A glance at the urodynamic database.
Three hundred sixty-four patients with urinary incontinence as their presenting complaint were evaluated in the urogynecology laboratory, Department of Obstetrics and Gynecology, University of Rochester, Rochester, New York. Of them, 226 (62%) were found to have genuine stress urinary incontinence (GSI). This subset of demonstrably incontinent patients was characterized as to symptoms of stress and urge incontinence, incidence of nulliparity, occurrence of incontinence during intercourse and influence of weight on bladder pressure. Using clusters of symptoms did not accurately distinguish GSI from the other types of urinary incontinence. Four percent of the GSI patients were nulliparous. All had a reasonable explanation for incontinence other than anatomic relaxation. Twenty-three percent of the 154 sexually active GSI patients acknowledged having incontinence with intercourse. None of the anatomic and urodynamic parameters evaluated distinguished that group from their GSI counterparts who did not lose urine with intercourse. Increasing weight, expressed as the body mass index, correlated with an increase in the vesical pressure in the supine and standing positions.


Forms and determinants of migration and HIV/AIDS-related stigma on the Mexican-Guatemalan border.
In this study we examined the origins and consequences of HIV/AIDS-related stigma on the Mexican-Guatemalan border. To explore these issues, an inductive/deductive approach was taken. Data were collected using qualitative methods including nonparticipant observation, in-depth interviews, and informal conversation. Informants included Central American immigrants, locals, and contextual key informants. Findings reveal that gender, social class, and race/ ethnicity function as key determinants of HIV/AIDS-related stigma, but serve also as the basis around which migration-related stigma is constructed within this particular context. These issues need to be taken into account in addressing the vulnerability of mobile populations, as well as the stigma attached to migration and HIV/AIDS. To be effective, responses should be based in the social and contextual realities faced by migrants and mobile populations, and be part of a more general process of empowerment that improves their legal, social, economic, and health status.


Supramolecular nanofibers self-assembled from cationic small molecules derived from repurposed poly(ethylene teraphthalate) for antibiotic delivery.
Low molecular weight cationic compounds were synthesized from re-purposed poly(ethylene teraphthalate) (PET) and used to self-assemble into high aspect ratio supramolecular nanofibers for encapsulation and delivery of anionic antibiotics. The antibiotic piperacillin/tazobactam (PT) was successfully loaded into the nanofibers through ionic interaction between anionic PT and the cationic nanofibers without loss of the nanofiber features. These PT-loaded nanofibers demonstrated high loading efficiency and sustained delivery for PT. The antimicrobial activity of PT-loaded nanofibers remained potent towards both Gram-positive and Gram-negative bacteria. Importantly, in a P. aeruginosa-infected mouse skin wound model, the treatment with the PT-loaded nanofibers was more effective than free PT for wound healing as evidenced by the significantly lower P. aeruginosa counts at the wound sites and histological analysis. This strategy can be applied to deliver a variety of anionic antibiotics for improved treatment efficacy of various infections.


In-beam γ-ray spectroscopy of ^34,36,38Mg: merging the N=20 and N=28 shell quenching.
Neutron-rich N=22, 24, 26 magnesium isotopes were studied via in-beam γ-ray spectroscopy at the RIKEN Radioactive Isotope Beam Factory following secondary fragmentation reactions on a carbon target at ≈200 MeV/nucleon. In the one- and two-proton removal channels from 39Al and 40Si beams, two distinct γ-ray transitions were observed in 38Mg, while in the one-proton removal reaction from 37Al a new transition was observed in addition to the known 2(1)(+)→0(g.s.)(+) decay. From the experimental systematics and comparison to theoretical predictions it is concluded that the transitions belong to the 2(1)(+)→0(g.s.)(+) and 4(1)(+)→2(1)(+) decays in 36Mg and 38Mg, respectively. For 34Mg, previously reported 2(1)(+) and 4(1)(+) level energies were remeasured. The deduced E(4(1)(+))/E(2(1)(+)) ratios for 34,36,38Mg of 3.14(5), 3.07(5), and 3.07(5) are almost identical and suggest the emergence of a large area of deformation extending from the N=20 to the N=28 shell quenching.


Vertical Rectus Abdominis Myocutaneous Versus Alternative Flaps for Perineal Repair After Abdominoperineal Excision of the Rectum in the Era of Laparoscopic Surgery.
Plastic surgical reconstruction of the perineum is often required after abdominoperineal excision of the rectum. Options for this reconstruction include a vertical rectus abdominis myocutaneous (VRAM) flap, gluteal fasciocutaneous flap, and gracilis myocutaneous flap. Although the VRAM flap is well established at most centers, less experience exists with the gluteal and gracilis flaps. In the era of laparoscopic colorectal resection, plastic surgeons are being forced to use gluteal and gracilis flaps because the VRAM flap must be tunnelled intra-abdominally requiring laparotomy. We therefore aimed to systematically review the evidence comparing VRAM, gluteal, and gracilis flaps. A comprehensive, structured literature search was conducted using Medline, Google Scholar, and Science Direct. Studies included were randomized control trials and observational studies documenting complication rates associated with the VRAM, gluteal, or gracilis flap. Eleven studies meeting all inclusion and exclusion criteria were identified. When meta-analyzed, the overall rate of any perineal wound or flap complication among VRAM patients (35.8%) was significantly lower than gluteal flap (43.7%) and gracilis flap patients (52.9%) (P = 0.041). The VRAM flap is well established for perineal reconstruction, and this study suggests that it may be superior to the gluteal and gracilis flaps in terms perineal wound and flap complication rates. This should be taken into account when weighing up the risks and benefits of a laparoscopic approach to abdominoperineal excision of the rectum. Large studies making direct comparisons between the flap options should be conducted.


Shared genetic influences do not explain the association between parent-offspring relationship quality and offspring internalizing problems: results from a Children-of-Twins study.
Associations between parenting and child outcomes are often interpreted as reflecting causal, social influences. However, such associations may be confounded by genes common to children and their biological parents. To the extent that these shared genes influence behaviours in both generations, a passive genetic mechanism may explain links between them. Here we aim to quantify the relative importance of passive genetic v. social mechanisms in the intergenerational association between parent-offspring relationship quality and offspring internalizing problems in adolescence. We used a Children-of-Twins (CoT) design with data from the parent-based Twin and Offspring Study of Sweden (TOSS) sample [909 adult twin pairs and their offspring; offspring mean age 15.75 (2.42) years], and the child-based Swedish Twin Study of CHild and Adolescent Development (TCHAD) sample [1120 adolescent twin pairs; mean age 13.67 (0.47) years]. A composite of parent-report measures (closeness, conflict, disagreements, expressions of affection) indexed parent-offspring relationship quality in TOSS, and offspring self-reported internalizing symptoms were assessed using the Child Behavior Checklist (CBCL) in both samples. A social transmission mechanism explained the intergenerational association [r = 0.21 (0.16-0.25)] in our best-fitting model. A passive genetic transmission pathway was not found to be significant, indicating that parental genetic influences on parent-offspring relationship quality and offspring genetic influences on their internalizing problems were non-overlapping. These results indicate that this intergenerational association is a product of social interactions between children and parents, within which bidirectional effects are highly plausible. Results from genetically informative studies of parenting-related effects should be used to help refine early parenting interventions aimed at reducing risk for psychopathology.


A study of the changes in the bioactivity of essential oils used singly and as mixtures in aromatherapy.
The assumption by aromatherapists that essential oils are more beneficial when applied as mixes of two or more was tested using several in vitro bioactivity parameters. These included assays against 25 different bacteria, pharmacological studies using a smooth muscle preparation (guinea-pig ileum) and also the predicted effect on the patient as a whole on the basis of chemical analysis (using gas chromatography). The results showed an enhancement in the antibacterial effect of some essential oils when used in mixes only when these were poor antibacterial agents on their own. The action on smooth muscle was often drastically changed when using mixes due to the combination of relaxant and contractile essential oils. A stimulant effect on patients was dependent almost entirely on a high monoterpene concentration. Due to the pharmacological changes achieved by mixing different essential oils, which cannot be predicted from animal studies, there is a possible danger in the indiscriminate usage of mixes on some susceptible patients, e.g., asthmatics and also during pregnancy and childbirth.


[Methods of research in subjective time experience].
The main aim of the study is to give a review of methods to analyse subjective time experience, e.g. interview techniques, psychometric scales, and events tests. An elaborated methodological inventory is now available in this area of research. But on the other side, the procedures to investigate time perspective are still rather heterogenous, especially with regard to various projective and graphic techniques which could not be described in the present study. Briefly discussed are terminological aspects and a theoretical model of subjective time experience and time perspective.


Comparative evaluation of push-out bond strength of ProRoot MTA, Biodentine, and MTA Plus in furcation perforation repair.
Few studies have comparatively evaluated the push-out bond strength of different calcium silicate-based materials (CSMs) used in furcal perforation repair. The objective of this in vitro study was to comparatively evaluate the push-out bond strength of commercially available CSMs used as furcation repair materials, in the presence of blood contamination. Furcal perforations were made in 120 molars and were divided on the basis of the repair material used (ProRoot MTA, Biodentine, and MTA Plus), blood contamination, and duration of setting time (24 h vs. 7 days). Push-out bond strength was measured and analyzed by three-way analysis of variance (ANOVA) test. Push-out bond strength increased with time. The 24-h push-out strength of MTA was less than that of Biodentine. Blood contamination affected the push-out bond strength of MTA Plus irrespective of the setting time. Caution should be taken while condensing restorative materials over furcation repair materials.


Circulating tumor cells in melanoma patients.
Circulating tumor cells (CTCs) are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X) from blood of melanoma patients using a simple centrifugation device (OncoQuick), and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF) were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively) compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001). There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001), and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50%) stained for both pan-cytokeratin (KRT) markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14). Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA) may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs). The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids, and their role in metastatic progression.


