The cost effectiveness of a quality improvement program to reduce maternal and fetal mortality in a regional referral hospital in Accra, Ghana.
To evaluate the cost-effectiveness of a quality improvement intervention aimed at reducing maternal and fetal mortality in Accra, Ghana. Quasi-experimental, time-sequence intervention, retrospective cost-effectiveness analysis. Data were collected on the cost and outcomes of a 5-year Kybele-Ghana Health Service Quality Improvement (QI) intervention conducted at Ridge Regional Hospital, a tertiary referral center in Accra, Ghana, focused on systems, personnel, and communication. Maternal deaths prevented were estimated comparing observed rates with counterfactual projections of maternal mortality and case-fatality rates for hypertensive disorders of pregnancy and obstetric hemorrhage. Stillbirths prevented were estimated based on counterfactual estimates of stillbirth rates. Cost-effectiveness was then calculated using estimated disability-adjusted life years averted and subjected to Monte Carlo and one-way sensitivity analyses to test the importance of assumptions inherent in the calculations. Incremental Cost-effectiveness ratio (ICER), which represents the cost per disability-adjusted life-year (DALY) averted by the intervention compared to a model counterfactual. From 2007-2011, 39,234 deliveries were affected by the QI intervention implemented at Ridge Regional Hospital. The total budget for the program was $2,363,100. Based on program estimates, 236 (±5) maternal deaths and 129 (±13) intrapartum stillbirths were averted (14,876 DALYs), implying an ICER of $158 ($129-$195) USD. This value is well below the highly cost-effective threshold of $1268 USD. Sensitivity analysis considered DALY calculation methods, and yearly prevalence of risk factors and case fatality rates. In each of these analyses, the program remained highly cost-effective with an ICER ranging from $97-$218. QI interventions to reduce maternal and fetal mortality in low resource settings can be highly cost effective. Cost-effectiveness analysis is feasible and should regularly be conducted to encourage fiscal responsibility in the pursuit of improved maternal and child health.


Population heterogeneity in Mycobacterium smegmatis and Mycobacterium abscessus.
Bacteria use population heterogeneity, the presence of more than one phenotypic variant in a clonal population, to endure diverse environmental challenges - a 'bet-hedging' strategy. Phenotypic variants have been described in many bacteria, but the phenomenon is not well-understood in mycobacteria, including the environmental factors that influence heterogeneity. Here, we describe three reproducible morphological variants in M. smegmatis - smooth, rough, and an intermediate morphotype that predominated under typical laboratory conditions. M. abscessus has two recognized morphotypes, smooth and rough. Interestingly, M. tuberculosis exists in only a rough form. The shift from smooth to rough in both M. smegmatis and M. abscessus was observed over time in extended static culture, however the frequency of the rough morphotype was high in pellicle preparations compared to planktonic culture, suggesting a role for an aggregated microenvironment in the shift to the rough form. Differences in growth rate, biofilm formation, cell wall composition, and drug tolerance were noted among M. smegmatis and M. abscessus variants. Deletion of the global regulator lsr2 shifted the M. smegmatis intermediate morphotype to a smooth form but did not fully phenocopy the naturally generated smooth morphotype, indicating Lsr2 is likely downstream of the initiating regulatory cascade that controls these morphotypes. Rough forms typically correlate with higher invasiveness and worse outcomes during infection and our findings indicate the shift to this rough form is promoted by aggregation. Our findings suggest that mycobacterial population heterogeneity, reflected in colony morphotypes, is a reproducible, programmed phenomenon that plays a role in adaptation to unique environments and this heterogeneity may influence infection progression and response to treatment.


Risk Factors and Center-Level Variation in Hepatocellular Carcinoma Under-Staging for Liver Transplantation.
Liver transplantation (LT) is curative for most patients with hepatocellular carcinoma (HCC). However, 10%-15% of patients experience HCC recurrence. Patients who are reported as within Milan criteria by imaging are frequently found to be outside the criteria on explant. This under-staging of HCC worsens post-LT outcomes. However, risk factors for under-staging have not been elucidated. Furthermore, it is not known if there is regional or center-level variation in under-staging. We conducted a retrospective analysis of adult patients transplanted for HCC in the United Network for Organ Sharing (UNOS) database between 2012 and 2016. Under-staging was determined on the basis of comparing pre-LT imaging to explant findings. Kaplan-Meier methods and Cox regression were used to evaluate the impact of under-staging on HCC recurrence and post-LT survival. Mixed effects logistic regression was used to identify risk factors for under-staging and to study regional and center-level variation in adjusted analyses. A total of 5424 patients were included in the cohort, of whom 24.9% (n = 1353) were under-staged. Post-LT HCC recurrence and death were significantly associated with under-staging (each P < 0.001). In adjusted analyses, independent predictors of under-staging included age (odds ratio [OR], 1.13 per 10 years; 95% confidence interval [CI], 1.03-1.25), male sex (OR, 1.61; 95% CI, 1.36-1.89), down-staging (OR, 4.03; 95% CI, 2.65-6.11), and pre-LT alpha-fetoprotein (P < 0.001). There was also significant variation in under-staging between UNOS regions and among transplant centers, ranging from 14.8% to 38.1%. We report novel risk factors for HCC under-staging, which worsens post-LT outcomes. Significant center-level and regional variation in under-staging highlights the need for standards that achieve greater uniformity in staging.


[Low accuracy of the anterior pelvic plane to guide the position of the cup with imageless computer assistance: variation of position in 106 patients].
The anterior pelvic plane, also called the Lewinnek plane, is commonly used as the reference plane to guide imageless computer assisted surgery for total hip arthroplasty (THA) because this plane is considered to be globally vertical in the standing position. To our knowledge, no study has evaluated this hypothesis or the potential variations in orientation as a function of gender, position of the subject, or THA insertion. The purpose of this work was to examine these different hypotheses in a radio-clinical study. The orientation of the anterior pelvic plane was measured in relation to the vertical plane on plain lateral x-rays of the pelvis in the standing position. X-rays were studied for 106 patients: 1) 82 patients with a THA (40 with at least one dislocation, 42 with a stable hip selected randomly, 19 with a standing lateral x-ray before and after arthroplasty) and 24 control subjects for whom lateral images were obtained in the supine and standing positions to assess potential position-related changes in orientation. The orientation of the anterior pelvic plane was not affected by gender or age. The anterior pelvic plane formed an angle greater than 5 degrees with the vertical plane in 38% of patients and more than 10 degrees in 13%. The orientation of the anterior pelvic plane was not significantly different between the study groups (control versus THA) nor between the THA groups (stable versus dislocated). The supine position modified significantly the orientation of the anterior pelvic plane which changed on average from 1.20 degrees to -2.25 degrees ; the change was greater than 7 degrees in twelve subjects. Implantation of a THA did not modify signi-ficantly the orientation of the anterior pelvic plane in the standing position for the 19 subjects [the variations were small (-1 degrees to 7 degrees on average, range -21 degrees to 8 degrees ) but greater than 5 degrees for 7 of 19 subjects]. Most teams use the anterior pelvic plane to guide computer-assisted navigation, considering that this plane is vertical in the standing position. Our findings show however that this is not true for 38% of subjects with a margin of error of 10 degrees , i.e. about half of the anatomic anteversion of the acetabulum. Moving to the standing position would produce a significant variation in the orientation of the anterior plane of the pelvis. This is a source of error which has not been integrated into most imageless navigation systems. Similarly variations in the position of the pelvis from the standing to sitting and supine positions which can produce impingement or dislocation have not been taken into consideration. Variations in the orientation of the anterior pelvic plane in relation to the vertical would suggest that this plane is not a reliable reference. To our knowledge, there is no reliable reference which can be easily identified during the operation which would take into account variations in the position of the pelvis. We thus believe it would be preferable to attempt to operate without a reference plane, relying on a more kinematic approach to guide computer-assisted implantation of the THA cup.


Dependence on epiphytic bacteria for freezing protection in an Antarctic moss, Bryum argenteum.
Mosses are the dominant flora of Antarctica, but their mechanisms of survival in the face of extreme low temperatures are poorly understood. A variety of Bryum argenteum from 77° S was previously shown to have strong ice-pitting activity, a sign of the presence of ice-binding proteins (IBPs) that mitigate freezing damage. Here, using samples that had been stored at -25(o) C for 10 years, it is shown that much if not all of the activity is due to bacterial ice-binding proteins secreted on the leaves of the moss. Sequencing of the leaf metagenome revealed the presence of hundreds of genes from a variety of bacteria (mostly Actinobacteria and Bacteroidetes) that encode a domain (DUF3494) that is associated with ice binding. The frequency of occurrence of this domain is one to two orders of magnitude higher than it is in representative mesophilic bacterial metagenomes. Genes encoding 42 bacterial IBPs with N-terminal secretion signals were assembled. There appears to be a commensal relationship in which the moss provides sustenance to the bacteria in return for freezing protection.


A model to explain the replacement of Schistosoma intercalatum by Schistosoma haematobium and the hybrid S. intercalatum x S. haematobium in areas of sympatry.
Numerous hypotheses have been postulated to explain the rapidly changing parasitological situation in Loum, Cameroon as a result of the interaction between Schistosoma haematobium and S. intercalatum. The aim of this study is to test the various hypotheses using a simple mathematical model, incorporating equal and unequal sex ratios of adult schistosomes, recombinations, and levels of compatibility with the intermediate molluscan hosts, B. forskalii and B. truncatus. The model assuming an equal sex ratio does not fit with the existing field data in that it predicts a continued presence of S. intercalatum, S. haematobium and the hybrids. The model assuming a sex bias in favour of males, which reflects the situation usually observed in schistosome populations, predicts the loss S. intercalatum which indeed concurs with the most recent data.


