfort during sex) among 45- to 74-year-olds from 7786 participants of the population-based Hamburg City Health Study. We analyzed cross-sectional self-report questionnaire data collected between 2016 and 2019 using descriptive statistics, comparative tests (Fisher test, Mann-Whitney U test), and logistic regression. Outcomes included sexual dysfunction frequencies - specifically, sexual difficulties experienced frequently or more often, over at least six months in the last year, causing severe or very severe distress, and not associated with physical health or relationship problems - and items on quality/avoidance of and discomfort during sex. Participants' median age was 62.0 years (IQR, 14) and 51.1% were women. The frequency of sexual dysfunction according to the DSM-5 was 9.3% (95% CI, 8.3%-10.4%) in women and 6.2% (95% CI, 5.4%-7.1%) in men, with women's sexual interest/arousal and men's erectile disorder being most common. Sexual dysfunction rates increased with age: whereas complaints were more frequent among women than men in the younger groups, participants aged ≥65 years with a sexual dysfunction were more often men. Quality/avoidance of and discomfort during sex were significantly associated with a diagnosis of sexual dysfunction. Results suggest that sexual dysfunction caused by other than physical health or relationship factors is important to consider in this population. In addition, the avoidance of, perceived quality of, and discomfort during sex serve as valuable diagnostic indicators for the presence of sexual dysfunction. This study draws on robust data from a large sample to give valuable insight on the frequency of sexual difficulties and dysfunctions as defined by DSM-5 criteria. Limitations represent the restriction to self-report questionnaire data, the focus on participants living in a metropolitan area, and the lack of experience of sexual difficulties due to a lack of sexual activity not being taken into account. The study provides estimates for DSM-5 sexual dysfunction frequencies among Germans from a metropolitan area and points to the diagnostic value of age-related changes as well as the quality/avoidance of and discomfort during sex.


Clarification of the type series of Amphibolurus barbatus microlepidotus Glauert, 1952 (= Pogona microlepidota) (Reptilia: Squamata: Agamidae).
Ludwig Glauert (1952, p. 168) established the name Amphibolurus barbatus microlepidotus (= Pogona microlepidota) for a new agamid species (family Agamidae) from the type locality of "Drysdale River Mission, North Kimberley", Western Australia and listed two specimens of the Western Australian Museum (WAM) collected by "Rev. Father [Raymundus] Salinas" in July 1922 as "types". The two registrations forming the type series presented by Glauert were WAM R591 and WAM R592, which in accordance with Article 72.1.1. of the International Code for Zoological Nomenclature (the Code; International Commission on Zoological Nomenclature 1999) are considered syntypes. The two registrations presented by Glauert in the original publication (WAM R591-592) are in error, both registrations are associated with specimens of other species not matching the description or collection data presented by Glauert in the original description of A. b. microlepidotus. The specimen associated with WAM R591 is a Pseudonaja affinis Günther, 1872 (Serpentes: Elapidae), collected by M. Sweeting from the suburb of Leederville in Perth, Western Australia and WAM R592 a specimen of Neelaps calonotus (Duméril, Bibron, Duméril, 1854) (Serpentes: Elapidae) collected by C. Thomas from the Perth suburb of West Guildford (now Bassendean), Western Australia (Fig. 1). The P. affinis specimen (WAM R591) is purportedly a whole specimen stored in a 75% ethanol solution; however, extensive searches failed to locate the specimen in the WAM collection and it is presumed lost or disposed of. In the early half of the 20th century, large and easily identifiable specimens were sometimes disposed following identification, registration and collection of morphological data due to their preservation and storage difficulty (see Smith 1981). The N. calonotus specimen (WAM R592) is now an alizarin-stained body in a glycol solution with skin stored separately in 75% ethanol (Fig. 1). The erroneous registration numbers provided by Glauert technically placed the name A. b. microlepidotus into synonymy with either N. calonotus or P. affinis depending on lectotype selection.


Benign neural invasion in chronic pancreatitis.
We describe two cases of benign neural invasion by proliferated islet cells in a background of chronic pancreatitis, and cite additional examples of benign neural invasion in other locations. This phenomenon, which represents the presence of collections of benign epithelial structures in a nerve or in a perineural space, is usually associated with an adjacent proliferative, but benign process, suggesting that mechanical forces may produce displacement along planes of least resistance. The important point is that neural invasion is not synonymous with malignancy, and that benign epithelial structures can be encountered in both a perineural and intraneural location.


