The approach of general surgeons to oncoplastic and reconstructive breast surgery in Turkey: a survey of practice patterns.
Oncoplastic Breast Surgery (OBS), which is a combination of oncological procedures and plastic surgery techniques, has recently gained widespread use. To assess the experiences, practice patterns and preferred approaches to Oncoplastic and Reconstructive Breast Surgery (ORBS) undertaken by general surgeons specializing in breast surgery in Turkey. Cross-sectional study. Between December 2013 and February 2014, an eleven-question survey was distributed among 208 general surgeons specializing in breast surgery. The questions focused on the attitudes of general surgeons toward performing oncoplastic breast surgery (OBS), the role of the general surgeon in OBS and their training for it as well as their approaches to evaluating cosmetic outcomes in Breast Conserving Surgery (BCS) and informing patients about ORBS preoperatively. Responses from all 208 surgeons indicated that 79.8% evaluated the cosmetic outcomes of BCS, while 94.2% informed their patients preoperatively about ORBS. 52.5% performed BCS (31.3% themselves, 21.1% together with a plastic surgeon). 53.8% emphasized that general surgeons should carry out OBS themselves. 36.1% of respondents suggested that OBS training should be included within mainstream surgical training, whereas 27.4% believed this training should be conducted by specialised centres. Although OBS procedure rates are low in Turkey, it is encouraging to see general surgeons practicing ORBS themselves. The survey demonstrates that our general surgeons aspire to learn and utilize OBS techniques.


Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice.
Activating signal cointegrator 2 (ASC-2), a cancer-amplified transcriptional coactivator of nuclear receptors and many other transcription factors, contains two LXXLL-type nuclear receptor interaction domains. Interestingly, the second LXXLL motif is highly specific to the liver X receptors (LXRs). In cotransfection, DN2, an ASC-2 fragment encompassing this motif, exerts a potent dominant-negative effect on transactivation by LXRs, which is rescued by ectopic coexpression of the full-length ASC-2 but not by other LXXLL-type coactivators, such as SRC-1 and TRAP220. In contrast, DN2/m, in which the LXXLL motif is mutated to LXXAA to abolish the interactions with LXRs, is without any effect. Accordingly, expression of DN2, but not DN2/m, in transgenic mice results in phenotypes that are highly homologous to those previously observed with LXRalpha(-/-) mice, including a rapid accumulation of large amounts of cholesterol and down-regulation of the known lipid-metabolizing target genes of LXRalpha in the liver upon being fed a high-cholesterol diet. These results identify ASC-2 as a physiologically important transcriptional coactivator of LXRs and demonstrate its pivotal role in the liver lipid metabolism.


Endonuclease specificity and sequence dependence of type IIS restriction enzymes.
Restriction enzymes that recognize specific sequences but cleave unknown sequence outside the recognition site are extensively utilized tools in molecular biology. Despite this, systematic functional categorization of cleavage performance has largely been lacking. We established a simple and automatable model system to assay cleavage distance variation (termed slippage) and the sequence dependence thereof. We coupled this to massively parallel sequencing in order to provide sensitive and accurate measurement. With this system 14 enzymes were assayed (AcuI, BbvI, BpmI, BpuEI, BseRI, BsgI, Eco57I, Eco57MI, EcoP15I, FauI, FokI, GsuI, MmeI and SmuI). We report significant variation of slippage ranging from 1-54%, variations in sequence context dependence, as well as variation between isoschizomers. We believe this largely overlooked property of enzymes with shifted cleavage would benefit from further large scale classification and engineering efforts seeking to improve performance. The gained insights of in-vitro performance may also aid the in-vivo understanding of these enzymes.


Estimating the Economic Burden of Rheumatoid Arthritis in Taiwan Using the National Health Insurance Database.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of the joints. This research aims to estimate the economic burden of RA in Taiwan. The National Health Insurance Research Database (NHIRD), a claims-based dataset encompassing 99 % of Taiwan's population, was applied. We used a micro-costing approach for direct healthcare costs and indirect social costs by estimating the quantities and prices of cost categories. Direct costs included surgeries, hospitalizations, medical devices and materials, laboratory tests, and drugs. The costs and quantities of the direct economic burden were calculated based on 2011 data of NHIRD. We identified RA patients and a control cohort matched 1:4 on demographic and clinical covariates to calculate the incremental cost related to RA. Indirect costs were evaluated by missed work (absenteeism) and worker productivity (presenteeism). For the indirect burden, we estimated the rate of absenteeism and presenteeism from a patient survey. Costs were presented in US dollars (US$1 = 30 TWD). A total of 41,269 RA patients were included in the database with incremental total direct cost of US$86,413,971 and indirect cost of US$138,492,987. This resulted in an average incremental direct cost of US$2050 per RA patient. Within direct costs, the largest burdens were associated with drugs (US$73,028,944), laboratory tests (US$6,132,395), and hospitalizations (US$3,208,559). For indirect costs, absenteeism costs and presenteeism costs were US$16,059,681 and US$114,291,687, respectively. The economic burden of RA in Taiwan is driven by indirect healthcare costs, most notably presenteeism.


Clinical and neuroradiological features of intracranial vertebrobasilar artery dissection.
We sought to determine the clinical and neuroradiological features of intracranial vertebrobasilar artery dissection. The clinical features and MR findings of 31 patients (20 men and 11 women) with intracranial vertebrobasilar artery dissections confirmed by vertebral angiography were analyzed retrospectively. The vertebral angiography revealed the double lumen sign in 11 patients (13 arteries) and the pearl and string sign in 20 patients (28 arteries). The patients ranged in age from 25 to 82 years (mean, 54.8 years). Clinical symptoms due to ischemic cerebellar and/or brain stem lesions were common, but in 3 cases the dissections were discovered incidentally while an unrelated disorder was investigated. Headache, which has been emphasized as the only specific clinical sign of vertebrobasilar artery dissection, was found in 55% of the patients. Intramural hematoma on T1-weighted images has been emphasized as a specific MR finding. The positive rate of intramural hematoma was 32%. Double lumen on 3-dimensional (3-D) spoiled gradient-recalled acquisition (SPGR) images after the injection of contrast medium was identified in 87% of the patients. The 3-D SPGR imaging method is considered useful for the screening of vertebrobasilar artery dissection. Intracranial vertebrobasilar artery dissection is probably much more frequent than previously considered. Such patients may present no or only minor symptoms. Neuroradiological screening for posterior circulation requires MR examinations, including contrast-enhanced 3-D SPGR. Angiography may be necessary for the definite diagnosis of intracranial vertebrobasilar artery dissection because the sensitivity of the finding of intramural hematoma is not satisfactory.


Antibiotic prophylaxis in the surgical management of miscarriage in low-income countries: a cost-effectiveness analysis of the AIMS trial.
There is ongoing debate on the clinical benefits of antibiotic prophylaxis for reducing pelvic infection after miscarriage surgery. We aimed to study the cost-effectiveness of antibiotic prophylaxis in the surgical management of miscarriage in low-income countries. We did an incremental cost-effectiveness analysis using data from 3412 women recruited to the AIMS trial, a randomised, double-blind, placebo-controlled trial designed to evaluate the effectiveness of antibiotic prophylaxis in the surgical management of miscarriage in Malawi, Pakistan, Tanzania, and Uganda. Economic evaluation was done from a health-care-provider perspective on the basis of the outcome of cost per pelvic infection avoided within 2 weeks of surgery. Pelvic infection was broadly defined by the presence of clinical features or the clinically identified need to administer antibiotics. We used non-parametric bootstrapping and multilevel random effects models to estimate incremental mean costs and outcomes. Decision uncertainty was shown via cost-effectiveness acceptability frontiers. The AIMS trial is registered with the ISRCTN registry, number ISRCTN97143849. Between June 2, 2014, and April 26, 2017, 3412 women were assigned to receive either antibiotic prophylaxis (1705 [50%] of 3412) or placebo (1707 [50%] of 3412) in the AIMS trial. 158 (5%) of 3412 women developed pelvic infection within 2 weeks of surgery, of whom 68 (43%) were in the antibiotic prophylaxis group and 90 (57%) in the placebo group. There is 97-98% probability that antibiotic prophylaxis is a cost-effective intervention at expected thresholds of willingness-to-pay per additional pelvic infection avoided. In terms of post-surgery antibiotics, the antibiotic prophylaxis group was US$0·27 (95% CI -0·49 to -0·05) less expensive per woman than the placebo group. A secondary analysis, a sensitivity analysis, and all subgroup analyses supported these findings. Antibiotic prophylaxis, if implemented routinely before miscarriage surgery, could translate to an annual total cost saving of up to $1·4 million across the four participating countries and up to $8·5 million across the two regions of sub-Saharan Africa and south Asia. Antibiotic prophylaxis is more effective and less expensive than no antibiotic prophylaxis. Policy makers in various settings should be confident that antibiotic prophylaxis in miscarriage surgery is cost-effective. UK Medical Research Council, Wellcome Trust, and the UK Department for International Development.