Correlates of youth vaping flavor preferences.
Among youth who use electronic nicotine delivery systems (ENDS), e-cigarettes are often the first tobacco product tried. Flavor is a common reason for experimentation with e-cigarettes. This study assessed flavor preferences and the choice of ENDS as an initial product among youth by selected demographic characteristics. The analysis sample included 1549 participants who had ever tried ENDS, drawn from a national online survey of youth aged 13-18 in 2017. Fruit was the most common favorite flavor among ENDS users, followed by menthol/mint/wintergreen. Preference for flavor varied by age, sex and racial/ethnic background. ENDS were the tobacco products most likely to be tried first, particularly among participants under age 17. Those who preferred fruit flavor were twice as likely to have tried ENDS first, compared to those with other flavor preferences, while those who preferred menthol/mint/wintergreen flavor were half as likely to have tried ENDS first. Our findings support an association between flavor and ENDS use. Our research supports previous findings indicating that: 1) flavor is one of the primary reasons for experimentation with ENDS among youth; 2) fruit flavor is strongly associated with use of ENDS as the first tobacco product; and 3) preference of fruit flavor varies by age, sex and racial/ethnic background. These findings have relevance for developing targeted messages for specific youth audiences and implications for tobacco regulatory policies. In addition to January 2020 federal regulations, the authors recommend tighter restrictions, specifically that the marketing and sale of all e-cigarette flavors other than tobacco be eliminated.


Improvements in ECG accuracy for diagnosis of left ventricular hypertrophy in obesity.
The electrocardiogram (ECG) is the most commonly used tool to screen for left ventricular hypertrophy (LVH), and yet current diagnostic criteria are insensitive in modern increasingly overweight society. We propose a simple adjustment to improve diagnostic accuracy in different body weights and improve the sensitivity of this universally available technique. Overall, 1295 participants were included-821 with a wide range of body mass index (BMI 17.1-53.3 kg/m(2)) initially underwent cardiac magnetic resonance evaluation of anatomical left ventricular (LV) axis, LV mass and 12-lead surface ECG in order to generate an adjustment factor applied to the Sokolow-Lyon criteria. This factor was then validated in a second cohort (n=520, BMI 15.9-63.2 kg/m(2)). When matched for LV mass, the combination of leftward anatomical axis deviation and increased BMI resulted in a reduction of the Sokolow-Lyon index, by 4 mm in overweight and 8 mm in obesity. After adjusting for this in the initial cohort, the sensitivity of the Sokolow-Lyon index increased (overweight: 12.8% to 30.8%, obese: 3.1% to 27.2%) approaching that seen in normal weight (37.8%). Similar results were achieved in the validation cohort (specificity increased in overweight: 8.3% to 39.1%, obese: 9.4% to 25.0%) again approaching normal weight (39.0%). Importantly, specificity remained excellent (>93.1%). Adjusting the Sokolow-Lyon index for BMI (overweight +4 mm, obesity +8 mm) improves the diagnostic accuracy for detecting LVH. As the ECG, worldwide, remains the most widely used screening tool for LVH, implementing these findings should translate into significant clinical benefit.


Metabolism of [3H] 17 beta-dihydroequilin and [3H] 17 beta-dihydroequilin sulfate in normal postmenopausal women.
The metabolism of 17 beta-dihydroequilin and 17 beta-dihydroequilin sulfate was investigated after intravenous administration of [3H] 17 beta-dihydroequilin and [3H] 17 beta-dihydroequilin sulfate to postmenopausal women. Urine was collected for 3 days and 46.2 +/- 10.5% and 54.5 +/- 8.7% of the injected dose of [3H] 17 beta-dihydroequilin and [17 beta-3H]dihydroequilin sulfate was excreted in the urine respectively. The estrogens present in urine were extracted and fractionated into unconjugated, sulfate, and glucuronide conjugated forms. With both precursors, the major amount (63-64%) of metabolites were excreted in the urine conjugated with glucuronic acid. From the unconjugated, sulfate, and glucuronide fraction, 17 beta-dihydroequilenin, 17 beta-dihydroequilin, equilenin, and equilin were isolated. The conversions with both precursors were similar and 17 beta-dihydroequilenin was the major metabolite isolated from all three fractions; however, the highest levels of all four metabolites were present in the glucuronide fraction. Along with these identifiable metabolites, a large amount (51-81%) of radioactivity was present in the form of metabolites which are more polar than any of the known ring-B unsaturated estrogens. These appear to be polyhydroxy 17 beta-reduced ring-B unsaturated estrogens which remain to be identified. The in-vivo formation of equilenin and 17 beta-dihydroequilenin indicates the presence of the enzyme 6.8(9) steroid dehydrogenase in humans.


[Identification of preterm labor: the role of fetal fibronectin in parents with symptoms].
To determine whether the presence of fetal fibronectin in vaginal secretions of patients with symptoms suggestive of preterm labor predicts preterm delivery. Fetal fibronectin, a large molecular weight glycoprotein produced in the chorion, is expressed in cervical and vaginal secretions in women with disruption of the choriodecidual junction by labor or by inflammation. A prospective observational longitudinal study from January 2013 till December 2013 was performed on patients between 24 and 32 weeks of gestation with symptoms of preterm labor, intact membranes, and cervical dilation < 4 cm (total patients = 86). The endpoint was the delivery at 34 weeks or more. The screening methods used were: the fFN test and the cervical length measurement by transvaginal according to an established protocol. The presence of FFN in vaginal or cervical secretions before 35 weeks is a is a strong predictor that preterm delivery is unlikely within the next 7 to 14 days. The predictive power of FFN is stronger at earlier gestation ages (24-29 wks) than it is later in pregnancy and is stronger for short-term prediction (7-14 d).


On the presence, structure and probable functional role of taste buds located on the laryngeal surface of the epiglottis in some domestic animals.
The authors have performed a systematic investigation on the epiglottis to determine the number and topography of taste buds possibly present. These chemoreceptors are constantly present in the ruminants studied (goat, cattle), while their finding is always negative in the pig, horse and ass and varying in the other animal species examined. Taste buds are, in the main, fairly numerous and show typical structure in very young kids and calves. On the contrary, in adult subjects degenerated taste buds can be found and their number usually increases with age. Sometimes such pictures can be observed also in young animals. The probable functional role of chemoreceptors located on the laryngeal surface of the epiglottis has been examined.


Purification of two ribonucleases from macrophage culture medium and studies on their effect on granulation-tissue fibroblasts.
Two ribonuclease activities have been isolated from macrophage culture medium. SDS-electrophoresis gave a molecular weight of 26,000 for both RNAases. The two RNAases differ only slightly in their enzymic properties. They are optimally active at neutral and slightly alkaline pH, and are not activated by monovalent or divalent cations or by spermine. Cu(II), Zn(II), Mn(II) and heparine inactivate them but they are not affected by the RNAase inhibitor from rat liver. They both degrade RNA endonucleolytically to mono- and oligonucleotides. They react to synthetic polynucleotides, especially poly(C), but do not degrade the synthetic double-stranded RNA poly(I) . poly(C), or double or single-stranded DNA. RNAase 1 inhibits DNA synthesis and increases degradation of RNA in granulation-tissue fibroblasts but RNAase 2 at the same concentration does not have these effects.


Is early morning flowering an effective trait to minimize heat stress damage during flowering in rice?
Higher spikelet sterility due to heat stress exposure during flowering in rice is becoming a major threat for sustaining productivity in tropical and sub-tropical regions. Therefore, exploiting and incorporating early morning flowering (EMF) trait into ongoing breeding pipelines could be an effective strategy to minimize the damage. In this study, we have focused on quantifying the time of day of flowering traits such as first spikelet opening time (FSOT) and peak spikelet opening time (PSOT) in a diverse set of cultivars (n = 289) representing major rice growing regions (13 tropical and 20 subtropical countries) over three years (wet season; WS-2012, dry season; DS-2013 and 2014), under field conditions. EMF traits (FSOT and PSOT) and spikelet sterility displayed significant (p < 0.001) variations among cultivars, both within and between seasons (WS and DS). Averaged across two dry seasons, the FSOT ranged between 2.35 h and 5.08 h after dawn compared to 3.05 h and 5.50 h during the WS, while, PSOT varied from 3.32 to 6.27 h in DS and from 3.50 to 7.05 h in WS. On average, PSOT was strongly associated with FSOT both in WS (R2 = 0.78) and DS (R2 = 0.77). A near-isogenic line (IR64 + qEMF3) effectively minimized the spikelet sterility by 71% during dry seasons under field conditions compared to 289 tropical and subtropical cultivars. None of the tropical and subtropical originated cultivars possess EMF trait including the popular IR64, thus indicating the usefulness of incorporating this trait to reduce heat stress damage under hotter climate. Our findings provide evidence for the effectiveness of the EMF trait in overcoming heat stress induced sterility under field conditions. Hence, it sounds logical to introgress EMF trait into currently growing popular rice cultivars for improving their resilience to heat stress episodes coinciding with flowering.


Molecular Characteristics and Virulence Gene Analysis of Non-O157 Shiga Toxin-Producing Escherichia coli from Cattle in Xinjiang.
Non-O157 Shiga toxin (stx)-producing Escherichia coli (STEC) is recognized as an important human diarrheal pathogen. Cattle are the principal reservoirs of STEC, although other animals can be carriers. Humans are mainly infected by consuming contaminated drinking water or food. This study aimed to evaluate the virulence potential of isolated bovine non-O157 STEC to humans in Xinjiang. During 2015-2017, 978 rectal swab samples collected from cattle of 5 farms were screened for the presence of Shiga toxin-encoding genes by polymerase chain reaction. Strains identified as STEC were isolated from rectal swab samples, and were characterized for stx subtype, virulence genes, O serogroup, phylogenetic group, and hemolytic phenotype. Among 125 non-O157 STEC isolates, the prevalence percentages of stx1 and stx2 were 22 and 21, respectively, and 57% of the isolates carried both Shiga toxins. The stx subtypes were mainly found in the combination of stx1a/stx2a (57%), stx2a (20%), stx1a (22%), stx1a/stx2a/stx2c (1%), and stx2a/stx2c (1%). The enterohemolysin (ehxA) gene was found in 94% of the isolates. No intimin (eae) was detected. Hemolysis was observed in 33% of the isolates. Two STEC serogroups O145 (17%) and O113 (2%) were found, which were reported to be associated with outbreaks of human disease. Phylotyping assays showed that most strains largely belong to groups A (91%) and B1 (7%). The results of this study can help improve our understanding of the epidemiological aspects of bovine STEC and devise strategies for protection against it.