Photoinduced electron transfer upon supramolecular complexation of (porphyrinato)Sn-viologen with cucurbit[7]uril.
The synthesis of (porphyrinato)Sn-viologen, 1, and its supramolecular complexation with cucurbit[7]uril (CB[7]) were studied. 1H NMR spectroscopic studies obviously reveal that 1 forms a 1 : 2 supramolecular complex with CB[7] through the inclusion of viologen moieties of 1 into the cavity of CB[7]. The cyclic voltammetric study supports that the binding affinity of the radical cation forms is comparable to that of the di-cation viologen toward CB[7]. The fluorescence arising from the porphyrin moiety is significantly quenched upon the complexation of 1 with CB[7]. The ps-time-resolved fluorescence and ns-transient absorption spectroscopic studies reveal that the photoinduced electron transfer (PET) between viologen and Sn(iv) porphyrin of 1 takes place from the first excited singlet (S1) state and the second excited triplet (T2) state of the porphyrin moiety upon complexation with CB[7], while the PET from the S1 state is negligible in the absence of CB[7].


A transcutaneous PO2 electrode incorporating a thermal clearance local blood flow sensor.
Several possible methods for estimating and recording skin blood flow by thermal clearance are presented. The method chosen for trial with an O2 electrode was to thermoregulate an annular anode which covered the cathode, surrounding it like a heat shell, and to measure the cooling of the cathode by blood flow, by implanting a thermistor near the surface of the cathode. This device is far less affected by ambient temperature than is simple measurement of heating power in an uninsulated tcPO2 electrode.


Gastric peritoneal carcinomatosis - a retrospective review.
To characterize patients with gastric peritoneal carcinomatosis (PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of care. We performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral centre. We studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority (n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175 (64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive Cancer Network Guidelines for Gastric Cancer Treatment. These patients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114 (66.7%), while cessation of chemotherapy occurred in 157 (91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not (10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not (8.7 mo vs 14.6 mo, P < 0.001). Gastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their survival outcomes in the long run.


Navoban (tropisetron, ICS 205-930) and dexamethasone combination in the prevention of vomiting for patients receiving preconditioning high-dose chemotherapy before marrow transplantation.
The anti-emetic efficacy of a combination of tropisetron and dexamethasone was studied in 33 patients who underwent bone marrow transplantation. Another 50 patients receiving conventional anti-emetic therapies in bone marrow transplantation served as control. On the first and second days of preconditioning chemotherapy, 51% and 36% respectively of patients in the tropisetron and dexamethasone group did not experience vomiting, compared with only 12% and 10% of control group patients (P < 0.001). The mean number of episodes of vomiting in the tropisetron and dexamethasone group was also significantly lower than in the control group (0.97+/-1.65 vs 3.50+/-2.45 and 1.30+/-1.40 vs 4.44+/-2.91 respectively, both P < 0.001). Control of vomiting in the two groups was not significantly different during days 3-6. Analysis of patients receiving busulfan and cyclophosphamide as the preconditioning regimen still showed better anti-emetic control in the tropisetron and dexamethasone group than in the control group on the first two days of treatment (total control rate 33.3% vs 6.5% and 44.4% vs 12.9% respectively, P < 0.001). Patients given tropisetron and dexamethasone combination more frequently suffered from dizziness and burning sensation of the chest. However, diarrhea and extrapyramidal symptoms were the most frequent adverse effects seen after using conventional anti-emetic combination. The combination of tropisetron and dexamethasone was thus superior to conventional anti-emetic combinations in preventing vomiting during preconditioning period of bone marrow transplantation. The adverse effects of this combination were minimal and well tolerated by patients.


The use of pre-natal diagnostic techniques for sex selection: the Indian scene.
The use of pre-natal diagnostic techniques only for sex determination followed by termination of pregnancy on a finding of female foetus, is an atrocious and unethical practice. The bias against a female has been stretched further back: from cradle to grave, it is now from womb to the grave. One cannot however ignore the conditions of the society which breed and encourage such practices. A girl suffers neglect and discrimination right from childhood; she is tortured, harassed and maltreated after marriage. At the work place she is exploited. A widow or a divorcee is looked down upon by the family and the society. All these things make her life miserable and not worth existence....