Soup with or without meatballs: Impact of nutritional factors on the MIC, kill-rates and growth-rates.
The Minimum Inhibitory Concentration (MIC) is a reference value for susceptibility testing of bacteria. However, the MIC is a net result of growth and killing after a certain duration of exposure under standardized favourable in vitro conditions. Killing and growth characteristics of a drug may yield more information on its activity and help to explain discrepancies between efficacy observed in vitro and in vivo. The MIC of meropenem was determined for P. aeruginosa ATCC 27853 both by microdilution and the E-test in dilutions of Mueller Hinton (MH) broth from 100% to 1%. Time-kill curves were obtained for twofold dilutions of meropenem. Growth rates and kill rates at each concentration and dilution were obtained by linear regression. The Hill equation was fit to the kill rates vs concentrations. Growths rates decreased log linearly from 0.63/h at 100% to 0.29/h at 6% MH. Over the 100-6% MH dilution range, there was a log-linear decrease of the MIC of meropenem of both the E-test and microdilution. The EC50s decreased from 0.29 mg/L to 0.07 mg/L, which is in agreement with the MIC results. There was a log-linear relationship between MIC and EC50 for the various dilutions MH. The availability of nutritional factors is related to the MIC, and a lower availability is related to both a lower growth rate and higher kill rate. Since nutritional factors are less abundantly available in vivo as compared to in vitro, this should be taken into account when translating in vitro to in vivo pharmacodynamics.


In the family: access to, and communication of, familial information in clinical practice.
How an individual's genetic information is governed by confidentiality, and how the interests of others-such as close relatives-in knowing such information might be respected, has been the topic of much debate ever since genetic testing has become more prevalent. In this paper, two authors who often appear to have different views on familial disclosure, discuss where they agree on this topic.


Impact of metastable defect structures on carrier recombination in solar cells.
The efficiency of a solar cell is often limited by electron-hole recombination mediated by defect states within the band gap of the photovoltaic (PV) semiconductor. The Shockley-Read-Hall (SRH) model considers a static trap that can successively capture electrons and holes. In reality however, true trap levels vary with both the defect charge state and local structure. Here we consider the role of metastable structural configurations in capturing electrons and holes, taking the tellurium interstitial in CdTe as an illustrative example. Consideration of the defect dynamics, and symmetry-breaking, changes the qualitative behaviour and activates new pathways for carrier capture. Our results reveal the potential importance of metastable defect structures in non-radiative recombination, in particular for semiconductors with anharmonic/ionic-covalent bonding, multinary compositions, low crystal symmetries or highly-mobile defects.


Anesthesia for peritonectomy with hyperthermic intraoperative peritoneal chemotherapy. Case report.
Pseudomyxoma peritonei is a rare condition related to epithelial neoplasia of the appendix and ovaries. Surgical cytoreduction, peritonectomy, and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the treatment of choice. Maintenance of normovolemia, normothermia, postoperative pain management and coagulation status are all responsibility of the anesthesiologist. The objective of this report was to describe a case of peritonectomy with HIPEC. This is a 37 year-old female, ASA I, with a history of appendectomy 3 months ago with an anatomopathological report of mucinous cystoadenoma. After review of the pathological sample, a pseudomyxoma peritonei was diagnosed with indication of peritonectomy with HIPEC. An epidural catheter (T11-T12) was placed and a test-dose, as well as morphine, was administered. Anesthesia was induced with remifentanil, 0.4 μg.kg⁻¹.min⁻¹, propofol, and rocuronium, besides rapid-sequence orotracheal intubation. Remifentanil, sevoflurane, and rocuronium were used for anesthesia maintenance according to the TOF. Ropivacaine 50mg, and fentanyl 10 μg. in 10 mL were administered through the epidural catheter 10 minutes before incision. During the surgery, CVP, SpO₂, FeCO₂, temperature, heart rate, MAP, and urine output maintained stable levels within normal limits, including during HIPEC. Reduction of the hematocrit and SvO₂, increased PT, and thrombocytopenia were corrected by administering blood products. After 13 hours of surgery, the patient was admitted to the ICU under controlled ventilation. She was extubated on the 1(st) postoperative day, being discharged from the hospital on the 17(th) day of hospitalization. Surgical cytoreduction and peritonectomy with HIPEC goes back to the decade of 1990 with several studies showing a significant increase in survival. Due to the complexity of the procedure and large surgery the vigilance of the anesthesiologist is fundamental for maintenance of clinical and laboratorial parameters, and recognition and treatment of any changes.


Explosive radiation or uninformative genes? Origin and early diversification of tachinid flies (Diptera: Tachinidae).
Molecular phylogenetic studies at all taxonomic levels often infer rapid radiation events based on short, poorly resolved internodes. While such rapid episodes of diversification are an important and widespread evolutionary phenomenon, much of this poor phylogenetic resolution may be attributed to the continuing widespread use of "traditional" markers (mitochondrial, ribosomal, and some nuclear protein-coding genes) that are often poorly suited to resolve difficult, higher-level phylogenetic problems. Here we reconstruct phylogenetic relationships among a representative set of taxa of the parasitoid fly family Tachinidae and related outgroups of the superfamily Oestroidea. The Tachinidae are one of the most species rich, yet evolutionarily recent families of Diptera, providing an ideal case study for examining the differential performance of loci in resolving phylogenetic relationships and the benefits of adding more loci to phylogenetic analyses. We assess the phylogenetic utility of nine genes including both traditional genes (e.g., CO1 mtDNA, 28S rDNA) and nuclear protein-coding genes newly developed for phylogenetic analysis. Our phylogenetic findings, based on a limited set of taxa, include: a close relationship between Tachinidae and the calliphorid subfamily Polleninae, monophyly of Tachinidae and the subfamilies Exoristinae and Dexiinae, subfamily groupings of Dexiinae+Phasiinae and Tachininae+Exoristinae, and robust phylogenetic placement of the somewhat enigmatic genera Strongygaster, Euthera, and Ceracia. In contrast to poor resolution and phylogenetic incongruence of "traditional genes," we find that a more selective set of highly informative genes is able to more precisely identify regions of the phylogeny that experienced rapid radiation of lineages, while more accurately depicting their phylogenetic context. Although much expanded taxon sampling is necessary to effectively assess the monophyly of and relationships among major tachinid lineages and their relatives, we show that a small number of well-chosen nuclear protein-coding genes can successfully resolve even difficult phylogenetic problems.


Headache in Pregnancy.
Headache disorders are extraordinarily common and disproportionately impact women of childbearing age. This article reviews the importance of proper diagnosis, natural history, and management of headache disorders in pregnant and postpartum women. Red flags for secondary headache specifically among pregnant women include elevated blood pressure and lack of a previous headache history, as well as a prolonged duration of the headache attack in those with a prior history of migraine. Migraine improvement is typical for most pregnant women, but the prognosis for women who have migraine with aura or chronic migraine is less predictable. Migraine is now an established risk factor for the development of preeclampsia. Recent data suggest hazards for compounds containing butalbital and possibly a better safety profile for triptans than previously believed during pregnancy. Peripheral nerve blocks and noninvasive neurostimulation devices are procedural and emerging therapies that have promising safety profiles for pregnant women with headache disorders. Acute headache occurring in pregnancy and the postpartum period is a red flag requiring diagnostic vigilance. Migraine frequency in women typically improves during pregnancy, although this trend is less certain when aura is present and after delivery. Acute and preventive treatment plans during pregnancy and lactation are plausible but may require shifts in therapeutic hierarchy. Relatively safe oral, parenteral, and procedural therapies are available for pregnant women. Noninvasive neuromodulation devices are already available and will likely play a greater role in the coming years. Migraine is associated with medical and obstetrical complications during pregnancy, and women with frequent migraine attacks may need to be considered high risk.


Quantitative analysis of 2H NMR T1Q, T1Z and T2 relaxation times in the SmA phase of a liquid crystal dendrimer.
In this work the 2H NMR spin-lattice relaxation times, T1Z and T1Q, and the spin-spin relaxation times measured by means of the quadrupolar echo sequence, T2, have been analyzed in order to study the dynamic processes of a liquid crystalline dendrimer labelled on the aromatic core of the lateral mesogenic units in the SmA phase. Several theoretical models describing both internal and overall molecular diffusion motions have been used to reproduce the temperature dependence of the spectral densities J(0)(0), J1(omega0) and J2(2omega0) experimentally determined at the Larmor frequency omega0 of 61.3 MHz. This analysis identifies in the internal rotation of the deuterated phenyl ring around its para axis the main contribution to the longitudinal relaxation. Moreover, the best fitting of the minimum in the trend of both T1Z and T1Q was obtained by introducing a distribution of activation energies for such internal motion, thus confirming previous hypothesis of dynamic heterogeneity. A much slower motion, affecting the sole transverse relaxation and ascribable to the reorientation of the whole macromolecular dendrimers, was modelled through the so called "slowly relaxing local structure" approach.