The Impact of Subthalamic Deep Brain Stimulation on Sleep-Wake Behavior: A Prospective Electrophysiological Study in 50 Parkinson Patients.
This prospective observational study was designed to systematically examine the effect of subthalamic deep brain stimulation (DBS) on subjective and objective sleep-wake parameters in Parkinson patients. In 50 consecutive Parkinson patients undergoing subthalamic DBS, we assessed motor symptoms, medication, the position of DBS electrodes within the subthalamic nucleus (STN), subjective sleep-wake parameters, 2-week actigraphy, video-polysomnography studies, and sleep electroencepahalogram frequency and dynamics analyses before and 6 months after surgery. Subthalamic DBS improved not only motor symptoms and reduced daily intake of dopaminergic agents but also enhanced subjective sleep quality and reduced sleepiness (Epworth Sleepiness Scale: -2.1 ± 3.8, p < .001). Actigraphy recordings revealed longer bedtimes (+1:06 ± 0:51 hours, p < .001) without shifting of circadian timing. Upon polysomnography, we observed an increase in sleep efficiency (+5.2 ± 17.6%, p = .005) and deep sleep (+11.2 ± 32.2 min, p = .017) and increased accumulation of slow-wave activity over the night (+41.0 ± 80.0%, p = .005). Rapid eye movement sleep features were refractory to subthalamic DBS, and the dynamics of sleep as assessed by state space analyses did not normalize. Increased sleep efficiency was associated with active electrode contact localization more distant from the ventral margin of the left subthalamic nucleus. Subthalamic DBS deepens and consolidates nocturnal sleep and improves daytime wakefulness in Parkinson patients, but several outcomes suggest that it does not normalize sleep. It remains elusive whether modulated activity in the STN directly contributes to changes in sleep-wake behavior, but dorsal positioning of electrodes within the STN is linked to improved sleep-wake outcomes.


IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection.
Polymorphisms near the IL28B gene, which code for interferon (IFN)-λ3, predict response to pegylated interferon-α (PEG-IFN) and ribavirin treatment in hepatitis C virus (HCV) genotype 1 infected patients. Follow-up studies of the effect of IL28B gene in HCV non-genotype 1 infected patients have almost always used predominantly HCV genotype 2-infected or mixed genotype 2/3-infected cohorts with results partly conflicting with HCV genotype 1. We performed a retrospective analysis of 281 patients infected with HCV genotype 3 for association of response to therapy with IL28B polymorphisms. We found that the HCV genotype 1 responder genotypes at rs12979860 and rs8099917 did not associate with sustained virological response to PEG-IFN/ribavirin therapy. However, the responder genotypes of both SNPs showed association with rapid viral response measured at 4 weeks (rs12979860, P = 3 × 10(-5) ; rs8099917, P = 3 × 10(-4) ). In multivariate analysis, age (<40 years), baseline viral load (<4 × 10(5) IU/mL) and the responder genotypes of SNPs rs12979860 or rs8099917 remained significant independent predictors of rapid viral response to therapy. Furthermore, we show that IL28B polymorphisms are associated with relapse in patients who achieve rapid viral response to PEG-IFN/ribavirin therapy. The responder genotypes also showed association with markers of stage and activity of liver disease, namely high aspartate aminotransferase platelet ratio index (APRI, rs12979860, P = 0.018; rs8099917, not significant) and high alanine aminotransferase (ALT, rs12979860, P = 0.002; rs8099917, P = 0.001), in addition to a high baseline viral load (rs12979860, P = 1.4 × 10(-5) ; rs8099917, P = 7.3 × 10(-6) ). Polymorphisms near the IL28B gene show association with rapid viral response but not sustained viral response to PEG-IFN/ribavirin therapy in HCV genotype 3-infected patients.


Gene expression in placentation of farm animals: an overview of gene function during development.
Eutherian mammals share a common ancestor that evolved into two main placental types, i.e., hemotrophic (e.g., human and mouse) and histiotrophic (e.g., farm animals), which differ in invasiveness. Pregnancies initiated with assisted reproductive techniques (ART) in farm animals are at increased risk of failure; these losses were associated with placental defects, perhaps due to altered gene expression. Developmentally regulated genes in the placenta seem highly phylogenetically conserved, whereas those expressed later in pregnancy are more species-specific. To elucidate differences between hemotrophic and epitheliochorial placentae, gene expression data were compiled from microarray studies of bovine placental tissues at various stages of pregnancy. Moreover, an in silico subtractive library was constructed based on homology of bovine genes to the database of zebrafish - a nonplacental vertebrate. In addition, the list of placental preferentially expressed genes for the human and mouse were collected using bioinformatics tools (Tissue-specific Gene Expression and Regulation [TiGER] - for humans, and tissue-specific genes database (TiSGeD) - for mice and humans). Humans, mice, and cattle shared 93 genes expressed in their placentae. Most of these were related to immune function (based on analysis of gene ontology). Cattle and women shared expression of 23 genes, mostly related to hormonal activity, whereas mice and women shared 16 genes (primarily sexual differentiation and glycoprotein biology). Because the number of genes expressed by the placentae of both cattle and mice were similar (based on cluster analysis), we concluded that both cattle and mice were suitable models to study the biology of the human placenta.


Sarcoid arthritis. A report of 2 cases.
Two patients with sarcoid arthritis are described. The first case is an example of early joint involvement, while the second demonstrates late joint disease in sarcoidosis. Both cases illustrate the perennial problem of differentiating tuberculosis from sarcoidosis in our clinical setting.


Degradation and endoplasmic reticulum retention of unassembled alpha- and beta-subunits of Na,K-ATPase correlate with interaction of BiP.
Assembly of alpha- and beta-subunits in the endoplasmic reticulum is a prerequisite for the structural and functional maturation of oligomeric P-type ATPases. In Xenopus oocytes, overexpressed, unassembled alpha- and beta-subunits of Xenopus Na,K-ATPase are retained in the endoplasmic reticulum (ER) and are degraded with different kinetics, while unassembled beta-subunits of gastric H, K-ATPase leave the ER. In this study, we have investigated the role of the immunoglobulin-binding protein, BiP, in the folding, assembly, and ER retention of ATPase subunits. We determined the primary sequence of Xenopus BiP and used polyclonal antibodies to examine the interaction with BiP of various wild type and mutant alpha- and beta-subunits overexpressed in Xenopus oocytes. Our results show that ER-retained, unassembled Na,K-ATPase beta-subunits, but not transport-competent H,K-ATPase beta-subunits, efficiently associate with BiP until assembly with alpha-subunits occurs. Furthermore, the kinetics of BiP interaction with unassembled wild type and with mutant Na,K-ATPase beta-subunits parallels their respective stability against cellular degradation. Finally, alpha-subunits that are overexpressed in oocytes and are rapidly degraded and endogenous oocyte alpha-subunits that are stably expressed as individual assembly-competent proteins also interact with oocyte or exogenous BiP, and the interaction time correlates with the protein's stability. These data demonstrate for the first time that BiP might be involved in a long term maturation arrest and/or in the ER quality control of a multimembrane-spanning protein and lend support for a universal chaperone function of BiP.


Seneca Valley virus 3Cpro degrades heterogeneous nuclear ribonucleoprotein A1 to facilitate viral replication.
Seneca Valley virus (SVV) is a recently-identified important pathogen that is closely related to idiopathic vesicular disease in swine. Infection of SVV has been shown to induce a variety of cellular factors and their activations are essential for viral replication, but whether heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) involved in SVV replication is unknown. The cytoplasmic redistribution of hnRNP A1 is considered to play an important role in the virus life cycle. Here, we demonstrated that SVV infection can promote redistribution of the nucleocytoplasmic shuttling RNA-binding protein hnRNP A1 to the cytoplasm from the nucleus, whereas hnRNP A1 remained mainly in the nucleus of mock-infected cells. siRNA-mediated knockdown of the gene encoding hnRNP A1 attenuated viral replication as evidenced by decreased viral protein expression and virus production, whereas its overexpression enhanced replication. Moreover, infection with SVV induced the degradation of hnRNP A1, and viral 3 C protease (3 Cpro) was found to be responsible for its degradation and translocation. Further studies demonstrated that 3 Cpro induced hnRNP A1 degradation through its protease activity, via the proteasome pathway. This degradation could be attenuated by a proteasome inhibitor (MG132) and inactivation of the conserved catalytic box in 3 Cpro. Taken together, these results presented here reveal that SVV 3 C protease targets cellular hnRNP A1 for its degradation and translocation, which is utilized by SVV to aid viral replication, thereby highlighting the control potential of strategies for infection of SVV.


Enzymic dephosphorylation of D-myo-inositol 1,4-bisphosphate in rat brain.
Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,4-bisphosphate [Ins(1,4)P2] phosphatase activities were measured in both 180,000 g (60 min) particulate and supernatant fractions of rat brain homogenates. Although Ins(1,4,5)P3 was mostly hydrolysed by a particulate phosphatase [Erneux, Delvaux, Moreau & Dumont (1986) Biochem. Biophys. Res. Commun. 134, 351-358], Ins(1,4)P2 phosphatase was predominantly soluble. The latter enzyme was Mg2+-dependent and sensitive to thiol-blocking agents (e.g. p-hydroxymercuribenzoate). In contrast with Ins(1,4,5)P3 phosphatase activity measured in the soluble fraction, Ins(1,4)P2 phosphatase was insensitive to 0.001-1 mM-2,3-bisphosphoglycerate. Lithium salts, widely used in psychiatric treatment, inhibited both Ins(1,4)P2 and Ins(1)P1 phosphatase activities of the crude soluble fraction. In particular, 50% inhibition of phosphatase activity, with 2 microM-Ins(1,4)P2 as substrate, was achieved at 3-5 mM-LiCl. At these concentrations, LiCl did not change Ins(1,4,5)P3 phosphatase activity measured in the same fraction with 1-4 microM-Ins(1,4,5)P3 as substrate. Chromatography of the soluble fraction of a rat brain homogenate on DEAE-cellulose resolved three phosphatase activities. These forms, peaks I, II and III, dephosphorylated Ins(1,4,5)P3, Ins(1)P1 and Ins(1,4)P2 respectively. If LiCl (10 mM) was included in the assay mixture, it inhibited both peak-II Ins(1)P1 phosphatase and peak-III Ins(1,4)P2 phosphatase, suggesting the existence of at least two Li+-sensitive phosphatases.


Osteoporosis and fracture risk associated with inhaled corticosteroid use among Swedish COPD patients: the ARCTIC study.
The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio 1.52 (95% CI 1.24-1.62)), while the corresponding estimate for low-dose ICS was 1.27 (95% CI 1.13-1.56) compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.