Design and Preclinical Characterization Program toward Asundexian (BAY 2433334), an Oral Factor XIa Inhibitor for the Prevention and Treatment of Thromboembolic Disorders.
Activated coagulation factor XI (FXIa) is a highly attractive antithrombotic target as it contributes to the development and progression of thrombosis but is thought to play only a minor role in hemostasis so that its inhibition may allow for decoupling of antithrombotic efficacy and bleeding time prolongation. Herein, we report our major efforts to identify an orally bioavailable, reversible FXIa inhibitor. Using a protein structure-based de novo design approach, we identified a novel micromolar hit with attractive physicochemical properties. During lead modification, a critical problem was balancing potency and absorption by focusing on the most important interactions of the lead series with FXIa while simultaneously seeking to improve metabolic stability and the cytochrome P450 interaction profile. In clinical trials, the resulting compound from our extensive research program, asundexian (BAY 2433334), proved to possess the desired DMPK properties for once-daily oral dosing, and even more importantly, the initial pharmacological hypothesis was confirmed.


Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo.
Antiphospholipid (aPL) antibodies are associated with thrombosis in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. Although aPL antibodies have been shown to inhibit protein C activation and activate endothelial cells (ECs) in vitro, no study has examined whether these antibodies activate ECs in vivo. Therefore, human affinity-purified aPL (ap aPL) antibodies from APS patients were tested in a mouse model of microcirculation using the cremaster muscle that allows direct microscopic examination of thrombus formation and adhesion of white blood cells (WBCs) to ECs as an indication of EC activation in vivo. Adhesion molecule expression on human umbilical vein endothelial cells (HUVECs) after aPL exposure was performed to confirm EC activation in vitro. All 6 ap aPL antibodies significantly increased the expression of VCAM-1 (2.3- to 4.4-fold), with one of the antibodies also increasing the expression of E-selectin (1.6-fold) on HUVECs in vitro. In the in vivo experiments, each ap aPL antibody except for 1 preparation increased WBC sticking (mean number of WBCs ranged from 22.7 to 50.6) compared with control (14.4), which correlated with enhanced thrombus formation (mean thrombus size ranged from 1098 to 6476 versus 594 microm2 for control). Activation of ECs by aPL antibodies in vivo may create a prothrombotic state on ECs, which may be the first pathophysiological event of thrombosis in APS.


Dynamic properties of thalamic neurons for vision.
A striking property of neurons in the lateral geniculate nucleus (LGN) of the thalamus is the ability to dynamically filter and transform the temporal structure of their retinal spike input. In particular, LGN neurons respond to visual stimuli with either burst spike responses or tonic spike responses. While much is known from in vitro studies about the cellular mechanisms that underlie burst and tonic spikes, relatively little is known about the sensory stimuli that evoke these two categories of spikes. This review examines recent progress that has been made towards understanding the spatiotemporal properties of visual stimuli that evoke burst and tonic spikes. Using white-noise stimuli and reverse-correlation analysis, results show that burst and tonic spikes carry similar, but distinct, information to cortex. Compared to tonic spikes, burst spikes (1) occur with a shorter latency between stimulus and response, (2) have a greater dependence on stimuli with transitions from suppressive to preferred states, and (3) prefer stimuli that provide increased drive to the receptive field center and even greater increased drive to the receptive field surround. These results are discussed with an emphasis placed on relating the cellular constraints for burst and tonic activity with the functional properties of the early visual pathway during sensory processing.


Nonlinear screening of charged macromolecules.
We present several aspects of the screening of charged macromolecules in an electrolyte. After a review of the basic mean field approach, based on the linear Debye-Hückel theory, we consider the case of highly charged macromolecules, where the linear approximation breaks down and the system is described by the full nonlinear Poisson-Boltzmann equation. Some analytical results for this nonlinear equation give some interesting insight on physical phenomena like the charge renormalization and the Manning counterion condensation.


Immunostimulatory activity of plumieride an iridoid in augmenting immune system by targeting Th-1 pathway in balb/c mice.
Plumieride, an iridoid glucoside isolated from Plumieria acutifolia leaves was investigated for its immunostimulatory activity on humoral, cell mediated and intracellular cytokine levels in sensitized and unsensitised balb/c mice. Plumieride restores the suppressed cell mediated, humoral immune response and also enhances the release of TNF- α, IFN-γ, and IL-2 (Th-1) in immune compromised cyclosporine and cyclophosphamide treated balb/c mice. It does not stimulate the IL-4 (Th-2) expression. Plumieride demonstrates significant augmentation of Th-1 response in immunosuppressed balb/c mice. Results of the present study suggested that plumieride can be developed as an immunostimulatory adjuvant to treat the immune suppression in various disease condition(s).


HERITABLE VARIATION IN RESOURCE UTILIZATION AND RESPONSE IN A WINERY POPULATION OF DROSOPHILA MELANOGASTER.
It has been found that Drosophila melanogaster lines from the "Chateau Tahbilk" winery cellar had higher larval ethanol resistance than lines originating from outside the cellar. Because the adaptive significance of this trait is unclear, we have reexamined genetic microdifferentiation at Tahbilk with other resources and different tests for ethanol adaptation. Cellar stocks tended to be more resistant to starvation after exposure to wine seepage than stocks originating from orchard traps outside the cellar. Lines from a grape residue pile were also more resistant to starvation after seepage exposure than orchard stocks even though these collection sites were a few meters apart. Cellar and orchard stocks did not differ in ethanol resistance as measured by larval viability tests on low sucrose medium. However, stocks from the grape residue pile showed an increase in adult longevity over ethanol vapor compared to those from the cellar or orchard stocks. These differences were not due to maternal effects. In laboratory tests of behavioral responses, cellar stocks were relatively more attracted to seepage than orchard stocks in one year but not in the other two years. The findings suggest some adaptive differentiation related to resource heterogeneity at Tahbilk.


Progesterone regulation of estradiol-induced rat uterine secretory protein, complement C3.
Previously, using DNA sequencing, Northern and Southern analysis, and immunohistochemical data, we identified an estrogen-stimulated secretory protein as the third component of complement (C3). In this study, we demonstrate that progesterone modulated the estradiol regulation of C3 in immature rats as well as during the normal reproductive cycle. C3 was most abundant during estrus and reached its lowest concentration in diestrus. Immunoprecipitations reveal that progesterone prevented the estradiol-stimulated increase in radiolabeled C3 both in the media and tissue. The mechanism for the progesterone inhibition of estrogen-stimulated C3 appeared to be at the level of transcription or possibly mRNA stability since progesterone blocked the estradiol-stimulated increase in C3 mRNA.


Expanding the Australian Newborn Blood Spot Screening Program using genomic sequencing: do we want it and are we ready?
Since the introduction of genome sequencing in medicine, the factors involved in deciding how to integrate this technology into population screening programs such as Newborn Screening (NBS) have been widely debated. In Australia, participation in NBS is not mandatory, but over 99.9% of parents elect to uptake this screening. Gauging stakeholder attitudes towards potential changes to NBS is vital in maintaining this high participation rate. The current study aimed to determine the knowledge and attitudes of Australian parents and health professionals to the incorporation of genomic sequencing into NBS programs. Participants were surveyed online in 2016 using surveys adapted from previous studies. The majority of parents (90%) self-reported some knowledge of NBS, with 77% expressing an interest in NBS using the new technology. This was significantly lower than those who would utilise NBS using current technologies (99%). Although, many health professionals (62%) felt that new technologies should currently not be used as an adjunct to NBS, 79% foresaw the use of genomic sequencing in NBS by 2026. However, for genomic sequencing to be considered, practical and technical challenges as well as parent information needs were identified including the need for accurate interpretation of data; pre-and post-test counselling; and appropriate parental consent and opt-out process. Therefore, although some support for implementing genomic sequencing into Australian NBS does exist, there is a need for further investigation into the ethical, social, legal and practical implications of introducing this new technology as a replacement to current NBS methods.


Application of bicellar systems on skin: diffusion and molecular organization effects.
The effect of bicelles formed by dipalmitoylphosphatidylcholine (DPPC)/dihexanoylphosphatidylcholine (DHPC) on stratum corneum (SC) lipids was studied by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy at different temperatures. Analysis of the lipid organization in terms of chain conformational order and lateral packing shows that the use of bicelles hampers the fluidification of SC lipids with temperature and leads to a lateral packing corresponding to a stable hexagonal phase. Grazing incidence small- and wide-angle X-ray scattering (GISAXS and GIWAXS) techniques confirm these results and give evidence of higher lamellar order after treatment with these bicelles. Additionally, the effects of DPPC/DHPC and dimyristoylphosphatidylcholine (DMPC)/DHPC bicelles at different SC depths were compared. The combination of ATR-FTIR spectroscopy and the tape-stripping method was very useful for this purpose.


Effect of Bushen Huoxue recipe on women with thin endometrial ovulation disorder and a rat model of thin endometrium resulted from kidney deficiency-related blood stasis.
To examine the therapeutic effect of Bushen Huoxue recipe (BHR) on women with thin endometrial ovulation disorder and on a rat model of kidney deficiency-related blood stasis. A total of 60 women with thin endometrial ovulation disorder was enrolled. The primary outcome of the study was the pregnancy rate three menstrual cycles after treatment. The study also examined the changes in the type and thickness of uterine artery, uterine artery pulsatility index (PI) and endometrial resistance index (RI). To establish kidney deficiency-related blood stasis in Sprague Dawley (SD) rats, an intragastric administration of hydroxyurea and a tail vein injection of Dextran were given, following with a flashing of the uterine cavity with 95% anhydrous ethanol. A combined regimen of BHR and estradiol valerate significantly increased the rate of pregnancy in women with thin endometrial ovulation disorder. The treatment was accompanied by a significant increase in endometrial thickness and decreases in uterine artery PI and endometrial RI. In rats, kidney deficiency-related blood stasis caused severe loss in endometrial architecture, thickness, and numbers of gland and blood vessel compared to the healthy SD rats. Treatment with BHR could ameliorate the endometrial damages associated with kidney deficiency-related blood stasis.


