Outcomes and potential mechanism of a protocol to optimize foot orthoses in patients with rheumatoid arthritis.
Foot problems are highly prevalent in patients with rheumatoid arthritis. Treatment of foot problems related to rheumatoid arthritis often consists of custom made foot orthoses. One of the assumed working mechanisms of foot orthoses is redistribution of plantar pressure by creating a larger weight bearing area. Overall, the reported treatment effect of foot orthoses on foot pain in rheumatoid arthritis is small to medium. Therefore, we developed a foot orthoses optimization protocol for evaluation and adaptation of foot orthoses by using the feedback of in-shoe plantar pressure measurements. The objectives of the present study were: 1) to evaluate the 3-months outcomes of foot orthoses developed according to the protocol on pain, physical functioning and forefoot plantar pressure in patients with foot problems related to rheumatoid arthritis, and 2) to determine the relationship between change in forefoot plantar pressure and change in pain and physical functioning. Forty-five patients with foot problems related to rheumatoid arthritis were included and received foot orthoses developed according to the protocol. Outcome measures were assessed at baseline and after three months of wearing foot orthoses in 38 patients. Change scores and effect sizes (ES) were calculated for pain, physical functioning and plantar pressure. In a subgroup of patients with combined forefoot pain and high plantar pressure, the relationship between change in plantar pressure and change in pain and physical functioning was analyzed. In the total group of 38 patients, statistically significant changes in pain (ES 0.69), physical functioning (ES 0.82) and forefoot plantar pressure (ES 0.35) were found. In the subgroup (n = 23) no statistically significant relationships were found between change in plantar pressure and change in pain or physical functioning. Foot orthoses developed according to a protocol for improving the plantar pressure redistribution properties lead to medium to large improvements in pain and physical functioning. The hypothesis that more pressure reduction would lead to better clinical outcomes could not be proven.


[Experimental study. Reduction of pressure in areas of risk of developing pressure ulcers with a hydrocellular dressing].
The handling of pressure is a basic measure in the prevention and treatment of bed sores. It is possible to reduce and ease pressure by various means including changes in posture, use of special surfaces for handling pressure as well as the use of local applications or external applications which reduce pressure. Today nurses have a large quantity of external applications available to use although only some hydrocellular ones are capable to reduce pressure due to their hydrocellular structure. An experimental study was designed to calculate the level of pressure before and after applying an Allevyn hydrocellular external application in the area of the sacrum, ischium, and heel of three healthy volunteers; first, Volunteer A, a 85 kg. 170 cm man; second, Volunteer B, a 54.3 kg. 159 cm woman; and third, Volunteer C, a 69.4 kg 164 cm man. Measures were taken on two types of surfaces: a viscoelastic foam mattress and a conventional hospital mattress. All measurements were repeated at 0, 30, 45 and 60 degrees of inclination. Pressure was determined by means of a Talley pressure monitor, Oxford Pressure Monitor MK II. A total of 144 pressure reading were taken. The overall average reduction after applying a external hydrocellular application on all volunteers, at all inclinations and on all surfaces for each of the three zones were 19.5% in the sacrum, 13.8% in the ischium and 20.15% in the heel. Even though our study has its limitations, such as young, healthy volunteers, we can establish that the external hydrocellular application studied does have a local reducing effect on pressure. Since every external hydrocellular application has its own specific structure, the results of our study can not be applied with certainty to other external applications inside the hydrocellular group.


Preventive counseling at adolescent ambulatory visits.
To evaluate factors that independently predict counseling for diet, exercise, sexually transmitted diseases (STDs), pregnancy, smoking, and injuries at adolescent well visits, and compare these rates to the frequency of counseling at adolescent acute visits. The 1997-2000 National Ambulatory Medical Care and National Hospital Ambulatory Medical Care Surveys were combined for patients aged 11-21 years. Acute visits were identified by ICD-9 code for: sexual health, obesity, asthma, injury, and well care. Bivariate analyses were used to determine differences in relevant counseling provided at acute visits compared with well visits. Logistic regression was used to assess factors that predict counseling on each of the above topics at well adolescent visits. Of 23,378 adolescent ambulatory visits, 1508 (6.5%) were for well care. Only 0.8% of visits were for obesity, 3.7% for sexual health, 2.6% for asthma, and 13% for injuries. Counseling was more frequent at acute than well visits for diet (72% vs. 28%), exercise (52% vs. 23%), human immunodeficiency virus/sexually transmitted diseases (HIV/STD; 14% vs. 6.2%), and family planning (FP) (24% vs. 10%), (all p values < .05). Pediatric clinicians were more likely than other specialists to provide counseling for diet (OR 2.3), HIV/STD (OR 2.7), FP (OR 2.9), tobacco use (OR 2.8), and injury prevention (OR 4.7). Blacks received less exercise counseling than Whites (OR 0.4), and counseling about sensitive issues (STDs, family planning) occurred more often in older adolescents (OR 1.3). Despite recommendations, more counseling occurs at acute rather than well visits, and still does not reach all those adolescents in need. There remains much room for improvement in physicians' adherence to national guidelines for adolescent care.


Plasmonic Nanoantennas Enable Forbidden Förster Dipole-Dipole Energy Transfer and Enhance the FRET Efficiency.
Förster resonance energy transfer (FRET) plays a key role in biochemistry, organic photovoltaics, and lighting sources. FRET is commonly used as a nanoruler for the short (nanometer) distance between donor and acceptor dyes, yet FRET is equally sensitive to the mutual dipole orientation. The orientation dependence complicates the FRET analysis in biological samples and may even lead to the absence of FRET for perpendicularly oriented donor and acceptor dipoles. Here, we exploit the strongly inhomogeneous and localized fields in plasmonic nanoantennas to open new energy transfer routes, overcoming the limitations from the mutual dipole orientation to ultimately enhance the FRET efficiency. We demonstrate that the simultaneous presence of perpendicular near-field components in the nanoantenna sets favorable energy transfer routes that increase the FRET efficiency up to 50% for nearly perpendicular donor and acceptor dipoles. This new facet of plasmonic nanoantennas enables dipole-dipole energy transfer that would otherwise be forbidden in a homogeneous environment. As such, our approach further increases the applicability of single-molecule FRET over diffraction-limited approaches, with the additional benefits of higher sensitivities and higher concentration ranges toward physiological levels.


Rodent phylogeny and a timescale for the evolution of Glires: evidence from an extensive taxon sampling using three nuclear genes.
Rodentia is the largest order of placental mammals, with approximately 2,050 species divided into 28 families. It is also one of the most controversial with respect to its monophyly, relationships between families, and divergence dates. Here, we have analyzed and compared the performance of three nuclear genes (von Willebrand Factor, interphotoreceptor retinoid-binding protein, and Alpha 2B adrenergic receptor) for a large taxonomic sampling, covering the whole rodent and placental diversity. The phylogenetic results significantly support rodent monophyly, the association of Rodentia with Lagomorpha (the Glires clade), and a Glires + Euarchonta (Primates, Dermoptera, and Scandentia) clade. The resolution of relationships among rodents is also greatly improved. The currently recognized families are divided here into seven well-defined clades (Anomaluromorpha, Castoridae, Ctenohystrica, Geomyoidea, Gliridae, Myodonta, and Sciuroidea) that can be grouped into three major clades: Ctenohystrica, Gliridae + Sciuroidea, and a mouse-related clade (Anomaluromorpha, Castoridae + Geomyoidea, and Myodonta). Molecular datings based on these three genes suggest that the rodent radiation took place at the transition between Paleocene and Eocene. The divergence between rodents and lagomorphs is placed just at the K-T boundary and the first splits among placentals in the Late Cretaceous. Our results thus tend to reconcile molecular and morphological-paleontological insights.


Trends in depression prevalence in the USA from 2005 to 2015: widening disparities in vulnerable groups.
Major depression is associated with significant disability, morbidity, and mortality. The current study estimated trends in the prevalence of major depression in the US population from 2005 to 2015 overall and by demographic subgroups. Data were drawn from the National Survey on Drug Use and Health (NSDUH), an annual cross-sectional study of US persons ages 12 and over (total analytic sample N = 607 520). Past-year depression prevalence was examined annually among respondents from 2005 to 2015. Time trends in depression prevalence stratified by survey year were tested using logistic regression. Data were re-analyzed stratified by age, gender, race/ethnicity, income, and education. Depression prevalence increased significantly in the USA from 2005 to 2015, before and after controlling for demographics. Increases in depression were significant for the youngest and oldest age groups, men, and women, Non-Hispanic White persons, the lowest income group, and the highest education and income groups. A significant year × demographic interaction was found for age. The rate of increase in depression was significantly more rapid among youth relative to all older age groups. The prevalence of depression increased significantly in the USA from 2005 to 2015. The rate of increase in depression among youth was significantly more rapid relative to older groups. Further research into understanding the macro level, micro level, and individual factors that are contributing to the increase in depression, including factors specific to demographic subgroups, would help to direct public health prevention and intervention efforts.


Characterization of MAST9/Hevin, a SPARC-like protein, that is down-regulated in non-small cell lung cancer.
In the search for genes down-regulated in non-small cell lung cancer (NSCLC), we have identified a cDNA fragment, termed MAST9. Cloning, sequencing, and characterization of the full-length MAST9 cDNA revealed that the entire 2808 nucleotide sequence had an open reading frame of 1992 nucleotides encoding a Mr 75,000 protein. Sequence analysis disclosed a striking homology to SPARC, known to be involved in tumorigenesis. The recently identified "Hevin" cDNA isolated from high endothelial venules is identical to MAST9. Using Northern and Western blot analysis, we showed that MAST9 was down-regulated in the tumor samples of nine non-small cell lung carcinoma patients. Furthermore, we demonstrated that both the bacterially expressed and the endogenous MAST9 proteins form homodimers. The lack of expression in non-small cell lung carcinomas and its homology to SPARC suggest a putative role of MAST9 in lung tumor formation.