The aquatic communities inhabiting internodes of two sympatric bamboos in Argentinean subtropical forest.
In order to determine if phytotelmata in sympatric bamboos of the genus Guadua might be colonized by different types of arthropods and contain communities of different complexities, the following objectives were formulated: (1) to analyze the structure and species richness of the aquatic macroinvertebrate communities, (2) to comparatively analyze co-occurrences; and (3) to identify the main predators. Field studies were conducted in a subtropical forest in Argentina, where 80 water-filled bamboo internodes of Guadua chacoensis (Rojas Acosta) Londoño and Peterson (Poales: Poaceae) and G. trinii (Nees) Nees and Rupr. were sampled. Morphological measurements indicated that G. chacoensis held more fluid than G. trinii. The communities differed between Guadua species, but many macroinvertebrate species used both bamboo species. The phytotelmata were mainly colonized by Diptera of the families Culicidae and Ceratopogonidae.


Genome-wide association study of survival in patients with pancreatic adenocarcinoma.
Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.


The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight.
The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. To perform the largest PD genome-wide association study restricted to a single country. We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain. © 2019 International Parkinson and Movement Disorder Society.


Advancement in the treatment of diminished ovarian reserve by traditional Chinese and Western medicine.
Diminished ovarian reserve (DOR) refers to the decreased production of mature ova in ovarium and decreased quality of oocyte, leading to deficiency of the female sex hormone and decreased fertility. DOR can also develop into premature ovarian failure, which affects female life quality and constitutes an important cause of female infertility. A fast lifestyle, environmental deterioration and accumulated understanding of this disease, have led to an increase in the incidence of DOR. Therefore, reasonable and effective treatment for DOR is particularly important to improve ovarian function and female life quality as well as reduce infertility. This mini review provides recent updates regarding DOR and a summary of advancements in the treatment of DOR using Chinese and Western Medicine.


Altered SPECT (123)I-iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa.
Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using (123)I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). "Depression-Dejection" and "Confusion" POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered in children with AN. This may be a state-related change, which could be used to monitor and guide the treatment of eating disorders.


Age-dependent evaluation of long-term depression responses in hyperthyroid rats: Possible roles of oxidative intracellular redox status.
According to the free radical theory, a gradual accumulation of the free radicals normally produced in the body underlies the changes associated with aging. Thyroid hormones (THs) are related to oxidative stress not only due to their stimulation of metabolism but also due to their effects on antioxidant mechanisms. Thyroid dysfunction increases with age; thus, changes in TH levels in elderly individuals could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear, based on current evidence regarding synaptic plasticity. Hippocampal long-term depression (LTD) and oxidative status in the hippocampus were evaluated at two different ages (2-3 and 12-14 months) in male rats. Rats were administered 0.2 mg/kg/day of l-thyroxine for 21 days starting at postnatal day 40 to induce hyperthyroidism. LTD was induced in the dentate gyrus using low frequency stimulation of the perforant pathway. Spectrophotometry was performed to measure catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, and total nitrite/nitrate (tNOx) and nitric oxide synthase (NOS) levels. A reliable LTD was elicited in young rats with hyperthyroidism, while the same protocol could induce a small magnitude of synaptic LTD in the absence of spike-LTD in control rats. In aged rats, controls did not express LTD, but a significant LTP of spike was induced in the absence of synaptic LTD in hyperthyroid rats. While CAT levels were significantly decreased, MDA levels were increased in the aged groups compared to the corresponding young groups. Young rats with euthyroidism had significantly lower GPx activity than each of the hyperthyroid groups. There was no significant difference in SOD levels among the groups. Compared with aged rats, young rats exhibited a hyperthyroidism-induced decrease in NOS levels. Nevertheless, neither the main effects of age and thyroxine administration nor the interaction between these factors reached significance for tNOx. These results indicate that hyperthyroidism-related changes in synaptic plasticity are modulated by aging. This modulation may explain the increased cognitive impairment in this disease at older ages, which probably depends on alterations in NOS levels.


On the Estimation of Disability-Free Life Expectancy: Sullivan' Method and Its Extension.
A rapidly aging population, such as the United States today, is characterized by the increased prevalence of chronic impairment. Robust estimation of disability-free life expectancy (DFLE), or healthy life expectancy, is essential for examining whether additional years of life are spent in good health and whether life expectancy is increasing faster than the decline of disability rates. Over 30 years since its publication, Sullivan's method remains the most widely used method to estimate DFLE. Therefore, it is surprising to note that Sullivan did not provide any formal justification of his method. Debates in the literature have centered around the properties of Sullivan's method and have yielded conflicting results regarding the assumptions required for Sullivan's method. In this article we establish a statistical foundation of Sullivan's method. We prove that, under stationarity assumptions, Sullivan's estimator is unbiased and consistent. This resolves the debate in the literature, which has generally concluded that additional assumptions are necessary. We also show that the standard variance estimator is consistent and approximately unbiased. Finally, we demonstrate that Sullivan's method can be extended to estimate DFLE without stationarity assumptions. Such an extension is possible whenever a cohort life table and either consecutive cross-sectional disability surveys or a longitudinal survey are available. Our empirical analysis of the 1907 and 1912 U.S. birth cohorts suggests that while mortality rates remain approximately stationary, disability rates decline during this time period.


Effects of audibility and multichannel wide dynamic range compression on consonant recognition for listeners with severe hearing loss.
This study examined the effects of multichannel wide-dynamic range compression (WDRC) amplification and stimulus audibility on consonant recognition and error patterns. Listeners had either severe or mild to moderate sensorineural hearing loss. Each listener was monaurally fit with a wearable hearing aid using typical clinical procedures, frequency-gain parameters, and a hybrid of clinically prescribed compression ratios for desired sensation level () and NAL-NL (). Consonant-vowel nonsense syllables were presented in soundfield at multiple input levels (50, 65, 80 dB SPL). Test conditions were four-channel fast-acting WDRC amplification and a control compression limiting (CL) amplification condition. Listeners identified the stimulus heard from choices presented on an on-screen display. A between-subject repeated measures design was used to evaluate consonant recognition and consonant confusion patterns. Fast-acting WDRC provided a considerable audibility advantage at 50 dB SPL, especially for listeners with severe hearing loss. Listeners with mild to moderate hearing loss received less audibility improvement from the fast-acting WDRC amplification, for conversational and high level speech, when compared with listeners with severe hearing loss. Analysis of WDRC benefit scores revealed that listeners had slightly lower scores with fast-acting WDRC amplification (relative to CL) when WDRC provided minimal improvement in audibility. The negative effect was greater for listeners with mild to moderate hearing loss compared with their counterparts with severe hearing loss. All listeners, but particularly the severe loss group, benefited from fast-acting WDRC amplification for low-level speech. For conversational and higher speech levels (i.e., when WDRC does not confer a significant audibility advantage), fast-acting WDRC amplification seems to slightly degrade performance. Listeners' consonant confusion patterns suggest that this negative effect may be partly due to fast-acting WDRC-induced distortions, which alter specific consonant features. In support of this view, audibility accounted for a greater percentage of the variance in listeners' performance with CL amplification compared with fast-acting WDRC amplification.


Suppressed Methionine γ-Lyase Expression Causes Hyperaccumulation of S-Methylmethionine in Soybean Seeds.
Several soybean (Glycine max) germplasms, such as Nishiyamahitashi 98-5 (NH), have an intense seaweed-like flavor after cooking because of their high seed S-methylmethionine (SMM) content. In this study, we compared the amounts of amino acids in the phloem sap, leaves, pods, and seeds between NH and the common soybean cultivar Fukuyutaka. This revealed a comparably higher SMM content alongside a higher free Met content in NH seeds, suggesting that the SMM-hyperaccumulation phenotype of NH soybean was related to Met metabolism in seeds. To investigate the molecular mechanism behind SMM hyperaccumulation, we examined the phenotype-associated gene locus in NH plants. Analyses of the quantitative trait loci in segregated offspring of the cross between NH and the common soybean cultivar Williams 82 indicated that one locus on chromosome 10 explains 71.4% of SMM hyperaccumulation. Subsequent fine-mapping revealed that a transposon insertion into the intron of a gene, Glyma.10g172700, is associated with the SMM-hyperaccumulation phenotype. The Glyma.10g172700-encoded recombinant protein showed Met-γ-lyase (MGL) activity in vitro, and the transposon-insertion mutation in NH efficiently suppressed Glyma.10g172700 expression in developing seeds. Exogenous administration of Met to sections of developing soybean seeds resulted in transient increases in Met levels, followed by continuous increases in SMM concentrations, which was likely caused by Met methyltransferase activity in the seeds. Accordingly, we propose that the SMM-hyperaccumulation phenotype is caused by suppressed MGL expression in developing soybean seeds, resulting in transient accumulation of Met, which is converted into SMM to avoid the harmful effects caused by excess free Met.