A 20-year experience of combined liver/kidney transplantation for primary hyperoxaluria (PH1): the European PH1 transplant registry experience 1984-2004.
Primary hyperoxaluria (PH1) is a condition caused by a hepatic-based enzyme defect which can lead to renal failure due to oxalate stone disease, obstructive uropathy and nephrocalcinosis. It has been shown that the underlying metabolic defect can be corrected by liver transplantation and in most cases (renal failure having already occurred) is accompanied by a kidney graft. This paper describes the current results of 127 liver transplants performed in 117 patients over a 20-year period from 1984 to 2004 in 35 European centres. The mean age at onset of symptoms was 5.6 +/- 7.8 years and the mean age at which a diagnosis was made was 8.8 +/- 9.5 years. The diagnosis was confirmed by liver biopsy proven decreased AGT activity in 68% of cases, hyperoxaluria in 74%, hyperglycolicaciduria in 37% and hyperoxalaemia in 50%. Patients were transplanted at a mean age of 16.5 +/- 11.4 years following a period of dialysis of 3.2 +/- 3.2 years (range 0-14.4 years). 1-, 5- and 10-year patient survival values were 86, 80 and 69%, respectively, and liver graft survival rates of 80, 72 and 60% at the same time intervals. There have been 27 deaths and 10 liver retransplants have been carried out. Patient outcomes are improved when prolonged periods on dialysis and the complications of systemic oxalosis have not occurred.


The Cardiac Care Bridge transitional care program for the management of older high-risk cardiac patients: An economic evaluation alongside a randomized controlled trial.
To evaluate the cost-effectiveness of the Cardiac Care Bridge (CCB) nurse-led transitional care program in older (≥70 years) cardiac patients compared to usual care. The intervention group (n = 153) received the CCB program consisting of case management, disease management and home-based cardiac rehabilitation in the transition from hospital to home on top of usual care and was compared with the usual care group (n = 153). Outcomes included a composite measure of first all-cause unplanned hospital readmission or mortality, Quality Adjusted Life Years (QALYs) and societal costs within six months follow-up. Missing data were imputed using multiple imputation. Statistical uncertainty surrounding Incremental Cost-Effectiveness Ratios (ICERs) was estimated by using bootstrapped seemingly unrelated regression. No significant between group differences in the composite outcome of readmission or mortality nor in societal costs were observed. QALYs were statistically significantly lower in the intervention group, mean difference -0.03 (95% CI: -0.07; -0.02). Cost-effectiveness acceptability curves showed that the maximum probability of the intervention being cost-effective was 0.31 at a Willingness To Pay (WTP) of €0,00 and 0.14 at a WTP of €50,000 per composite outcome prevented and 0.32 and 0.21, respectively per QALY gained. The CCB program was on average more expensive and less effective compared to usual care, indicating that the CCB program is dominated by usual care. Therefore, the CCB program cannot be considered cost-effective compared to usual care.


The relationship between low-level air pollution exposure and short-term changes in lung function in Dutch children.
Following air pollution episodes in the winters of 1985 and 1987, a series of studies was initiated to investigate short-term changes in health status in children in relationship to short-term changes in air pollution concentrations. Air pollution exposure was characterized by measurements of SO2, NO2, PM10, nitrate, sulfate, H+, and HONO. Panels of unselected children were studied in four winters (1987-1991). Lung function was measured repeatedly with spirometry in these children. In the winter of 1990/1991, a panel of children with chronic respiratory symptoms was studied as well, with repeated observations of Peak Expiratory Flow made at the home. The three winters of 87/88, 88/89 and 89/90 were very mild; no air pollution episodes with long range transport from the east occurred. In these three winters, lung function was measured on 86 different days. Altogether, over 800 children participated. H+ concentrations (expressed as H2SO4) were generally below 0.6 microgram/m3, with a maximum of only 3 micrograms/m3. Daily mean SO2 concentrations never exceded 100 micrograms/m3 in this period. Nevertheless, lung function in these unselected children was found to decrease with increasing levels of especially particulate matter air pollution. In the winter of 1990/1991, a minor air pollution episode occurred. Maximum SO2 and PM10 concentrations were 105 micrograms/m3 and 174 micrograms/m3 respectively. This episode was associated with decreased lung function in a group of about 112 unselected children. There was also a relationship with decreased daily PEF readings in a panel of 73 children with chronic respiratory symptoms.


Carbon Dioxide, Blood Pressure, and Perioperative Stroke: A Retrospective Case-Control Study.
The relationship between intraoperative physiology and postoperative stroke is incompletely understood. Preliminary data suggest that either hypo- or hypercapnia coupled with reduced cerebrovascular inflow (e.g., due to hypotension) can lead to ischemia. This study tested the hypothesis that the combination of intraoperative hypotension and either hypo- or hypercarbia is associated with postoperative ischemic stroke. We conducted a retrospective, case-control study via the Multicenter Perioperative Outcomes Group. Noncardiac, nonintracranial, and nonmajor vascular surgical cases (18 yr or older) were extracted from five major academic centers between January 2004 and December 2015. Ischemic stroke cases were identified via manual chart review and matched to controls (1:4). Time and reduction below key mean arterial blood pressure thresholds (less than 55 mmHg, less than 60 mmHg, less than 65 mmHg) and outside of specific end-tidal carbon dioxide thresholds (30 mmHg or less, 35 mmHg or less, 45 mmHg or greater) were calculated based on total area under the curve. The association between stroke and total area under the curve values was then tested while adjusting for relevant confounders. In total, 1,244,881 cases were analyzed. Among the cases that screened positive for stroke (n = 1,702), 126 were confirmed and successfully matched with 500 corresponding controls. Total area under the curve was significantly associated with stroke for all thresholds tested, with the strongest combination observed with mean arterial pressure less than 55 mmHg (adjusted odds ratio per 10 mmHg-min, 1.17 [95% CI, 1.10 to 1.23], P < 0.0001) and end-tidal carbon dioxide 45 mmHg or greater (adjusted odds ratio per 10 mmHg-min, 1.11 [95% CI, 1.10 to 1.11], P < 0.0001). There was no interaction effect observed between blood pressure and carbon dioxide. Intraoperative hypotension and carbon dioxide dysregulation may each independently increase postoperative stroke risk.


Beta-D-xyloside induced modulations of glycosaminoglycans, proliferation, and cytoskeletal organization of rat liver myofibroblast-like cells (transformed fat storing cells).
Transformed fat storing cells, i.e. myofibroblast-like cells are the major source of proteoglycans in injured liver. In the present study p-nitrophenyl-beta-D-xylopyranoside (PNP-Xyl), a specific metabolic inhibitor of proteoglycan synthesis, was used to analyze some details of altered glycosaminoglycan metabolism, proliferation, morphology and cytoskeletal organization of myofibroblast-like cells (secondary cultures of fat storing cells) under conditions of abrogated proteoglycan synthesis. PNP-Xyl increased dose-dependently the synthesis of [35S] sulfate-labelled medium glycosaminoglycans, among which chondroitin sulfate formation was stimulated predominantly. The distribution and composition of glycosaminoglycans in the cellular and cell surface compartments were affected differently. Production of medium hyaluronan was reduced by more than 40% at 5 mM PNP-Xyl. The compound inhibited dose-dependently the mitotic activity of myofibroblast-like cells without affecting viability. The morphologic appearance was changed at 5 mM PNP-Xyl and the organization and expression of desmin and smooth muscle iso-alpha-actin, both important markers of myofibroblast-like cells, were also modified by PNP-Xyl. Inhibition of proliferation, morphologic changes, and cytoskeletal disorganization were fully and rapidly reversible upon removal of the drug. The results support the notion of a direct or indirect role of proteoglycans in maintaining important functions of myofibroblast-like cells in culture.


Presence of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in southern Kettle Moraine State Forest, Wisconsin, and characterization of strain W97F51.
Lyme disease, caused by Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt & Brenner; babesiosis, caused by Babesia microti Franca; and human granulocytic ehrlichiosis, caused by Anaplasma phagocytophilum Bakken & Dumler have been reported in Wisconsin, mainly in the endemic areas of the northwestern part of the state. People exposed to blacklegged ticks, Ixodes scapularis Say, from this region can potentially contract one or all of these diseases concurrently. Within the past several years, there have been cases of Lyme disease reported from southeastern Wisconsin, an area that contains deer, mice, and similar vegetation found at regions with high endemicity. However, past white-tailed deer surveys suggested no existence of I. scapularis in southeastern Wisconsin. However, in 1996, we identified questing adult I. scapularis in the southernmost part of the Southern Kettle Moraine State Forest, Walworth County. To determine whether an established population of I. scapularis exists in this region, we performed a detailed survey of the abundance of host-seeking I. scapularis adults and the presence and abundance of subadults feeding on white-footed mice, Peromyscus leucopus Rafinesque. We also tested for possible infections of B. burgdorferi, Ba. microti, and A. phagocytophilum in ticks and B. burgdorferi harbored by mice. In 1997 and 1998, a total of 249 P. leucopus mice and 118 questing adult I. scapularis ticks, in addition to 157 larvae and seven nymphs feeding on mice, were collected and their locations were recorded from the Nordic trails of the Southern Kettle Moraine State Forest. Only one P. leucopus and its attached engorged I. scapularis nymph were infected with B. burgdorferi, whereas none of the engorged larvae attached to mice were infected. However, 4.2% of questing adult I. scapularis were infected with B. burgdorferi. The abundance of questing adult I. scapularis was 1.6 ticks per hour. The prevalence of subadult ticks on mice was 27%, with a mean intensity on infested mice of 2.0. I. scapularis adults were not infected with either Ba. microti or A. phagocytophilum. A unique strain of B. burgdorferi s.l. (W97F51) was discovered, showing 33 nucleotide substitutions and one codon insertion in a 567-bp fragment of the OspB gene, compared with Borrelia bissettii (strain Ca389). The sequences of ospA, ospB, ospC,fla, and rrs genes and the rrf-rrl intergenic spacer region were compared between W97F51 and other B. burgdorferi s.l. species. Although W97F51 was most genetically related to B. bissettii, the genetic identity of W97F51 was less than that of B. bissettii conspecifics. This study documents the existence of an established population of I. scapularis and the presence of B. burgdorferi with a novel strain in southeastern Wisconsin.