Inhibition of the calcineurin-NFAT interaction by small organic molecules reflects binding at an allosteric site.
Transcriptional signaling from the Ca(2+)-calmodulin-activated phosphatase calcineurin to its substrate NFAT (nuclear factor of activated T cells, also termed NFATc) is critically dependent on a protein-protein docking interaction between calcineurin and the PXIXIT motif in NFAT. Several inhibitors of NFAT-calcineurin association (INCA compounds) prevent binding of NFAT or the peptide ligand PVIVIT to calcineurin. Here we show that the binding site on calcineurin for INCA1, INCA2, and INCA6 is centered on cysteine 266 of calcineurin Aalpha and does not coincide with the core PXIXIT-binding site. Although ample evidence indicates that INCA1 and INCA2 react covalently with cysteine 266, covalent derivatization alone is not sufficient for maximal inhibition of the calcineurin-PVIVIT interaction, because the maleimide INCA12 reacts with the same site and produces only very modest inhibition. Thus, inhibition arises through an allosteric change affecting the PXIXIT docking site, which may be assisted by covalent binding but depends on other specific features of the ligand. The spatial arrangement of the binding sites for PVIVIT and INCA makes it probable that the change in conformation involves the beta11-beta12 loop of calcineurin. The finding that an allosteric site controls NFAT binding opens new alternatives for inhibition of calcineurin-NFAT signaling.


Association between periodontitis and chronic kidney disease: Systematic review and meta-analysis.
A systematic review and meta-analysis were conducted to evaluate the association between periodontitis (PD) and chronic kidney disease (CKD) and to explore the potential influence of periodontal treatment in patients with CKD. Databases (PubMed, Web of Science, Science direct, Cochrane Database) were screened for relevant articles, focusing on the periodontal status of patients with CKD, published until December 2017. Five hundred and fifty-three articles were identified, and 37 fulfilled the inclusion criteria and were considered in this systematic review. Seventeen articles were included in the meta-analysis and 7 in the review focusing on the impact of periodontal treatment. Most of the identified studies indicated an increased incidence of PD in patients with CKD. Meta-analysis showed an association between CKD and PD, and strength of this association was increased when severe PD was considered (OR = 2.39 (1.70-3.36)). The association could be observed even after adjustment for major CKD risk factors or use of precise diagnosis criteria (OR = 2.26 for severe PD (1.69-3.01)). Analysis of cohort studies indicated an incident rate ratio (IRR) of 1.73. Periodontitis is associated with CKD after multivariable adjustment. Further studies are necessary to determine whether prevention or treatment of PD can reduce the incidence and/or severity of CKD.


Euryhaliotrema spp. (Monogenoidea: Dactylogyridae) Parasitic on the Gill Lamellae of Perciform Fishes in Moreton Bay, Queensland, Australia, with the Description of Euryhaliotrema solenophallus sp. nov. from the Silver Moony Monodactylus argenteus (Linnaeus) (Monodactylidae).
The present paper represented the third installment on the monogenoidean parasites collected during a workshop exploring the diversity of the parasites of fishes in Moreton Bay, Queensland, Australia. Previous reports on monogenoids collected during the workshop included species parasitizing beloniform and gerreid fishes. During January 2016, the author, having responsibility for the identification and description of monogenoids, participated in a workshop supported by an Australian Biological Resources Study Grant to Drs. Thomas Cribb and Scott Cutmore, University of Queensland, to explore the diversity of parasites infecting the fishes of Moreton Bay, Queensland, Australia. Approximately 100 species of marine fishes were necropsied for parasites. Standard procedures for collecting, mounting, drawing, and measuring of monogenoids were employed. A new species of Euryhaliotrema was collected and described from the silver moony Monodactylus argenteus (Monodactylidae) and the first recording of Euryhaliotrema spirotubiforum on the dory snapper Lutjanus fulviflamma and Russell's snapper Lutjanus russellii (both Lutjanidae) in Moreton Bay was reported. The results suggested that the diversity of dactylogyrids off eastern Australia is under estimated in the literature.


Simple bone cyst of the mandibular condyle.
Simple bone cysts (SBCs) are benign lesions often found in the long bones of children between their first and second decades. They occasionally occur in the mandible but rarely in the mandibular condyle. A case of a 7-year-old female child with an increasing enlargement of the left mandibular condyle is presented. A 2 cm × 3 cm lytic lesion was explored and curetted through an intraoral vestibular incision and proved to be an SBC. Postoperative recovery was uncomplicated with remodeling of the condylar observed at 3 years follow-up.


Novel phage group infecting Lactobacillus delbrueckii subsp. lactis, as revealed by genomic and proteomic analysis of bacteriophage Ldl1.
Ldl1 is a virulent phage infecting the dairy starter Lactobacillus delbrueckii subsp. lactis LdlS. Electron microscopy analysis revealed that this phage exhibits a large head and a long tail and bears little resemblance to other characterized phages infecting Lactobacillus delbrueckii. In vitro propagation of this phage revealed a latent period of 30 to 40 min and a burst size of 59.9 +/- 1.9 phage particles. Comparative genomic and proteomic analyses showed remarkable similarity between the genome of Ldl1 and that of Lactobacillus plantarum phage ATCC 8014-B2. The genomic and proteomic characteristics of Ldl1 demonstrate that this phage does not belong to any of the four previously recognized L. delbrueckii phage groups, necessitating the creation of a new group, called group e, thus adding to the knowledge on the diversity of phages targeting strains of this industrially important lactic acid bacterial species.


Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations.
A third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72) and progranulin (GRN). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in the disease but few have studied naming in detail. We investigated performance on the Boston Naming Test (BNT) in the GENetic Frontotemporal dementia Initiative cohort of 499 mutation carriers and 248 mutation-negative controls divided across three genetic groups: C9orf72, MAPT and GRN. Mutation carriers were further divided into 3 groups according to their global CDR plus NACC FTLD score: 0 (asymptomatic), 0.5 (prodromal) and 1 + (fully symptomatic). Groups were compared using a bootstrapped linear regression model, adjusting for age, sex, language and education. Finally, we identified neural correlates of anomia within carriers of each genetic group using a voxel-based morphometry analysis. All symptomatic groups performed worse on the BNT than controls with the MAPT symptomatic group scoring the worst. Furthermore, MAPT asymptomatic and prodromal groups performed significantly worse than controls. Correlates of anomia in MAPT mutation carriers included bilateral anterior temporal lobe regions and the anterior insula. Similar bilateral anterior temporal lobe involvement was seen in C9orf72 mutation carriers as well as more widespread left frontal atrophy. In GRN mutation carriers, neural correlates were limited to the left hemisphere, and involved frontal, temporal, insula and striatal regions. This study suggests the development of early anomia in MAPT mutation carriers, likely to be associated with impaired semantic knowledge. Clinical trials focused on the prodromal period within individuals with MAPT mutations should use language tasks, such as the BNT for patient stratification and as outcome measures.


Gravidity, blood pressure, and hypertension among white women in the Second National Health and Nutrition Examination Survey.
Gravidity and parity have been hypothesized as possible protective factors for hypertension in women, but results of previous studies have been conflicting; none of three U.S. studies has clearly demonstrated this relation. We studied the association of number of pregnancies to blood pressure and hypertension in a cross-sectional study of 4,626 white women, ages 20-74 years, examined in the Second National Health and Nutrition Examination Survey. In univariate analyses, neither mean systolic blood pressure, mean diastolic blood pressure, nor prevalence of hypertension varied systematically with the number of pregnancies. In multivariate analyses that included age, body size, smoking, oral contraceptive use, education, poverty status, and alcohol use, systolic blood pressure declined modestly with greater gravidity. The association of gravidity with systolic blood pressure was stronger for younger premenopausal women. The odds of hypertension also declined with each additional pregnancy as compared with no pregnancies: there was an odds ratio of 0.90 (95% confidence interval = 0.81-0.99) for premenopausal women and an odds ratio of 0.95 (95% confidence interval = 0.92-0.98) for postmenopausal women. These findings indicate a slight negative relation of number of pregnancies to both blood pressure and hypertension.


Susceptibility contrast in high field MRI of human brain as a function of tissue iron content.
Magnetic susceptibility provides an important contrast mechanism for MRI. Increasingly, susceptibility-based contrast is being exploited to investigate brain tissue microstructure and to detect abnormal levels of brain iron as these have been implicated in a variety of neuro-degenerative diseases. However, it remains unclear to what extent magnetic susceptibility-related contrast at high field relates to actual brain iron concentrations. In this study, we performed susceptibility weighted imaging as a function of field strength on healthy brains in vivo and post-mortem brain tissues at 1.5 T, 3 T and 7 T. Iron histology was performed on the tissue samples for comparison. The calculated susceptibility-related parameters R(2)(*) and signal frequency shift in four iron-rich regions (putamen, globus pallidus, caudate, and thalamus) showed an almost linear dependence (r>or=0.90 for R(2)(*); r>or=0.83 for phase, p<0.01) on field strength, suggesting that potential ferritin saturation effects are not relevant to susceptibility-weighted contrast for field strengths up to 7 T. The R(2)(*) dependence on the putative (literature-based) iron concentration was 0.048 Hz/T/ppm. The histological data from brain samples confirmed the linear dependence of R(2)(*) on field strength and showed a slope against iron concentration of 0.0099 Hz/T/ppm dry-weight, which is equivalent to 0.05 Hz/T/ppm wet-weight and closely matched the calculated value in vivo. These results confirm the validity of using susceptibility-weighted contrast as an indicator of iron content in iron-rich brain regions. The absence of saturation effects opens the way to exploit the benefits of MRI at high field strengths for the detection of iron distributions with high sensitivity and resolution.


Disseminating findings from a drug class review: using best practices to inform prescription of antiepileptic drugs for bipolar disorder.
Evidence from drug class reviews is often not accessible to practicing clinicians nor is it presented in a way that allows clinicians to use the information to guide treatment and prescribing decisions. Nevertheless, information from such reviews can be very helpful to clinicians as they evaluate the "evidence" provided to them through marketing strategies implemented, primarily, by the pharmaceutical industry and designed to influence their prescribing behavior. Unfortunately, these marketing strategies can be used to promote the off-label use of drugs that may not be efficacious. One example is the pharmaceutical marketing to promote off-label use of gabapentin (Neurontin) for the treatment of bipolar disorder, the legality of which was later addressed in a major lawsuit by the National Association of Attorneys General. We describe an effort to use counter-marketing strategies to compete with those implemented by the pharmaceutical industry and to help clinicians, principally psychiatrists, make use of available evidence to inform their prescription of antiepileptic drugs (AEDs) in the treatment of bipolar disorder. A growing body of literature describes industry marketing practices designed to influence prescriber behavior. This literature suggests that use of competing approaches involving the same underlying strategies to deliver highly credible information from trusted sources can inform prescriber knowledge and prescribing practice. We describe our use of existing evidence to develop accurate and convincing messages and materials to be disseminated nationally to counter industry misinformation and promote evidence-based prescription of AEDs.