Effect of active control of electric potential of filter medium on depth filtration.
The effect of active control of electric potential of filter medium on depth filtration was explored experimentally. Activated carbon particles were selected as the conductive filter medium. The filter medium potential was controlled with an external DC power supply. Kaolin particles were used as the model suspended solid. The activated carbon and kaolin had negative zeta potential around neutral pH. When the filter medium potential against a counter electrode was greater than or equal to + 0.2 V, rejection rate of particles was 1.8 times higher than that when the potential was less than + 0.2 V. Thus adsorption of particles by interaction of electric double layers was enhanced by maintaining a positive charge on the filter media. Desorption of kaolin trapped on the filter media was also confirmed by changing the filter medium potential from positive to negative. The percentage of kaolin particles desorbed was 11% of the kaolin trapped on the filter media. The desorption rate was not high, but this technique will enhance refreshment of the filter media when combined with back washing.


Anti-malarial market and policy surveys in sub-Saharan Africa.
At a recent meeting (Sept 18, 2009) in which reasons for the limited access to artemisinin-based combination therapy (ACT) in sub-Saharan Africa were discussed, policy and market surveys on anti-malarial drug availability and accessibility in Burundi and Sierra Leone were presented in a highly interactive brainstorming session among key stakeholders across private, public, and not-for-profit sectors. The surveys, the conduct of which directly involved the national malaria control programme managers of the two countries, provides the groundwork for evidence-based policy implementation. The results of the surveys could be extrapolated to other countries with similar socio-demographic and malaria profiles. The meeting resulted in recommendations on key actions to be taken at the global, national, and community level for better ACT accessibility. At the global level, both public and private sectors have actions to take to strengthen policies that lead to the replacement of loose blister packs with fixed-dose ACT products, develop strategies to ban inappropriate anti-malarials and regulate those bans, and facilitate technology and knowledge transfer to scale up production of fixed-dose ACT products, which should be readily available and affordable to those patients who are in the greatest need of these medicines. At the national level, policies that regulate the anti-malarial medicines market should be enacted and enforced. The public sector, including funding donors, should participate in ensuring that the private sector is engaged in the ACT implementation process. Research similar to the surveys discussed is important for other countries to develop and evaluate the right incentives at a local level. At the community level, community outreach and education about appropriate preventive and treatment measures must continue and be strengthened, with service delivery systems developed within both public and private sectors, among other measures, to decrease access to ineffective and inappropriate anti-malarial medicines. What was clear during the meeting is that continuing commitment, strengthened interaction and transparency among various stakeholders, with focus on communities, national governments, and evidence-based policy and action are the only way to sustainably address the control of malaria, a disease which continues to have a significant health and socio-economic impact worldwide, particularly in sub-Saharan Africa. Details on the methodology employed in carrying out the studies discussed at this meeting, as well as more detailed results, data analysis and discussion of the studies are soon to be published.


Connections between prolactin and ovarian cancer.
Ovarian cancer (OC) is characterized by a high morbidity and mortality, highlighting a great need for a better understanding of biological mechanisms that affect OC progression and improving its early detection methods. This study investigates effects of prolactin (PRL) on ovarian cancer cells, analyzes PRL receptors (PRLR) in tissue micro arrays and relates PRLR expression to survival of ovarian cancer. A database, composed of transcript profiles from OC, was searched for PRLR expression and results were put in relation to survival. Expression of PRLR in OC tissue sections and OC cell lines SKOV3, OV2008 and OVSAHO was assessed using immunohistochemistry, western blots and quantitative real-time PCR. The biological function of PRLR was evaluated by proliferation, colony formation and wound healing assays. Levels of PRLR mRNA are related to survival; in epithelial OC a high PRLR mRNA expression is related to a shorter survival. Analysis of a tissue micro array consisting of 84 OC showed that 72% were positive for PRLR immuno-staining. PRLR staining tended to be higher in OC of high grade tumors compared to lower grades. PRLR mRNA and protein can further be detected in OC cell lines. Moreover, in vitro treatment with PRL significantly activated the JAK/STAT pathway. PRLR expression is associated with OC survivals. PRL and its receptor may play an onco-modulatory role and promote tumor aggressiveness in OC. Alternatively, increased PRLR levels may form a base for the development of PRLR antagonist or PRLR antagonist-drug conjugate to increase selective uptake of anti-cancer drugs.


The four ages of Down syndrome.
Down syndrome (DS) affects approximately 1 per 650-1000 live births and is the most common known genetic cause of intellectual disability. A highly significant change in the survival of people with DS has occurred during the last two generations, with life expectancy estimates increasing from 12 to nearly 60 years of age. Detailed information on 1332 people in Western Australia with DS was abstracted from a specialist statewide database for the period 1953-2000 and electronically linked with three other state or national health and mortality data sources and the state Birth Defects Registry. Over the last 25 years the percentage of women over 35 years giving birth increased from 4.8 to 18.6%, accompanied by an increase in the overall prevalence of DS from 1.1 to 2.9 per 1000 births. Four life stages of DS were identified: prenatal, childhood and early adulthood, adulthood, and senescence. Although pneumonia, or other types of respiratory infections, was the most common cause of death across the entire lifespan, ranging from 23% of deaths in adulthood to 40% in senescence, each life stage exhibited a particular profile of comorbidities. Congenital heart defects were common causes in childhood (13%) and adulthood (23%), whereas in senescence coronary artery disease (10%) and cardiac, renal, and respiratory failure (9%) were leading causes of mortality. A major re-appraisal in attitudes towards DS is required to ensure that the medical and social needs of people with the disorder are adequately met across their entire lifespan. In particular, specific recognition of the comorbidities that can arise at different ages is needed, accompanied by the provision of appropriate levels of care and management.


Cities may save some threatened species but not their ecological functions.
Urbanization is one of the main causes of biodiversity loss worldwide. Wildlife responses to urbanization, however, are greatly variable and, paradoxically, some threatened species may achieve much larger populations in urban than in natural habitats. Urban conservation hotspots may therefore help some species avoid regional or even global extinctions, but not conserve their often overlooked ecological functions in the wild. We aim to draw attention to this issue using two species of globally threatened parrots occurring in the Dominican Republic: the Hispaniolan amazon (Amazona ventralis) and the Hispaniolan parakeet (Psittacara chloropterus). We conducted a large-scale roadside survey in June 2017 across the country to estimate the relative abundance of parrots in natural habitats, rural habitats, and cities. We combined this with informal interviews with local people to collect information on past and current human impacts on parrot populations. We also looked for foraging parrots to assess their potential role as seed dispersers, an ecological function that has been overlooked until very recently. Relative abundances of both parrot species were negligible in rural areas and very low in natural habitats. They were generally between one and two orders of magnitude lower than that of congeneric species inhabiting other Neotropical ecosystems. Relative abundances were six times higher in cities than in natural habitats in the case of the Hispaniolan parakeet and three times higher in the case of the Hispaniolan amazon. People indicated hunting for a source food and to mitigate crop damage as causes of parrot population declines, and a vigorous illegal trade for parrots (131 individuals recorded, 75% of them poached very recently), mostly obtained from protected areas where the last small wild populations remain. We observed parrots foraging on 19 plant species from 11 families, dispersing the fruits of 14 species by carrying them in their beaks and consuming them in distant perching trees. They discarded undamaged mature seeds, with the potential to germinate, in 99.5% of cases (n = 306), and minimum dispersal distances ranged from 8 to 155 m (median = 37 m). The loss of ecological functions provided by some species when they disappear from natural habitats and only persist in cities may have long-term, unexpected effects on ecosystems. Our example demonstrates how two cities may soon be the last refuges for two endemic parrots if overharvesting continues, in which case their overlooked role as seed dispersers would be completely lost in nature. The functional extinction of these species could strongly affect vegetation communities in an island environment where seed-dispersal species are naturally scarce. While conservation plans must include urban populations of threatened species, greater efforts are needed to restore their populations in natural habitats to conserve ecological functions.