High prevalence of HIV infection and unprotected anal intercourse among older men who have sex with men in China: a systematic review and meta-analysis.
China has the largest number of the elderly in the world. As the proportion of elderly is rapidly increasing among national reported HIV/AIDS cases, it is a concern about HIV epidemic among older MSM in China. However, studies on HIV prevalence and unprotected anal intercourse (UAI) among Chinese older MSM were relatively few or generally had small sample sizes. English and Chinese articles published in peer-reviewed journals were identified by systematically searching 5 electronic databases including PubMed and through cross-referencing. Summary prevalence rates of HIV infection and UAI with male sexual partners were calculated, and analyses were performed using the software Comprehensive Meta-Analysis V2.0 and SPSS V17.0. Subgroup analyses were performed separately by sample size, study year, study location, recruitment settings and sampling method. Twenty eligible cross-sectional studies (3 in English and 17 in Chinese), published between 2005 and 2013, with a total of 2812 older MSM participants, were identified. Our meta-analyses showed that the prevalence of HIV, syphilis and UAI in the last 6 months were 11.6% (95% confidence interval [CI]: 8.0%-16.6%), 23.0% (95% CI: 15.8%-32.3%) and 79.5% (95% CI: 72.7%-84.9%), respectively. HIV prevalence increased over the study period (6.3% in 2003-2007; 8.6% in 2008-2009, and 11.5% in 2010-2011, trend test Chi-square = 7.02, p = 0.008). The pooled prevalence of HIV (11.6% vs. 5.2%, Chi-square value = 36.2, p < 0.001) and UAI (79.5% vs. 52.6%, Chi-square value = 440.04, p < 0.001) among older MSM were both significantly higher than among younger age group (age < 50 years). Older Chinese MSM have high prevalence of HIV and syphilis. Unprotected anal sex is common and further puts them at high risks of acquiring and transmitting HIV, which was one of reasons for the rapid increasing of national reported older male HIV/AIDS cases. Prevention intervention programs should be specially tailored for this high risk MSM subgroup.


The Podospora anserina lytic polysaccharide monooxygenase PaLPMO9H catalyzes oxidative cleavage of diverse plant cell wall matrix glycans.
The enzymatic conversion of plant biomass has been recently revolutionized by the discovery of lytic polysaccharide monooxygenases (LPMO) that catalyze oxidative cleavage of polysaccharides. These powerful enzymes are secreted by a large number of fungal saprotrophs and are important components of commercial enzyme cocktails used for industrial biomass conversion. Among the 33 AA9 LPMOs encoded by the genome of Podospora anserina, the PaLPMO9H enzyme catalyzes mixed C1/C4 oxidative cleavage of cellulose and cello-oligosaccharides. Activity of PaLPMO9H on several hemicelluloses has been suggested, but the regioselectivity of the cleavage remained to be determined. In this study, we investigated the activity of PaLPMO9H on mixed-linkage glucans, xyloglucan and glucomannan using tandem mass spectrometry and ion mobility-mass spectrometry. Structural analysis of the released products revealed that PaLPMO9H catalyzes C4 oxidative cleavage of mixed-linkage glucans and mixed C1/C4 oxidative cleavage of glucomannan and xyloglucan. Gem-diols and ketones were produced at the non-reducing end, while aldonic acids were produced at the reducing extremity of the products. The ability of PaLPMO9H to target polysaccharides, differing from cellulose by their linkages, glycosidic composition and/or presence of sidechains, could be advantageous for this coprophilous fungus when catabolizing highly variable polysaccharides and for the development of optimized enzyme cocktails in biorefineries.