Pressure induced excellent thermoelectric behavior in skutterudites CoSb3 and IrSb3.
Utilizing the first-principle calculations combined with Boltzmann transport equation (BTE) and semiclassical analysis, we have systematically investigated the electronic structure, lattice thermal conductivity κL, Seebeck coefficient S, and the dimensionless figure of merit zT as a function of hydrostatic pressure P in crystalline skutterudites CoSb3 and IrSb3. Interestingly, as the pressure increases, the band gap and κL show an approximate parabolic trend, which results in extraordinarily high S and excellent thermoelectric properties, and zT even exceeds 1.4(1.09) in IrSb3(CoSb3) at 54(58) GPa. This anomalous behavior arises from the electron distribution and intrinsic scattering processes. Further analyses indicate that (i) nonbonding electron pairs of Sb atoms are gradually transferred to the region between Co(Ir) and Sb atoms as the pressure increases, which leads to the formation of a partial metallic bond and thus the band gap first expands and then shrinks; (ii) the change of the strength of the anharmonic phonon scattering process results in the variation of κL. As a result, these behaviors cause excellent thermoelectric properties. Our results provide insight into the thermal transport properties of skutterudites, meanwhile, forecast potential high pressure applications for thermoelectric materials.


Evaluation of stimbiotic on growth performance and intestinal development of broilers fed corn- or wheat-based diets.
In the antibiotics-free era, stimbiotic (STB) has been suggested as a new alternative of antibiotic growth promoters to modulate intestinal health via stimulating dietary fiber utilization in poultry production. The aim of this study was to evaluate the effects of STB supplementation in corn- or wheat-basal diet on growth performance, intestinal development, and function of broilers. A total of 512 one-day-old Arbor Acres(AA)broilers were randomly allocated 4 treatments, including corn group (CG), corn + 100 g/t STB (CG + STB), wheat group (WG), wheat + 100 g/t STB (WG + STB). The broilers were weighed at the days of 14, 28, and 42, of which 8 repetitions per treatment were randomly selected to determine the intestinal morphology, intestinal barrier, and cecal microbiota and metabolites. Our data showed that STB increased (P < 0.05) feed intake, body weight and reduced FCR for the overall period (0-42 d). At 28 d of age, significant increases in villus height and the villus height-to-crypt depth ratio (V/C) were found in the STB supplementation groups (P < 0.05). Addition of STB significantly increased intestinal mucosal DAO and AMPK enzyme activity and the gene expression of OCLN, CLDN1, ZO1, MUC2, SGLT1, PEPT1, FABP2, Ghrelin, and GCG in jejunum (P < 0.05), and significantly decreased the expression of the PYY gene. In addition, STB increased the relative abundance of beneficial bacteria, such as Akkermansia, Bifidobacterium, and Oscillospirales (P < 0.05). A significant increase in cecal short-chain fatty acid (SCFAs) concentration was also observed in the STB supplementation groups. At the cellular level, STB cannot directly increase the expression of small intestinal epithelial cells, and may indirectly improve intestinal barrier function by increasing the level of sodium butyrate. Overall, these results indicated that STB supplementation could improve the growth performance, intestinal development and barrier functions, and fiber fermentation in cecum of broiler chickens.


Human B cell growth and differentiation in the spleen of immunodeficient mice.
Human mAbs (HumAbs) have therapeutic potential against infectious diseases and cancer. Heretofore, their production has been hampered by ethical constraints preventing the isolation of Ag-specific activated B cells by in vivo immunization. Alternatively, severe combined immune deficient (SCID) mice, transplanted i.p. with human (Hu)-PBLs, allow the in vivo stimulation of human Ab responses without the usual constraints. Unfortunately, human B cells only represent a minor fraction of the surviving graft, they are scattered all over the animal body, and thus are hard to isolate for subsequent immortalization procedures. To prevent this dispersion and to provide the human B cells with a niche for expansion and maturation, SCID mice were engrafted with Hu-PBL directly into the spleen. Simultaneously endogenous murine NK cell activity was depleted by treatment with an anti-mouse IL-2 receptor beta-chain Ab. During engraftment, human B lymphocytes became activated, divided intensely, and differentiated into plasmacytoid cells. In vivo exposure to a recall Ag after cell transfer induced expansion of Ag-specific B cell clones. One week after inoculation, human B cells were abundant in the spleen and could easily be recovered for fusion with a heteromyeloma line. This resulted in the formation of stable hybridoma cell lines that secreted Ag-specific HumAbs. Thus transplantation of human lymphoid cells in the spleens of immune deficient mice represents a model for the study of human T cell-dependent B cell activation and proves to be an excellent tool for the successful production of HumAbs.


Ca2+ sensor synaptotagmin-1 mediates exocytosis in mammalian photoreceptors.
To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca2+ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous release frequency was unchanged in cones but increased in rods lacking Syt1. Loss of Syt1 did not alter synaptic anatomy or reduce Ca2+ currents. These results suggest that Syt1 mediates both phasic and tonic release at photoreceptor synapses, revealing unexpected flexibility in the ability of Syt1 to regulate Ca2+-dependent synaptic transmission.


Duloxetine for the treatment of generalized social anxiety disorder: a preliminary randomized trial of increased dose to optimize response.
This is the first trial examining duloxetine for generalized social anxiety disorder (GSAD) and the effect of increased dose for those without early remission. Individuals (n=39) with GSAD received 6 weeks of open-label duloxetine 60 mg/day; those with a Liebowitz Social Anxiety Disorder Scale (LSAS) score >30 at week 6 were randomized in double-blind fashion to an additional 18 weeks of continued duloxetine 60 mg/day or to duloxetine 120 mg/day. Duloxetine was associated with a significant LSAS reduction at week 6 (91.3 [17.7] to 69.8 [28.5], paired t [df]=5.2 [38], P<.0001), and randomized participants overall continued to improve at week 24 (74.6 [23.9] to 60.3 [29.7]; paired t [df]=3.3 [27], P=.0026). Though the increased dose strategy was associated with a moderate effect size (Cohen's d=.57), there was no significant difference at week 24 endpoint in LSAS reduction (20.5 [26.0] versus 7.3 [17.2], t [df]=1.6 [26], P=.13) nor remission (33% versus 8%) for duloxetine with dose increased to 120 mg/day compared to duloxetine continued at 60 mg/day. Overall, 44% (17/39) discontinued prior to week 24. Though with limited power, these data provide preliminary support for the efficacy of duloxetine for GSAD, and suggest continued improvement but limited remission overall at 24 weeks for individuals remaining symptomatic at week 6. These observations warrant further controlled study.


Neutralizing antibodies against porcine circovirus type 2 in liquid pooled plasma contribute to the biosafety of commercially manufactured spray-dried porcine plasma.
Neutralizing antibodies (NA) inherently present in pooled plasma collected at commercial abattoirs may provide some protection against potential porcine circovirus type 2 (PCV2) infectivity of plasma. Moreover, these NA may also contribute to the biosafety of spray-dried porcine plasma (SDPP). The objective of the study was to characterize and quantify the PCV2 antibody neutralizing capacity in pooled liquid porcine plasma and SDPP samples collected from industrial spray-drying facilities located in the Southeast and Midwest regions of the United States and the Northeast region of Spain. In the United States, PCV2 NA was determined in 1 sample of pooled liquid plasma from commercial spray-drying plants in the Southeast and 1 from the Midwest region. Obtained results were compared with those of a plasma sample from a PCV2 vaccinated sow and 1 from a PCV2 antibody negative sow. In Spain, 15 pooled liquid porcine plasma samples and 10 SDPP samples were collected at a commercial spray-drying plant total and NA against PCV2 were determined. Results with pooled liquid porcine plasma from commercial spray-drying facilities in the United States indicated that NA titers against PCV2 in these samples (log2 8.33 ± 0.41 and 9.0 ± 0.0) were similar or greater than the plasma from the PCV2-vaccinated sow (log2 6.33 ± 0.41). The analysis of U.S. samples indicated that liquid plasma diluted to 1:256 (10(-2.41)) was able to neutralize between 100 to 200 PCV2 virus particles or about 4 logs10 median tissue culture infective dose (TCID50) per milliliter. Similarly, samples from the Spanish pooled liquid plasma and the SDPP samples indicated an increased amount of NA activity against PCV2. Specifically, a dilution of 10(-2.47 ± 0.33) of plasma was able to inactivate 100 PCV2 virus particles; therefore, the inactivation capacity of commercial liquid plasma was greater than 10(4) TCID50/mL. The calculated 90% reduction in infected cells because of NA in pooled plasma samples (log2 8.2 ± 0.38) was less (P < 0.05) than in its concentrate form of SDPP (mean, log2 10.2 ± 0.85). In conclusion, PCV2 NA contained in liquid pooled plasma from market pigs was detected at greater concentrations than that from a vaccinated sow and that after spray-drying biological neutralizing activity was conserved, which implies that the inherent NA in liquid plasma may have an important role in the biosafety of commercially produced SDPP.


TRPV1 (Transient Receptor Potential Vanilloid 1) Cardiac Spinal Afferents Contribute to Hypertension in Spontaneous Hypertensive Rat.
Hypertension is associated with increased sympathetic activity. A component of this sympathoexcitation may be driven by increased signaling from sensory endings from the heart to the autonomic control areas in the brain. This pathway mediates the so-called cardiac sympathetic afferent reflex, which is also activated by coronary ischemia or other nociceptive stimuli in the heart. The cardiac sympathetic afferent reflex has been shown to be enhanced in the heart failure state and in renal hypertension. However, little is known about its role in the development or progression of hypertension or the phenotype of the sensory endings involved. To investigate this, we used the selective afferent neurotoxin, resiniferatoxin (RTX) to chronically abolish the cardiac sympathetic afferent reflex in 2 models of hypertension; the spontaneous hypertensive rats (SHRs) and AngII (angiotensin II) infusion (240 ng/kg per min). Blood pressure (BP) was measured in conscious animals for 2 to 8 weeks post-RTX. Epidural application of RTX to the T1-T4 spinal segments prevented the further BP increase in 8-week-old SHR and lowered BP in 16-week-old SHR. RTX did not affect BP in Wistar-Kyoto normotensive rats nor in AngII-infused rats. Epicardial application of RTX (50 µg/mL) in 4-week-old SHR prevented the BP increase whereas this treatment does not lower BP in 16-week-old SHR. When RTX was administered into the L2-L5 spinal segments of 16-week-old SHR, no change in BP was observed. These findings indicate that signaling via thoracic afferent nerve fibers may contribute to the hypertension phenotype in the SHR but not in the Ang II infusion model of hypertension.


