Variable virological outcomes according to the center providing antiretroviral therapy within the PharmAdapt clinical trial.
Differences in virological response between HIV-infected patients at different study centers were analyzed as a substudy of PharmAdapt, a multicenter prospective randomized study to evaluate the utility of therapeutic drug monitoring after a genotypic-based treatment adaptation. After 12 weeks, the percentage of patients participating in PharmAdapt with HIV RNA < 200 copies/mL ranged from 17% to 69% between centers providing antiretroviral care. In a multivariate analysis, independent factors predictive of viral load <200 HIV RNA copies/mL at Week 12 included: lower baseline viral load, lower nonnucleoside reverse transcriptase inhibitor resistance, lower protease inhibitor resistance, and the center providing antiretroviral therapy. To evaluate the final factor, study sites were divided into two groups based on Week 12 HIV RNA values above or below the median. Using this definition, observed differences between centers included the use of stavudine, abacavir-, and/or efavirenz-based regimens and use of online expert advice.


The Listeria monocytogenes DnaK chaperone is required for stress tolerance and efficient phagocytosis with macrophages.
Listeria monocytogenes is a facultative intracellular pathogen which can escape bactericidal mechanisms and grow within macrophages. The intracellular environment of macrophages is one of the most stressful environments encountered by an invading bacterium during the course of infection. To study the role of the major stress protein, DnaK, of L. monocytogenes in survival under intracellular stress induced by macrophage-phagocytosis as well as under extracellular environmental stresses, we cloned, sequenced, and analyzed the dnaK locus from L. monocytogenes. Then we constructed an insertional mutation in the dnaK gene by homologous recombination and characterized it. Sequencing has revealed that the dnaK locus consists of four open reading frames in the order hrcA-grpE-dnaK-dnaJ. The mutant grows neither at temperatures above 39 degrees C nor under acidic conditions e.g. pH 3.0. Using the macrophage cell line JA-4, the ability of the dnaK mutant to grow intracellularly was examined. Immediately after phagocytosis, the number of viable dnaK mutant bacteria found within macrophages was significantly lower compared to that of intracellular wild type bacteria. However, following a 1-3 h latency period, the mutant multiplied in a similar fashion to the wild type within macrophage cells. A quantitative analysis of intracellular bacteria in macrophage cells by microscope and a binding assay of bacteria to the surface of macrophages by ELISA revealed that the lower number of viable dnaK mutant in macrophages after phagocytosis is due to the low efficiency of phagocytosis resulting from the reduced binding capacity of the dnaK mutant. These results demonstrate that DnaK of L. monocytogenes is essentially required for survival under high temperatures and acidic conditions. Though it does not largely contribute to the survival of L. monocytogenes in macrophage cells, it is essential for efficient phagocytosis. This is the first evidence that DnaK is required for the efficient phagocytosis of a facultative intracellular pathogen with macrophages.


Prescribed dietary phosphate restriction and survival among hemodialysis patients.
Hyperphosphatemia is common among hemodialysis patients. Although prescribed dietary phosphate restriction is a recommended therapy, little is known about the long-term effects on survival. We conducted a post hoc analysis of data from the Hemodialysis Study (n = 1751). Prescribed dietary phosphate was recorded at baseline and annually thereafter. Marginal structural proportional hazard models were fit to estimate the adjusted association between dietary phosphate restriction and mortality in the setting of time-dependent confounding. At baseline, prescribed daily phosphate was restricted to levels ≤ 870, 871 to 999, 1000, 1001 to 2000 mg, and not restricted in 300, 314, 307, 297, and 533 participants, respectively. More restrictive prescribed dietary phosphate was associated with poorer indices of nutritional status on baseline analyses and a persistently greater need for nutritional supplementation but not longitudinal changes in caloric or protein intake. On marginal structural analysis, there was a stepwise trend toward greater survival with more liberal phosphate prescription, which reached statistical significance among subjects prescribed 1001 to 2000 mg/d and those with no specified phosphate restriction: hazard ratios (95% CIs) 0.73 (0.54 to 0.97) and 0.71 (0.55 to 0.92), respectively. Subgroup analysis suggested a more pronounced survival benefit of liberal dietary phosphate prescription among nonblacks, participants without hyperphosphatemia, and those not receiving activated vitamin D. Prescribed dietary phosphate restriction is not associated with improved survival among prevalent hemodialysis patients, and increased level of restriction may be associated with greater mortality particularly in some subgroups.