Regimes of Head-On Collisions of Equal-Sized Binary Droplets.
Through molecular dynamics simulations, head-on collision processes of two identical droplets with a diameter of 10.9 nm are elaborately scrutinized over a wide range of impact Weber numbers (from 6.7 to 1307) both in vacuum and in an ambient of nitrogen gas. As the impact Weber number exceeds a certain critical value, a hole or multiple holes in apparently random locations are observed in the disklike structure formed by two colliding droplets. We name this a new "hole regime" of droplet collisions, which has not yet been reported in previous studies. As the impact Weber number increases, the number of holes increases. The hole or holes may disappear unless a second critical impact Weber number is exceeded, when the merged droplet is likely to experience dramatic shattering. It is also found that the existence of ambient gas provides a "cushion effect" which resists droplet deformation, thus delaying or even preventing the appearance of hole formation and shattering regimes. Moreover, increasing ambient pressure suppresses hole formation. A model based on energy balance is proposed to predict droplet behaviors, which provides a more accurate estimate of the maximum spreading factor compared to previous models. Finally, we further extend the current nanoscale droplet collision regime map and analyze the similarities and dissimilarities between nano- and macroscale droplet collision. Our study extends the current understanding on nanodroplet collisions.


Characterization of and genetic variation for tomato seed thermo-inhibition and thermo-dormancy.
Exposing imbibed seeds to high temperatures may lead to either thermo-inhibition of germination or thermo-dormancy responses. In thermo-inhibition, seed germination is inhibited but quickly resumed when temperatures are lowered. Upon prolonged exposure to elevated temperatures, thermo-dormancy may be induced and seeds are not able to germinate even at optimal temperatures. In order to explore underlying physiological and molecular aspects of thermo-induced secondary dormancy, we have investigated the physiological responses of tomato seeds to elevated temperatures and the molecular mechanisms that could explain the performance of tomato seeds at elevated temperature. In order to investigate how tomato seeds respond to high temperature we used two distinct tomato accessions: Solanum lycopersicum (cv. Moneymaker) (MM) and Solanum pimpinellifolium accession CGN14498 (PI). MM seeds did not germinate under high temperature conditions while seeds of PI reached a maximum germination of 80%. Despite the high germination percentage of PI, germinated seeds did not produce healthy seedling at 37 °C. By using a candidate gene approach we have tested if similar molecular pathways (abscisic acid (ABA) and gibberellic acid (GA)) present in lettuce and Arabidopsis, are regulating thermo-inhibition and thermo-dormancy responses in tomato. We showed that the ABA biosynthesis pathway genes NCED1 and NCED9 were upregulated whereas two of the GA-biosynthesis regulators (GA3ox1 and GA20ox1) were downregulated in tomato thermo-dormant seeds at elevated temperature. To identify novel regulators of tomato seed performance under high temperature, we screened a Recombinant Inbred Line (RIL) population derived from a cross between the two tomato accessions MM and PI for thermo-inhibition and dormancy induction. Several QTLs were detected, particularly for thermo-dormancy, which may be caused by new regulators of thermo-inhibition and thermo-dormancy in tomato. None of the genes studied in this research were co-locating with the detected QTLs. The new QTLs discovered in this study will therefore be useful to further elucidate the molecular mechanisms underlying the responses of tomato seeds to high temperature and eventually lead to identification of the causal genes regulating these responses.


SmdA is a Novel Cell Morphology Determinant in Staphylococcus aureus.
Cell division and cell wall synthesis in staphylococci need to be precisely coordinated and controlled to allow the cell to multiply while maintaining its nearly spherical shape. The mechanisms ensuring correct placement of the division plane and synthesis of new cell wall have been studied intensively. However, hitherto unknown factors and proteins are likely to play key roles in this complex interplay. Here, we identified and investigated a protein with a major influence on cell morphology in Staphylococcus aureus. The protein, named SmdA (for staphylococcal morphology determinant A), is a membrane protein with septum-enriched localization. By CRISPRi knockdown and overexpression combined with different microscopy techniques, we demonstrated that proper levels of SmdA were necessary for cell division, including septum formation and cell splitting. We also identified conserved residues in SmdA that were critical for its functionality. Pulldown and bacterial two-hybrid interaction experiments showed that SmdA interacted with several known cell division and cell wall synthesis proteins, including penicillin-binding proteins (PBPs) and EzrA. Notably, SmdA also affected susceptibility to cell wall targeting antibiotics, particularly in methicillin-resistant S. aureus (MRSA). Together, our results showed that S. aureus was dependent on balanced amounts of membrane attached SmdA to carry out proper cell division. IMPORTANCE Staphylococcus aureus is an important human and animal pathogen. Antibiotic resistance is a major problem in the treatment of staphylococcal infections, and cell division and cell wall synthesis factors have previously been shown to modulate susceptibility to antibiotics in this species. Here, we investigated the function of a protein named SmdA, which was identified based on its septal localization and knockdown phenotype resulting in defective cellular morphologies. We demonstrated that this protein was critical for normal cell division in S. aureus. Depletion of SmdA sensitized resistant staphylococci to β-lactam antibiotics. This work revealed a new staphylococcal cell division factor and a potential future target for narrow-spectrum antimicrobials or compounds to resensitize antibiotic-resistant staphylococcal strains.