Detection of Trypanosoma brucei spp. in human blood by a nonradioactive branched DNA-based technique.
We have developed a nonradioactive branched DNA (bDNA)-based assay for the diagnosis of the African trypanosomiases in simple buffy coat preparations of human blood. Two repetitive DNA sequences specific to the Trypanosoma brucei complex were chosen as targets of the bDNA assay, a technique which amplifies the signal from a target molecule rather than the target itself. Comparable sensitivities were observed with cloned target sequences, purified T. brucei DNA, procyclic trypanosomes, and bloodstream trypomastigotes. The results of bDNA analysis of human blood samples from Côte d'Ivoire (n = 50) showed excellent agreement with those of buffy coat microscopy. The bDNA technology offers certain advantages over alternative molecular biological techniques, including the simplicity of sample preparation and of the procedure itself, the stability of the reagents, the ability to process large numbers of samples simultaneously, and freedom from crosscontamination artifacts. We have successfully applied the bDNA technique to the detection of T. brucei in clinical samples from regions where T. brucei infection is endemic; to our knowledge, this is the first report of the molecular detection of T. brucei in human blood.


Redox Property of Enamines.
Enamines are electron-rich compounds bearing intriguing redox properties. Herein, a series of secondary enamines condensed from primary amine and β-ketocarbonyls were synthesized and their electrochemical oxidation properties were systematically studied by cyclic voltammetry. Furthermore, theoretical calculation of oxidation potentials of enamines, particularly those catalytic intermediates, was also conducted to further broaden the scope investigated. Possible structural factors on oxidation and the nature of the resulted radical cation intermediates were revealed and discussed. Correlation of redox potentials with molecular properties such as highest occupied molecular orbital energies and natural population analysis charge were explored, and there appears no simple linear correlation. On the other hand, a good correlation with Mayr's nucleophilicity parameter N was noted among a range of catalytically relevant enamines. Spin population analysis disclosed that enamine radical cations mainly exhibit the carbon-center free radical feature. Taking experimental and computation data together, a comprehensive picture about the redox property of enamines is presented, which would provide guidance in the development of oxidative enamine catalysis and transformations.


Thymus-dependent and thymus-independent antibody responses: contrasting patterns of immunosuppression.
The effects of mitoclomine, an anti-tumour agent, and of cortisone acetate on the antibody response of mice to thymus-dependent and thymus-independent antigens were compared. Both agents yielded patterns of immunosuppression which differed from that seen after X-rays, an agent which is likely to be active equally against T and B cells. Mitoclomine, at low doses, depressed thymus-independent responses the most; this effect can be explained if the drug is more active against B than T cells. Cortisone acetate at low doses, while depressing thymus-dependent responses, increased thymus-independent responses; this can be explained if the drug is more active against T than B cells. Thus three different patterns of immunosuppression (for X-rays, mitoclomine and cortisone acetate) can be interpreted in terms of effects simply on T or B cells.


The effect of endotracheal tubes versus laryngeal mask airways on perioperative respiratory adverse events in infants: a randomised controlled trial.
Perioperative respiratory adverse events (PRAE) are the most common critical incidents in paediatric anaesthesia and occur more often in infants. Use of laryngeal mask airways (LMAs) is associated with reduced PRAE compared with endotracheal tubes in older children (>1 year). We aimed to evaluate the effect of these devices on the incidence of PRAE in infants. We did a randomised controlled trial at the Princess Margaret Hospital for Children in Perth (WA, Australia) by recruiting infants (aged 0-12 months) undergoing general (with or without regional or local) anaesthesia with anticipated fentanyl dose 1 μg/kg or lower for minor elective surgery. We excluded patients contraindicated for LMA or endotracheal tube; who had known cardiac disease or airway or thoracic malformations; who were receiving midazolam premedication; who were undergoing airway, thoracic, or abdomen surgery at the time of participation; and if the parents did not speak English. Written parental or guardian consent was obtained before enrolment. Participants were randomly assigned (1:1), by computer-generated variable block randomisation, to receive an LMA (PRO-Breathe, Well Lead Medical Co Ltd, Panyu, China) or an endotracheal tube (Microcuff, Halyard Health Inc, Atlanta, GA, USA). Sealed randomisation envelopes were used to conceal device assignment. An interim analysis was planned once half the number of infants needed (145) had been recruited. The primary outcome was incidence of PRAE, assessed in the intention-to-treat population. The institutional ethics committee at the Princess Margaret Hospital for Children granted ethical approval (1786/EP). The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000250033). The trial began on July 8, 2010, and was ended early on May 7, 2015, after the interim analysis results met the study stopping rules. During this time, 239 infants were assessed and 181 eligible infants were randomly assigned to receive an LMA (n=85) or an endotracheal tube (n=95). Four infants were not included in the analysis (two due to cancelled procedures, one did not meet inclusion criteria, and one with missing dataset). In the intention-to-treat analysis, PRAE occurred in 50 (53%) infants in the endotracheal tube group and in 15 (18%) infants in the LMA group (risk ratio [RR] 2·94, 95% CI 1·79-4·83, p<0·0001). Laryngospasm and bronchospasm (major PRAE) were recorded in 18 (19%) infants in the endotracheal tube group and in three (4%) infants in the LMA group (RR 5·30, 95% CI 1·62-17·35, p=0·002). No deaths were reported. In infants undergoing minor elective procedures, LMAs were associated with clinically significantly fewer PRAE and lower occurrence of major PRAE (laryngospasm and bronchospasm) than endotracheal tubes. This difference should be a consideration in airway device selection. Princess Margaret Hospital Foundation, National Health and Australian Medical Research Council, Stan Perron Charitable Trust, and Callahan Estate.


Some psychological and engineering aspects of the extravehicular activity of astronauts.
One of the main in-flight problems being fulfilled by astronauts is the preparation for and realization of egress into open space for the purpose of different kinds of extravehicular activity, such as, the performance of scientific experiments, repairing and dismantling operations etc. The astronaut's activity outside the space vehicle is the most difficult item of the space flight programme, which is complicated by a number of space factors affecting a man, viz. dynamic weightlessness, work in a space suit under conditions of excessive pressure, difficulties of space orientation etc. The peculiarities mentioned require special training of the cosmonaut. The physical training involves a series of exercises forming the body-control habits necessary for work in a state of weightlessness. In a new kind of training use is made of equipment simulating the state of weightlessness. From analysis of the available data and the results of my own investigations during ground training and the Soyuz 4 and 5 flights one can establish the following peculiarities of the astronaut's extravehicular activity: (1) Operator response lag in the planned algorithm; (ii) systematic appearance of some stereotype errors in the mounting and dismantling of the outer equipment and in scientific-technical experiments; (iii) a high degree of emotional strain and 30-35% decrease in in-flight working capacity of the astronaut compared with the ground training data; (iv) a positive influence of space adaptation on the cosmonaut and the efficiency of his work in open space; (v) the necessity for further engineering and psychological analysis of the astronaut's activity under conditions of the long space flight of the multi-purpose orbital station. One of the main reasons for the above peculiarities is the violation of the control-coordination functions of the astronaut in the course of the dynamical operations. The paper analyses the extravehicular activity of the astronaut and presents some recommendations for its more efficient realization. Proposals are given concerning the complex engineering, psychological and technical investigations to be made during in-flight egress.


Factors Associated With 30-Day Readmission After Primary Total Hip Arthroplasty: Analysis of 514 455 Procedures in the UK National Health Service.
Thirty-day readmission to hospital after total hip arthroplasty (THA) has significant direct costs and is used as a marker of hospital performance. All-cause readmission is the only metric in current use, and risk factors for surgical readmission and those resulting in return to theater (RTT) are poorly understood. To determine whether patient-related predictors of all-cause, surgical, and RTT readmission after THA differ and which predictors are most significant. Analysis of all primary THAs recorded in the National Health Service (NHS) Hospital Episode Statistics database from 2006 to 2015. The effect of patient-related factors on 30-day readmission risk was evaluated by multilevel logistic regression analysis. The analysis comprised all acute NHS hospitals in England and all patients receiving primary THA. Thirty-day readmission rate for all-cause, surgical (defined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision primary admission diagnoses), and readmissions resulting in RTT. Across all hospitals, 514 455 procedures were recorded. Seventy-nine percent of patients were older than 60 years, 40.3% were men, and 59.7% were women. There were 30 489 all-cause readmissions (5.9%), 16 499 surgical readmissions (3.2%), and 4286 RTT readmissions (0.8%); 54.1% of readmissions were for surgical causes. Comorbidities with the highest odds ratios (ORs) of RTT included those likely to affect patient behavior: drug abuse (OR, 2.22; 95% CI, 1.34-3.67; P = .002), psychoses (OR, 1.83; 95% CI, 1.16-2.87; P = .009), dementia (OR, 1.57; 95% CI, 1.11-2.22; P = .01), and depression (OR, 1.52; 95% CI, 1.31-1.76; P < .001). Obesity had a strong independent association with RTT (OR, 1.46; 95% CI, 4.45-6.43; P < .001), with one of the highest population attributable fractions of the comorbidities (3.4%). Return to theater in the index episode was associated with a significantly increased risk of RTT readmission (OR, 5.35; 95% CI, 4.45-6.43; P < .001). Emergency readmission to the hospital in the preceding 12 months increased the risk of readmission significantly, with the association being most pronounced for all-cause readmission (for >2 emergency readmissions, OR, 2.33; 95% CI, 2.11-2.57; P < .001). Hip resurfacing was associated with a lower risk of RTT when compared with cemented implants (OR, 0.69; 95% CI, 0.54-0.88; P = .002) but for other types of readmission, implant type had no significant association with readmission risk. Increasing age and length of stay were strongly associated with all-cause readmission. Many patient-related risk factors for surgical and RTT readmission differ from those for all-cause readmission despite the latter being the only measure in widespread use. Clinicians and policy makers should consider these alternative readmission metrics in strategies for risk reduction and cost savings.