Bioanalytical LC-MS of therapeutic oligonucleotides.
Therapeutic oligonucleotides (OGNTs) are important biopharmaceutical drugs for the future, due to their ability to selectively reduce or knockout the expression of target genes. For the development of OGNTs, reliable and relatively high-throughput bioanalytical methods are required to perform the quantitative bioanalysis of OGNTs and their metabolites in biological fluids (e.g., plasma, urine and tissue). Although immunoaffinity methods, especially ELISA, are currently widely applied for this purpose, the potential of LC-MS in OGNT analysis is under investigation. Owing to its inherent ability to monitor the individual target OGNTs as well as their metabolites, LC-MS is now evolving into the method-of-choice for the bioanalysis of OGNTs. In this paper, the state-of-the-art of bioanalytical LC-MS of OGNTs and their metabolites in biological fluids is critically reviewed and its advantages and limitations highlighted. Finally, the future perspective of bioanalytical LC-MS, that is, lower detection levels and potential generic LC-MS methodology, is discussed.


Transcriptomic and morphological maturation of human astrocytes in cerebral organoids.
Cerebral organoids (CerOrgs) derived from human induced pluripotent stem cells (iPSCs) are a valuable tool to study human astrocytes and their interaction with neurons and microglia. The timeline of astrocyte development and maturation in this model is currently unknown and this limits the value and applicability of the model. Therefore, we generated CerOrgs from three healthy individuals and assessed astrocyte maturation after 5, 11, 19, and 37 weeks in culture. At these four time points, the astrocyte lineage was isolated based on the expression of integrin subunit alpha 6 (ITGA6). Based on the transcriptome of the isolated ITGA6-positive cells, astrocyte development started between 5 and 11 weeks in culture and astrocyte maturation commenced after 11 weeks in culture. After 19 weeks in culture, the ITGA6-positive astrocytes had the highest expression of human mature astrocyte genes, and the predicted functional properties were related to brain homeostasis. After 37 weeks in culture, a subpopulation of ITGA6-negative astrocytes appeared, highlighting the heterogeneity within the astrocytes. The morphology shifted from an elongated progenitor-like morphology to the typical bushy astrocyte morphology. Based on the morphological properties, predicted functional properties, and the similarities with the human mature astrocyte transcriptome, we concluded that ITGA6-positive astrocytes have developed optimally in 19-week-old CerOrgs.


Childhood and adolescence risk factors and development of depressive symptoms: the 32-year prospective Young Finns follow-up study.
Environmental risks in childhood have been shown to predict later depressive symptoms. In this study, we examined whether various environmental risk domains in childhood and adolescence, socioeconomic, psychoemotional, parental lifestyle and life-events, predict depressive symptom trajectories in adulthood individually by domain and as a cumulative risk score across domains. Participants were a nationally representative sample of 1289 men and 1585 women from the Young Finns study, aged 3-18 years at study entry in 1980. They responded to questions on depressive symptoms (modified version of the Beck Depression Inventory) at four study phases from 1997 to 2012. Findings from longitudinal repeated multilevel modelling showed that all clusters of risk within domain and the cumulative risk score were associated with later depressive symptoms (regression coefficient range from 0.07 to 0.34). Socioeconomic risk, psychoemotional risk and the cumulative risk score predicted later depressive symptoms after adjustment for the effects of adulthood risk. No interaction with time was observed. Our findings suggest that environment risks in childhood and adolescence, particularly in the socioeconomic and psychoemotional domains, are associated with a higher risk, but not an increased progression, of depressive symptoms in adulthood.


Discovery of inhibitors of aberrant gene transcription from Libraries of DNA binding molecules: inhibition of LEF-1-mediated gene transcription and oncogenic transformation.
The screening of a >9000 compound library of synthetic DNA binding molecules for selective binding to the consensus sequence of the transcription factor LEF-1 followed by assessment of the candidate compounds in a series of assays that characterized functional activity (disruption of DNA-LEF-1 binding) at the intended target and site (inhibition of intracellular LEF-1-mediated gene transcription) resulting in a desired phenotypic cellular change (inhibit LEF-1-driven cell transformation) provided two lead compounds: lefmycin-1 and lefmycin-2. The sequence of screens defining the approach assures that activity in the final functional assay may be directly related to the inhibition of gene transcription and DNA binding properties of the identified molecules. Central to the implementation of this generalized approach to the discovery of DNA binding small molecule inhibitors of gene transcription was (1) the use of a technically nondemanding fluorescent intercalator displacement (FID) assay for initial assessment of the DNA binding affinity and selectivity of a library of compounds for any sequence of interest, and (2) the technology used to prepare a sufficiently large library of DNA binding compounds.


Impact of derived global weather data on simulated crop yields.
Crop simulation models can be used to estimate impact of current and future climates on crop yields and food security, but require long-term historical daily weather data to obtain robust simulations. In many regions where crops are grown, daily weather data are not available. Alternatively, gridded weather databases (GWD) with complete terrestrial coverage are available, typically derived from: (i) global circulation computer models; (ii) interpolated weather station data; or (iii) remotely sensed surface data from satellites. The present study's objective is to evaluate capacity of GWDs to simulate crop yield potential (Yp) or water-limited yield potential (Yw), which can serve as benchmarks to assess impact of climate change scenarios on crop productivity and land use change. Three GWDs (CRU, NCEP/DOE, and NASA POWER data) were evaluated for their ability to simulate Yp and Yw of rice in China, USA maize, and wheat in Germany. Simulations of Yp and Yw based on recorded daily data from well-maintained weather stations were taken as the control weather data (CWD). Agreement between simulations of Yp or Yw based on CWD and those based on GWD was poor with the latter having strong bias and large root mean square errors (RMSEs) that were 26-72% of absolute mean yield across locations and years. In contrast, simulated Yp or Yw using observed daily weather data from stations in the NOAA database combined with solar radiation from the NASA-POWER database were in much better agreement with Yp and Yw simulated with CWD (i.e. little bias and an RMSE of 12-19% of the absolute mean). We conclude that results from studies that rely on GWD to simulate agricultural productivity in current and future climates are highly uncertain. An alternative approach would impose a climate scenario on location-specific observed daily weather databases combined with an appropriate upscaling method.


Evaluation of genetic variants in the reduced folate carrier and in glutamate carboxypeptidase II for spina bifida risk.
Genetic variants in folate metabolism have been reported to increase risk for neural tube defects (NTD). The first such sequence change was the 677C-->T substitution in methylenetetrahydrofolate reductase (MTHFR), but additional sequence changes have been identified in enzymes or transporters for folates. Two recently identified variants are the 1561C-->T (H475Y) mutation in glutamate carboxypeptidase II (GCPII) and the 80A-->G (H27R) change in the reduced folate carrier RFC-1. We examined a group of mothers of spina bifida offspring, and a group of control women, for the above polymorphisms to assess their impact on NTD risk as well as on homocysteine and nutrient (RBC folate, serum folate, and serum cobalamin) levels. The GCPII variant (in the heterozygous state) did not influence NTD risk or metabolite levels; homozygous mutant (YY) women were not observed in our study group. The homozygous mutant (RR) genotype for the RFC-1 gene was not associated with a significant difference in NTD risk (OR=1.39, 95% CI=0.55-3.54), but there was a borderline significant (p=0.065) decrease in RBC folate levels, compared with the HH genotype. However, the combination of the RR genotype for RFC-1 and low RBC folate was associated with a significant 4.6-fold increase in NTD risk (OR=4.6, 95% CI=1.47-14.37). Since this small study is the first to demonstrate increased risk for women with the RFC-1 variant for having a child with a NTD, additional larger studies are required to confirm this change as another potential genetic modifier for spina bifida risk.


CYP1B1 and MYOC variants in neonatal-onset versus infantile-onset primary congenital glaucoma.
To compare CYP1B1 and MYOC variants in a cohort of neonatal-onset (NO) and infantile-onset (IO) primary congenital glaucoma (PCG). This prospective observational study included 43 infants with PCG (14 NO and 29 IO) presenting between January 2017 and January 2019 with a minimum 1-year follow-up. CYP1B1 and MYOC genes were screened using Sanger sequencing with in-silico analysis of the variants using Polymorphism Phenotyping v.2 and Protein Variation Effect Analyser platforms. Allelic frequency was estimated using Genome Aggregation Database (gnomAd). Disease presentation and outcome were correlated to the genetic variants in both groups. Babies with CYP1B1 mutations had more severe disease at presentation and worse outcomes. Six of 14 (42.8%) NO glaucoma and 5 of 29 (17.2%) IO harboured CYP1B1 mutations. Five of six babies in the NO group and three of five in the IO group harboured the variant c.1169G>A, [p.R390H]. They required more surgeries and had a poorer outcome. On in-silico analysis c.1169G>A, [p.R390H] scored very likely pathogenic. Two patients in the IO group who had the c.1294C>G, [p.L432V] variant had a good outcome. Five of 14 NO-PCG and 8 of 29 IO-PCG harboured the variant c.227G>A, [p.R76K] in the MYOC gene, which was scored benign by in-silico analysis, and was also found in 2 of 15 normal controls. Patients with CYP1B1 pathogenic variants had a poorer outcome than those without. We found more NO PCG babies with CYP1B1 mutations compared with IO PCG. This may be one of the reasons for NO PCG having a poorer prognosis compared with IO PCG.


[Discovery of herpes simplex virus (HSV)-like particles in biopsy samples of cervical carcinoma].
The tissue of cervical cancer and HSV-2 infected baby rabbit kidney (BRK) cells were studied comparatively by electron microscope. In 2 out of 12 samples from patients with cervical carcinoma, some virus-like particles were observed in the cytoplasm or intercellular space. Some particles seemed to be enveloped by endoplasmic reticulum. According to their size, structure and morphology, these particles resembled the herpes simplex virus. The relationship between the discovery of herpes simplex virus-like particles in tissue of cervical cancer and the development of this cancer is discussed.


Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type 1 immunity by licensing host dendritic cells to produce IL-12.
Substance-P and hemokinin-1 are proinflammatory neuropeptides with potential to promote type 1 immunity through agonistic binding to neurokinin-1 receptor (NK1R). Dendritic cells (DCs) are professional antigen-presenting cells that initiate and regulate the outcome of innate and adaptive immune responses. Immunostimulatory DCs are highly desired for the development of positive immunization techniques. DCs express functional NK1R; however, regardless of their potential DC-stimulatory function, the ability of NK1R agonists to promote immunostimulatory DCs remains unexplored. Here, we demonstrate that NK1R signaling activates therapeutic DCs capable of biasing type 1 immunity by inhibition of interleukin-10 (IL-10) synthesis and secretion, without affecting their low levels of IL-12 production. The potent type 1 effector immune response observed following cutaneous administration of NK1R-signaled DCs required their homing in skin-draining lymph nodes (sDLNs) where they induced inflammation and licensed endogenous-conventional sDLN-resident and -recruited inflammatory DCs to secrete IL-12. Our data demonstrate that NK1R signaling promotes immunostimulatory DCs, and provide relevant insight into the mechanisms used by neuromediators to regulate innate and adaptive immune responses.


Oligodendrocytes, BK channels and the preservation of myelin.
Oligodendrocytes wrap multiple lamellae of their membrane, myelin, around axons of the central nervous system (CNS), to improve impulse conduction. Myelin synthesis is specialised and dynamic, responsive to local neuronal excitation. Subtle pathological insults are sufficient to cause significant neuronal metabolic impairment, so myelin preservation is necessary to safeguard neural networks. Multiple sclerosis (MS) is the most prevalent demyelinating disease of the CNS. In MS, inflammatory attacks against myelin, proposed to be autoimmune, cause myelin decay and oligodendrocyte loss, leaving neurons vulnerable. Current therapies target the prominent neuroinflammation but are mostly ineffective in protecting from neurodegeneration and the progressive neurological disability. People with MS have substantially higher levels of extracellular glutamate, the main excitatory neurotransmitter. This impairs cellular homeostasis to cause excitotoxic stress. Large conductance Ca2 +-activated K + channels (BK channels) could preserve myelin or allow its recovery by protecting cells from the resulting excessive excitability. This review evaluates the role of excitotoxic stress, myelination and BK channels in MS pathology, and explores the hypothesis that BK channel activation could be a therapeutic strategy to protect oligodendrocytes from excitotoxic stress in MS. This could reduce progression of neurological disability if used in parallel to immunomodulatory therapies.


Online adaptive radiotherapy potentially reduces toxicity for high-risk prostate cancer treatment.
With daily, MR-guided online adapted radiotherapy (MRgART) it may be possible to reduce the PTV in pelvic RT. This study investigated the potential reduction in normal tissue complication probability (NTCP) of MRgART compared to standard radiotherapy for high-risk prostate cancer. Twenty patients treated with 78 Gy to the prostate and 56 Gy to elective pelvic lymph nodes were included. VMAT plans were generated with standard clinical PTV margins. Additionally to the planning MR, patients had three MRI scans during treatment to simulate an MRgART. A reference plan with PTV margins determined for MRgART was created per patient and adapted to each of the following MRs. Adapted plans were warped to the planning MR for dose accumulation. The standard plan was rigidly registered to each adaptation MR before it was warped to the planning MR for dose accumulation. Dosimetric impact was compared by DVH analysis and potential clinical effects were assessed by NTCP modeling. MRgART yielded statistically significant lower doses for the bladder wall, rectum and peritoneal cavity, compared to the standard RT, which translated into reduced median risks of urine incontinence (ΔNTCP 2.8%), urine voiding pain (ΔNTCP 2.8%) and acute gastrointestinal toxicity (ΔNTCP 17.4%). Mean population accumulated doses were as good or better for all investigated OAR when planned for MRgART as standard RT. Online adapted radiotherapy may reduce the dose to organs at risk in high-risk prostate cancer patients, due to reduced PTV margins. This potentially translates to significant reductions in the risks of acute and late adverse effects.


Cancer prevention today: from healthy lifestyle and early detection to integrative multidisciplinary prevention and treatment.
Cancer prevention is recognized to be one the most efficient strategy in reducing cancer incidence and mortality. The world leading experts in the field of basic, clinical, epidemiologic and behavioral science presented their most innovative and promising findings and achievements during the Eighth Annual AACR International Conference on Frontiers in Cancer Prevention Research held from December 6-9, 2009, in Houston, TX, USA. In total around 800 participants from all over the world took an active part in the rich variety of the Conference session formats covering wide area of the most vital cancer research problems with strong emphasis on the early detection research, the latest developments in the tumor microenvironment, international prevention mechanisms, integrative prevention, targeted prevention and treatment, and efficient implementation of basic sciences into clinical practice.


Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects.
The complete blood count (CBC) is used to evaluate health status in the contexts of various clinical situations such as anemia, infection, inflammation, trauma, malignancies, etc. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are required. The study aim was to define the BVs of CBC parameters employing a strict protocol. Blood samples, drawn from 30 healthy subjects (17 females, 13 males) once weekly for 10 weeks, were analyzed using a Sysmex XN 3000 instrument. The data were assessed for normality, trends, outliers and variance homogeneity prior to coefficient of variation (CV)-analysis of variance (ANOVA). Sex-stratified within-subject (CVI) and between-subjects (CVG) BV estimates were determined for 21 CBC parameters. For leukocyte parameters, with the exception of lymphocytes and basophils, significant differences were found between female/male CVI estimates. The mean values of all erythrocyte-, reticulocyte- and platelet parameters differed significantly between the sexes, except for mean corpuscular hemoglobin concentration, mean corpuscular volume and platelet numbers. Most CVI and CVG estimates appear to be lower than those previously published. Our study, based on a rigorous protocol, provides updated and more stringent BV estimates for CBC parameters. Sex stratification of data is necessary when exploring the significance of changes in consecutive results and when setting analytical performance specifications.


[Effects of different multiple cropping systems on paddy field weed community under long term paddy-upland rotation].
Based on a long term field experiment, this paper studied the effects of different multiple cropping systems on the weed community composition and species diversity under paddy-upland rotation. The multiple cropping rotation systems could significantly decrease weed density and inhibited weed growth. Among the rotation systems, the milk vetch-early rice-late maize --> milk vetchearly maize intercropped with early soybean-late rice (CCSR) had the lowest weed species dominance, which inhibited the dominant weeds and decreased their damage. Under different multiple cropping systems, the main weed community was all composed of Monochoia vaginalis, Echinochloa crusgalli, and Sagittaria pygmae, and the similarity of weed community was higher, with the highest similarity appeared in milk vetch-early rice-late maize intercropped with late soybean --> milk vetch-early maize-late rice (CSCR) and in CCSR. In sum, the multiple cropping rotations in paddy field could inhibit weeds to a certain extent, but attentions should be paid to the damage of some less important weeds.


Delay-Aware Reverse Approach for Data Aggregation Scheduling in Wireless Sensor Networks.
Many time-sensitive applications require data to be aggregated from wireless sensor networks with minimum latency. However, the minimum latency aggregation scheduling problem has not been optimally solved due to its NP-hardness. Most existing ideas rely on local information (e.g., node degree, number of children) to organize the schedule order, hence results in solutions that might be far from optimal. In this work, we propose RADAS: a delay-aware Reverse Approach for Data Aggregation Scheduling that determines the transmissions sequence of sensors in a reverse order. Specifically, RADAS iteratively finds the transmissions starting from the last time slot, in which the last sender delivers data to the sink, down to the first time slot, when the data aggregation begins. In each time slot, RADAS intends to maximize the number of concurrent transmissions, while giving higher priority to the sender with potentially higher aggregation delay. Scheduling such high-priority sender first would benefit the maximum selections in subsequent time slots and eventually shorten the schedule length. Simulation results show that our proposed algorithm dominates the existing state-of-the-art schemes, especially in large and dense networks, and offers up to 30% delay reduction.


Beverage specific alcohol intake in a population-based study: evidence for a positive association between pulmonary function and wine intake.
Lung function is a strong predictor of cardiovascular and all-cause mortality. Previous studies suggest that alcohol exposure may be linked to impaired pulmonary function through oxidant-antioxidant mechanisms. Alcohol may be an important source of oxidants; however, wine contains several antioxidants. In this study we analyzed the relation of beverage specific alcohol intake with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in a random sample of 1555 residents of Western New York, USA. We expressed pulmonary function as percent of predicted normal FEV1 (FEV1%) and FVC (FVC%) after adjustment for height, age, gender and race. To obtain information on alcohol intake we used a questionnaire that reliably queries total alcohol and beverage specific recent (past 30 days) and lifetime alcohol consumption. Using multiple linear regression analysis after adjustment for covariates (pack-years of smoking, weight, smoking status, education, nutritional factors and for FEV1%, in addition, eosinophil count), we observed no significant correlation between total alcohol intake and lung function. However, we found positive associations of recent and lifetime wine intake with FEV1% and FVC%. When we analyzed white and red wine intake separately, the association of lung function with red wine was weaker than for white wine. While total alcohol intake was not related to lung function, wine intake showed a positive association with lung function. Although we cannot exclude residual confounding by healthier lifestyle in wine drinkers, differential effects of alcoholic beverages on lung health may exist.


A modified suture placement technique to avoid suture drag or "cheese wire" effect.
A modified technique is described for microsurgical suture placement, irrespective of the closure technique, to prevent suture drag and loosening of the suture following postoperative wound edema. Fine, elastic, non-absorbable sutures which loosen as a result of suture drag or "cheese wiring" have no more reliability than do absorbable or silk sutures. Predictable and reproducible results of suture placement are necessary to allow the surgeon to effectively use the operating keratometer in the control and modification of corneal astigmatism following anterior segment surgery.