Public beliefs about the causes of obesity and attitudes towards policy initiatives in Great Britain.
To assess attributions for overweight and the level of support for policy initiatives in Great Britain. Cross-sectional. Respondents indicated their agreement (5-point scales: strongly disagree to strongly agree) to three potential causes of overweight (environment, genes, willpower) and five policies (free weight-loss treatment, taxing unhealthy foods, healthy lifestyle campaigns, food labelling, advertising restrictions). Data were collected as part of a computer-assisted, face-to-face Omnibus survey of adults (aged >15 years) from across Great Britain in April 2012 carried out by a market research company. A population-representative sample of British adults (n 1986). More people attributed overweight to the food environment (61 %) and lack of willpower (57 %) than to genes (45 %). Policy support was highest for healthy lifestyle campaigns (71 %) and food labelling (66 %), and lowest for taxing unhealthy foods (32 %). Food environment attributions were associated with higher support for all policies (P < 0·001). Genetic attributions were associated with higher support for free weight-loss treatments and healthy lifestyle campaigns (P < 0·001), but not other policies. Attributions to lack of willpower were not associated differentially with support for any policies (P > 0·01). Belief that overweight is caused by the food environment or genes – both seen as outside individual control – was associated with greater support for government policies to prevent and treat obesity. Improving awareness of the multiple causes of obesity could facilitate acceptance of policy action to reduce obesity prevalence.


Rate of recovery after flexor tendon repair in zone II. A prospective longitudinal study of 145 digits.
A series of 145 digits were treated with three controlled motion programmes after flexor tendon repair in zone II. Active interphalangeal joint motion was measured four, six and 12 weeks; six months and one year after operation. Although there were differences in the final results among the groups, the rate of recovery from the end of the controlled motion period (four weeks after operation), was not significantly different in the three treatment groups. Overall, a mean of 37% of the final distal interphalangeal joint range of motion and 9% of the final proximal interphalangeal joint range of motion was recovered between three months and one year postoperatively. In only 10 of 27 digits with a poor result (combined interphalangeal joint range of motion less than 90 degrees) at three months, was the result still poor at one year; 10 regained another 40 degrees or more, and eight another 50 degrees or more. The results indicate that it is worth waiting six or 12 months before considering tenolysis.


Overproduction and large-scale preparation of deoxyuridine triphosphate nucleotidohydrolase from Escherichia coli.
A recombinant plasmid, pHW1, directing the overproduction of the enzyme deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase, EC 188.8.131.52) from Escherichia coli has been constructed. A 1900-base DNA fragment carrying the structural gene for the enzyme (dut) has been recloned into a runaway replication vector that also carries the strong leftward promoter (pL) of bacteriophage lambda. Upon temperature shift, an E. coli strain carrying the new plasmid gives an increase in dUTPase activity of about 600-fold in rich medium compared to wild-type bacteria. The 64-kDa protein corresponding to the mature form of the enzyme reaches 20% of the total protein content of the bacterial cell. Using this strain, a simplified procedure has been developed for the purification of dUTPase. The purification steps consist of extraction of the cytoplasmic proteins, ammonium sulfate precipitation, anion-exchange chromatography and gel filtration on FPLC. The new overproducing plasmid and the simplified purification procedure developed will make it possible to purify dUTPase in sufficient amounts for detailed characterization studies.