Dominant negative inhibition of human immunodeficiency virus particle production by the nonmyristoylated form of gag.
Myristoylation of human immunodeficiency virus (HIV) Gag protein is essential for membrane targeting of Gag and production of viral particles. We show here that coexpression of wild-type and nonmyristoylated forms of HIV Gag resulted in severe inhibition of viral particle production, indicating that the nonmyristoylated counterpart had a dominant negative effect on particle release. When coexpressed, the nonmyristoylated Gag partially incorporated into membrane and lipid raft fractions, likely through coassembly with the wild-type Gag. The membrane and raft associations of the wild-type Gag appeared unaffected, and yet particle production was severely impaired. When viral particles produced from the coexpressing cells were analyzed, the wild-type Gag was more abundant than the nonmyristoylated Gag. Confocal microscopy showed that both forms of Gag were diffusely distributed in the cytoplasm of coexpressing cells but that a portion of the wild-type Gag population was accumulated in EEA1- and CD63-positive endosomes. The intracellular accumulation of Gag was more frequently observed at late time points. The Gag accumulation was also observed on the cell surface protrusion. Electron microscopy of the coexpressing cells revealed budding arrest phenotypes, including the occurrence of interconnected virions on the plasma membrane, and intracellular budding. We also show that the inhibition of particle production and the Gag accumulation to endosomes were suppressed when the nucleocapsid (NC) domain was deleted from the nonmyristoylated Gag, although the NC-deleted Gag was still capable of coassembly. Overall, our data indicate that coassembly with the nonmyristoylated Gag impairs HIV particle release, a phenomenon that may involve NC-mediated Gag-Gag interaction.


Individual differences in rhythm perception modulate music-related motor learning: a neurobehavioral training study with children.
Rhythm and motor function are intrinsically linked to each other and to music, but the rhythm-motor interplay during music training, and the corresponding brain mechanisms, are underexplored. In a longitudinal training study with children, we examined the role of rhythm predisposition in the fine motor improvements arising from music training, and which brain regions would be implicated. Fifty-seven 8-year-olds were assigned to either a 6-month music training (n = 21), sports training (n = 18), or a control group (n = 18). They performed rhythm and motor tasks, and structural brain scans before and after training were collected. Better ability to perceive rhythm before training was related to less gray matter volume in regions of the cerebellum, fusiform gyrus, supramarginal gyrus, ventral diencephalon, amygdala, and inferior/middle temporal gyri. Music training improved motor performance, and greater improvements correlated with better pre-training rhythm discrimination. Music training also induced a loss of gray matter volume in the left cerebellum and fusiform gyrus, and volume loss correlated with higher motor gains. No such effects were found in the sports and control groups. In summary, children with finer-tuned rhythm perception abilities were prone to finer motor improvements through music training, and this rhythm-motor link was to some extent subserved by the left cerebellum and fusiform gyrus. These findings have implications for models on music-related plasticity and rhythm cognition, and for programs targeting motor function.


Epidemic dynamics revealed in dengue evolution.
Dengue is an emerging tropical disease infecting tens of millions of people annually. A febrile illness with potentially severe hemorrhagic manifestations, dengue is caused by mosquito-borne viruses (DENV-1 to -4) that are maintained in endemic transmission in large urban centers of the tropics with periodic epidemic cycles at 3- to 5-year intervals. Puerto Rico (PR), a major population center in the Caribbean, has experienced increasingly severe epidemics since multiple dengue serotypes were introduced beginning in the late 1970s. We document the phylodynamics of DENV-4 between 1981 and 1998, a period of dramatic ecological expansion during which evolutionary change also occurs. The timescale of viral evolution is sufficiently short that viral transmission dynamics can be elucidated from genetic diversity data. Specifically, by combining virus sequence data with confirmed case counts in PR over these two decades, we show that the pattern of cyclic epidemics is strongly correlated with coalescent estimates of effective population size that have been estimated from sampled virus sequences using Bayesian Markov Chain Monte Carlo methods. Thus, we show that the observed epidemiologic dynamics are correlated with similar fluctuations in diversity, including severe interepidemic reductions in genetic diversity compatible with population bottlenecks that may greatly impact DENV evolutionary dynamics. Mean effective population sizes based on genetic data appear to increase prior to isolation counts, suggesting a potential bias in the latter and justifying more active surveillance of DENV activity. Our analysis explicitly integrates epidemiologic and sequence data in a joint model that could be used to further explore transmission models of infectious disease.


[Familial multiple polyposis].
The familial multiple polyposis is a hereditary disease, autosomic, dominant, heterocigotous, not bound with sex and usually develops with puberty. If the patients are not treated at time, they will develops irremediably a cancer. We must build a pedigree and all the family members have to be investigated. This disease can be associated with other types of tumors and they are present concomitant with this polyposis, preceding it or appearing posteriorly, so, if we find one of these pathologies, we have to investigate the others. The treatment can be a proctocolectomy with permanent ileostomy or with rectum conservation and ileorectal or low ileosigmoid anastomosis with extirpation and fulguration of the rectal polyps before the colectomy or after it depending of the circumstances. They should have an endoscopic control of the preserved rectum each three months.


Validation of the Kidney Disease Quality of Life (KDQOL) cognitive function subscale.
Formal cognitive function testing is cumbersome, and no self-administered instruments for estimating cognitive function in persons with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been validated. The goal of this study was to determine the validity of the Kidney Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of cognitive impairment in persons with kidney disease. We administered the KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross-sectional study of cognitive function. Scores on the Modified Mini-Mental State Exam (3MS) were considered the gold standard measure of global cognitive function. Performance characteristics of the KDQOL-CF were assessed using correlation coefficients, Bland-Altman plots, and receiver operating characteristic curves. Median scores on the KDQOL-CF were 73 (interquartile range 60-87) for subjects with ESRD and 87 (interquartile range 73-100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global cognitive impairment as a 3MS score < 80, a cut-point of 60 on the KDQOL-CF accurately classified 76% of subjects, with 52% sensitivity and 81% specificity. On multivariable analysis, cerebral and peripheral vascular disease, benzodiazepine use, and higher serum phosphorus concentrations were associated with lower KDQOL-CF scores, while beta blocker use, education, and higher serum albumin concentrations were associated with higher KDQOL-CF scores. The KDQOL-CF is a valid instrument for estimating cognitive function in patients with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected individuals may prove to be an effective and efficient strategy for identifying cognitive impairment in patients with kidney disease.


Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy.
To explore the use of SD/01 (a polyethylene glycol-conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia. Thirteen patients with non-small-cell lung cancer were randomized to receive daily filgrastim (5 microg/kg/d) or a single injection of SD/01 (30, 100, or 300 microg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed. Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg. Dose-limiting toxicities were not noted. CD34(+) cells were mobilized in all cohorts. A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34(+) cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.


The role of the gut microbiome and diet in the pathogenesis of non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with a prevalence that is increasing in parallel with the global rise in obesity and type 2 diabetes mellitus. The pathogenesis of NAFLD is complex and multifactorial, involving environmental, genetic and metabolic factors. The role of the diet and the gut microbiome is gaining interest as a significant factor in NAFLD pathogenesis. Dietary factors induce alterations in the composition of the gut microbiome (dysbiosis), commonly reflected by a reduction of the beneficial species and an increase in pathogenic microbiota. Due to the close relationship between the gut and liver, altering the gut microbiome can affect liver functions; promoting hepatic steatosis and inflammation. This review summarises the current evidence supporting an association between NAFLD and the gut microbiome and dietary factors. The review also explores potential underlying mechanisms underpinning these associations and whether manipulation of the gut microbiome is a potential therapeutic strategy to prevent or treat NAFLD.


Digital Quantum Simulation of the Spin-Boson Model under Markovian Open-System Dynamics.
Digital quantum computers have the potential to simulate complex quantum systems. The spin-boson model is one of such systems, used in disparate physical domains. Importantly, in a number of setups, the spin-boson model is open, i.e., the system is in contact with an external environment which can, for instance, cause the decay of the spin state. Here, we study how to simulate such open quantum dynamics in a digital quantum computer, for which we use an IBM hardware. We consider in particular how accurate different implementations of the evolution result as a function of the level of noise in the hardware and of the parameters of the open dynamics. For the regimes studied, we show that the key aspect is to simulate the unitary portion of the dynamics, while the dissipative part can lead to a more noise-resistant simulation. We consider both a single spin coupled to a harmonic oscillator, and also two spins coupled to the oscillator. In the latter case, we show that it is possible to simulate the emergence of correlations between the spins via the oscillator.


Fkbp52 regulates androgen receptor transactivation activity and male urethra morphogenesis.
Hypospadias is a common birth defect in humans, yet its etiology and pattern of onset are largely unknown. Recent studies have shown that male mice with targeted ablation of FK506-binding protein-52 (Fkbp52) develop hypospadias, most likely due to actions of Fkbp52 as a molecular co-chaperone of the androgen receptor (AR). Here, we further dissect the developmental and molecular mechanisms that underlie hypospadias in Fkbp52-deficient mice. Scanning electron microscopy revealed a defect in the elevation of prepucial swelling that led to the onset of the ventral penile cleft. Interestingly, expression of Fkbp52 was highest in the ventral aspect of the developing penis that undergoes fusion of the urethral epithelium. Although in situ hybridization and immunohistochemical analyses suggested that Fkbp52 mutants had a normal urethral epithelium signaling center and epithelial differentiation, a reduced apoptotic cell index at ventral epithelial cells at the site of fusion and a defect of genital mesenchymal cell migration were observed. Supplementation of gestating females with excess testosterone partially rescued the hypospadic phenotype in Fkbp52 mutant males, showing that loss of Fkbp52 desensitizes AR to hormonal activation. Direct measurement of AR activity was performed in mouse embryonic fibroblast cells treated with dihydrotestosterone or synthetic agonist R1881. Reduced AR activity at genes controlling sexual dimorphism and cell growth was found in Fkbp52-deficient mouse embryonic fibroblast cells. However, chromatin immunoprecipitation analysis revealed normal occupancy of AR at gene promoters, suggesting that Fkbp52 exerts downstream effects on the transactivation function of AR. Taken together, our data show Fkbp52 to be an important molecular regulator in the androgen-mediated pathway of urethra morphogenesis.