Global and regional cerebral metabolic rate of 2-[18F]fluoro-2-deoxy-D-glucose in the presence of ofloxacin, a gamma-aminobutyric acid a receptor antagonist.
We investigated the effects of ofloxacin, a new antibacterial quinolone gamma-aminobutyric acid A receptor antagonist, on the global and regional cerebral metabolic rates of glucose (cMRgl). Twelve healthy normal male volunteers (mean age, 26.7 years) were studied in a double-blind, placebo-controlled protocol of 11 days' duration. Results of a total of 42 positron emission tomography studies were obtained for these subjects: 12 base line, 18 during placebo, and 12 during ofloxacin administration. The conditions under which repeat positron emission tomography studies of the same subject were performed were reproduced as closely as possible. cMRgl was measured in 24 brain regions. The global cMRgl for base line, placebo, and ofloxacin were 8.82 +/- 1.17, 8.24 +/- 1.17, and 8.79 +/- 1.18 mg/min/100 g, respectively (mean +/- 1 standard deviation). The mean global differences between base line and placebo and between ofloxacin and placebo were 5.1 and 6.6%, respectively. Analysis of variance of both the global and the regional cMRgl showed no statistical difference between base-line, placebo, and ofloxacin studies. Variations in cMRgl found in this study were not related to the presence of ofloxacin. Results of our study demonstrate that ofloxacin does not increase or decrease cMRgl beyond the limits of variability of the study.


Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease.
Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract remains the major cause of morbidity and nonrelapse mortality after BM transplantation (BMT). The Paneth cell protein regenerating islet-derived 3α (REG3α) is a biomarker specific for GI GVHD. REG3α serum levels rose in the systematic circulation as GVHD progressively destroyed Paneth cells and reduced GI epithelial barrier function. Paradoxically, GVHD suppressed intestinal REG3γ (the mouse homolog of human REG3α), and the absence of REG3γ in BMT recipients intensified GVHD but did not change the composition of the microbiome. IL-22 administration restored REG3γ production and prevented apoptosis of both intestinal stem cells (ISCs) and Paneth cells, but this protection was completely abrogated in Reg3g-/- mice. In vitro, addition of REG3α reduced the apoptosis of colonic cell lines. Strategies that increase intestinal REG3α/γ to promote crypt regeneration may offer a novel, nonimmunosuppressive approach for GVHD and perhaps for other diseases involving the ISC niche, such as inflammatory bowel disease.


Safety and efficacy of laparoscopic radical nephrectomy with manual specimen morcellation for stage cT1 renal-cell carcinoma.
Specimen morcellation during laparoscopic radical nephrectomy for renal-cell carcinoma is controversial, and supporting literature remains sparse. We seek to evaluate the safety and efficacy of morcellation for specimen removal after laparoscopic radical nephrectomy for management of renal lesions of malignant potential at a single institution. We retrospectively reviewed the records of all patients who underwent laparoscopic radical nephrectomy at Northwestern Memorial and Evanston Hospital from 2001 to 2006. Twenty-two patients were identified who underwent specimen morcellation for extraction after laparoscopic nephrectomy that was performed for enhancing solid or cystic renal masses. Laparoscopic radical nephrectomy was performed on all the patients. Patient age ranged from 36 to 96 years old. All patients were clinical stage T(1)N(0)M(0). The specimen was mechanically morcellated within Cook Lap Sac under direct and laparoscopic vision. Average tumor size after morcellation was 3.0 cm. On histologic review of the morcellated specimen, 18 patients were confirmed to have renal-cell carcinoma, 2 had an oncocytoma, and 2 had benign cysts. One patient with renal-cell carcinoma had a pathologic upgrade to stage T(3b). Average operating time was 268 minutes (range 110 to 389 min). With the exception of the patient who became anephric after nephrectomy, average hospital stay was 2.6 days. A mean clinical and radiographic follow-up of 434 days failed to show any known disease progression or port site recurrence in patients with renal-cell carcinoma. Intracorporeal, mechanical morcellation after laparoscopic radical nephrectomy appears to be safe and effective in clinical stage T1 renal-cell carcinoma. This study adds to current literature that promotes the use of morcellation as an alternative for intact specimen removal in properly selected patients. Further prospective studies are necessary to show long-term oncologic outcomes.