Analysis of hydrocyclone behaviors in the separation of particulates from highway rainfall runoff.
In this study, the separation behaviors of particles in highway rainfall runoff using a Ø7.5 cm hydrocyclone were examined. The volume fraction and the total suspended solids concentrations in the overflow and underflow from the hydrocyclone were analyzed. The results indicated that the overflow volume fraction increased with increasing operational pressure, but decreased with decreasing ratio of underflow outlet to inlet sizes (D(u)/D(i)), while the underflow volume fraction showed contrary behavior. The TSS concentration ratio between the overflow and inflow (TSS(over)/TSS(in)) decreased as a function of the operational pressure, while the corresponding ratio of underflow to inflow (TSS(under)/TSS(in)) increased. There was no visible difference in the TSS(over)/TSS(in) ratio with increasing D(u)/D(i) ratio but the TSS(under)/TSS(in) decreased sharply. The particle removal efficiency was affected mainly by the particle size. The hydrocyclone can work well using 1.6 m natural water head, and it is more space saving and more efficient in the separation of fine particles than the sedimentation method.


Comparison of visceral leishmaniasis diagnostic antigens in African and Asian Leishmania donovani reveals extensive diversity and region-specific polymorphisms.
Visceral leishmaniasis (VL), caused by infection with Leishmania donovani complex, remains a major public health problem in endemic regions of South Asia, East Africa, and Brazil. If untreated, symptomatic VL is usually fatal. Rapid field diagnosis relies principally on demonstration of anti-Leishmania antibodies in clinically suspect cases. The rK39 immunochromatographic rapid diagnostic test (RDT) is based on rK39, encoded by a fragment of a kinesin-related gene derived from a Brazilian L. chagasi, now recognised as L. infantum, originating from Europe. Despite its reliability in South Asia, the rK39 test is reported to have lower sensitivity in East Africa. A reason for this differential response may reside in the molecular diversity of the rK39 homologous sequences among East African L. donovani strains. Coding sequences of rK39 homologues from East African L. donovani strains were amplified from genomic DNA, analysed for diversity from the rK39 sequence, and compared to South Asian sequences. East African sequences were revealed to display significant diversity from rK39. Most coding changes in the 5' half of repeats were non-conservative, with multiple substitutions involving charge changes, whereas amino acid substitutions in the 3' half of repeats were conservative. Specific polymorphisms were found between South Asian and East African strains. Diversity of HASPB1 and HASPB2 gene repeat sequences, used to flank sequences of a kinesin homologue in the synthetic antigen rK28 designed to reduce variable RDT performance, was also investigated. Non-canonical combination repeat arrangements were revealed for HASPB1 and HASPB2 gene products in strains producing unpredicted size amplicons. We demonstrate that there is extensive kinesin genetic diversity among strains in East Africa and between East Africa and South Asia, with ample scope for influencing performance of rK39 diagnostic assays. We also show the importance of targeted comparative genomics in guiding optimisation of recombinant/synthetic diagnostic antigens.


Geriatric Patient Safety Indicators Based on Linked Administrative Health Data to Assess Anticoagulant-Related Thromboembolic and Hemorrhagic Adverse Events in Older Inpatients: A Study Proposal.
Frail older people with multiple interacting conditions, polypharmacy, and complex care needs are particularly exposed to health care-related adverse events. Among these, anticoagulant-related thromboembolic and hemorrhagic events are particularly frequent and serious in older inpatients. The growing use of anticoagulants in this population and their substantial risk of toxicity and inefficacy have therefore become an important patient safety and public health concern worldwide. Anticoagulant-related adverse events and the quality of anticoagulation management should thus be routinely assessed to improve patient safety in vulnerable older inpatients. This project aims to develop and validate a set of outcome and process indicators based on linked administrative health data (ie, insurance claims data linked to hospital discharge data) assessing older inpatient safety related to anticoagulation in both Switzerland and France, and enabling comparisons across time and among hospitals, health territories, and countries. Geriatric patient safety indicators (GPSIs) will assess anticoagulant-related adverse events. Geriatric quality indicators (GQIs) will evaluate the management of anticoagulants for the prevention and treatment of arterial or venous thromboembolism in older inpatients. GPSIs will measure cumulative incidences of thromboembolic and bleeding adverse events based on hospital discharge data linked to insurance claims data. Using linked administrative health data will improve GPSI risk adjustment on patients' conditions that are present at admission and will capture in-hospital and postdischarge adverse events. GQIs will estimate the proportion of index hospital stays resulting in recommended anticoagulation at discharge and up to various time frames based on the same electronic health data. The GPSI and GQI development and validation process will comprise 6 stages: (1) selection and specification of candidate indicators, (2) definition of administrative data-based algorithms, (3) empirical measurement of indicators using linked administrative health data, (4) validation of indicators, (5) analyses of geographic and temporal variations for reliable and valid indicators, and (6) data visualization. Study populations will consist of 166,670 Swiss and 5,902,037 French residents aged 65 years and older admitted to an acute care hospital at least once during the 2012-2014 period and insured for at least 1 year before admission and 1 year after discharge. We will extract Swiss data from the Helsana Group data warehouse and French data from the national health insurance information system (SNIIR-AM). The study has been approved by Swiss and French ethics committees and regulatory organizations for data protection. Validated GPSIs and GQIs should help support and drive quality and safety improvement in older inpatients, inform health care stakeholders, and enable international comparisons. We discuss several limitations relating to the representativeness of study populations, accuracy of administrative health data, methods used for GPSI criterion validity assessment, and potential confounding bias in comparisons based on GQIs, and we address these limitations to strengthen study feasibility and validity.


Parechoviruses in children: understanding a new infection.
Human parechoviruses (HPeVs) within the large and growing family of Picornaviridaeare common human pathogens associated with a wide spectrum of disease presentations. Although 10 different HPeV types have been published to date, there is increasing evidence for a specific role of HPeV type 3 (HPeV3) in severe neonatal disease. In this review, we will describe both the disease associations and underlying epidemiological and/or biological basis for the often marked differences in disease outcomes between HPeV types. Application of molecular-based diagnostic techniques has revealed an association between neonatal sepsis, encephalitis and hepatitis with HPeV3 but not with other parechovirus types. HPeV3 shows evidence for very recent emergence in human populations as well as inferred differences in cellular receptor usage. The recently discovered HPeV3 has been shown to play an important role in severe neonatal infections, observations possibly linked to its very recent emergence or possibly different cellular tropism that underlie its targeting of the most susceptible individuals. HPeV infections are currently under-diagnosed and should be considered in the clinical and diagnostic evaluation of severe neonatal disease presentations.


Single-channel properties of four calcium channel types in rat motoneurons.
Previous studies have demonstrated multiple components of whole-cell calcium currents in hypoglossal motoneurons (HMs); HMs possess a low-voltage-activated (LVA) current and three types of high-voltage-activated (HVA) calcium currents based on sensitivity to omega-Aga IVA, omega-Conotoxin GVIA (omega-CgTx) and dihydropyridine analogs (DHPs). In the present study, we recorded single-calcium channel activities from HMs using a cell-attached patch-clamp method and found four types of channels that could be discriminated based on kinetics, voltage dependency, DHP sensitivity, and single-channel conductances. The average single-channel conductances with 110 mM barium as a charge carrier were 7, 14, 20, and 28 pS. T-type channels had a single-channel conductance of 7 pS, activated at the most negative potentials for the calcium channels and inactivated during depolarization. L-type channels (DHP-sensitive channels) did not inactivate during depolarization and had a 28-pS single-channel conductance. Based on kinetics and sensitivity to holding potential, it is likely that the channels with conductances of 14 pS and 20 pS represent N-type and P-type channels, respectively. The N-type channel (14 pS) was sensitive to holding potential, showed modal gating, and inactivated during maintained depolarizations, whereas the P-type channel (20 pS) was rather insensitive to holding potential and did not inactivate during depolarization.


Student perspectives on problem-based learning in an occupational therapy curriculum: a multiyear qualitative evaluation.
Problem-based learning (PBL) is increasingly being used within health care professional educational programs to develop critical thinking skills via a learner-centered approach. However, few studies have evaluated the effect of participation in a PBL-centered curriculum on occupational therapy knowledge and skill development over time from the perspective of the students involved. This study examined student evaluations of the first three class cohorts participating in a PBL-based curriculum. A participatory action design study involving qualitative, student-led focus groups was conducted with 154 students across 2 years of the education program. Fourteen focus groups were audiotaped, and those audiotapes were transcribed by an outside expert, followed by two levels of analysis by program faculty members and a member check by student participants. Themes that emerged from the data analysis related to (a) defining elements of PBL, (b) the role of students and faculty members, (c) learning strategies used by students in a PBL versus traditional education program, (d) the challenges of a PBL approach, and (e) PBL's relationship to clinical reasoning and occupational therapy practice. Students perceived that a PBL approach adopted consistently across the curriculum contributed to the development of information management, critical reasoning, communication, and team-building skills; however, identified challenges were time and role management, information access, instructor versus PBL expectations and practices, and coping with the ambiguity of knowledge and reasoning.


Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
Protein kinases are pivotal regulators of cell signaling that modulate each other's functions and activities through site-specific phosphorylation events. These key regulatory modifications have not been studied comprehensively, because low cellular abundance of kinases has resulted in their underrepresentation in previous phosphoproteome studies. Here, we combine kinase-selective affinity purification with quantitative mass spectrometry to analyze the cell-cycle regulation of protein kinases. This proteomics approach enabled us to quantify 219 protein kinases from S and M phase-arrested human cancer cells. We identified more than 1000 phosphorylation sites on protein kinases. Intriguingly, half of all kinase phosphopeptides were upregulated in mitosis. Our data reveal numerous unknown M phase-induced phosphorylation sites on kinases with established mitotic functions. We also find potential phosphorylation networks involving many protein kinases not previously implicated in mitotic progression. These results provide a vastly extended knowledge base for functional studies on kinases and their regulation through site-specific phosphorylation.


Emergency department frequent user: pilot study of intensive case management to reduce visits and computed tomography.
Emergency department (ED) frequent users account for a large number of annual ED visits and often receive radiological studies as a part of their evaluation. We report a pilot study of a case management program for ED frequent users to reduce ED usage and radiation exposure. This observational retrospective study was performed at a community hospital ED. Between May 2006 and April 2008, 96 patients were enrolled in a case management program and were followed through November 2008. The case management program consisted of a multi-disciplinary team of physicians, nurses, social services and specialists in pain management and behavioral health. Patients were enrolled if they had five or more visits to the ED in the previous month, if a concern about a patient's ED use was raised by staff, or if they were identified by the California prescription monitoring program. Case management addressed specific patient issues and assisted with receiving consistent outpatient care. The number of ED visits per patient and the number of radiological studies at each of these visits was recorded. When reviewing data for analysis, we used the number of total images in all computed tomography (CT) scans during the given time period. In the six months prior to enrollment, patients averaged 2.3 ED visits per patient per month. In the six months after enrollment, patients averaged 0.6 ED visits per patient per month (P<0.0001), and all visits after enrollment up to November 2008 averaged 0.4 visits per patient per month (P<0.0001). In the six months prior to enrollment, these patients averaged 25.6 CT images per patient per month. In the six months after enrollment, patients averaged 10.2 CT images per patient per month (P=0.001), and all CT images after enrollment up to November 2008 averaged 8.1 CT images per patient per month (P=0.0001). This represents a decrease in ED use by 83% and a decrease in radiation exposure by 67%. Case management can significantly reduce ED use by frequent users, and can also decrease radiation exposure from diagnostic imaging.


Differential Response of Wheat Cultivars to Pseudomonas brassicacearum and Take-All Decline Soil.
2,4-Diacetylphloroglucinol (DAPG)-producing Pseudomonas spp. in the P. fluorescens complex are primarily responsible for a natural suppression of take-all of wheat known as take-all decline (TAD) in many fields in the United States. P. brassicacearum, the most common DAPG producer found in TAD soils in the Pacific Northwest (PNW) of the United States, has biological control, growth promoting and phytotoxic activities. In this study, we explored how the wheat cultivar affects the level of take-all suppression when grown in a TAD soil, and how cultivars respond to colonization by P. brassicacearum. Three cultivars (Tara, Finley, and Buchanan) supported similar rhizosphere population sizes of P. brassicacearum when grown in a TAD soil, however they developed significantly different amounts of take-all. Cultivars Tara and Buchanan developed the least and most take-all, respectively, and Finley showed an intermediate amount of disease. However, when grown in TAD soil that was pasteurized to eliminate both DAPG producers and take-all suppression, all three cultivars were equally susceptible to take-all. The three cultivars also responded differently to the colonization and phytotoxicity of P. brassicacearum strains Q8r1-96 and L5.1-96, which are characteristic of DAPG producers in PNW TAD soils. Compared with cultivar Tara, cultivar Buchanan showed significantly reduced seedling emergence and root growth when colonized by P. brassicacearum, and the response of Finley was intermediate. However, all cultivars emerged equally when treated with a DAPG-deficient mutant of Q8r1-96. Our results indicate that wheat cultivars grown in a TAD soil modulate both the robustness of take-all suppression and the potential phytotoxicity of the antibiotic DAPG.


Social capital and post-disaster mental health.
Despite national and international policies to develop social capital in disaster-affected communities, empiric evidence on the association between social capital and disaster mental health is limited and ambiguous. The study explores the relationship between social capital and disaster mental health outcomes (PTSD, anxiety, and depression) in combination with individual factors (appraisal, coping behavior, and social support). This is a community-based cross-sectional study in a flood-affected town in northern England. The study is part of the MICRODIS multi-country research project that examines the impact of natural disasters. It included 232 flood-affected respondents. The findings showed that a considerable part of the association between cognitive and structural social capital and mental health is exerted through individual appraisal processes (i.e. property loss, primary and secondary appraisal), social support, and coping behavior. These individual factors were contingent on social capital. After the inclusion of individual characteristics, cognitive social capital was negatively related to lower mental health problems and structural social capital was positively associated to experiencing anxiety but not to PTSD or depression. Depression and anxiety showed a different pattern of association with both components of social capital. Individual oriented stress reducing interventions that use appraisal processes, social support, and coping as starting points could be more effective by taking into account the subjective experience of the social context in terms of trust and feelings of mutual support and reciprocity in a community. Findings indicate that affected people may especially benefit from a combination of individual stress reducing interventions and psychosocial interventions that foster cognitive social capital.


Plant Biology: Proteolytic Release of Damage Signals.
Plants protect their wounds against pathogen invasion by releasing damage signals that induce immune responses in neighboring cells. A new study shows that a conserved bioactive peptide is released from its cytoplasmic precursor upon wounding by a metacaspase that is activated by calcium influx into the injured cell.


Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis.
The reported incidence, prevalence and outcomes of atrial fibrillation (AF) in patients with end-stage renal disease (ESRD) are variable. The risks and benefits of warfarin anticoagulation need to be defined as the risk of bleeding in ESRD patients may overwhelm the benefits of embolic stroke prevention. We undertook a systematic literature review to clarify these issues. A literature search was undertaken using Medline and EMBASE from 1990 to September 2011. Studies that reported incidence, prevalence or selected outcomes in ESRD patients with AF were included. Cross-sectional, cohort and randomized controlled trials with >25 participants were included. The lists of authors and abstracts from the search were reviewed by two investigators to determine the manuscripts for full text review. Data were abstracted to a form designed specifically for this study. The quality of the studies was assessed using the Newcastle-Ottawa scale. Event rates were calculated using a random-effects model. Twenty-five studies met our inclusion criteria. The prevalence of AF was 11.6% and the overall incidence was 2.7/100 patient-years. The risk of mortality and stroke was increased in ESRD patients with AF at 26.9 and 5.2/100 patient-years versus 13.4 and 1.9/100 patient-years compared with ESRD patients without AF. The majority of studies do not support a protective effect for warfarin in ESRD patients with AF. The incidence and prevalence of AF in ESRD patients are higher than in the general population and are associated with an increased risk of stroke and mortality. An appropriately designed randomized controlled trial is required to determine whether anticoagulation is an appropriate therapeutic strategy in patients with end-stage renal disease and atrial fibrillation.


A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks.
One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the 'one child policy' and the 'empty-nest elderly' phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of 'exercising more, eating less', while other anti-ageing molecules from molecular gerontologists could help to improve 'healthspan' in the elderly. Machine learning, 'Big Data', and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).


ENIGMA-Viewer: interactive visualization strategies for conveying effect sizes in meta-analysis.
Global scale brain research collaborations such as the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium are beginning to collect data in large quantity and to conduct meta-analyses using uniformed protocols. It becomes strategically important that the results can be communicated among brain scientists effectively. Traditional graphs and charts failed to convey the complex shapes of brain structures which are essential to the understanding of the result statistics from the analyses. These problems could be addressed using interactive visualization strategies that can link those statistics with brain structures in order to provide a better interface to understand brain research results. We present ENIGMA-Viewer, an interactive web-based visualization tool for brain scientists to compare statistics such as effect sizes from meta-analysis results on standardized ROIs (regions-of-interest) across multiple studies. The tool incorporates visualization design principles such as focus+context and visual data fusion to enable users to better understand the statistics on brain structures. To demonstrate the usability of the tool, three examples using recent research data are discussed via case studies. ENIGMA-Viewer supports presentations and communications of brain research results through effective visualization designs. By linking visualizations of both statistics and structures, users can gain more insights into the presented data that are otherwise difficult to obtain. ENIGMA-Viewer is an open-source tool, the source code and sample data are publicly accessible through the NITRC website ( http://www.nitrc.org/projects/enigmaviewer_20 ). The tool can also be directly accessed online ( http://enigma-viewer.org ).