[Long-term clinical results with Procera AllCeram full-ceramic crowns].
The aim of this prospective clinical study was to investigate the long-term survival rate of Procera AllCeram full-ceramic crowns, which were fabricated with aluminiumoxide cores. In 50 patients, 155 Procera crowns with a conventional or reduced core (porcelain collar) were placed on natural abutment teeth. 78% of this group (39 patients with 135 crowns) were examined between May and August 2005 according to the modified USPHS-Criteria. These crowns had been in place for a period of one to 92 months (mean 55 months). Almost half of the crowns were located in the molar region, while 28% were premolars and 24% anterior crowns. Due to one crown fracture the cumulative survival rate was 99% after five and seven years. The clinical success was achieved irrespective of the tooth position, tooth vitality, the preparation margin and the cementum medium used (composite resin or glasionomer cement). In addition, survival was neither influenced by the core design with reduced or conventional margin nor by the core thickness, which measured regularly 0.6 mm in the majority of the specimens. Based on the present findings, it can be concluded that Procera AllCeram is a predictable technique for metal-free, esthetic full-ceramic crowns in the anterior and posterior region.


Correcting COVID-19 vaccine misinformation in 10 countries.
What can be done to reduce misperceptions about COVID-19 vaccines? We present results from experiments conducted simultaneously on YouGov samples in 10 countries (N = 10 600), which reveal that factual corrections consistently reduce false beliefs about vaccines. With results from these 10 countries, we find that exposure to corrections increases belief accuracy by 0.16 on a 4-point scale, while exposure to misinformation decreases belief accuracy by 0.09 on the same scale. We are unable to find evidence that either misinformation or factual corrections affect intent to vaccinate or vaccine attitudes. Our findings on effect duration are less conclusive; when we recontacted participants two weeks later, we observed 39% of the initial accuracy increase, yet this result narrowly misses conventional thresholds of statistical significance (p = 0.06). Taken together, our results illustrate both the possibilities and limitations of factual corrections. Evidence from 10 highly diverse populations shows that exposure to factual information reduces belief in falsehoods about vaccines, but has minimal influence on subsequent behaviours and attitudes.


Factors Associated with Family Planning Status and Voluntary Childlessness in Women of Childbearing Age with Inflammatory Bowel Diseases.
Women with Inflammatory Bowel Diseases (IBD) have fewer children and stay childless more often. The decision-making process around family planning choices remains incompletely understood. We examined family status in women who at recruitment to the UK IBD Bioresource had not had children yet via an electronic survey. The primary outcome was the proportion of women with voluntary childlessness. Secondary outcomes were factors associated with family planning status. Of 326 responders, 10.7% had either given birth, were currently pregnant or were currently trying to conceive; 12.6% were planning to conceive within 12 months; 54.4% were contemplating conception in the distant future (vague plans); and 22.3% were voluntarily childless. Factors associated with family planning status fell into three areas: general background (age, household income, perceived support to raise a child), relationship status (sexual orientation, being single, not cohabiting, perception of being 'in the right relationship to raise a child', perception of a good sex life) and the expression of having a child as a goal in life. On binary logistics regression analysis with voluntary childlessness versus vague family plans as the outcomes of choice, having a household income of <£30,000 (p = 0.046), not seeing a child as a life goal (p < 0.0001) and identifying as lesbian or bisexual (p = 0.047) were independent predictors of voluntary childlessness. Clinicians should consider sexual orientation, income, younger age, current relationship and lack of expression of having a child as a life goal as important factors for family planning when providing care. Pre-pregnancy advice should be made widely available for women with IBD.


A simple classification of orthognathic surgery complications.
Although orthognathic surgery has now become a routine part of oral and maxillofacial surgery practice, the complexity of such surgery together with the detailed planning involved makes it a difficult area of surgery to follow in the literature. The plethora of literature on the subject of complications in orthognathic surgery makes it essential to devise a simple classification of complications so that comparative studies can be identified and grouped together for more meaningful interpretation. The aim of this article is to present a brief and coherent overview of the main complications associated with orthognathic surgery for the purpose of establishing a simple classification of complications for future reference.