Using intervention mapping to design and implement a multicomponent intervention to improve antibiotic and NSAID prescribing.
Successfully changing prescribing behavior to reduce inappropriate antibiotic and nonsteroidal anti-inflammatory drug (NSAID) prescriptions often requires combining components into a multicomponent intervention. However, multicomponent interventions often fail because of development and implementation complexity. To increase the likelihood of successfully changing prescribing behavior, we applied a systematic process to design and implement a multicomponent intervention. We used Intervention Mapping to create a roadmap for a multicomponent intervention in unscheduled outpatient care settings in the Veterans Health Administration. Intervention Mapping is a systematic process consisting of six steps that we grouped into three phases: (i) understand behavioral determinants and barriers to implementation, (ii) develop the intervention, and (iii) define evaluation plan and implementation strategies. A targeted literature review, combined with 25 prescriber and 25 stakeholder interviews, helped identify key behavioral determinants to inappropriate prescribing (e.g. perceived social pressure from patients to prescribe). We targeted three desired prescriber behaviors: (i) review guideline-concordant prescribing and patient outcomes, (ii) manage diagnostic and treatment uncertainty, and (iii) educate patients and caregivers. The intervention consisted of components for academic detailing, prescribing feedback, and alternative prescription order sets. Implementation strategies consisted of preparing clinical champions, conducting readiness assessments, and incentivizing use of the intervention. We chose a mixed-method study design with a commonly used evaluation framework to assess effectiveness and implementation outcomes in a subsequent trial. This study furthers knowledge about causes of inappropriate antibiotic and NSAID prescribing and demonstrates how theoretical, empirical, and practical information can be systematically applied to develop a multicomponent intervention to help address these causes.


Riboflavin improves grain yield, 2-acetyl-1-pyrroline accumulation, and antioxidative properties of fragrant rice.
Riboflavin, a vital water-soluble vitamin with antioxidative activity, plays a critical role in maintaining overall bodily health and defense responses. However, its impact on fragrant rice yield and aroma remains unexplored. In a 2022 pot experiment with Meixiangzhan and Yuxiangyouzhan fragrant rice cultivars, we applied riboflavin foliar treatments at concentrations of 0 (CK), 10 (R10), 20 (R20), and 40 (R40) mg L-1 during the initial heading stage. Riboflavin increased rice yield, 2-acetyl-1-pyrroline (2-AP) content, and antioxidative properties. It boosted 2-AP level by 13.1-50.1% for Meixiangzhan and 22.3-35.3% for Yuxiangyouzhan, with the highest levels in R20 and R10 treatments. This increase is significantly correlated with elevated levels of proline, pyrroline-5-carboxylic acid, pyrroline, and methylglyoxal, as well as heightened enzyme activities, including those of proline dehydrogenase, ornithine aminotransferase, and pyrroline-5-carboxylic acid synthetase (P5CS). The R20 treatment resulted in the highest yield due to an improved seed-setting rate. Importantly, a positive correlation emerged between 2-AP content and yield, both significantly linked to superoxide dismutase, proline, hydrogen peroxide, P5CS, catalase, and pyrroline. Riboflavin maintained enzyme activities, regulated substance synthesis pathways, and increased 2-AP and yield, especially in the R20 treatment. These insights advance fragrant rice production theory by uncovering riboflavin's role in the development of fragrant rice. © 2023 Society of Chemical Industry.