Predicting a 10 repetition maximum for the free weight parallel squat using the 45 degrees angled leg press.
The purpose of this research was to devise prediction equations whereby a 10 repetition maximum (10RM) for the free weight parallel squat could be predicted using the following predictor variables: 10RM for the 45 degrees angled leg press, body mass, and limb length. Sixty men were tested over a 3-week period, with 1 testing session each week. During each testing session, subjects performed a 10RM for the free weight parallel squat and 45 degrees angled leg press. Stepwise multiple regression analysis showed leg press mass lifted to be a significant predictor of squat mass lifted for both the advanced and the novice groups (p < 0.05). Leg press mass lifted accounted for approximately 25% of the variance in squat mass lifted for the novice group and 55% of the variance in squat mass lifted for the advanced group. Limb length and body mass were not significant predictors of squat mass lifted for either group. The following prediction equations were devised: (a) novice group squat mass = leg press mass (0.210) + 36.244 kg, (b) advanced group squat mass = leg press mass (0.310) + 19.438 kg, and (c) subject pool squat mass = leg press mass (0.354) + 2.235 kg. These prediction equations may save time and reduce the risk of injury when switching from the leg press to the squat exercise.


Lesions of hippocampal circuitry define synaptosomal-associated protein-25 (SNAP-25) as a novel presynaptic marker.
Synaptosomal-associated protein, 25 kD, (SNAP-25) is a novel protein containing a possible transition metal binding site and encoded by a neuronal-specific mRNA. We examined the distribution of SNAP-25 mRNA and protein in the hippocampal formation of the adult rat following kainic acid, colchicine, and entorhinal lesions. The results show that destruction of granule cells of the dentate gyrus and CA3 pyramidal cells did not diminish SNAP-25 immunoreactivity in the dendritic fields of these cells. In contrast, lesioned neurons exhibited an extensive loss of immunoreactivity at the site of their axonal projections. These results support the identification of SNAP-25 as a novel presynaptic protein. In addition, SNAP-25 immunoreactivity was increased in afferent fibers which project to areas adjacent to the deafferented region, and expression of SNAP-25 mRNA was increased in neurons deafferented by the lesion. Examination of SNAP-25 immunoreactivity and mRNA expression may provide a useful marker of major hippocampal pathways and of axonal plasticity in neurological disorders such as Alzheimer's disease and temporal lobe epilepsy.


Efficiency in DIEP Flap Breast Reconstruction: The Real Benefit of Computed Tomographic Angiography Imaging.
In deep inferior epigastric perforator (DIEP) flap breast reconstruction, many surgeons use preoperative imaging for perforator mapping as a method to plan the operation, reduce operative times, and potentially limit morbidity. This study compared operative times for specific portions of DIEP flap harvest with and without preoperative computed tomographic angiography imaging. Two patient groups undergoing DIEP flap breast reconstruction were studied prospectively. In the experimental group, the harvesting surgeon was blinded to the preoperative computed tomographic angiography scan; in the control group, the harvesting surgeon assessed the scan preoperatively. Times for initial perforator identification, perforator selection, flap harvest time, and total procedure times were compared. Perforator choice was evaluated. Correlation of perforator choice preoperatively and intraoperatively was also performed. Times were recorded in 60 DIEP flaps (27 blinded and 33 unblinded). The nonblinded group was more efficient in all categories: time to first perforator identification (28.6 minutes versus 17.8 minutes; p < 0.0001), time to perforator decision-making (23.1 minutes versus 5.6 minutes; p < 0.0001), time to flap harvest (128 minutes versus 80 minutes; p < 0.0001), and total operative time (417 minutes versus 353 minutes; p < 0.001). Perforator location was not different between groups. Blinded intraoperative decisions correlated with preoperative imaging in 74 percent of flaps. More perforators were included in the blinded flaps compared to the nonblinded flaps (2.3 versus 1.4; p < 0.001). Use of preoperative computed tomographic angiography leads to decreased operative times, specifically with regard to perforator identification and perforator selection. Without preoperative computed tomographic angiography, surgeons included more perforators in the flaps. Therapeutic, II.


Angiogenesis--a new goal in peripheral artery occlusive disease therapy.
The vasculature is mostly quiescent in the normal adult, with the exception of the growth of new blood vessels during the female reproductive cycle. Recent advances in the knowledge concerning the molecular changes and the identification of genetic events in this vascular quiescence, as well as in vascular growth, has led to an increasing number of studies in which these phenomena are manipulated. Angiogenesis is the growth of new vessels from existing ones. Although new vessel formation is involved in many pathologic situations, like tumour growth, therapeutic angiogenesis has been presented as a novel method for the treatment of ischemic diseases, like peripheral arterial occlusive disease (PAOD). In experimental studies therapeutic angiogenesis has been produced by recombinant growth-factor protein application as well as by growth factor gene therapy. Most widely studied factors belong to vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) families. Studies have also shown that, angiogenic growth factors stimulate endothelial cell migration and accelerate endothelial repair by enhancing post-injury re-endothelization. In clinical studies angiogenic therapy has been evaluated in patients with severe vascular diseases. The results have revealed that therapy is well tolerated as well as safe and that angiogenic therapy has a clear biologic effect. However, controlled studies are still needed to answer the question whether therapeutic angiogenesis offers a real clinical benefit to patients with PAOD.


Syntax-based transfer learning for the task of biomedical relation extraction.
Transfer learning aims at enhancing machine learning performance on a problem by reusing labeled data originally designed for a related, but distinct problem. In particular, domain adaptation consists for a specific task, in reusing training data developedfor the same task but a distinct domain. This is particularly relevant to the applications of deep learning in Natural Language Processing, because they usually require large annotated corpora that may not exist for the targeted domain, but exist for side domains. In this paper, we experiment with transfer learning for the task of relation extraction from biomedical texts, using the TreeLSTM model. We empirically show the impact of TreeLSTM alone and with domain adaptation by obtaining better performances than the state of the art on two biomedical relation extraction tasks and equal performances for two others, for which little annotated data are available. Furthermore, we propose an analysis of the role that syntactic features may play in transfer learning for relation extraction. Given the difficulty to manually annotate corpora in the biomedical domain, the proposed transfer learning method offers a promising alternative to achieve good relation extraction performances for domains associated with scarce resources. Also, our analysis illustrates the importance that syntax plays in transfer learning, underlying the importance in this domain to privilege approaches that embed syntactic features.


Cell-free protein synthesis system: A new frontier for sustainable biotechnology-based products.
Cell-free protein synthesis (CFPS) system is an innovative technology with a wide range of potential applications that could challenge current thinking and provide solutions to environmental and health issues. CFPS system has been demonstrated to be a successful way of producing biomolecules in a variety of applications, including the biomedical industry. Although there are still obstacles to overcome, its ease of use, versatility, and capacity for integration with other technologies open the door for it to continue serving as a vital instrument in synthetic biology research and industry. In this review, we mainly focus on the cell-free based platform for various product productions. Moreover, the challenges in the bio-therapeutic aspect using cell-free systems and their future prospective for the improvement and sustainability of the cell free systems.


A novel cytochrome P450 is implicated in brassinosteroid biosynthesis via the characterization of a rice dwarf mutant, dwarf11, with reduced seed length.
We have characterized a rice (Oryza sativa) dwarf mutant, dwarf11 (d11), that bears seeds of reduced length. To understand the mechanism by which seed length is regulated, the D11 gene was isolated by a map-based cloning method. The gene was found to encode a novel cytochrome P450 (CYP724B1), which showed homology to enzymes involved in brassinosteroid (BR) biosynthesis. The dwarf phenotype of d11 mutants was restored by the application of the brassinolide (BL). Compared with wild-type plants, the aberrant D11 mRNA accumulated at higher levels in d11 mutants and was dramatically reduced by treatment with BL, implying that the gene is feedback-regulated by BL. Precise determination of the defective step(s) in BR synthesis in d11 mutants proved intractable because of tissue specificity and the complex control of BR accumulation in plants. However, 6-deoxotyphasterol (6-DeoxoTY) and typhasterol (TY), but not any upstream intermediates before these compounds, effectively restored BR response in d11 mutants in a lamina joint bending assay. Multiple lines of evidence together suggest that the D11/CYP724B1 gene plays a role in BR synthesis and may be involved in the supply of 6-DeoxoTY and TY in the BR biosynthesis network in rice.


Efficient production of hydrogen from formic acid using a covalent triazine framework supported molecular catalyst.
A heterogeneous molecular catalyst based on Ir(III) Cp* (Cp*=pentamethylcyclopentadienyl) attached to a covalent triazine framework (CTF) is reported. It catalyses the production of hydrogen from formic acid with initial turnover frequencies (TOFs) up to 27,000 h(-1) and turnover numbers (TONs) of more than one million in continuous operation. The CTF support, with a Brunauer-Emmett-Teller (BET) surface area of 1800 m(2) g(-1), was constructed from an optimal 2:1 ratio of biphenyl and pyridine carbonitrile building blocks. Biphenyl building blocks induce mesoporosity and, therefore, facilitate diffusion of reactants and products whereas free pyridinic sites activate formic acid towards β-hydride elimination at the metal, rendering unprecedented rates in hydrogen production. The catalyst is air stable, produces CO-free hydrogen, and is fully recyclable. Hydrogen production rates of more than 60 mol L(-1) h(-1) were obtained at high catalyst loadings of 16 wt % Ir, making it attractive towards process intensification.


Mechanisms for intracellular calcium regulation in heart. I. Stopped-flow measurements of Ca++ uptake by cardiac mitochondria.
Initial velocities of energy-dependent Ca(++) uptake were measured by stopped-flow and dual-wavelength techniques in mitochondria isolated from hearts of rats, guinea pigs, squirrels, pigeons, and frogs. The rate of Ca(++) uptake by rat heart mitochondria was 0.05 nmol/mg/s at 5 microM Ca(++) and increased sigmoidally to 8 nmol/mg/s at 200 microM Ca(++). A Hill plot of the data yields a straight line with slope n of 2, indicating a cooperativity for Ca(++) transport in cardiac mitochondria. Comparable rates of Ca(++) uptake and sigmoidal plots were obtained with mitochondria from other mammalian hearts. On the other hand, the rates of Ca(++) uptake by frog heart mitochondria were higher at any Ca(++) concentrations. The half-maximal rate of Ca(++) transport was observed at 30, 60, 72, 87, 92 microM Ca(++) for cardiac mitochondria from frog, squirrel, pigeon, guinea pig, and rat, respectively. The sigmoidicity and the high apparent K(m) render mitochondrial Ca(++) uptake slow below 10 microM. At these concentrations the rate of Ca(++) uptake by cardiac mitochondria in vitro and the amount of mitochondria present in the heart are not consistent with the amount of Ca(++) to be sequestered in vivo during heart relaxation. Therefore, it appears that, at least in mammalian hearts, the energy-linked transport of Ca(++) by mitochondria is inadequate for regulating the beat-to-beat Ca(++) cycle. The results obtained and the proposed cooperativity for mitochondrial Ca(++) uptake are discussed in terms of physiological regulation of intracellular Ca(++) homeostasis in cardiac cells.