The complete map of the Ig heavy chain constant gene region reveals evidence for seven IgG isotypes and for IgD in the horse.
This report contains the first map of the complete Ig H chain constant (IGHC) gene region of the horse (Equus caballus), represented by 34 overlapping clones from a new bacterial artificial chromosome library. The different bacterial artificial chromosome inserts containing IGHC genes were identified and arranged by hybridization using overgo probes specific for individual equine IGHC genes. The analysis of these IGHC clones identified two previously undetected IGHC genes of the horse. The newly found IGHG7 gene, which has a high homology to the equine IGHG4 gene, is located between the IGHG3 and IGHG4 genes. The high degree of conservation shared between the nucleotide sequences of the IGHG7 and IGHG4 genes is unusual for the IGHG genes of the horse and suggests that these two genes duplicated most recently during evolution of the equine IGHG genes. Second, we present the genomic nucleotide sequence of the equine IGHD gene, which is located downstream of the IGHM gene. Both the IGHG7 and IGHD genes were found to be expressed at the mRNA level. The order of the 11 IGHC genes in the IGH-locus of the horse was determined to be 5'-M-D-G1-G2-G3-G7-G4-G6-G5-E-A-3', confirming previous studies using lambda phage clones, with the exception that the IGHG5 gene was found to be the most downstream-located IGHG gene. Fluorescence in situ hybridization was used to localize the IGHC region to Equus caballus (ECA) 24qter, the horse chromosome corresponding to human chromosome 14, where the human IGH locus is found.


A single glutaredoxin or thioredoxin gene is essential for viability in the yeast Saccharomyces cerevisiae.
Glutaredoxins and thioredoxins are small heat-stable oxidoreductases that have been conserved throughout evolution. The yeast Saccharomyces cerevisiae contains two gene pairs encoding cytoplasmic glutaredoxins (GRX1, GRX2) and thioredoxins (TRX1, TRX2). We report here that the quadruple trx1 trx2 grx1 grx2 mutant is inviable and that either a single glutaredoxin or a single thioredoxin (i.e. grx1 grx2 trx1, grx1 grx2 trx2, grx1 trx1 trx2, grx2 trx1 trx2) is essential for viability. Loss of both thioredoxins has been reported previously to lead to methionine auxotrophy consistent with thioredoxins being the sole reductants for 3'-phosphoadenosine 5'-phosphosulphate reductase (PAPS) in yeast. However, we present evidence for the existence of a novel yeast hydrogen donor for PAPS reductase, as strains lacking both thioredoxins assimilated sulphate under conditions that minimized the generation of reactive oxygen species (low aeration and absence of functional mitochondria). In addition, the assimilation of [35S]-sulphate was approximately 60-fold higher in the trx1 trx2 grx1 and trx1 trx2 grx2 mutants compared with the trx1 trx2 mutant. Furthermore, in contrast to the trx1 trx2 mutant, the trx1 trx2 grx2 mutant grew on minimal agar plates, and the trx1 trx2 grx1 mutant grew on minimal agar plates under anaerobic conditions. We propose a model in which the novel reductase activity normally functions in the repair of oxidant-mediated protein damage but, under conditions that minimize the generation of reactive oxygen species, it can serve as a hydrogen donor for PAPS reductase.


Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2.
Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation. We first tested the effect of two proliferative as well as differentiative neurogenic stimuli, one pharmacological (fluoxetine), the other cognitive (the Morris water maze (MWM) training). Both effectively enhanced the number of new dentate gyrus neurons produced, and fluoxetine also reduced the S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the rate of differentiation of control cells, but neither factor enhanced the defective rate of differentiation. In contrast, the defect of terminal differentiation was fully rescued by in vivo infection of proliferating dentate gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of neural differentiation, or expressing NeuroD2, a proneural gene expressed in terminally differentiated dentate gyrus neurons. This is the first demonstration that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate gyrus neurons, complementing a defect of differentiation. It also highlights how the rate of differentiation of dentate gyrus neurons is regulated genetically at several levels and that a neurogenic stimulus for amplification of neural stem/progenitor cells may not be sufficient in itself to modify this rate.


Exercise-induced pulmonary haemorrhage (EIPH) in horses results from locomotory impact induced trauma--a novel, unifying concept.
Exercise-induced pulmonary haemorrhage (EIPH) in horses, although of major welfare and economic importance worldwide, is of uncertain cause. It is accepted that the dorsocaudal region of the lung is particularly prone to the condition, but present theories of causation cannot satisfactorily explain the mechanism or pattern of occurrence. We propose that EIPH results from locomotory impact induced trauma; the mechanism being similar to that producing lung tissue damage following thoracic impact injury. In impact injury, the localised impulsive load on the chest wall is transmitted by pressure waves through the lung at a slower speed than in the chest wall. The waves are subsequently reflected from the distal chest wall and other structures, producing a complex pattern of wave motion; waves travelling from regions of large cross-section to narrower ones are amplified in magnitude, consequently these regions can experience very high local stresses. Compression/dilation and shear waves are produced within the parenchyma and the latter particularly have been implicated as the cause of parenchymal damage and rupture with oedema and haemorrhage. This form of soft tissue damage has been shown to occur at remarkably low loads with an impact velocity greater than about 11 m/s and pressure exceeding approximately 14 kPa. In the horse, the lung is subjected to comparable levels of locomotory derived impulsive force during moderate to high speed exercise and this is the basis of the mechanism causing EIPH. During locomotion, the force following ground-strike of the front legs is transmitted, with some attenuation, through the forelimbs to the scapulae. The anatomical arrangement of the scapula, coupled with the direction of the force at the shoulder (scapulo humeral joint) produces an impulsive force on the rib cage, approximately just below mid height of the frontal aspect of the chest approximately over the fourth rib. As a result, pressure waves are transmitted through the lung parenchyma towards the dorsal and caudal regions; these waves are subsequently reflected at the distal chest wall, spine and diaphragm causing a complex pattern of wave interaction. The observed locations of EIPH are at the sites where wave intensity is expected to be greatest due to changes in cross section and reflection. Based on available information, it is estimated that impulsive forces of more than 100 kPa, lasting approximately 10 ms, would be applied to the chest wall by each scapula in a 500 kg horse when galloping; this level of force would be sufficient to cause oedema and haemorrhage as observed in impact induced injury.


Unprecedented family of heterometallic LnIII[18-metallacrown-6] complexes: syntheses, structures, and magnetic properties.
Herein, a new family of LnIII[18-metallacrown-6] compounds with the formula [Fe6O2Ln(tBu-sao)6(OH)(MeO)4(MeOH)(H2O)]·6MeOH [Ln = DyIII (1), TbIII (2), GdIII (3), and YIII (4), tBu-saoH2 = 3,5-di-tert-butylsalicylaldoxime] was synthesized through one-pot reactions using tBu-saoH2, Fe(ClO4)3·6H2O, and Ln(NO3)3·6H2O. The four compounds are isostructural, and the encapsulation of a Ln ion in the ring cavity of 18-metallacrown-6 (18-MC-6) was exhibited for the first time. The structural analysis shows a ship-like 18-MC-6 core with a beset lanthanide ion connecting six ring oxygen atoms (OMC). Magnetic measurements reveal domain antiferromagnetic coupling interactions between metal ions and field-dependent slow magnetic relaxation in 1-3.


Towards real-time cardiovascular magnetic resonance guided transarterial CoreValve implantation: in vivo evaluation in swine.
Real-time cardiovascular magnetic resonance (rtCMR) is considered attractive for guiding TAVI. Owing to an unlimited scan plane orientation and an unsurpassed soft-tissue contrast with simultaneous device visualization, rtCMR is presumed to allow safe device navigation and to offer optimal orientation for precise axial positioning. We sought to evaluate the preclinical feasibility of rtCMR-guided transarterial aortic valve implatation (TAVI) using the nitinol-based Medtronic CoreValve bioprosthesis. rtCMR-guided transfemoral (n = 2) and transsubclavian (n = 6) TAVI was performed in 8 swine using the original CoreValve prosthesis and a modified, CMR-compatible delivery catheter without ferromagnetic components. rtCMR using TrueFISP sequences provided reliable imaging guidance during TAVI, which was successful in 6 swine. One transfemoral attempt failed due to unsuccessful aortic arch passage and one pericardial tamponade with subsequent death occurred as a result of ventricular perforation by the device tip due to an operating error, this complication being detected without delay by rtCMR. rtCMR allowed for a detailed, simultaneous visualization of the delivery system with the mounted stent-valve and the surrounding anatomy, resulting in improved visualization during navigation through the vasculature, passage of the aortic valve, and during placement and deployment of the stent-valve. Post-interventional success could be confirmed using ECG-triggered time-resolved cine-TrueFISP and flow-sensitive phase-contrast sequences. Intended valve position was confirmed by ex-vivo histology. Our study shows that rtCMR-guided TAVI using the commercial CoreValve prosthesis in conjunction with a modified delivery system is feasible in swine, allowing improved procedural guidance including immediate detection of complications and direct functional assessment with reduction of radiation and omission of contrast media.


Particle-based simulations of red blood cells-A review.
Particle-based methods have been increasingly attractive for solving biofluid flow problems, because of the ease and flexibility in modeling complex structure fluids afforded by the methods. In this review, we focus on popular particle-based methods widely used in red blood cell (RBC) simulations, including dissipative particle dynamics (DPD), smoothed particle hydrodynamics (SPH), and lattice Boltzmann method (LBM). We introduce their basic ideas and formulations, and present their applications in RBC simulations which are divided into three classes according to the number of RBCs in the simulation: a single RBC, two or multiple RBCs, and RBC suspension. Furthermore, we analyze their advantages and disadvantages. On weighing the pros and cons of the methods, a combination of the immersed boundary (IB) method and some forms of smoothed dissipative particle hydrodynamics (SDPD) methods may be required to deal effectively with RBC simulations.