Health burden and economic impact of measles-related hospitalizations in Italy in 2002-2003.
A large measles outbreak occurred in Italy in 2002-2003. This study evaluates the health burden and economic impact of measles-related hospitalizations in Italy during the specified period. Hospital discharge abstract data for measles hospitalizations in Italy during 2002-2003 were analysed to obtain information regarding number and rates of measles hospitalizations by geographical area and age group, length of hospital stay, and complications. Hospitalization costs were estimated on the basis of Diagnosis-Related Groups. A total of 5,154 hospitalizations were identified, 3,478 (67%) of which occurred in children <15 years of age. Most hospitalizations occurred in southern Italy (71 %) and children below 1 year of age presented the greatest hospitalization rates (46.2/100,000 and 19.0/100,000, respectively in 2002 and 2003). Pneumonia was diagnosed in 594 cases (11.5%) and encephalitis in 138 cases (2.7%). Total hospital charges were approximately euro 8.8 million. The nationwide health burden associated with measles during the 2002-2003 outbreak was substantial and a high cost was incurred by the Italian National Health Service for the thousands of measles-related hospitalizations which occurred. By assuming that hospital costs represent 40-50% of the direct costs of measles cases, direct costs of measles for the two years combined were estimated to be between 17.6-22.0 million euros, which equates to the vaccination of 1.5-1.9 million children (3-4 birth cohorts) with one dose of MMR. The high cost of measles and the severity of its complications fully justify the commitment required to reach measles elimination.


Short-term efficacy of reducing screen media use on physical activity, sleep, and physiological stress in families with children aged 4-14: study protocol for the SCREENS randomized controlled trial.
During the recent decade presence of digital media, especially handheld devices, in everyday life, has been increasing. Survey data suggests that children and adults spend much of their leisure on screen media, including use of social media and video services. Despite much public debate on possible harmful effects of such behavioral shifts, evidence from rigorously conducted randomized controlled trials in free-living settings, investigating the efficacy of reducing screen media use on physical activity, sleep, and physiological stress, is still lacking. Therefore, a family and home-based randomized controlled trial - the SCREENS trial - is being conducted. Here we describe in detail the rationale and protocol of this study. The SCREENS pilot trial was conducted during the fall of 2018 and spring of 2019. Based on experiences from the pilot study, we developed a protocol for a parallel group randomized controlled trial. The trial is being conducted from May 2019 to ultimo 2020 in 95 families with children 4-14 years recruited from a population-based survey. As part of the intervention family members must handover most portable devices for a 2-week time frame, in exchange for classic mobile phones (not smartphones). Also, entertainment-based screen media use during leisure must be limited to no more than 3 hours/week/person. At baseline and follow-up, 7-day 24-h physical activity will be assessed using two triaxial accelerometers; one at the right hip and one the middle of the right thigh. Sleep duration will be assessed using a single channel EEG-based sleep monitor system. Also, to assess physiological stress (only assessed in adults), parameters of 24-h heart rate variability, the cortisol awakening response and diurnal cortisol slope will be quantified using data sampled over three consecutive days. During the study we will objectively monitor the families' screen media use via different software and hardware monitoring systems. Using a rigorous study design with state-of-the-art methodology to assess outcomes and intervention compliance, analyses of data from the SCREENS trial will help answer important causal questions of leisure screen media habits and its short-term influence on physical activity, sleep, and other health related outcomes among children and adults. NCT04098913 at https://clinicaltrials.gov [20-09-2019, retrospectively registered].


Effective topical delivery systems for corticosteroids: dermatological and histological evaluations.
Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220-350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (∼13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.


Fully Electrical Post-Fabrication Trimming of Resistive Sensors.
A compact and efficient IC architecture is presented as an alternative to laser-trimmed precision thin-film resistors or look-up tables. The objective is to keep the device, such as a four-terminal Wheatstone bridge, but to compensate for post-manufacturing offset and to avoid the so-induced degradation of performances in terms of full-scale, non-linearity, power supply noise rejection and scale factor. Expected advantages are a reduced cost due to the electrical-only implementation and a possible on-field calibration of high-end sensors. Application of the proposed solution is illustrated on an example to demonstrate improvement factors on offset and sensitivity accuracy of 32 and 10, respectively. Additionally, the power supply rejection ratio is improved by 30 dB. The experimental results finally demonstrate both efficiency and versatility of the proposed solution thanks to a first silicon prototype, fabricated in a 0.35 μm Technology from AMS, connected to an off-the-shelf pressure sensor.


[Bilateral abscess of cavernous bodies].
Report of a rare case of abscess in both cavernous bodies. Its peculiarity is based on the location, the bilateral nature and the absence of a clear causative factor, although it was probably related of a local septic focus (rectal or prostatic). Diagnosis was established with CAT because of the primarily posterior location and the significant peripheral inflammatory reaction. The patient was treated successful with a vigorous antibiotic therapy and open drainage from both cavernous bodies with no development of sequelae such as fibrosis and penial incurvation or impotence.