Influence of Secondary Hyperparathyroidism Induced by Low Dietary Calcium, Vitamin D Deficiency, and Renal Failure on Circulating Rat PTH Molecular Forms.
Rats(r) with secondary hyperparathyroidism were studied to define the relationship between vitamin D metabolites and rPTH levels measured by 3 different rat ELISAs. Controls and renal failure (RF) rats were on a normal diet, while 2 groups on a low-calcium (-Ca) or a vitamin D-deficient (-D) diet. RF was induced surgically. Mild RF rats had normal calcium and 25(OH)D but reduced 1,25(OH)(2)D levels (P < .001) with a 2.5-fold increased in rPTH (P < .001). Severe RF rats and those on a -Ca or -D diet had reduced calcium (P < .01) and 25(OH)D levels (P < .05), with rPTH increased by 2 (-Ca diet; P < .05), 4 (-D diet; P < .001), and 20-folds (RF; P < .001) while 1,25(OH)(2)D was high (-Ca diet: P < .001) or low (-D diet, RF: P < .001). 25(OH)D and 1,25(OH)(2)D were positively and negatively related on the -Ca and -D diets, respectively. rPTH molecular forms behaved as expected in RF and on -Ca diet, but not on -D diet with more C-rPTH fragments when less were expected. This may be related to the short-time course of this study compared to prior studies.


Aortic Annuloplasty: Focus on the Use of an External Teflon Ring.
Aortic annuloplasty has been clearly demonstrated to have a protective influence in aortic valve repair. Over the past 20 years, different annuloplasty concepts have been proposed by different groups. However, the most appropriate approach to enable long-term annular stability remains highly controversial. The aim of this article is to give a general overview of all types of aortic annuloplasty, particularly focusing on the use of an external Teflon ring, as proposed by our group. In this technique, external root dissection is performed in the same fashion as for reimplantation; the only difference is that it is necessary to go below the coronary ostia take-off. A series of pledgeted sutures (usually between 6 and 9 sutures) are placed at the level of the virtual basal ring. The external ring is made using a Teflon strip with a length of 8 to 9 cm, to reduce the annulus to a diameter of between 21 and 23 mm. The sub-annular sutures are then passed at the appropriate level through the Teflon strip and the strip is parachuted outside the aortic root base, passing under the coronary ostia. The two ends of the Teflon strip are tied at the level of the non-coronary sinus. Aortic annuloplasty is a crucial step to improve valve competence and stabilization. While several techniques offer good mid- to long-term results, annuloplasty with an external Teflon ring appears to be a simple and effective alternative to guarantee stable root diameters. Longer follow-up studies are needed to confirm the mid- to long-term results.


New Direct Oral Anticoagulants (DOAC) and Their Use Today.
The ideal anticoagulant is oral, has a wide therapeutic range, predictable pharmacokinetics and pharmacodynamics, a rapid onset of action, an available antidote, minimal side effects and minimal interactions with other drugs or food. With the development of the novel direct oral anticoagulants (DOAC), we now have an alternative to the traditional vitamin K antagonists (VKA) for the prevention and treatment of thrombosis. DOACs have limited monitoring requirements and very predictable pharmacokinetic profiles. They were shown to be non-inferior or superior to VKA in the prophylaxis or treatment of thromboembolic events. Particularly in terms of safety they were associated with less major bleeding, including intracranial bleeding, thus providing a superior benefit for the prevention of stroke in patients with atrial fibrillation. Despite these advantages, there are remaining limitations with DOACs: their dependence on renal and hepatic function for clearance and the lack of an approved reversal agent, whereas such antidotes are successively being made available. DOACs do not need regular monitoring to assess the treatment effect but, on the other hand, they interact with other drugs and interfere with functional coagulation assays. From a practical point of view, the properties of oral administration, simple dosing without monitoring, a short half-life allowing for the possibility of uncomplicated switching or bridging, and proven safety overwhelm the disadvantages, making them an attractive option for short- or long-term anticoagulation.