Compound heterozygosity for two alpha-globin gene defects, Hb Taybe (alpha 1; 38 or 39 minus Thr) and a poly A mutation (alpha 2; AATAAA-->AATAAG), results in a severe hemolytic anemia.
We have identified two alpha-globin gene variations in an Arabian male with severe hemolytic disease through sequencing of amplified DNA of his alpha 2- and alpha 1-globin genes. One of the abnormalities involves a CAC (ACC or CCA) deletion between codons 36 and 41 of the alpha 1-globin gene. This leads to the synthesis of an abnormal alpha chain with one instead of two threonine residues at positions 38-39 and to the formation of the unstable Hb Taybe. The second variation is a mutation located in the poly A site of the alpha 2-globin gene (AATAAA-->AATAAG) which is common among Arabian people. Family studies have shown that the two variations are located on opposite chromosomes. The hemolytic disease in this man, resembling Hb H disease, is likely the result of a severe downregulation of both alpha-globin genes on the chromosome with the alpha 2 poly A mutation, and the instability of the alpha-Taybe chain being the product of an alpha 1-globin gene; this leaves only one alpha 2-globin gene normally active.


United States Patients' Perspective of Living With Migraine: Country-Specific Results From the Global "My Migraine Voice" Survey.
Migraine is associated with debilitating symptoms that can affect daily functioning. "My Migraine Voice" was a large, cross-sectional, multi-country online survey aimed at understanding disease burden directly from people with migraine. This study reports on the social and economic impacts of migraine, specifically the impact on activities of daily living and the costs of migraine, from the point of view of people with migraine in the United States. The online survey was administered to adults with a self-reported diagnosis of migraine who experienced 4 or more monthly migraine days each month for the previous 3 months. Prespecified screening quotas were used so that 90% of respondents reported current or past use of preventive migraine medication, 80% of whom switched treatment (ie, changed their prescribed preventive medication at least once). The remaining 10% were preventive treatment naïve (ie, never used any prescribed preventive medication). Burden of migraine on activities of daily living and caregivers (eg, functional limitations, fear of next migraine attack, sleep problems) and economic burden (eg, out-of-pocket costs, impact on work productivity using the validated work productivity and activity impairment questionnaire) reported by respondents from the United States are presented. Results are stratified by employment status, migraine frequency (chronic vs episodic migraine), and history of preventive treatment. Thousand hundred and one individuals with migraine from the United States responded to the survey. Respondents reported limitations completing daily activities during all migraine phases, including during the premonitory/aura and postdrome phases. Most (761/1101 (69%)) relied on family, friends, or others for help with daily tasks and reported being helped a median of 9 days (25th percentile 5 days, 75th percentile 15 days) within the last 3 months. Respondents with chronic migraine reported being helped for more days (median 10 days, 25th percentile 5 days, 75th percentile 23 days) in the last 3 months. Almost all (962/1101 (87%)) experienced sleep difficulties and 41% (448/1101) (48% (336/697) of those with 2 or more preventive treatment failures) were very or extremely fearful of a next migraine attack. Median (25th percentile, 75th percentile) monthly out-of-pocket costs of $90.00 ($30.00, $144.00) in doctor's fees (n = 504), $124.00 ($60.00, $234.00) in health insurance (n = 450), $40.00 ($20.00, $100.00) for prescriptions (n = 630), and $50.00 ($0.00, $100.00) for complementary therapies (n = 255) were reported. Those with 2 or more preventive treatment failures reported higher monthly out-of-pocket doctor fees (median $99.00 ($30.00, $150.00), n = 388). Among employed respondents (n = 661), migraine resulted in 22% absenteeism, 60% presenteeism, 65% work productivity loss, and 64% activity impairment. Migraine impacts individuals' activities of daily living, work-life, and financial status, especially individuals with high needs, namely those with 4 or more monthly migraine days and prior treatment failures. People with migraine are impaired during all migraine phases, experience fear of their next migraine attack and sleep difficulties, and pay substantial monthly out-of-pocket costs for migraine. Burden is even greater among those who have had 2 or more preventive treatment failures. Impacts of migraine extend beyond probands to caregivers who help people with migraine with daily tasks, employers who are affected by employee absenteeism, presenteeism, and reduced productivity, and society which is burdened by lost and reduced economic productivity and healthcare costs.


[Gastroenterology and hepatology in 2016].
This article aims to detail the major innovations occurred in Gastro-enterology in 2016, including the introduction of a new molecule, the vonoprazan, for the treatment of refractory gastroesophagal reflux disease (GERD) and a new way of eradication of H. pylori. The possibility to use an intermittent dose of PPI rather than continuously in severe gastric and duodenal ulcers after successful endoscopic hemostasis is also discussed as well as the withdrawal of corticosteroids in the treatment of autoimmune pancreatitis. The formulation of corticosteroids in the treatment of eosinophilic esophagitis, the interest of the chromo-endoscopy during colonoscopy highlighting small polyps (from 1 to 5 mm = « diminutive polyps ») and the introduction on the Swiss market for biosimilars in the treatment of inflammatory bowel disease (IBD) are also discussed.


Respiratory Symptoms and Lung Function in Never-Smoking Male Workers Exposed To Hardwood Dust.
Results from many studies suggest that workplace exposure to organic dust may lead to adverse respiratory effects in exposed workers. In order to assess the respiratory effects of the workplace exposure to hardwood dust we performed a cross-sectional study of never-smoking male workers employed in parquet manufacture and never-smoking male office workers as a control. We performed a cross-sectional study including 37 never-smoking male workers employed in parquet manufacture and an equal number of never-smoking male office workers studied as a control. Evaluation of examined subjects included completion of a questionnaire for respiratory symptoms in the last 12 months and baseline spirometry performed according to the actual recommendations. We found a higher prevalence of respiratory symptoms in parquet manufacturers than in office workers with significant difference for cough and phlegm. Majority of the respiratory symptoms in the parquet manufacturers were work-related. The mean values of all spirometric parameters with exception of forced ventilatory capacity (FVC) were significantly lower in the parquet manufacturers as compared to their mean values in the office workers. We found close relationship between both the prevalence of respiratory symptoms and the reduction of spirometric parameters in the parquet manufacturers and the duration of the workplace exposure to wood dust. Our data suggest that workplace exposure to hardwood dust may lead to adverse respiratory effects indicating the need of adequate preventive measures in order to protect the respiratory health of exposed workers.


Time delay in necrotic core formation.
A simple model of avascular solid tumor dynamics is studied in the paper. The model is derived on the basis of reaction-diffusion dynamics and mass conservation law. We introduce time delay in a cell proliferation process. In the case studied in this paper, the model reduces to one ordinary functional-differential equation of the form that depends on the existence of necrotic core. We focus on the process of this necrotic core formation and the possible influence of delay on it. Basic mathematical properties of the model are studied. The existence, uniqueness and stability of steady state are discussed. Results of numerical simulations are presented.


Reduced dynamics of a one-dimensional Janus particle.
A Janus particle diffusing on a line is considered. Aside from its own driving force f acting forward or backward according to its stochastic orientation, it moves in a position-dependent potential U(x). We propose here the mapping scheme generating the effective generalized Fick-Jacobs equation, describing motion of the particle in the spatial coordinate x only; the orientation is understood as the transverse coordinate. The self-propulsion, driving the system out of equilibrium, is reflected as an additional effective potential -γ(x) in the reduced picture. It enables us to understand peculiarities of this system in a handy way. The additionally corrected potential redistributes the confined particles in quasiequilibrium causing their piling at the walls. In periodic asymmetric channels, it acquires a growing contribution, responsible for driving the ratchet effect.


Changing epidemiology of bloodstream infection pathogens over time in adult non-specialty patients at an Australian tertiary hospital.
The epidemiology of bloodstream infections (BSI) has been changing over time in developed countries. However, overview reports of BSI trends are limited in Australia. This descriptive epidemiological study analysed general and age-group specific trends, and antimicrobial susceptibility patterns of blood culture isolates between 2001 and 2009 in non-specialty adult patients at an Australian tertiary referral centre. A total of 3,051 isolates from 2,172 patients (60% males) were analysed. Both community onset (1,790 isolates, 59%) and hospital onset (1,261 isolates, 41%) BSIs were included. The mean age of patients was 59 ± 20 years; 930 patients (43%) were 70 years of age or over. Overall, 1,493 (49%) gram positive bacteria, 1,389 (46%) gram negative bacteria and 169 (5.5%) fungi were isolated. The proportion of gram negative isolates increased over the 9 years, (44% to 53%, P = 0.006) whilst gram positives decreased (49% to 45%, P = 0.045). These trends were significant in community onset infections but not hospital onset infections, and also in adult patients aged 20 years to less than 70 years but not in the elderly (≥70 years). Gram negative pathogens were most prevalent amongst the elderly (53% in the ≥70 years age group, P<0.0001 vs. 41% in the ≥20 to <70 years age group), attributable to an age-dependent increase in Escherichia coli infections and a decrease in Staphylococcus aureus infections (P<0.0001 for both). Most gram negative isolates remained susceptible to commonly prescribed antibiotics. By contrast, methicillin-resistant S. aureus rates decreased from 54% in 2001 to 28% in 2009 (P=0.007). This study found that gram negative BSIs appeared to be re-emerging, particularly in community onset infections and also amongst the younger patients at the study institution. Such epidemiological trends have important implications for antimicrobial choices for the treatment of undifferentiated sepsis.


Length-Controlled Nanofiber Micelleplexes as Efficient Nucleic Acid Delivery Vehicles.
Micelleplexes show great promise as effective polymeric delivery systems for nucleic acids. Although studies have shown that spherical micelleplexes can exhibit superior cellular transfection to polyplexes, to date there has been no report on the effects of micelleplex morphology on cellular transfection. In this work, we prepared precision, length-tunable poly(fluorenetrimethylenecarbonate)-b-poly(2-(dimethylamino)ethyl methacrylate) (PFTMC16-b-PDMAEMA131) nanofiber micelleplexes and compared their properties and transfection activity to those of the equivalent nanosphere micelleplexes and polyplexes. We studied the DNA complexation process in detail via a range of techniques including cryo-transmission electron microscopy, atomic force microscopy, dynamic light scattering, and ζ-potential measurements, thereby examining how nanofiber micelleplexes form, as well the key differences that exist compared to nanosphere micelleplexes and polyplexes in terms of DNA loading and colloidal stability. The effects of particle morphology and nanofiber length on the transfection and cell viability of U-87 MG glioblastoma cells with a luciferase plasmid were explored, revealing that short nanofiber micelleplexes (length < ca. 100 nm) were the most effective delivery vehicle examined, outperforming nanosphere micelleplexes, polyplexes, and longer nanofiber micelleplexes as well as the Lipofectamine 2000 control. This study highlights the potential importance of 1D micelleplex morphologies for achieving optimal transfection activity and provides a fundamental platform for the future development of more effective polymeric nucleic acid delivery vehicles.