Depression in Europe. Geographical distribution among older people.
This is the first report of results from the EURODEP Programme. To assess the prevalence of depression judged suitable for intervention in randomised samples of those aged > or = 65 in nine European centres. The GMS-AGECAT package. Differences in prevalence are apparent, 8.8% (Iceland) to 236% (Munich). When sub-cases and cases are added together, five high- and four low-scoring centres emerge. Women predominated over men. Proportions of sub-cases to cases revealed striking differences but did not explain prevalence. There was no constant association between prevalence and age. A meta-analysis (n = 13,808) gave an overall prevalence of 12.3%, 14.1% for women and 8.6% for men. Considerable variation occurs in the levels of depression across Europe, the cause for which is not immediately obvious. Case and sub-case levels taken together show greater variability, suggesting that it is not a matter of case/sub-case selection criteria, which were standardised by computer. Substantial levels of depression are shown but 62-82% of persons had no depressive level. Opportunities for treatment exist.


A charge-transfer-induced spin transition in a discrete complex: the role of extrinsic factors in stabilizing three electronic isomeric forms of a cyanide-bridged co/fe cluster.
A series of bimetallic, trigonal bipyramidal clusters of type {[Co(N-N)(2)](3)[Fe(CN)(6)](2)} are reported. The reaction of {Co(tmphen)(2)}(2+) with [Fe(CN)(6)](3)(-) in MeCN affords {[Co(tmphen)(2)](3)[Fe(CN)(6)](2)} (1). The cluster can exist in three different solid-state phases: a red crystalline phase, a blue solid phase obtained by exposure of the red crystals to moisture, and a red solid phase obtained by desolvation of the blue solid phase in vacuo. The properties of cluster 1 are extremely sensitive to both temperature and solvent content in each of these phases. Variable-temperature X-ray crystallography; (57)Fe Mossbauer, vibrational, and optical spectroscopies; and magnetochemical studies were used to study the three phases of 1 and related compounds, Na{[Co(tmphen)(2)](3)[Fe(CN)(6)](2)}(ClO(4))(2) (2), {[Co(bpy)(2)](3)[Fe(CN)(6)](2)}[Fe(CN)(6)](1/3) (3), and {[Ni(tmphen)(2)](3)[Fe(CN)(6)](2)} (4). The combined structural and spectroscopic investigation of 1-4 leads to the unambiguous conclusion that 1 can exist in different electronic isomeric forms, {Co(III)(2)Co(II)Fe(II)(2)} (1A), {Co(III)Co(II)(2)Fe(III)Fe(II)} (1B), and {Co(II)(3)Fe(III)(2)} (1C), and that it can undergo a charge-transfer-induced spin transition (CTIST). This is the first time that such a phenomenon has been observed for a Co/Fe molecule.


Person-Centered Interventions for Autistic Adolescents Ages 13-19 Years (2013-2021).
Systematic review briefs provide a summary of findings from systematic reviews developed in conjunction with the Evidence-Based Practice Program of the American Occupational Therapy Association. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings from a systematic review of family- and person-centered planning interventions for autistic1 adolescents aged 13-19 yr gathered from literature published between 2013 and 2021.


Sperm DNA Integrity is Unaffected by Thiopurine Treatment in Men With Inflammatory Bowel Disease.
Sperm DNA integrity, concentration, and motility are suspected to be altered by thiopurines (azathioprine [AZA] and 6-mercaptopurine [6-MP]). We investigated the impact of thiopurines on semen quality in men with inflammatory bowel disease [IBD], by a comprehensive panel of semen analyses. Semen from 40 men with IBD, in remission on AZA/6-MP therapy, was prospectively collected and compared with samples from 40 healthy volunteers. Paired samples [off and on AZA/6-MP] were obtained from a subset of IBD patients, and blood and semen were collected to determine 6-MP transmission to the ejaculate. Sperm DNA fragmentation was evaluated via sperm chromatin structure assay [SCSA] and Comet analysis. Conventional World Health Organization [WHO] parameters, i.e. semen volume and sperm concentration, motility, and morphology, were assessed. Additionally, we measured thioguanine nucleotide [TGN] incorporation in sperm cell DNA. Sperm DNA fragmentation levels did not differ between men with IBD on AZA/6-MP and healthy volunteers when evaluated by SCSA [p = 0.23] and Comet analysis [p = 0.72]. IBD patients on AZA/6-MP had significantly lower total and progressive sperm motility than healthy volunteers [48.5% versus 64.5%, p = 0.0003; 27.4% versus 43.3%, p = 0.0004; respectively], with no differences in concentration, volume, or morphology. The same trend was observed in the 10 paired samples. TGN incorporation was not detectable in sperm DNA, but 6-MP was detected in seminal plasma and correlated to blood levels [rs = 0.79, p = 0.02]. Thiopurines do not increase sperm DNA fragmentation but may impair sperm motility in this IBD cohort. Our findings support existing epidemiological data that thiopurine therapy is safe during preconception and should not be abandoned.