A review of ablative techniques in the treatment of breast fibroadenomata.
Breast fibroadenomata (FAD) are benign lesions which occur in about 10 % of all women. Diagnosis is made by triple assessment (physical examination, imaging and/or histopathology/cytology). For a definitive diagnosis of FAD, the treatment is conservative unless the patient is symptomatic. For symptomatic patients, the lumps can be surgically excised or removed interventionally by vacuum-assisted mammotomy (VAM). Ablative techniques like high-intensity focused ultrasound (HIFU), cryo-ablation and laser ablation have also been used for the treatment of FAD, providing a minimally invasive treatment without scarring or poor cosmesis. This review summarises current trials using minimally invasive ablative techniques in the treatment of breast FAD. A comprehensive review of studies using minimally invasive ablative techniques was performed. There are currently several trials completed or recruiting patients using HIFU, cryo-ablation and laser ablation in the treatment of breast FAD. The results look very promising but cannot be compared at this point due to heterogeneity between studies. Minimally invasive ablative techniques like HIFU, cryo-ablation and laser ablation are promising in the treatment of breast FAD. Future trials should be randomised and contain larger numbers of patients to determine the effectiveness of ablative techniques with more precision.


Using milk urea nitrogen to evaluate diet formulation and environmental impact on dairy farms.
Reducing nitrogen (N) excretion by dairy cattle is the most effective means to reduce N losses (runoff, volatilization, and leaching) from dairy farms. The objectives of this review are to examine the use of milk urea nitrogen (MUN) to measure N excretion and utilization efficiency in lactating dairy cows and to examine impacts of overfeeding N to dairy cows in the Chesapeake Bay drainage basin. A mathematical model was developed and evaluated with an independent literature data set to integrate MUN and milk composition to predict urinary and fecal excretion, intake, and utilization efficiency for N in lactating dairy cows. This model was subsequently used to develop target MUN concentrations for lactating dairy cattle fed according to National Research Council (NRC) recommendations. Target values calculated in this manner were 8 to 14 mg/dl for a typical lactation and were most sensitive to change in milk production and crude protein intake. Routine use of MUN to monitor dairy cattle diets was introduced to dairy farms (n = 1156) in the Chesapeake Bay watershed. Participating farmers (n = 454) were provided with the results of their MUN analyses and interpretive information monthly for a period of 6 months. The average MUN across all farms in the study increased in the spring, but the increase was 0.52 mg/dl lower for farmers receiving MUN results compared to those who did not participate in the program. This change indicated that participating farmers reduced N feeding compared to nonparticipants. Average efficiency of feed N utilization (N in milk / N in feed x 100) was 24.5% (SD = 4.5). On average, farmers fed 6.6% more N than recommended by the NRC, resulting in a 16% increase in urinary N and a 2.7% increase in fecal N compared to feeding to requirement. N loading to the Chesapeake Bay from overfeeding protein to lactating dairy cattle was estimated to be 7.6 million kg/year. MUN is a useful tool to measure diet adequacy and environmental impact from dairy farms.


Evaluation of prognostic factors and treatment modalities in ovarian cancer patients with brain metastases.
The objective of this study is to evaluate the impact of different clinical variables and treatment modalities on survival in patients with brain metastases from ovarian carcinoma. Methods included: (1) retrospective chart review of all patients with ovarian cancer and brain metastases from 1986 to 2000 at Roswell Park Cancer Institute and (2) Medline search was performed to extract data from all published reports with three or more cases of ovarian cancer with brain metastases. Cox regression analysis, Kaplan-Meier test, and log rank test were used to calculate survival and compare the impacts of clinical variables and treatment modalities. Fifteen patients with brain metastases out of 1042 women with ovarian carcinoma were identified from our institution, an incidence of 1.4%. The median time from initial diagnosis to detection of brain metastases was 22 months. Patients who were not treated after brain metastasis had a median survival of 0.5 month versus 6 months with therapy. In the subgroup of patients treated with a combination of radiation, surgery, and chemotherapy, the median survival was 22 months. Literature analysis combined with our data generated 124 patients. The only clinically significant variable impacting survival was the presence or absence of additional distant recurrence with median survivals of 3 and 8 months, respectively (P = 0.005). Among patients who received treatment, the combination of radiation and surgery with or without chemotherapy appears to be beneficial, with a median survival of 20 months (P < 0.001). Patients with brain metastases from ovarian cancer without any evidence of disease in other sites appear to benefit from aggressive combined treatment with external radiation and surgery with or without chemotherapy with a median survival of 20 months.


Human immunodeficiency virus type 1 infection increases the in vivo capacity of peripheral monocytes to cross the blood-brain barrier into the brain and the in vivo sensitivity of the blood-brain barrier to disruption by lipopolysaccharide.
Human immunodeficiency virus type 1 (HIV-1), introduced into the brain by HIV-1-infected monocytes which migrate across the blood-brain barrier (BBB), infects resident macrophages and microglia and initiates a process that causes HIV-1-associated neurocognitive disorders. The mechanism by which HIV-1 infection circumvents the BBB-restricted passage of systemic leukocytes into the brain and disrupts the integrity of the BBB is not known. Circulating lipopolysaccharide (LPS), which can compromise the integrity of the BBB, is significantly increased in HIV-1-infected individuals. We hypothesized that HIV-1 infection increases monocyte capacity to migrate across the BBB, which is further facilitated by a compromise of BBB integrity mediated by the increased systemic LPS levels present in HIV-1-infected individuals. To investigate this possibility, we examined the in vivo BBB migration of monocytes derived from our novel mouse model, JR-CSF/EYFP mice, which are transgenic for both a long terminal repeat-regulated full-length infectious HIV-1 provirus and ROSA-26-regulated enhanced yellow fluorescent protein. We demonstrated that JR-CSF/EYFP mouse monocytes displayed an increased capacity to enter the brain by crossing either an intact BBB or a BBB whose integrity was partially compromised by systemic LPS. We also demonstrated that the JR-CSF mouse BBB was more susceptible to disruption by systemic LPS than the control wild-type mouse BBB. These results demonstrated that HIV-1 infection increased the ability of monocytes to enter the brain and increased the sensitivity of the BBB to disruption by systemic LPS, which is elevated in HIV-1-infected individuals. These mice represent a new in vivo system for studying the mechanism by which HIV-1-infected monocytes migrate into the brain.


Ligand-mediated changes in conformational dynamics of NpmA: implications for ribosomal interactions.
Aminoglycosides are broad-spectrum antibiotics that bind to the 30S ribosomal subunit (30S) of bacteria and disrupt protein translation. NpmA, a structurally well-characterized methyltransferase identified in an E. coli clinical isolate, catalyzes methylation of 30S at A1408 of the 16S rRNA and confers aminoglycoside resistance. Using sucrose cushion centrifugation and isothermal titration calorimetry, we first confirmed the binding between NpmA and 30S. Next, we performed amide Hydrogen/Deuterium Exchange Mass Spectrometry (HDXMS) of apo NpmA and in the presence and absence of SAM/SAH. We observed that ligand binding resulted in time-dependent differences in deuterium exchange not only at the ligand-binding pocket (D25-D55 and A86-E112) but also in distal regions (F62-F82 and Y113-S144) of NpmA. These results provide insights into methylation group donor cofactor-mediated allostery in NpmA in the ligand-bound states, which could not be observed in the static endpoint crystal structures. We predict that the two distal sites in NpmA form part of the allosteric sites that importantly are part of the main 16S rRNA binding interface. Thus HDXMS helped uncover allosteric communication relays that couple SAM/SAH binding sites with the ribosome-binding site. This highlights how HDXMS together with X-ray crystallography can provide important allosteric insights in protein-ligand complexes.


Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial.
Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0-2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52-0·79) and those without diabetes (0·50, 0·35-0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45-0·73] vs 0·51 [0·34-0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53-0·92] vs 0·79 [0·40-1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56-0·98] vs 0·52 [0·29-0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51-0·78), glomerulonephritides (n=695; 0·43, 0·26-0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44-1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29-1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease. AstraZeneca.


Squaraine based solution processed inverted bulk heterojunction solar cells processed in air.
Inverted bulk heterojunction solar cells based on low temperature solution processed squaraine (SQ) and [6,6]-phenyl C71 butyric acid methyl-ester (PC71BM) with varying blend ratios were made in air. An optimized bulk heterojunction device of SQ and PC71BM (with a blend ratio of 1 : 6) showed a power conversion efficiency (PCE) of 2.45% with an incident photon to current conversion efficiency of 65% at 680 nm and a spectral window extending to the NIR region. The devices also showed an enhanced PCE value of 4.12% upon continuous illumination from an AM1.5G light source of intensity 1 Sun. The intensity dependent photocurrent studies showed a monomolecular recombination mechanism in the photovoltaic device performance. The device stored in air showed reasonable stability for a period of one month.