Carbon dioxide insufflation in routine colonoscopy is safe and more comfortable: results of a randomized controlled double-blinded trial.
Many patients experience pain and discomfort after colonoscopy. Carbon dioxide (CO(2)) can reduce periprocedural pain although air insufflation remained the standard procedure. The objective of this double-blinded, randomized controlled trial was to evaluate whether CO(2) insufflation does decrease pain and bloating during and after colonoscopy compared to room air. Methods. 219 consecutive patients undergoing colonoscopy were randomized to either CO(2) or air insufflation. Propofol was used in all patients for sedation. Transcutaneous CO(2) was continuously measured with a capnograph as a safety parameter. Pain, bloating, and overall satisfaction were assessed at regular intervals before and after the procedure. Results(data are mean ±SD). 110 patients were randomized to CO(2) and 109 to room air. The baseline characteristics were similar in both groups. The mean propofol dose was not different between the treatments, as were the time to reach the ileum and the withdrawal time. pCO(2) at the end of the procedure was 35.2 ± 4.3 mmHg (CO(2) group) versus 35.6 ± 6.0 mmHg in the room air group (P > .05). No relevant complication occurred in either group. There was significantly less bloating for the CO(2) group during the postprocedural recovery period (P < .001) and over the 24-hour period (P < .001). Also, patients with CO(2) insufflation experienced significantly less pain (P = .014). Finally, a higher overall satisfaction (P = .04 ) was found in the CO(2) group. Conclusions. This trial provides compelling evidence that CO(2) insufflation significantly reduces bloating and pain after routine colonoscopy in propofol-sedated patients. The procedure is safe with no significant differences in CO(2) between the two groups.


Surgical treatment of intrathyroid metastases: preliminary results of a multicentric study.
Intrathyroid metastases (ITM) are rare and usually have a dismal prognosis. The aim of this study was to detect which neoplasms metastasize most often to the thyroid gland, their clinical features and treatment options. Retrospective analysis of clinical files of 17,122 patients submitted to surgery for thyroid disease between 1995 and 2005. Twenty-five patients (median age 61 years) were affected by ITM. The site of the primary tumor was: kidney (15), lung (4), colon (3), breast (1), melanoma (1), and unknown in 1 patient. Ten patients (40%) complained of preoperative symptoms, in the others, thyroid involvement was incidentally discovered during the follow-up for the primary cancer. Twenty patients (80%) underwent total thyroidectomy, 3 received thyroid lobectomy and 2 palliative procedures. Morbidity was 16%, mortality was nil. The median follow-up was 24 months. ITM should always be suspected in any patient with a previous history of malignancy. Fine-needle agobiopsy (FNAB) with immunohistochemical stains may help in preoperative workup. A long delay between the primary tumor and the recurrence warrants surgery and total thyroidectomy seems to be the treatment of choice because of the multifocality of metastasis to the thyroid gland.


Increased production of the exopolysaccharide succinoglycan enhances Sinorhizobium meliloti 1021 symbiosis with the host plant Medicago truncatula.
The nitrogen-fixing rhizobial symbiont Sinorhizobium meliloti 1021 produces acidic symbiotic exopolysaccharides that enable it to initiate and maintain infection thread formation on host legume plants. The exopolysaccharide that is most efficient in mediating this process is succinoglycan (exopolysaccharide I [EPSI]), a polysaccharide composed of octasaccharide repeating units of 1 galactose and 7 glucose residues, modified with succinyl, acetyl, and pyruvyl substituents. Previous studies had shown that S. meliloti 1021 mutants that produce increased levels of succinoglycan, such as exoR mutants, are defective in symbiosis with host plants, leading to the hypothesis that high levels of succinoglycan production might be detrimental to symbiotic development. This study demonstrates that increased succinoglycan production itself is not detrimental to symbiotic development and, in fact, enhances the symbiotic productivity of S. meliloti 1021 with the host plant Medicago truncatula cv. Jemalong A17. Increased succinoglycan production was engineered by overexpression of the exoY gene, which encodes the enzyme responsible for the first step in succinoglycan biosynthesis. These results suggest that the level of symbiotic exopolysaccharide produced by a rhizobial species is one of the factors involved in optimizing the interaction with plant hosts.


Circadian variation in glucose tolerance and associated changes in plasma insulin and somatostatin levels in normal volunteers.
The day-time variations of blood sugar and associated changes in plasma insulin and somatostatin levels in response to glucose-glucagon load were investigated in eight healthy volunteers. The glucose-glucagon test was performed in the same subjects at 9.00 a.m., at 5.00 p.m. and at midnight after 10 hrs of fasting. The blood sugar values were higher in the midnight while the corresponding plasma insulin levels were significantly lower. Plasma somatostatin levels did not differ at the different times of the day. These results suggest that the circadian variations of the glucose tolerance are correlated to a simultaneous circadian rhythmicity in the insulin response in the sense of a decreased insulin release later in the day. Somatostatin does not seem involved in the circadian variation of beta cell responsiveness observed in healthy volunteers.


Daytime pulsatile growth hormone secretion during childhood and adolescence.
Spontaneous GH secretory patterns were studied in 91 subjects (84 children, 2-18 yr old, at various stages of pubertal development and 7 healthy adults). Plasma GH was determined every 20 min for 6 h (0900-1500 h), and at least 1 spontaneous GH secretory episode (peak, greater than or equal to 5 ng/ml) was evident in 61 children and 5 of 7 adults. There was no significant difference in the mean number of GH secretory episodes or the mean 6-h plasma GH levels in 40 children with short stature compared to those in children of the same sex and pubertal maturation with normal or tall stature. The mean number of GH secretory episodes observed during the sampling period was significantly less in Tanner Stage II males (1.3 +/- 0.15) than in Tanner Stage III males (2.1 +/- 0.20; P less than 0.05). Also, the mean 6-h plasma GH level and the amplitude of the highest GH peak in Tanner Stage III (or greater) boys were greater than those in the prepubertal, early pubertal, or adult male subjects. Among females there was no difference in the number of peaks, mean 6-h plasma GH, or mean peak amplitude in prepubertal, pubertal, or adult subjects. Furthermore, there was no significant difference in overall mean 6-h plasma GH levels between male and female subjects. The frequency of GH secretory bursts was greater between 0830-0930 and 1330-1430 h. The GH secretory profiles were not different in children fed 1 or 2 meals. Children failing to show spontaneous peaks had GH deficiency secondary to central nervous system pathology (n = 10), psychosocial GH deficiency (n = 4), estrogen-dependent GH deficiency (n = 2), and optic nerve hypoplasia (n = 3). There were 2 false negatives and 2 children who were not retested. Pulsatile GH secretion is present during the daytime in children of all ages and stages of puberty. Determination of spontaneous GH secretory bursts is a safe and effective method for assessing GH deficiency.


Multimodal In-training Examination in an Emergency Medicine Residency Training Program: A Longitudinal Observational Study.
In-training examination (ITE) has been widely adopted as an assessment tool to measure residents' competency. We incorporated different formats of assessments into the emergency medicine (EM) residency training program to form a multimodal, multistation ITE. This study was conducted to examine the cost and effectiveness of its different testing formats. We conducted a longitudinal study in a tertiary teaching hospital in Taiwan. Nine EM residents were enrolled and followed for 4 years, and the biannual ITE scores were recorded and analyzed. Each ITE consisted of 8-10 stations and was categorized into four formats: multiple-choice question (MCQ), question and answer (QA), oral examination (OE), and high-fidelity simulation (HFS) formats. The learner satisfaction, validity, reliability, and costs were analyzed. 486 station scores were recorded during the 4 years. The numbers of MCQ, OE, QA, and HFS stations were 45 (9.26%), 90 (18.5%), 198 (40.7%), and 135 (27.8%), respectively. The overall Cronbach's alpha reached 0.968, indicating good overall internal consistency. The correlation with EM board examination was highest for HFS (ρ = 0.657). The average costs of an MCQ station, an OE station, and an HFS station were ~3, 14, and 21 times that of a QA station. Multi-dimensional assessment contributes to good reliability. HFS correlates best with the final training exam score but is also the most expensive format among ITEs. Increased testing domains with various formats improve ITE's overall reliability. Program directors must understand each test format's strengths and limitations to bring forth the best combination of exams under the local context.


Characterization of Wood and Graphene Nanoplatelets (GNPs) Reinforced Polymer Composites.
This paper investigates the utilization of commercial masterbatches of graphene nanoplatelets to improve the properties of neat polymer and wood fiber composites manufactured by conventional processing methods. The effect of aspect ratio of the graphene platelets (represented by the different number of layers in the nanoplatelet) on the properties of high-density polyethylene (HDPE) is discussed. The composites were characterized for their mechanical properties (tensile, flexural, impact) and physical characteristics (morphology, crystallization, and thermal stability). The effect of the addition of nanoplatelets on the thermal conductivity and diffusivity of the reinforced polymer with different contents of reinforcement was also investigated. In general, the mechanical performance of the polymer was enhanced at the presence of either of the reinforcements (graphene or wood fiber). The improvement in mechanical properties of the nanocomposite was notable considering that no compatibilizer was used in the manufacturing. The use of a masterbatch can promote utilization of nano-modified polymer composites on an industrial scale without modification of the currently employed processing methods and facilities.