Phenolic composition and antioxidant activity in seed coats of 60 Chinese black soybean (Glycine max L. Merr.) varieties.
Phenolics in black soybean seed coat (BSSC) are considered to be responsible for the health benefits of black soybean. BSSCs of 60 Chinese varieties were examined for phenolic contents, anthocyanin profiles, and antioxidant activity. Total phenolic and condensed tannin contents ranged from 512.2 to 6057.9 mg gallic acid equivalents/100 g and from 137.2 to 1741.1 mg (+)-catechin equivalents/100 g, respectively. Six anthocyanins (delphinidin-3-glucoside, cyanidin-3-galactoside, cyanidin-3-glucoside, petunidin-3-glucoside, peonidin-3-glucoside, and malvidin-3-glucoside) were detected by HPLC. Total anthocyanin contents (TAC) were from 98.8 to 2132.5 mg/100 g, and cyanidin-3-glucoside was the most abundant anthocyanin in all varieties, with a distribution of 48.8-94.1% of TAC. Antioxidant properties detected by DPPH, FRAP, and ORAC methods all showed wide variations ranging from 4.8 to 65.3 μg/100 mL (expressed as EC(50)), from 17.5 to 105.8 units/g, and from 42.5 to 1834.6 μmol Trolox equivalent/g, respectively. Sixty varieties were classified into four groups by hierarchical clustering analysis, and group 4 consisting of nine varieties had the highest phytochemicals content and antioxidant activity.


Ribavirin with or without alpha interferon for chronic hepatitis C.
Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy is not established. To assess the efficacy and safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders with chronic hepatitis C. Eligible trials were identified through searches on electronic databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted. We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo, or alpha interferon for chronic hepatitis C. The primary outcome measures were the 'sustained' (six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the 'end of treatment' and 'sustained' biochemical response, the 'end of treatment' virologic response, histology, quality of life, and adverse events. We included eight trials in which 271 patients were randomised to ribavirin versus placebo or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI) 0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy, combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84) or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events. Combination therapy increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological response, but also the occurrence of adverse events.


Liquid biopsy in ovarian cancer using circulating tumor DNA and cells: Ready for prime time?
Liquid biopsies hold the potential to inform cancer patient prognosis and to guide treatment decisions at the time when direct tumor biopsy may be impractical due to its invasive nature, inaccessibility and associated complications. Specifically, circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have shown promising results as companion diagnostic biomarkers for screening, prognostication and/or patient surveillance in many cancer types. In ovarian cancer (OC), CTC and ctDNA analysis allow comprehensive molecular profiling of the primary, metastatic and recurrent tumors. These biomarkers also correlate with overall tumor burden and thus, they provide minimally-invasive means for patient monitoring during clinical course to ascertain therapy response and timely treatment modification in the context of disease relapse. Here, we review recent reports of the potential clinical value of CTC and ctDNA in OC, expatiating on their use in diagnosis and prognosis. We critically appraise the current evidence, and discuss the issues that still need to be addressed before liquid biopsies can be implemented in routine clinical practice for OC management.


Evaluation of a Childhood Obesity Prevention Online Training Certificate Program for Community Family Educators.
Community family educators have the opportunity to incorporate childhood obesity prevention concepts in their programming with families of young children, but often lack formal health and nutrition education. The purpose of this feasibility study was to create an online training certificate program for community family educators and assess the program's effectiveness at improving participant's knowledge, attitudes, and intended and actual behaviors related to healthy lifestyles. Community family educators (n = 68) completed an online pretest, viewed 13 brief videos (8-15 min) focused on childhood obesity related topics and took mini-knowledge self-checks after each video followed by an online posttest. At posttest, paired t tests showed participants' childhood obesity prevention related knowledge (i.e., nutrition, physical activity, screen time and sleep) improved significantly (p < 0.001). Participants' attitudes toward parenting behaviors related to feeding practices, family meals, physical activity, screen time control and parent modeling significantly (p < 0.05) improved. Improvements also were seen in participants' intentions to promote obesity prevention behaviors (i.e., age appropriate portions sizes, adequate physically active, and parental role modeling). Furthermore, changes in personal health behaviors at posttest revealed participants had significantly (p < 0.05) greater dietary restraint, improvements in sleep quality, and reductions of use of electronic devices during meals and snacks. Overall, participants were very satisfied with the training program, felt comfortable with skills acquired, and enjoyed the program. Findings suggest this online training program is a feasible and effective method for improving community family educators' knowledge, attitudes, and intentions for obesity-prevention related parenting practices.


Assembly of A- and B-type lamins studied in vivo with the baculovirus system.
We have expressed an A-type lamin (Xenopus lamin A), a probable A-type lamin (Drosophila lamin C), two B-type lamins (Xenopus lamin LI, Drosophila lamin Dmo), and two mutants of Xenopus lamin A in Sf9 cells. All proteins were synthesized at high levels resulting in formation of paracrystals with an axial repeat of 18.5-20.0 nm by A-type lamins; in contrast B-type lamins assembled into aggregates with a fibrillar ultrastructure. Of the four wild-type proteins analyzed only lamin Dmo was found in the nuclear compartment of Sf9 cells in association with the lamina whereas the three other lamins assembled into polymers localized in the cytoplasm as well as the nucleoplasm. The Xenopus lamin A mutant lacking the complete carboxy-terminal tail assembled in the cytoplasm into long filament bundles consisting of fibrils of less than 6 nm diameter. In vitro the non-helical amino-terminal head domain of lamins is required for the formation of 'head-to-tail' polymers. A lamin A mutant lacking this domain could be efficiently extracted from Sf9 cells with physiological buffers containing Triton X-100, demonstrating the importance of this domain for lamin assembly in vivo.


The cooperative effect of size and crystallinity degree on the resorption of biomimetic hydroxyapatite for soft tissue augmentation.
Two kinds of hydroxyapatite (HA) crystals were studied as subcutaneous fillers in order to evaluate how their different degree of crystallinity and dimensions influence in vivo resorption. By appropriately adjusting the synthesis temperature, poorly crystalline HA (HApc) and highly crystalline HA (HAhc) were synthesized into clusters of needle-shaped crystals of about 50 nm and plate-shaped crystals of about 100 nm, respectively. The clusters of HApc had larger dimensions (30 µm) than those of HAhc (3 µm). Subcutaneous in vivo inoculations were performed in ten 6-month-old FVB female mice. HAhc underwent complete macroscopic resorption already 4 weeks after the implantation while HApc still showed agglomerates at the eighth week. This unexpected finding may be ascribed to the different size and morphology of the HAhc nanocrystals responsible for a lower aggregation and microcluster dimension than HApc nanocrystals.


Factors associated with refractory pain in emergency patients admitted to emergency general surgery.
Oligoanalgesia in emergency departments (EDs) is multifactorial. A previous study reported that emergency providers did not adequately manage patients with severe pain despite objective findings for surgical pathologies. Our study aims to investigate clinical and laboratory factors, in addition to providers' interventions, that might have been associated with oligoanalgesia in a group of ED patients with moderate and severe pains due to surgical pathologies. We conducted a retrospective study of adult patients who were transferred directly from referring EDs to the emergency general surgery (EGS) service at a quaternary academic center between January 2014 and December 2016. Patients who were intubated, did not have adequate records, or had mild pain were excluded. The primary outcome was refractory pain, which was defined as pain reduction <2 units on the 0-10 pain scale between triage and ED departure. We analyzed 200 patients, and 58 (29%) had refractory pain. Patients with refractory pain had significantly higher disease severity, serum lactate (3.4±2.0 mg/dL vs. 1.4±0.9 mg/dL, P=0.001), and less frequent pain medication administration (median [interquartile range], 3 [3-5] vs. 4 [3-7], P=0.001), when compared to patients with no refractory pain. Multivariable logistic regression showed that the number of pain medication administration (odds ratio [OR] 0.80, 95% confidence interval [95% CI] 0.68-0.98) and ED serum lactate levels (OR 3.80, 95% CI 2.10-6.80) were significantly associated with the likelihood of refractory pain. In ED patients transferring to EGS service, elevated serum lactate levels were associated with a higher likelihood of refractory pain. Future studies investigating pain management in patients with elevated serum lactate are needed.


Evaluation of procalcitonin-guided antimicrobial stewardship in patients admitted to hospital with COVID-19 pneumonia.
Procalcitonin is a biomarker that may be able to identify patients with COVID-19 pneumonia who do not require antimicrobials for bacterial respiratory tract co-infections. To evaluate the safety and effectiveness of a procalcitonin-guided algorithm in rationalizing empirical antimicrobial prescriptions in non-critically ill patients with COVID-19 pneumonia. Retrospective, single-site, cohort study in adults hospitalized with confirmed or suspected COVID-19 pneumonia and receiving empirical antimicrobials for potential bacterial respiratory tract co-infection. Regression models were used to compare the following outcomes in patients with and without procalcitonin testing within 72 h of starting antimicrobials: antimicrobial consumption (DDD); antimicrobial duration; a composite safety outcome of death, admission to HDU/ICU or readmission to hospital within 30 days; and length of admission. Procalcitonin levels of ≤0.25 ng/L were interpreted as negatively predictive of bacterial co-infection. Effects were expressed as ratios of means (ROM) or prevalence ratios (PR) accordingly. 259 patients were included in the final analysis. Antimicrobial use was lower in patients who had procalcitonin measured within 72 h of starting antimicrobials: mean antimicrobial duration 4.4 versus 5.4 days, adjusted ROM 0.7 (95% CI 0.6-0.9); mean antimicrobial consumption 6.8 versus 8.4 DDD, adjusted ROM 0.7 (95% CI 0.6-0.8). Both groups had similar composite safety outcomes (adjusted PR 0.9; 95% CI 0.6-1.3) and lengths of admission (adjusted ROM 1.3; 95% CI 0.9-1.6). A procalcitonin-guided algorithm may allow for the safe reduction of antimicrobial usage in hospitalized non-critically ill patients with COVID-19 pneumonia.