Aldehyde dehydrogenase expression in Metaphire posthuma as a bioindicator to monitor heavy metal pollution in soil.
Soil contamination and associated pollution plays a detrimental role in soil flora and fauna. Soil is processed and remodeled by subterranean earthworms, accordingly are referred to as soil chemical engineers. These worms, besides processing carbon and nitrogen, serve as minors for processing metals. In heavy metal contaminated soils, they accumulate heavy metals, which in turn cause altered gene expression, including aldehyde dehydrogenase (ALDH) enzymes. This study explores the possibility of ALDH expression in earthworms as a novel biomarker for the heavy metal contamination of soil. Earthworms cultured in contaminated soils accumulated significantly higher levels of Pb and Cd. Similarly, significantly higher levels of ALDH enzyme activities were observed in earthworms cultured in soils contaminated with Pb and Cd. The ALDH activity was found to be highest in worms cultured in 5 ppm heavy metal contaminated soils. Although, ALDH activities decreased as the heavy metal concentration in soil increased, they were significantly higher when compared to control worms cultured in uncontaminated soils. The accumulation of heavy metal in earthworms measured after 28 days decreased as the heavy metal concentration in soil increased. Levels of ALDH expression correlated with total Pb and Cd concentration in the earthworm tissue. This study showed that the ALDH activity in earthworms could potentially be used as a biomarker to show heavy metal pollution in soil.


Unidirectional signaling triggered through 2B4 (CD244), not CD48, in murine NK cells.
Engagement of 2B4 (CD244) with CD48 results in activation, costimulation, or inhibition of NK cell activities, depending on the cell types and the stage of differentiation. In vivo, 2B4+ NK cells can interact with CD48+ NK cells and also with surrounding CD48+ hematopoietic cells. Similarly, CD48+ NK cells may be triggered by adjacent 2B4+ NK cells or other hematopoietic cells expressing 2B4, e.g., monocytes, basophils, γδ T cells, etc. As CD48 was also shown to function as an activating receptor, 2B4/CD48 binding in the settings of NK-to-NK or NK-to-non-NK cell interactions may generate bidirectional signals. To address this question, we examined the consequence of CD48 or 2B4 ligation using two experimental settings: one with target (syngeneic EL4 and allogeneic P815) cells, ectopically expressing surface 2B4 or CD48, and the other with direct cross-linking with plate-bound mAb. Here, we report that ligation of CD48 with 2B4+ EL4 or 2B4+ P815 targets, in the absence of other receptor engagement, did not alter NK cell cytotoxicity or proliferation significantly. Similarly, cross-linking of NK cells with plate-bound anti-CD48 mAb in the absence or presence of a suboptimal dose of IL-2 did not modulate NK proliferation, cytotoxicity, or cytokine production. Nonetheless, 2B4 cross-linking promoted NK cell proliferation and effector functions consistently in both settings. Therefore, our results demonstrate unequivocally that CD48 on surrounding NK or non-NK cells serves primarily as a ligand to stimulate 2B4 on the adjacent NK cells in mice.


[Influence of helminthic infections and nutritional status on immune response in Venezuelan children].
We investigated the influence of nutritional status, as determined from anthropometric measurement, and of helminthic infections on the immune response of children of low socioeconomic status in two rural communities in Venezuela: El Cardón in the state of Nueva Esparta and San Daniel in the state of Miranda. A total of 125 boys and girls between 2 and 15 years old participated in the study. Their socioeconomic stratum was determined by a modified Graffar method. A physical examination was performed, as was also an anthropometric evaluation that took into account three indicators--weight-for-height, weight-for-age, and height-for-age--according to parameters established by the World Health Organization. Other examinations included feces, secretory IgA in saliva, total serum IgE, and anti-Ascaris-specific immunoglobulins. The children in both of the communities were in strata IV and V of the of Graffar scale, with a significantly greater number of stratum V inhabitants in San Daniel (P < 0.001). The results suggest that exposure level and individual susceptibility to the parasites are determining factors in parasitic infection and immune system behavior. The intensity of the parasitic burden plays an important role in stimulating polyclonal IgE, which diminishes the effectiveness of the specific response to those infections. On the other hand, nutritional deficiencies could change the immune mechanisms of the mucous membranes, negatively influence the synthesis of secretory IgA, and stimulate the production of polyclonal IgE. Poor sanitary and socioeconomic conditions promote more exposure to gastrointestinal parasites and a deficient nutritional status, which modulates the immune response and affects serum IgE and secretory IgA production mechanisms.


Multimodality imaging of intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinomas account for approximately 20% of cases of cholangiocarcinomas. Three growth patterns or morphologic subtypes exist, including mass-forming, periductal-infiltrating, and intraductal-growth subtypes. Knowledge of these morphologic subtypes and their radiologic appearance aids in timely diagnosis, a key to optimizing patient outcomes. The morphologic variability of intrahepatic cholangiocarcinomas has a direct impact on the diagnostic sensitivity and specificity of various diagnostic imaging modalities, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP), and positron emission tomography (PET). The following review emphasizes optimal imaging technique for each of these modalities and reviews the imaging appearance of each morphologic subtype of intrahepatic cholangiocarcinoma.


Force generation by kinesin and myosin cytoskeletal motor proteins.
Kinesins and myosins hydrolyze ATP, producing force that drives spindle assembly, vesicle transport and muscle contraction. How do motors do this? Here we discuss mechanisms of motor force transduction, based on their mechanochemical cycles and conformational changes observed in crystal structures. Distortion or twisting of the central β-sheet - proposed to trigger actin-induced Pi and ADP release by myosin, and microtubule-induced ADP release by kinesins - is shown in a movie depicting the transition between myosin ATP-like and nucleotide-free states. Structural changes in the switch I region form a tube that governs ATP hydrolysis and Pi release by the motors, explaining the essential role of switch I in hydrolysis. Comparison of the motor power strokes reveals that each stroke begins with the force-amplifying structure oriented opposite to the direction of rotation or swing. Motors undergo changes in their mechanochemical cycles in response to small-molecule inhibitors, several of which bind to kinesins by induced fit, trapping the motors in a state that resembles a force-producing conformation. An unusual motor activator specifically increases mechanical output by cardiac myosin, potentially providing valuable information about its mechanism of function. Further study is essential to understand motor mechanochemical coupling and energy transduction, and could lead to new therapies to treat human disease.


Hospital mergers and antitrust: an economic analysis.
The hospital industry has recently experienced substantial merger activity. This paper examines several actual and proposed hospital mergers to determine the extent of competition in the affected markets and the effect these mergers may have on competition. Our focus is on mergers between hospitals in the same market. We define the relevant product and geographic market for hospitals, then develop criteria for evaluating hospital mergers and analyze several merger cases using these criteria. We conclude that these mergers threaten the competition that exists in most of the markets discussed, and that the claimed efficiency justification for mergers is not convincing.


Determining the gluten content of nonprescription drugs: information for patients with celiac disease.
To determine whether the information on the gluten content of nonprescription drugs is readily available from the manufacturer/supplier, to identify how patients are directed on the product labeling to obtain answers to questions that they have about the nonprescription medication, and to determine the time needed to obtain information about the gluten content of the product when contacting manufacturers/suppliers. Descriptive, exploratory, nonexperimental study. United States during July 2010. Manufacturers/suppliers of 41 nonprescription drug products. The packaging of the products was reviewed for information on gluten content. The manufacturer/supplier listed on each product's packaging was contacted using the phone number provided and questioned about the gluten content of the product. A uniform script was used for the telephone inquiry. The responses provided and the duration of the phone calls were documented. The manufacturer's websites also were reviewed for pertinent information. Gluten status of products, time spent on phone to determine gluten status, and availability of online information regarding gluten status. Information concerning the gluten content was not included on any of the products' packaging. The mean time required to receive a response was 6.2 minutes (median 5 minutes). A total of 15 products were reported to be gluten free; 13 products were not tested, but the manufacturer/supplier stated that they did not add gluten to the products; 9 products did not have any gluten added by the manufacturer/ supplier, but no guarantee was made that the raw ingredients were gluten free; 2 products contained gluten; and 2 products had no available gluten status information. Gluten information was found on product websites for a total of six products. Four of those six websites indicated gluten status that was different from the information provided via the telephone call with the manufacturer. Information concerning the gluten content of many nonprescription drugs is relatively easy for patients to obtain if the manufacturer/supplier is contacted. Although the time to obtain a response was quite short for many of the inquiries, it took a substantial amount of time to receive the requested information from some of the companies.