Interaction of metabolism of aspartate and inosine and energy state of malignant cells.
1. Oxidation of glutamine in Ehrlich ascites-carcinoma cells results in a large accumulation of aspartate. 2. The addition of inosine causes a marked decrease in aspartate production from glutamine. This may be related to the resynthesis of AMP from aspartate and IMP, the latter being produced from inosine via the salvage pathway for purine nucleotides. In accordance with this assumption, a significant production of lactate was observed, which comes probably from the ribose moiety of inosine. Since lactate is known to inhibit production of aspartate from glutamine, this may explain the effect of inosine. 3. Addition of glutamine together with inosine increased cellular ATP content. This was not the case if glutamine or inosine was present separately or if inosine was added together with lactate, pyruvate or glucose. The effect did not occur if amino-oxyacetate, an inhibitor of transaminases, was added. These findings suggested again that production of aspartate is important for resynthesis of ATP from IMP via the purine nucleotide cycle. 4. If the cells were exposed to prolonged anaerobic incubation, addition of glutamine and inosine markedly increased O2 uptake and [ATP], suggesting the crucial importance of aspartate production by glutamine oxidation for the recovery of energy metabolism in the cells.


An intervention to decrease narcotic-related adverse drug events in children's hospitals.
Narcotic-related adverse drug events are the most common adverse drug events in hospitalized children. Despite multiple published studies describing interventions that decrease adverse drug events from narcotics, large-scale collaborative quality improvement efforts to address narcotic-related adverse drug events in pediatrics have not been described. The purpose of this study was to evaluate collaborative-wide narcotic-related adverse drug event rates after a collection of expert panel-defined best practices was implemented. All 42 children's hospitals in the Child Health Corporation of America were invited to participate in the Institute for Healthcare Improvement-style quality improvement collaborative aimed at reducing narcotic-related adverse drug events. A collection of interventions known or suspected to reduce narcotic-related adverse drug events was recommended by an expert panel, with each site implementing >or=1 of these best practices on the basis of local need. Narcotic-related adverse drug event rates were compared between the baseline (December 1, 2004, to March 31, 2005) and postimplementation periods (January 1, 2006, to March 31, 2006) after an a priori-defined intervention ramp-up time (April 1, 2005, and December 31, 2005). Secondary outcome measures included constipation rates and narcotic-related automated drug-dispensing-device override percentages. Median narcotic-related adverse drug event rates decreased 67% between the baseline and postimplementation time frames across the 14-site collaborative. Constipation rates decreased 68.9%, and automated drug-dispensing-device overrides decreased from 10.18% to 5.91% of all narcotic doses administered. Implementation of >or=1 expert panel-recommended interventions at each participating site resulted in a significant decrease in narcotic-related adverse drug events, constipation, and automated drug-dispensing-device overrides in a 12-month, 14-site children's hospital quality collaborative.


Repetitive transcranial magnetic stimulation: a tool for human cerebellar plasticity.
Non-invasive brain stimulation methods, such as repetitive transcranial magnetic stimulation (rTMS), are currently used to modulate the excitability of the cerebral cortex, providing important insights into mechanisms of cortical plasticity. Used to create long-lasting changes in the excitability of synapses, rTMS has been intensively investigated as a therapeutic tool in several neurological and psychiatric conditions and given some promising results. Recent studies have shown that rTMS of cerebellar structures is capable of inducing long-lasting changes in the excitability of cerebello-thalamo-cortical pathways. Thus, this novel approach may be important for investigating the functions of cerebellar plasticity. Indeed, cerebellar rTMS has been shown to modulate motor control, cognitive functions, emotion and mood. Moreover, recent studies seem to indicate that long-lasting modifications of cerebellar pathways could be usefully exploited in the treatment of several pathological conditions characterized by altered cortical excitability, such as Parkinson's disease, stroke, depression and schizophrenia. The high potential of cerebellar rTMS as a therapeutic tool in neurology could depend on the possibility of modulating several interconnected remote areas, through the activation of different systems, such as the cerebello-thalamo-cortical and limbic-thalamo-cortical networks.


The use of pass/fail grades to assess academic achievement and house staff performance.
The advantages of a formal grading system in assessing a student's capability to practice medicine remain controversial. Students prefer the pass/fail method, while faculty lean toward the traditional approach. The efficacy of a modified pass/fail grading system in detecting superior academic achievement, as well as in predicting house staff performance, was evaluated. Mean scores on the examinations of the National Board of Medical Examiners of students selected fo Alpha Omega Alpha were significantly higher than those of other students, although the faculty was unaware of these results when selecting candidates. Chairmen in institutions where 125 students had served their first graduate year of training felt that 85 percent of the dean's letters summarizing the student's academic performance over a three-year period accurately indicated subsequent performance on the house staff. These results suggest that a modified pass/fail grading system can detect superior students as well as provide relevant information with respect to subsequent performance as a physician.


Reduced risk of nontuberculous mycobacteria in cystic fibrosis adults receiving long-term azithromycin.
Azithromycin reduces exacerbations in cystic fibrosis (CF) patients. Our aim was to investigate its association with nontuberculous mycobacteria isolation and macrolide susceptibility. From 2006 to 2010, all adult CF subjects at Cochin Hospital (Paris, France) harboring at least one positive NTM isolate were identified (Cases). In a nested case-control study, each Case was individually matched for age and gender with up to 4 CF adults with no NTM isolate (Controls). Clinical data at the time of first NTM isolate (index date) in Cases were compared with those of Controls using multivariate conditional regression analysis. CF subjects with positive NTM isolates (Cases, n=41) were matched to 155 Controls. Among Cases, 48.7% had isolates from Mycobacterium avium complex and 58.5% from Mycobacterium abscessus complex, and 31 Cases fulfilled the 2007 American Thoracic Society criteria for NTM infection (ATS+ Cases). Cases and ATS+ Cases were more likely to have low body mass index and colonization with Aspergillus fumigatus. Azithromycin was associated with a two-fold reduction in NTM isolates. Only one M. avium complex isolate had acquired macrolide resistance. These data suggest that azithromycin is a primary prophylaxis for NTM infection in CF adults.


Application of enzyme-linked immunosorbent assay to detect antimicrobial peptides in human intestinal lumen.
Intestinal transplantation is the definitive treatment for intestinal failure. However, tissue rejection and graft-versus-host disease are relatively common complications, necessitating aggressive immunosuppression that can itself pose further complications. Tracking intraluminal markers in ileal effluent from standard ileostomies may present a noninvasive and sensitive way to detect developing pathology within the intestinal graft. This would be an improvement compared to current assessments, which are limited by poor sensitivity and specificity, contributing to under or over-immunosuppression, respectively, and by the need for invasive biopsies. Herein, we report an approach to reproducibly analyze ileal fluid obtained through stoma sampling for antimicrobial peptide/protein concentrations, reasoning that these molecules may provide an assessment of intestinal homeostasis and levels of intestinal inflammation over time. Concentrations of lysozyme (LYZ), myeloperoxidase (MPO), calprotectin (S100A8/A9) and β-defensin 2 (DEFB2) were assessed using adaptations of commercially available enzyme-linked immunosorbent assays (ELISAs). The concentration of α-defensin 5 (DEFA5) was assessed using a newly developed sandwich ELISA. Our data support that with proper preparation of ileal effluent specimens, precise and replicable determination of antimicrobial peptide/protein concentrations can be achieved for each of these target molecules via ELISA. This approach may prove to be reliable as a clinically useful assessment of intestinal homeostasis over time for patients with ileostomies.


Intersecting Stories of the Phagocyte NADPH Oxidase and Chronic Granulomatous Disease.
Neutrophils serve as the circulating cells that respond early and figure prominently in human host defense to infection and in inflammation in other settings. Optimal oxidant-dependent antimicrobial activity by neutrophils relies on the ability of stimulated phagocytes to utilize a multicomponent NADPH oxidase to generate oxidants. The frequent, severe, and often fatal infections experienced by individuals with chronic granulomatous disease (CGD), an inherited disorder in which one of the NADPH oxidase components is absent or dysfunctional, underscore the link between a functional phagocyte NADPH oxidase and robust host protection against microbial infection.The history of the discovery and characterization of the normal neutrophil NADPH oxidase and the saga of recognizing CGD and its underlying causes together illustrate how the observations of astute clinicians and imaginative basic scientists synergize to forge new understanding of both basic cell biology and pathogenesis of human disease.In this chapter, we review the events in the stepwise evolution of our understanding of the phagocyte NADPH oxidase, both in the context of normal human neutrophil function and in the setting of CGD. The phagocyte oxidase complex employs a heterodimeric transmembrane protein composed of gp91phox and p22phox to relay electrons from NADPH to molecular oxygen, while other cofactors contribute to localization and regulation of the activity of the assembled oxidase. The b-type cytochrome gp91phox, also known as NOX2, serves as the catalytic component of this multicomponent enzyme complex. Although many of the features of the composition and regulation of the phagocyte oxidase may apply as well to NOX2 expressed in non-phagocytes and to other members of the NOX protein family, exceptions exist and pose special challenges to investigators exploring the biology of NADPH oxidases.


Towards development of a 3-state self-paced brain-computer interface.
Most existing brain-computer interfaces (BCIs) detect specific mental activity in a so-called synchronous paradigm. Unlike synchronous systems which are operational at specific system-defined periods, self-paced (asynchronous) interfaces have the advantage of being operational at all times. The low-frequency asynchronous switch design (LF-ASD) is a 2-state self-paced BCI that detects the presence of a specific finger movement in the ongoing EEG. Recent evaluations of the 2-state LF-ASD show an average true positive rate of 41% at the fixed false positive rate of 1%. This paper proposes two designs for a 3-state self-paced BCI that is capable of handling idle brain state. The two proposed designs aim at detecting right- and left-hand extensions from the ongoing EEG. They are formed of two consecutive detectors. The first detects the presence of a right- or a left-hand movement and the second classifies the detected movement as a right or a left one. In an offline analysis of the EEG data collected from four able-bodied individuals, the 3-state brain-computer interface shows a comparable performance with a 2-state system and significant performance improvement if used as a 2-state BCI, that is, in detecting the presence of a right- or a left-hand movement (regardless of the type of movement). It has an average true positive rate of 37.5% and 42.8% (at false positives rate of 1%) in detecting right- and left-hand extensions, respectively, in the context of a 3-state self-paced BCI and average detection rate of 58.1% (at false positive rate of 1%) in the context of a 2-state self-paced BCI.