Adipokines and sublingual immunotherapy: preliminary report.
Several studies have outlined a possible relationship between an increased body mass index (BMI) and respiratory allergic diseases, such as asthma and rhinitis. Very recently, it has been demonstrated that serum adipokines, such as leptin and adiponectin, may be increased in patients with allergic rhinitis. The aim of the study was to evaluate the serum leptin and adiponectin levels in a cohort of patients with pollen-induced allergic rhinitis, before and after a single preseasonal course of sublingual immunotherapy (SLIT). A total of 41 patients (22 male and 19 female, median age 39 years) with AR due to pollen allergy, along with 34 normal subjects, were included in the study. Blood sampling for assessing serum adipokines, immunoglobulin E (IgE) levels, and eosinophils were performed in all subjects before and after the SLIT course. An increasing trend of both adipokines was observed after SLIT, albeit without statistical significance and with gender difference. Leptin was significantly related to some clinical parameters and peripheral eosinophil counts. Conversely, adinopectin showed an inverse significant correlation with peripheral eosinophils counts but only for men. In conclusion, the results of this preliminary study show that a single preseasonal SLIT course does not induce significant modifications in serum adipokines levels but induces only a slight increase.


Costs of diagnosing dementia: results from SveDem, the Swedish Dementia Registry.
Diagnostic of different dementia disorders is an important part of dementia care. So far, there is limited knowledge about how dementia is diagnosed in clinical routine, and there are few reports on the costs of the dementia work-up leading to a diagnosis. Here, we examine the costs of diagnostic dementia work-up in Sweden. The analyses were made on the data from the Swedish Dementia Registry (SveDem) and included 11,561 dementia patients diagnosed during 2007-2010, mainly not only in specialist care (SC) (n = 53) but also some primary care centres (PC). We have studied differences in the use of investigations for dementia diagnostics such as cognitive tests, blood and cerebrospinal fluid analyses, radiological examinations and assessments of functions. Unit costs for each diagnostic investigation were combined with the use of these investigations for all cases in the database. Results are presented versus gender and stratified for age. The number of diagnostic tests performed was 2.8 in PC and 4.6 in SC. The average costs (€1 = SEK9 and US$1 = SEK7 in 2010) were SEK6777 in PC and SEK11,682 in SC. Age was the strongest cost predictor while there were no gender differences. There were also regional differences, ranging from SEK8231 to SEK14,734 in SC. The SveDem database offers valuable information on the diagnostic procedures for dementia in daily clinical practice. The differences between PC and SC in diagnostic costs reflect national guidelines. The age effect needs to be studied more.


Gene set enrichment meta-learning analysis: next- generation sequencing versus microarrays.
Reproducibility of results can have a significant impact on the acceptance of new technologies in gene expression analysis. With the recent introduction of the so-called next-generation sequencing (NGS) technology and established microarrays, one is able to choose between two completely different platforms for gene expression measurements. This study introduces a novel methodology for gene-ranking stability analysis that is applied to the evaluation of gene-ranking reproducibility on NGS and microarray data. The same data used in a well-known MicroArray Quality Control (MAQC) study was also used in this study to compare ranked lists of genes from MAQC samples A and B, obtained from Affymetrix HG-U133 Plus 2.0 and Roche 454 Genome Sequencer FLX platforms. An initial evaluation, where the percentage of overlapping genes was observed, demonstrates higher reproducibility on microarray data in 10 out of 11 gene-ranking methods. A gene set enrichment analysis shows similar enrichment of top gene sets when NGS is compared with microarrays on a pathway level. Our novel approach demonstrates high accuracy of decision trees when used for knowledge extraction from multiple bootstrapped gene set enrichment analysis runs. A comparison of the two approaches in sample preparation for high-throughput sequencing shows that alternating decision trees represent the optimal knowledge representation method in comparison with classical decision trees. Usual reproducibility measurements are mostly based on statistical techniques that offer very limited biological insights into the studied gene expression data sets. This paper introduces the meta-learning-based gene set enrichment analysis that can be used to complement the analysis of gene-ranking stability estimation techniques such as percentage of overlapping genes or classic gene set enrichment analysis. It is useful and practical when reproducibility of gene ranking results or different gene selection techniques is observed. The proposed method reveals very accurate descriptive models that capture the co-enrichment of gene sets which are differently enriched in the compared data sets.


Laparoscopic cholecystectomy can be performed safely with only three ports in the majority of cases.
Reducing the number of ports used to perform laparoscopic cholecystectomy (LC) is indicated as means of further minimising postoperative pain, allowing a rapid return to activity and work, and obtaining patient satisfaction and better cosmetic results. It is still debatable whether the three-port technique is comparably safe. Since 2001, 374 consecutive patients underwent laparoscopic cholecystectomy in elective and emergency surgery. Three ports were routinely positioned and the need for a fourth cannula was evaluated during the surgical procedure. Of the 374 consecutive cholecystectomies performed, 204 were completed with three ports and 161 needed a fourth port to be completed, while 9 required conversion to laparotomy. Patients who were operated on with just three ports were significantly younger and mostly female. Complications of procedures completed with three ports were negligible and those of procedures completed with four ports were in line with the recent literature. Our experience shows that the three-port technique is always a good initial option when performing laparoscopic cholecystectomy. It is safe and requires conversion to four-port placement in only a minority of cases overall.


Using Impedance Measurements to Characterize Surface Modified with Gold Nanoparticles.
With the increased practice of preventative healthcare to help reduce costs worldwide, sensor technology improvement is vital to patient care. Point-of-care (POC) diagnostics can reduce time and lower labor in testing, and can effectively avoid transporting costs because of portable designs. Label-free detection allows for greater versatility in the detection of biological molecules. Here, we describe the use of an impedance-based POC biosensor that can detect changes in the surface modification of a micro-fabricated chip using impedance spectroscopy. Gold nanoparticles (GNPs) have been employed to evaluate the sensing ability of our new chip using impedance measurements. Furthermore, we used impedance measurements to monitor surface functionalization progress on the sensor's interdigitated electrodes (IDEs). Electrodes made from aluminum and gold were employed and the results were analyzed to compare the impact of electrode material. GNPs coated with mercaptoundecanoic acid were also used as a model of biomolecules to greatly enhance chemical affinity to the silicon substrate. The portable sensor can be used as an alternative technology to ELISA (enzyme-linked immunosorbent assays) and polymerase chain reaction (PCR)-based techniques. This system has advantages over PCR and ELISA both in the amount of time required for testing and the ease of use of our sensor. With other techniques, larger, expensive equipment must be utilized in a lab environment, and procedures have to be carried out by trained professionals. The simplicity of our sensor system can lead to an automated and portable sensing system.


Characteristics of the Arcing Plasma Formation Effect in Spark-Assisted Chemical Engraving of Glass, Based on Machine Vision.
Spark-assisted chemical engraving (SACE) is a non-traditional machining technology that is used to machine electrically non-conducting materials including glass, ceramics, and quartz. The processing accuracy, machining efficiency, and reproducibility are the key factors in the SACE process. In the present study, a machine vision method is applied to monitor and estimate the status of a SACE-drilled hole in quartz glass. During the machining of quartz glass, the spring-fed tool electrode was pre-pressured on the quartz glass surface to feed the electrode that was in contact with the machining surface of the quartz glass. In situ image acquisition and analysis of the SACE drilling processes were used to analyze the captured image of the state of the spark discharge at the tip and sidewall of the electrode. The results indicated an association between the accumulative size of the SACE-induced spark area and deepness of the hole. The results indicated that the evaluated depths of the SACE-machined holes were a proportional function of the accumulative spark size with a high degree of correlation. The study proposes an innovative computer vision-based method to estimate the deepness and status of SACE-drilled holes in real time.


Motivational effects mu- and kappa-opioid agonists following acute and chronic restraint stress: involvement of dopamine D(1) and D(2) receptors.
The influence of both acute and chronic restraint stress on the rewarding properties of morphine (1, 2 or 3 mg/kg i.p.) and the aversive effects of naloxone (0.5 mg/kg i.p. x3 or 1.0 mg/kg i.p.) or bremazocine (0.4 mg/kg i.p.) was investigated. An acute (2 h) but not chronic restraint (2 h daily for 7 days) enhanced the morphine place preference, and elicited a place aversion with a subthreshold dose of bremazocine. This enhancing effect on the reinforcing properties induced by the drugs was prevented by either R(+)-SCH-23390 hydrochloride (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H3-benzazepine, 30 microg/kg i.p.) or (+/-)-sulpiride (60 mg/kg i.p.), 10-20 min prior to the stress session. Naltrexone pretreatment (1 mg/kg i.p.) abolished the stress effect on morphine place preference but not that on bremazocine aversion. Instead, nor-BNI (30 microg/3 microl i.c.v.) abolished the stress's effects on bremazocine aversion, but did not modify those on morphine preference. These results show that: (1) acute stress enhanced the morphine and bremazocine conditioned reinforcing effects meanwhile chronic stress did not modify them; (2) the stimulation of D(1) and D(2) dopamine receptors is necessary for the development of restraint stress-induced sensitization to the conditioned reinforcing effects of drugs; and (3) the stimulation mu/delta- and kappa-opioid receptors seems to be differentially involved.


Silicone index: an alternative approach for tooth fragment reattachment.
Tooth fragment reattachment is a simple, conservative, fast, and affordable treatment option for fractured teeth when the fragment is available. However, this technique can present some difficulties, among which is the possibility of the fragment being positioned and bonded inadequately. To avoid this situation, it is necessary to establish a reference for the adequate positioning of the fragment using a silicone index. This article presents an alternative approach for better handling of tooth fragments resulting from trauma by using a silicone index as a guide to proper positioning and bonding.


[Incomplete duplication of the urethra with intra-rectal opening of the posterior chanel (author's transl)].
We have described two cases of urethro-rectal fistulae: outstanding by their absence of anorectal abnormality. This type of malformation must be separated from the fistula observed in imperforated anus. We consider it as an incomplete duplication of the urethra; the posterior part ending in the rectum: this is a very rare abnormality. The treatment involves a separation of the posterior urethra from the rectum to bring it up to the preneum then continue as in an hypospadias usig the Duplay and Leveuf (Cecil) techniques. Seemingly normal urethra is hypoplastic in part or entirely.