[A case of calcineurin-inhibitor induced pain syndrome associated with tacrolimus therapy for ulcerative colitis].
A 23-year-old woman was admitted with a relapse of ulcerative colitis. Tacrolimus therapy was initiated following inadequate response to corticosteroid therapy. Although the symptoms partially improved, she suddenly developed severe pain localized to the lower limbs on day 16 of tacrolimus therapy. By day 17, she was unable to move. Magnetic resonance imaging revealed born marrow edema in the lower limbs. We suspected calcineurin-inhibitor induced pain syndrome (CIPS) due to tacrolimus therapy. The pain improved within approximately four weeks of tacrolimus cessation. CIPS that is not associated with organ transplantation is a rare occurrence. Here we report a rare case of CIPS that was caused by tacrolimus therapy in a patient with ulcerative colitis.


Sexual Health History: Techniques and Tips.
Family physicians should use a proactive, integrated, patient-centered approach to sexual health that includes, but is not limited to, disease identification and treatment. Successfully delivering positive, affirming, nonjudgmental sexual health care requires intentionally creating safe spaces for all patients. Physician and staff training could include identifying individual implicit bias around sexuality and sexual topics, adverse childhood experiences, and trauma-informed care. Models such as the five Ps (partners, practices, protection from sexually transmitted diseases, past history of sexually transmitted diseases, and pregnancy plans) and ExPLISSIT (extended permission giving, limited information, specific suggestions, and intensive therapy) can help physicians organize their approach to sexual health histories. Preventive health strategies include screening for sexually transmitted diseases and sexually transmitted infections, screening for and offering preexposure prophylaxis for HIV, behavioral counseling to reduce the risk of sexually transmitted infections, and preconception care for all patients, including gender-diverse patients. Because sexual health concerns are quite common, family physicians should be prepared to discuss topics such as erectile dysfunction, dyspareunia, and arousal disorders.


Cost-benefit analysis of extended antifungal prophylaxis in ventricular assist devices.
This report defines the cost and benefit of extended antifungal prophylaxis in ventricular assist device (VAD) patients (pts). Extended antifungal prophylaxis is defined as prophylaxis with fluconazole or nystatin that is given until pts are extubated and off antibiotics. These data are compared with that obtained from earlier VAD patients who only received anti-fungal drugs for documented fungal colonization or infection. Thirty-six patients had HeartMate (n = 15) or Thoratec (n = 21) VADs between 1989 and 1997. Cultures positive for fungus (n = 52 cultures) were obtained from 16 of 36 patients (44% of patients). Forty-three fungal cultures were in the preprophylaxis and nine in the postprophylaxis era. There was one death attributable to fungal sepsis in the preprophylaxis era and none in the postprophylaxis era. The total cost of antifungal drugs in the preprophylaxis era was $3,840 over 1,498 patient days (PD) (mean $2.56 per PD), versus $70,670 over 1,525 PD in the postprophylaxis era (mean $46.34 per PD). Extended antifungal prophylaxis was not cost effective in VAD patients at this institution. However, short-term perioperative antifungal prophylaxis was not addressed by this study. We are now using short-term antifungal prophylaxis with fluconazole and nystatin in VAD patients because of the potential for serious morbidity and mortality that is associated with fungal device infections. A future analysis will determine the usefulness of this change in strategy.


Binding of monoclonal antibodies to the movement protein (MP) of Tobacco mosaic virus: influence of subcellular MP localization and phosphorylation.
Monoclonal antibodies (mAbs) to recombinant movement protein (MP(REC)) of Tobacco mosaic virus (TMV) were used to reveal the dependence of MP epitope accessibility to mAbs on subcellular MP localization and post-translational MP phosphorylation. Leaves of Nicotiana benthamiana or N. tabacum were inoculated mechanically with TMV or agroinjected with an MP expression vector. At different time post-inoculation, ER membrane- and cell wall-enriched fractions (ER-MP and CW-MP, respectively) were isolated and analysed. The N-terminal region (residues 1-30) as well as regions 186-222 and 223-257 of MP from the CW and ER fractions were accessible for interaction with mAbs. By contrast, the MP regions including residues 76-89 and 98-129 were not accessible. The C-terminal TMV MP region (residues 258-268) was inaccessible to mAbs not only in CW-MP, but also in ER-MP fractions. Evidence is presented that phosphorylation of the majority of TMV MP C-terminal sites occurred on ER membranes at an early stage of virus infection, i.e. not after, but before reaching the cell wall. C-terminal phosphorylation of purified MP(REC) abolished recognition of C-proximal residues 258-268 by specific mAbs, which could be restored by MP dephosphorylation. Likewise, accessibility to mAbs of the C-terminal MP epitope in ER-MP and CW-MP leaf fractions was restored by dephosphorylation. Substitution of three or four C-terminal Ser/Thr residues with non-phosphorylatable Ala also resulted in abolition of interaction of mAbs with MP.


Early Identification of Undesirable Outcomes for Transport Accident Injured Patients Using Semi-Supervised Clustering.
Identifying those patient groups, who have unwanted outcomes, in the early stages is crucial to providing the most appropriate level of care. In this study, we intend to find distinctive patterns in health service use (HSU) of transport accident injured patients within the first week post-injury. Aiming those patterns that are associated with the outcome of interest. To recognize these patterns, we propose a multi-objective optimization model that minimizes the k-medians cost function and regression error simultaneously. Thus, we use a semi-supervised clustering approach to identify patient groups based on HSU patterns and their association with total cost. To solve the optimization problem, we introduce an evolutionary algorithm using stochastic gradient descent and Pareto optimal solutions. As a result, we find the best optimal clusters by minimizing both objective functions. The results show that the proposed semi-supervised approach identifies distinct groups of HSUs and contributes to predict total cost. Also, the experiments prove the performance of the multi-objective approach in comparison with single- objective approaches.


Traditional elderflower beverages: a rich source of phenolic compounds with high antioxidant activity.
Traditional elderflower beverages are very popular due to their pleasing taste and pro-health properties. Phenolics were quantified in three elderflower extracts (methanolic extraction and two water extracts prepared as fresh drinks according to local recipes) with HPLC-MS. Chromatographic patterns of methanolic and water extracts were quite similar; however, content levels of individual compounds differed between the two extraction solvents. Two feruloylquinic acids and two p-coumaroyl-caffeoylquinic acids and different flavonol glycosides have been identified in elderflowers for the first time. Hydroxycinnamic acids and flavonol glycosides were the major phenolic constituents in elderflowers. Methanolic extract contained higher levels of all phenolic groups compared to water-extracted samples. The yield of elderflower extracts depended on extract solution and time of extraction. Elderflower beverages were characterized by high total phenolic content (91.09 to 746.63 mg GAE/L). The results confirmed that elderflower beverages (sabesa, syrup) should be recommended as a good source of phenolics in human diet.


Anti-Adipogenic Activity of High-Phenolic Sorghum Brans in Pre-Adipocytes.
Obesity is one of the leading public health problems that can result in life-threatening metabolic and chronic diseases such as cardiovascular diseases, diabetes, and cancer. Sorghum (Sorghum bicolor (L.) Moench) is the fifth most important cereal crop in the world and certain genotypes of sorghum have high polyphenol content. PI570481, SC84, and commercially available sumac sorghum are high-polyphenol genotypes that have demonstrated strong anti-cancer activities in previous studies. The objective of this study was to explore a potential anti-obesity use of extracts from sorghum bran in the differentiation of 3T3-L1 preadipocytes and to investigate cellular and molecular responses in differentiated adipocytes to elucidate related mechanisms. None of the four different sorghum bran extracts (PI570481, SC84, Sumac, and white sorghum as a low-polyphenol control) caused cytotoxicity in undifferentiated and differentiated 3T3-L1 cells at doses used in this study. Sorghum bran extracts (PI570481, SC84, and Sumac) reduced intracellular lipid accumulation and expression of adipogenic and lipogenic proteins in a dose-dependent manner in differentiated 3T3-L1 cells. The same polyphenol containing sorghum bran extracts also repressed production of reactive oxygen species (ROS) and MAPK signaling pathways and repressed insulin signaling and glucose uptake in differentiated 3T3-L1 cells. These data propose a potential use of high-phenolic sorghum bran for the prevention of obesity.


International classification of primary care: an Indian experience.
India is in the process of transition to universal health coverage for Indian citizens. The focus is to strengthen the primary and secondary level services. Coupled with this national scenario, the development of Family medicine as a distinct discipline is in a crucial stage. There is a nation-wide urge to build family medicine training units and service centers across the country to fulfill the unmet health needs of the population. This study aimed to bring out reasons for encounter (RFE) and morbidity pattern of patients seen in a family physician run urban health center in South India. The study was conducted in an urban health center of a tertiary care hospital. Clinicians entered the data using International Classification of Primary Care (ICPC) codes. Data included were demographics, 3 RFE, 3 diagnoses, 3 outcomes of care that include prescriptions, investigations, procedures, and referrals made. During 47,590 patient encounters, 59,647 RFE, 62,283 diagnoses and 68269 outcomes of care were recorded. The majority of RFEs and diagnoses are in the following ICPC chapters: Endocrinology (38.6%), cardiovascular (35.91%), respiratory (20.26%), digestive (7.68% and musculo-skeletal (6.8%). The most frequent outcome of care was prescriptions, followed by counseling and nebulization. This study is the first to report on the RFE in India. This study demonstrated the breadth of clinical conditions seen by family physicians across all ages and in both genders. This study attempts to highlight the need for family physician based services as a training ground for trainees.


Frozen embryos and the obligation to adopt.
Rob Lovering has developed an interesting new critique of views that regard embryos as equally valuable as other human beings: the moral argument for frozen human embryo adoption. The argument is aimed at those who believe that the death of a frozen embryo is a very bad thing, and Lovering concludes that some who hold this view ought to prevent one of these deaths by adopting and gestating a frozen embryo. Contra Lovering, we show that there are far more effective strategies for preserving the lives of frozen embryos than adoption. Moreover, we point out that those who regard the deaths of frozen embryos as a very bad thing will generally regard the deaths of all embryos as a very bad thing, whether they are discarded embryos, aborted embryos or embryos that spontaneously abort. This entails that these other embryos must be taken into account when considering moral obligations, as well as other human lives at risk from preventable causes.