Health and economic burden of obesity in elderly individuals with asthma in the United States.
The health and economic burden of obesity among elderly individuals with asthma has not been adequately studied. This study assessed the association between obesity and asthma among the elderly and examined the impact of obesity on asthma-related and total health care costs among elderly individuals with asthma. This was a retrospective analysis of the 2006-2010 Medical Expenditure Panel Survey (MEPS) data. Individuals aged 65 years or older were included in the study. Individuals with asthma were identified by an International Classification of Diseases, Ninth Revision code of 493 or a Clinical Classification Code of 128. Individuals with a self-reported body mass index ≥ 30 kg/m(2) were considered to be obese. Logistic regression was used to assess the relationship between obesity and asthma. Generalized linear models with gamma distribution and log link were used to assess the relationship between obesity and asthma-related and total direct medical costs. All analyses were conducted while accounting for the complex survey design of MEPS. In all, 675 elderly individuals were identified as having asthma, 292 of whom were obese. Obese elderly individuals were more likely to suffer from asthma as compared to the nonobese (odds ratio, 1.71; 95% confidence interval [CI],1.37-2.12). Obesity was a significant predictor of asthma-related costs (β: 0.537; 95% CI: 0.18-0.89; P= 0.003) and total health care costs (β: 0.154; 95% CI: 0.08-0.23; P = 0.001) among elderly individuals with asthma after controlling for sociodemographics and comorbidities. Appropriate weight management measures should be recommended to obese elderly individuals with asthma to improve asthma control and reduce health care costs.


The Use of Small Electronic Devices and Health: Feasibility of Interventions for a Forthcoming Crossover Design.
Modern lifestyle is heavily affected by technology such as smartphones, tablets, and other small computers; yet it remains unclear how our health and well-being are affected by the heavy use of these devices. This feasibility study aims to test two different interventions of an experimental protocol for a forthcoming large-scale community-based study and get estimates of parameters for sample size calculation. The aim of the large-scale study is to investigate the effect of (1) a wearable tracking device on aerobic capacity (VO2max/kg) and the effect of (2) restricting media use on total sleep time. Twenty healthy participants were included and equipped with a wrist-worn device tracking physical activity and sleep. Participants were allocated to either a physical activity group, which was instructed to use the wrist-worn device to support exercise, or a sleep silent group, which was instructed to remove or switch off all electronic devices in the bedroom (except the wrist-worn tracking device). The intervention lasted approximately 4 weeks. Data collected included blood pressure, submaximal cycle ergometer test, self-reported technology use, and compliance of using the wearable tracking device. All participants wore the wearable tracking device 95.8% (SD 4.4%) of the time. Participants in the physical activity group increased aerobic capacity from 30.38 (SD 8.98) to 32.1 (SD 8.71) mL/kg/min (t=-2.31, P=.046) and decreased their systolic blood pressure from 126.5 (SD 15.8) mm Hg to 121.8 (SD 11.7) mm Hg (t=2.72, P=.02). The sleep silent group prolonged their time offline before bedtime from 18.1 (SD 19.4) minutes to 27.2 (SD 17.3) minutes (t=-2.94, P=.02). The two interventions are feasible to conduct. Participants were willing to wear the tracking device on their wrist and restrict all media use in their bedroom and thereby reduce bedtime technology use. Our results also suggest that tracking physical activity using a wearable device is accompanied by noteworthy health benefits. We outline necessary adjustments for a forthcoming large-scale study.


Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-D-aspartate receptor.
Ethanol has been shown to inhibit N-methyl-D-aspartate (NMDA)-stimulated calcium influx into cerebellar granule cells grown in culture. Because NMDA-mediated responses are modulated by a number of substances, we investigated the effects of several of these agents on ethanol-induced inhibition of calcium flux. Ethanol (50 mM) inhibited NMDA-dependent Ca2+ influx by approximately 50%. The percentage of inhibition remained constant with increasing NMDA concentrations (5-250 microM). Increasing Mg2+ concentrations in the assay medium inhibited NMDA-stimulated calcium influx but the EC50 for Mg2+ was unchanged in the presence of ethanol. Glycine at concentrations of 0.3-100 microM potentiated the effects of NMDA. Glycine at concentrations in excess of 10 microM decreased ethanol-mediated inhibition of NMDA-stimulated calcium influx. D-Serine was shown to have effects similar to those of glycine, whereas L-serine was significantly less active in potentiating NMDA-stimulated activity and reversing the ethanol-induced inhibition of calcium influx. N-Methylglycine and L-leucine were ineffective in potentiating NMDA actions but high concentrations (1 mM) of N-methylglycine attenuated ethanol-induced inhibition, whereas L-leucine (1 mM) had no effect. High concentrations of N-methylglycine were shown to reduce glycine-induced enhancement at the NMDA receptor, whereas L-leucine did not affect the glycine response. Glycine did not affect kainate-stimulated calcium influx and did not alter the small amount of inhibition produced by ethanol in the response of the cells to kainate. The results demonstrate that the in vivo actions of ethanol on the NMDA systems of brain may be dependent on glycine concentrations at these receptor sites.


Insecticidal activity of essential oil from leaves of Eugenia stipitata McVaugh against Aedes aegypti.
Aedes aegypti, a mosquito, is responsible for the spread of many diseases, including dengue, zika, and chikungunya. However, due to this mosquito's developed resistance to conventional pesticides, effectively controlling it has proven to be challenging. This study aimed to evaluate the insecticidal potential of the essential oil from the leaves of Eugenia stipitata against Ae. aegypti, offering a natural and sustainable alternative for mosquito control. Tests were conducted using third-stage larvae to evaluate larvicidal activity and pupae collected up to 14 h after transformation to investigate pupicidal activity. Throughout the bioassays, the organisms were exposed to various essential oil concentrations. The findings demonstrated that the essential oil of E. stipitata exhibited larvicidal action, resulting in 100% larval mortality after 24 h and an LC50 value of 0.34 mg/mL. The effectiveness of essential oil as a pupicidal agent was also demonstrated by its LC50 value of 2.33 mg/mL and 100% larval mortality in 24 h. It can be concluded that the essential oil of E. stipitata holds promise as a natural pest control agent. Its use may reduce the reliance on conventional chemical pesticides, providing a more sustainable and effective strategy to combat diseases spread by mosquitoes.


Pelvic inflammatory disease. Key treatment issues and options.
--To examine available data regarding optimal antimicrobial therapy for pelvic inflammatory disease (PID) and to address selected treatment issues confronting clinicians caring for women with PID. --Studies evaluated to help establish the Centers for Disease Control's 1989 Sexually Transmitted Diseases Treatment Guidelines and other reports published since 1985. A MEDLINE search of English-language literature was conducted using the indexing terms "pelvic inflammatory disease" or "pelvic infections" or "salpingitis" and "treatment". In addition, abstracts and bibliographies of articles and books were reviewed. --Studies were selected for detailed review if they evaluated the effectiveness of an antimicrobial regimen for treatment of PID. --All studies were evaluated to determine the numbers of women treated and the percentage with clinical or microbiologic evidence of cure. --A variety of combination antimicrobial regimens are highly effective in providing clinical and microbiologic evidence of cure; few data are available to assess optimal therapy for prevention of late sequelae. Because PID is polymicrobial in cause, recommended antimicrobial regimens are broad-spectrum in coverage. --No single agent that provides sufficient coverage is currently available. Several combination regimens appear highly effective clinically even among women with tubo-ovarian abscess formation. Uncertainties regarding the effectiveness of antimicrobial therapy for prevention of late sequelae complicate decisions regarding the choice among regimens and the appropriateness of ambulatory treatment of women with PID. Pending better data, hospitalization should be strongly considered, where feasible, particularly for those women with PID desiring further childbearing. Sex partners of all women with PID should be treated.


Novel Strategy to Enhance Human Mesenchymal Stromal Cell Immunosuppression: Harnessing Interferon-Gamma Presentation in Metal-Organic Frameworks Embedded on Heparin/Collagen Multilayers.
The immunomodulatory potential of human mesenchymal stromal cells (hMSCs) can be boosted when exposed to interferon-gamma (IFN-γ). While pretreating hMSCs with IFN-γ is a common practice to enhance their immunomodulatory effects, the challenge lies in maintaining a continuous IFN-γ presence within cellular environments. Therefore, in this research, we investigate the sustainable presence of IFN-γ in the cell culture medium by immobilizing it in water-stable metal-organic frameworks (MOFs) [PCN-333(Fe)]. The immobilized IFN-γ in MOFs was coated on top of multilayers composed of combinations of heparin (HEP) and collagen (COL) that were used as a bioactive surface. Multilayers were created by using a layer-by-layer assembly technique, with the final layer alternating between collagen (COL) and heparin (HEP). We evaluated the viability, differentiation, and immunomodulatory activity of hMSCs cultured on (HEP/COL) coated with immobilized IFN-γ in MOFs after 3 and 6 days of culture. Cell viability, compared to tissue culture plastic, was not affected by immobilized IFN-γ in MOFs when they were coated on (HEP/COL) multilayers. We also verified that the osteogenic and adipogenic differentiation of the hMSCs remained unchanged. The immunomodulatory activity of hMSCs was evaluated by examining the expression of indoleamine 2,3-dioxygenase (IDO) and 11 essential immunomodulatory markers. After 6 days of culture, IDO expression and the expression of 11 immunomodulatory markers were higher in (HEP/COL) coated with immobilized IFN-γ in MOFs. Overall, (HEP/COL) multilayers coated with immobilized IFN-γ in MOFs provide a sustained presentation of cytokines to potentiate the hMSC immunomodulatory activity.