American Academy of Sleep Medicine (AASM) Position Paper for the Use of Telemedicine for the Diagnosis and Treatment of Sleep Disorders.
The American Academy of Sleep Medicine's (AASM) Taskforce on Sleep Telemedicine supports telemedicine as a means of advancing patient health by improving access to the expertise of Board-Certified Sleep Medicine Specialists. However, such access improvement needs to be anchored in attention to quality and value in diagnosing and treating sleep disorders. Telemedicine is also useful to promote professionalism through patient care coordination and communication between other specialties and sleep medicine. Many of the principles and key concepts adopted here are based on U.S. industry standards, with special consideration given to the body of work by the American Telemedicine Association (http://www.americantelemed.org/), and abide by standards endorsed by the American Medical Association (http://www.ama-assn.org/). Practitioners who wish to integrate sleep telemedicine into their practice should have a clear understanding of the salient issues, key terminology, and the following recommendations from the AASM. The Taskforce recommends the following: • Clinical care standards for telemedicine services should mirror those of live office visits, including all aspects of diagnosis and treatment decisions as would be reasonably expected in traditional office-based encounters. • Clinical judgment should be exercised when determining the scope and extent of telemedicine applications in the diagnosis and treatment of specific patients and sleep disorders. • Live Interactive Telemedicine for sleep disorders, if utilized in a manner consistent with the principles outlined in this document, should be recognized and reimbursed in a manner competitive or comparable with traditional in-person visits. • Roles, expectations, and responsibilities of providers involved in the delivery of sleep telemedicine should be defined, including those at originating sites and distant sites. • The practice of telemedicine should aim to promote a care model in which sleep specialists, patients, primary care providers, and other members of the healthcare team aim to improve the value of healthcare delivery in a coordinated fashion. • Appropriate technical standards should be upheld throughout the telemedicine care delivery process, at both the originating and distant sites, and specifically meet the standards set forth by the Health Insurance Portability and Accountability Act (HIPAA). • Methods that aim to improve the utility of telemedicine exist and should be explored, including the utilization of patient presenters, local resources and providers, adjunct testing, and add-on technologies. • Quality Assurance processes should be in place for telemedicine care delivery models that aim to capture process measures, patient outcomes, and patient/provider experiences with the model(s) employed. • Time for data management, quality processes, and other aspects of care delivery related to telemedicine encounters should be recognized in value-based care delivery models. • The use of telemedicine services and its equipment should adhere to strict professional and ethical standards so as not to violate the intent of the telemedicine interaction while aiming to improve overall patient access, quality, and/or value of care. • When billing for telemedicine services, it is recommended that patients, providers, and others rendering services understand payor reimbursements, and that there be financial transparency throughout the process. • Telemedicine utilization for sleep medicine is likely to rapidly expand, as are broader telehealth applications in general; further research into the impact and outcomes of these are needed. This document serves as a resource by defining issues and terminology and explaining recommendations. However, it is not intended to supersede regulatory or credentialing recommendations and guidelines. It is intended to support and be consistent with professional and ethical standards of the profession.


[Reference values for arterial oxygen content].
In clinical practice, oxygen saturation as measured by photoplethysmography and arterial oxygen tension as determined by blood gas analysis are the parameters used frequently to estimate the oxygen status of a patient. Additionally, the cardiac output CO and the arterial oxygen content CaO2 are critical for the delivery of oxygen ḊO2 to organs and tissues. So far, CaO2 reference values published by Mertzlufft and Zander (1984) and Siggaard-Andersen (1990) are widely used. The aim of the present study was to reevaluate previously published results using the results of a population-based study. Furthermore, the impact of smoking on CaO2 will be assessed. Data of 1018 volunteers from the Study of Health in Pomerania (SHIP) were analyzed. CaO2 was calculated from blood gas analysis of capillary blood obtained from a hyperemised ear lobe. Reference value equations controlled for sex, age and smoking were derived with quantile regression analysis and fractional polynomials. Lower limits of normal (LLN) decline with age. Current smoking has no significant influence on LLN for CaO2. Sex, age and smoking-specific normal values can be calculated using the current equations.


β-Cyanoalanine synthase protects mites against Arabidopsis defenses.
Glucosinolates are antiherbivory chemical defense compounds in Arabidopsis (Arabidopsis thaliana). Specialist herbivores that feed on brassicaceous plants have evolved various mechanisms aimed at preventing the formation of toxic isothiocyanates. In contrast, generalist herbivores typically detoxify isothiocyanates through glutathione conjugation upon exposure. Here, we examined the response of an extreme generalist herbivore, the two-spotted spider mite Tetranychus urticae (Koch), to indole glucosinolates. Tetranychus urticae is a composite generalist whose individual populations have a restricted host range but have an ability to rapidly adapt to initially unfavorable plant hosts. Through comparative transcriptomic analysis of mite populations that have differential susceptibilities to Arabidopsis defenses, we identified β-cyanoalanine synthase of T. urticae (TuCAS), which encodes an enzyme with dual cysteine and β-cyanoalanine synthase activities. We combined Arabidopsis genetics, chemical complementation and mite reverse genetics to show that TuCAS is required for mite adaptation to Arabidopsis through its β-cyanoalanine synthase activity. Consistent with the β-cyanoalanine synthase role in detoxification of hydrogen cyanide (HCN), we discovered that upon mite herbivory, Arabidopsis plants release HCN. We further demonstrated that indole glucosinolates are sufficient for cyanide formation. Overall, our study uncovered Arabidopsis defenses that rely on indole glucosinolate-dependent cyanide for protection against mite herbivory. In response, Arabidopsis-adapted mites utilize the β-cyanoalanine synthase activity of TuCAS to counter cyanide toxicity, highlighting the mite's ability to activate resistant traits that enable this extreme polyphagous herbivore to exploit cyanogenic host plants.


Migraine treatment in developmental age: guidelines update.
There is a serious lack of controlled studies on the pharmacological treatment of primary migraine in the developmental age; there is, consequently, an urgent need for new, evidence-based approaches to this long-neglected field of research. Moreover, previous studies have stated that the placebo response is greater in pediatric patients than in adults and that a reduction in the attack frequency in the absence of any pharmacological treatment is observed more frequently in pediatric migraine patients than in adults. Besides these preliminary considerations, the shorter duration of migraine attacks and other characteristic semeiological features of the clinical picture in children are such that the design of randomized controlled trial (RCT) is more problematic in the developmental age than in the adult. Bearing in mind all these weak points, the aim of this review was to summarize and update recent guidelines for the treatment of primary migraine in children and adolescents. The most recent guidelines are those published by the Italian Society for the study of Headache, the French Society for the study of Migraine and Headache, and the American Academy of Neurology. We have incorporated into these guidelines the results from the few, recent RCTs, clinical controlled trials, open-label studies, meta-analyses and reviews that have been published since 2004; owing to the lack of strong evidence in this field of research, we have sometimes even mentioned pilot non-controlled studies, case series and expert opinions. Lastly, evidence was classified and the recommendations were categorized according to different levels.


Atom Interferometry with Coherent Enhancement of Bragg Pulse Sequences.
We report here on the realization of light-pulse atom interferometers with large-momentum-transfer atom optics based on a sequence of Bragg transitions. We demonstrate momentum splitting up to 200 photon recoils in an ultracold atom interferometer. We highlight a new mechanism of destructive interference of the losses leading to a sizable efficiency enhancement of the beam splitters. We perform a comprehensive study of parasitic interferometers due to the inherent multiport feature of the quasi-Bragg pulses. Finally, we experimentally verify the phase shift enhancement and characterize the interferometer visibility loss.


Fingertip forces during object manipulation in children with hemiplegic cerebral palsy. I: anticipatory scaling.
Previous studies of grasping and object manipulation in children with cerebral palsy (CP) have suggested a dichotomy in the ability to use anticipatory control (planning) of the fingertip force output, depending on the type of sensory information (tactile or proprioceptive) on which it is based. The present study further explores this issue by testing the ability of 15 children with hemiplegic CP aged between 8 and 14 years to scale the fingertip force output in advance during the lifting of small objects whose weight and surface texture are varied. The results indicate that children with hemiplegia can use anticipatory control based on both the weight and texture of the object, but require a greater number of trials than age-matched children without CP (control children) before they can do so. We suggest that the initial lack of anticipatory control results from an indistinct internal representation of the object's physical properties due to disturbed sensory mechanisms, which may have direct implications for therapeutic intervention.


The effectiveness and safety of Wu tou decoction on rheumatoid arthritis: A protocol for systematic review and/or meta-analysis.
Rheumatoid arthritis (RA) is one of the common inflammatory diseases with arthritis due to a malfunction of the immune system. The treatments for RA include surgery, physiotherapy, occupational therapies, and medication. The representative treatment is medication and its usage has improved through several guidelines. However, it has some limitations and occurs adverse effects. Meanwhile, traditional Chinese medicine treatments have been used for RA treatment and Wu tou decoction (WTD) is one of them. Regardless of recent studies about WTD's efficacy on RA, there has been no systematic review on this issue. Therefore, this review will focus on the effectiveness and safety of WTD on RA. The search for randomized controlled trial about WTD on RA will be performed using multiple electronic databases, manual searches, and the author's e-mail if necessary. According to predefined criteria, randomized controlled trials will be selected and summarization will be performed by the data on study participants, result measurements, interventions, adverse events, and risk of bias. Disease activity score including effective rate, swollen joint count, tender joint count, morning stiffness will be primary outcome measures while blood test about RA including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factors, and adverse events will be secondary outcome measures. We will perform meta-analysis by using Review Manager software, assess the risk of bias by Cochrane Collaboration "risk of bias" tool, and determine the quality of evidence by Grades of Recommendation, Assessment, Development, and Evaluation. This study we will investigate the clinical evidence of the effectiveness and safety of WTD on RA. For the RA patients and clinicians, our study will be informative. It can be also a great help for the researchers and policy makers who concentrates on conservative management for RA. INPLASY; INPLASY202220099.


Intellectual disability in Indigenous Australians: issues and challenges.
Literature on Indigenous Australians (Aboriginal and Torres Strait Islander people) and intellectual disability (ID) is summarized in order to identify current state of knowledge, gaps, and areas for further research. A selective review of psychiatric literature using relevant medical databases was undertaken. Key articles were identified and their findings described. ID is reported to be more prevalent in Indigenous Australians. Sociocultural constructs and a lack of validated psychometric measures affect what is considered to be ID in Indigenous communities. Prenatal, perinatal, and postnatal factors impair brain development and contribute to ID in Indigenous communities. Comorbid physical and psychiatric disorders need to be assessed and managed. ID is an emerging area of health concern for general and mental health professionals working with Indigenous Australians. This important area requires further research, appropriate training, and resourcing.