Surgical treatment of nutcracker syndrome results in improved pain and quality of life.
Left renal vein (LRV) compression, or nutcracker phenomenon, describes the compression of the LRV, most commonly between the aorta and the superior mesenteric artery. The outflow obstruction that occurs from the compression causes venous hypertension leading to the development of pelvic collaterals, lumbar vein engorgement and gonadal vein reflux. The symptoms associated with LRV compression include abdominal pain, left flank pain, back pain, headache, pelvic pain/pressure, and hematuria. Symptomatic LRV compression can cause chronic pain and disability that impedes activities of daily living. Left renal auto transplantation (LR-AT) is one mode of treatment, leading to decreased pain with no significant vascular or urological complications. Herein we present a five patient case series with symptomatic LRV compression who underwent LR-AT with improved pain and quality of life after surgery. Five patients underwent LR-AT between June 2020-December 2020 to resolve their symptomatic LRV compression. These patients were given three validated surveys pre- and post- intervention, then again at their three month follow up visit to assess their pain and health-related quality of life. The five patients were all female with the average age of 36.8 years old (36-41) and underwent LR-AT to treat their symptomatic LRV compression. The average Numeric Rating Scale (NRS) pain score pre intervention was 8.3 (range 6.7 to 10) which improved to pain rating 5.22 (range 2.7 to 6) post intervention, p-value = 0.013. The average pain NRS score at 3 month follow up was 3.86 (range 1.3-6), p-value = 0.006 when compared to pre-intervention pain scores. The average pain intensity pre intervention was 4.5 (4 to 5) and 2.7 (1 to 4.3) post intervention, p-value = 0.024. The average pain intensity score at 3 month follow up was 2.24 (range 1.3-3.3), p-value = 0.002 when compared to pre-intervention. The VascuQoL-6 survey score pre intervention averaged score of 9.6 (range 7-12) which improved to an average score of 20.6 (range 18-24), p-value = 0.001. The average VascuQoL score at 3 month follow up was 22.6 (range 22-24), p-value = < 0.001 when compared to pre intervention QoL scores all showing a statistically significant improvement of health-related quality of life. The diagnosis of LRV compression can be challenging due to the non-descript symptoms and overall lack of awareness. Understanding venous tributary pathways and drainage can help clarify why patients present with unusual symptoms. Surgical treatment of LRV compression through LR-AT can improve patients' pain and improve vascular quality of life.


Low plasma orexin-A levels were improved by continuous positive airway pressure treatment in patients with severe obstructive sleep apnea-hypopnea syndrome.
We have previously shown that plasma levels of orexin-A, a neuropeptide with an arousal-stimulating action, were decreased in parallel with the severity of the disease in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). To clarify the effects of nasal continuous positive airway pressure (nCPAP) treatment on plasma orexin-A levels in patients with this syndrome. Sleep tests and blood sample collections were conducted at the sleep-related respiratory disorders clinic and the sleep laboratory of the Iwate Medical University Hospital. We studied 27 patients with OSAHS (apnea-hypopnea index [AHI], >/= 20 by polysomnography) who were treated with nCPAP for 3 to 6 months. These patients were divided into the following two groups according to the arousal index (AI): group A (n = 11), >/= 60; group B (n = 16), < 60. Plasma samples were obtained before and after the nCPAP treatment for 3 to 6 months. Plasma immunoreactive (IR)-orexin-A concentrations were measured by radioimmunoassay after the extraction using cartridges. Plasma IR-orexin-A concentrations were inversely correlated with the AI (r = -0.807; p < 0.0001) and AHI (r = -0.661; p < 0.0001) in 27 patients before the nCPAP treatment. Mean (+/- SEM) plasma IR-orexin-A concentrations were significantly lower in group A (1.0 +/- 0.3 pmol/L) than in group B (4.6 +/- 0.4 pmol/L). Mean plasma IR-orexin-A concentrations were significantly increased after the nCPAP treatment in group A (to 3.4 +/- 1.2 pmol/L; p = 0.0069), whereas they were not significantly changed in group B. The increases in plasma IR-orexin-A concentrations after the nCPAP treatment were in parallel with the improvements in AI and Epworth sleepiness scale (a marker of severity of daytime excessive sleepiness) score in group A. The low plasma orexin-A levels were increased by the nCPAP treatment in patients with severe OSAHS, suggesting that orexin-A is a plasma marker that reflects the severity of OSAHS and the response to treatment.


[Temporal and spatial distribution of the crab Callinectes sapidus (Decapoda: Portunidae) in Chetumal Bay, Quintana Roo, Mexico].
In order to determine temporal and spatial distribution patterns of Callinectes sapidus, samplings were carried out during the cold-front (January-February), dry (May-June) and rainy (August-September, 2002) climatic seasons, in 30 sampling stations of Chetumal Bay, grouped in sectors A (14 stations), B (eight stations) and C (eight stations). In each sampling station crabs were collected from two transects parallel to the coast, each with three traps, separated by 30 m. Sediments were calcareous coarse and medium sand, white or lightly gray. A total of 1 031 specimens were collected. CPEU (Capture Per Effort Unit) differed spatially and temporally. Highest CPEU was found in sector C with 1.3 ind.trap(-1), and in the rainy season with 1.1 ind.trap(-1). Population was predominantly composed of male individuals. The male:female ratio was 15:1. Males and adults (group II) CPEU was significant different between sectors and climatic seasons. Both males and adults (group II) had a greater CPEU in sector C (1.2 ind.trap-) and in the rainy season (1.1 ind.trap(-1)). Abundance of female and juvenile individuals (group I) was low during the sampling period whereas group 0 juvenile individuals were not found. A greater relative frequency between sectors and climatic seasons were observed in 130-139 mm and 140-149 mm size interval (CW). C. sapidus occurred on sandy sediments in Chetumal Bay. Pearson product moment correlations exhibited significant relationships between CPEU and temperature, salinity and dissolved oxygen. In Chetumal Bay, the spatial and temporal distribution of C. sapidus can be related to salinity, temperature, habitat quality, food availability, recruitment and reproduction events of individuals.


A theoretical investigation on boron-ligand cooperation to activate molecular hydrogen by a frustrated Lewis pair and subsequent reduction of carbon dioxide.
The role of boron-ligand cooperation in activating molecular hydrogen by a set of six frustrated Lewis pair (FLP) systems is explored using density functional theory. The results obtained from thermochemical calculations show that all the studied FLP systems are capable of activating molecular hydrogen as the activation free energies are not too high (17.6-25.6 kcal mol-1). Sulphur based FLP 6 is the most promising one as it results in the smallest activation barrier among the studied sets. For a given FLP, the introduction of an electron donating -NMe2 group at the para position of the pyridine ring somewhat lowers the barrier and enhances the B-X (X = O, N, S) interaction. The B-X bond present within the FLPs plays a crucial role in facilitating the H2 activation process where it gets changed from the B+-X- type of interaction in the FLP to the B ← X dative bond upon H2 activation as understood from the energy decomposition analysis in combination with the natural orbital for chemical valence theory (EDA-NOCV). This mode of operation is termed as boron-ligand cooperation in analogy with the metal-ligand cooperation in transition metal complexes. The EDA-NOCV results obtained at the TS also support an electron transfer model where simultaneous electron transfer takes place from the Lewis basic center (N) of the FLP to σ*(H2) and from σ(H2) to the Lewis acidic center (B) of the FLP, resulting in a weakened H-H bond. The change in the aromaticity of the pyridine rings during the course of H2 activation is also monitored by nucleus independent chemical shift calculations. Finally, the ability of the studied FLP systems to act as hydrogenation catalysts is elucidated by studying the hydrogenation of CO2 to yield formic acid.


Cigarette smoking and invasive cervical cancer.
A case-control study of 480 patients with invasive cervical cancer and 797 population controls, conducted in five geographic areas in the United States, included an evaluation of the relationship of several cigarette smoking variables to cervical cancer risk. Although smoking was correlated with both age at first intercourse and number of sexual partners, a significant smoking-related risk persisted for squamous cell carcinoma after adjustment for these factors (relative risk, 1.5). The risk of squamous cell cancers increased significantly with intensity and duration of smoking. Twofold excess risks were seen for those smoking 40 or more cigarettes per day and those smoking for 40 or more years. In addition, users of nonfilter cigarettes were at particularly high risk. Increased risks, however, were observed only among recent and continuous smokers. In contrast to squamous cell cancer, no relationship was observed between smoking and risk of adenocarcinoma or adenosquamous carcinoma (n = 63). These results suggest a causal relationship between cigarette smoking and invasive squamous cell cervical cancer, perhaps through a late-stage or promotional event, although the mechanisms of action require further elucidation.


Oxidation reactions of a phosphine-borane-stabilised dialkylstannylene.
The acyclic dialkylstannylene [(Me(3)Si){Me(2)P(BH(3))}CH](2)Sn (7) reacts with any of methyl iodide, neopentyl iodide or benzyl bromide to yield the corresponding oxidative addition products [(Me(3)Si){Me(2)P(BH(3))}CH](2)Sn(Me)(I) (8), [(Me(3)Si){Me(2)P(BH(3))}CH](2)Sn(CH(2)CMe(3))(I) (9), and [(Me(3)Si){Me(2)P(BH(3))}CH](2)Sn(CH(2)Ph)(Br) (10), respectively. The crystal structures of 8, 9, and 10 reveal that there are no close B-H...Sn contacts. In addition, 7 reacts with benzil or elemental sulfur to yield [{Me(2)P(BH(3))}(Me(3)Si)CH](2)Sn(OCPh=CPhO) (11) and [{Me(2)P(BH(3))}(Me(3)Si)CH](2)Sn(S) (12), respectively, as confirmed by multinuclear NMR spectroscopy and elemental analysis.