Tuning the formation and rupture of single ligand-receptor bonds by hyaluronan-induced repulsion.
We used a combination of laminar flow chamber and reflection interference microscopy to study the formation and rupture of single bonds formed between Fc-ICAM-1 attached to a substrate and anti-ICAM-1 carried by micrometric beads in the presence of a repulsive hyaluronan (HA) layer adsorbed onto the substrate. The absolute distance between the colloids and the surface was measured under flow with an accuracy of a few nanometers. We could verify the long-term prediction of classical lubrication theory for the movement of a sphere near a wall in a shear flow. The HA polymer layer exerted long-range repulsive steric force on the beads and the hydrodynamics at the boundary remained more or less unchanged. By incubating HA at various concentrations, the thickness of the layer, as estimated by beads most probable height, was tuned in the range 20-200 nm. Frequency of bond formation was decreased by more than one order of magnitude by increasing the thickness of the repulsive layer, while the lifetime of individual bonds was not affected. This study opens the way for further quantitative studies of the effect of molecular environment and separation distance on ligand-receptor association and dissociation.


Singapore Paediatric Resuscitation Guidelines 2016.
We present the revised 2016 Singapore paediatric resuscitation guidelines. The International Liaison Committee on Resuscitation's Pediatric Taskforce Consensus Statements on Science and Treatment Recommendations, as well as the updated resuscitation guidelines from the American Heart Association and European Resuscitation Council released in October 2015, were debated and discussed by the workgroup. The final recommendations for the Singapore Paediatric Resuscitation Guidelines 2016 were derived after carefully reviewing the current available evidence in the literature and balancing it with local clinical practice.


Xenogeneic chimera-Generated by blastocyst complementation-As a potential unlimited source of recipient-tailored organs.
Blastocyst complementation refers to the injection of cells into a blastocyst. The technology allows for the creation of chimeric animals, which have the potential to be used as an unlimited source of organ donors. Pluripotent stem cells could be generated from a patient in need of a transplantation and injected into a large animal blastocyst (potentially of a pig), leading to the creation of organ(s) allowing immunosuppression-free transplantation. Various chimera combinations have already been generated, but one of the most recent steps leads to the creation of human-pig chimeras, which could be studied at an embryo stage. Although still far from clinical reality, the potential application is almost unlimited. The present review illustrates the historical steps of intra- and interspecific blastocyst complementation in rodents and large animals, specifically looking at its potential for generation of organ grafts. We also speculate on how it could change transplant indications, on its economic impact, and on the linked ethical concerns.


Changes in folate status in overweight/obese women following two different weight control programmes based on an increased consumption of vegetables or fortified breakfast cereals.
The modification of folate status was analysed in a group of sixty-seven overweight/obese women of childbearing age (20-35 years). Subjects were randomly assigned to one of two slightly hypocaloric diets: diet V (increased consumption of vegetables) or diet C (increased consumption of breakfast cereals). Dietetic, anthropometric and biochemical data were collected at the start of the study and again at 2 and 6 weeks. At 6 weeks a weight loss of 2.0 (sd 1.3) kg was achieved in V subjects and of 2.8 (sd 1.4) kg in C subjects (P < 0.05). At the start of the study, 64.2 % of all subjects had a folate intake of < 67 % of the recommended intake; this fell to just 3 % (7.14 % of V subjects and 0 % of C subjects) by week 6. Significant increases were only seen in C subjects in serum folate concentrations (both at 2 and 6 weeks), accompanied by a significant reduction in serum homocysteine (at week 6). Some 62.1 % of all subjects had serum folate concentrations of > or = 13.6 nmol/l (associated with a very low risk of neural tube defects) at the start of the study, while 87.0 % (85.2 % of V subjects and 88.9 % of C subjects) had concentrations of > or = 13.6 nmol/l at 6 weeks (P < 0.01). Increasing the relative consumption of vegetables/cereals in the context of a slightly hypocaloric diet may therefore be a good way to lose body weight. Breakfast cereals may be of special help with respect to folate status and serum homocysteine levels in overweight/obese young women following energy restriction diets.


TSH suppressive therapy: an overview of long-term clinical consequences.
An overview of long-term clinical consequences of TSH suppressive therapy provides evidence that serum TSH levels should be maintained at levels <0.1 mU/l in high-risk (stage III and IV) patients, whereas lower-risk patients should be allowed to have their TSH levels rise into the normal range after residual disease has been ruled out by imaging and/or stimulated thyroglobulin measurement. The proper management of patients with known residual thyroid cancer, who are also elderly or who have underlying serious comorbidities (e.g., osteoporosis, cardiovascular disease, diabetes), is uncertain and requires a high degree of clinical experience and judgment.