Intrinsic innervation of the urinary bladder of kangaroo and albino rats.
A comparative study of the intrinsic innervation in desert rodents (kangaroo rats) and others (albino rats) was carried out in an attempt to understand the functional anatomy of the bladder in these animals which are known to sustain severe water restraint. The bladder of the albino rat was innervated by predominantly thin nerves, more numerous beaded endings and few ganglia. That of the kangaroo rat had more numerous thick nerves (pre-ganglionic), large verve trunks, and ganglia which were extensively distributed in the wall. These findings indicate that the bladder of the albino rat depends mainly on the intrinsic innervation and facilatory micturition reflexes, while that of the kangaroo rat is intrinsically regulated, depending on a short neuron system. It was concluded that all the structural differences found might be essential for constant urine retention.


Asymmetric effects of native and exotic invasive shrubs on ecology of the West Nile virus vector Culex pipiens (Diptera: Culicidae).
Exotic invasive plants alter the structure and function of native ecosystems and may influence the distribution and abundance of arthropod disease vectors by modifying habitat quality. This study investigated how invasive plants alter the ecology of Culex pipiens, an important vector of West Nile virus (WNV) in northeastern and midwestern regions of the United States. Field and laboratory experiments were conducted to test the hypothesis that three native leaf species (Rubus allegheniensis, blackberry; Sambucus canadensis, elderberry; and Amelanchier laevis, serviceberry), and three exotic invasive leaf species (Lonicera maackii, Amur honeysuckle; Elaeagnus umbellata, autumn olive; and Rosa multiflora, multiflora rose) alter Cx. pipiens oviposition site selection, emergence rates, development time, and adult body size. The relative abundance of seven bacterial phyla in infusions of the six leaf species also was determined using quantitative real-time polymerase chain reaction to test the hypothesis that variation in emergence, development, and oviposition site selection is correlated to differences in the diversity and abundance of bacteria associated with different leaf species, important determinants of nutrient quality and availability for mosquito larvae. Leaf detritus from invasive honeysuckle and autumn olive yielded significantly higher adult emergence rates compared to detritus from the remaining leaf species and honeysuckle alleviated the negative effects of intraspecific competition on adult emergence. Conversely, leaves of native blackberry acted as an ecological trap, generating high oviposition but low emergence rates. Variation in bacterial flora associated with different leaf species may explain this asymmetrical production of mosquitoes: emergence rates and oviposition rates were positively correlated to bacterial abundance and diversity, respectively. We conclude that the displacement of native understory plant species by certain invasive shrubs may increase production of Cx. pipiens with potential negative repercussions for human and wildlife health. These findings may be relevant to mosquito control and invasive plant management practices in the geographic range of Cx. pipiens. Further, our discovery of a previously unknown ecological trap for an important vector of WNV has the potential to lead to novel alternatives to conventional insecticides in mosquito control by exploiting the apparent "attract-kill" properties of this native plant species.


The Birthday Party Test (BPT): A new picture description test to support the assessment of simultanagnosia in patients with acquired brain injury.
There is broad consensus on the utility of complex pictures in the assessment of simultanagnosia in patients with acquired brain injury (ABI). To overcome various shortcomings of current instruments, we have developed the Birthday Party Test (BPT); a picture description test that contains a neutral scene, a balanced representation of events, and provides clear instructions and a scoring-aid. We have applied the BPT in a large group of patients with ABI (n = 502) and in an age-matched healthy control group (n = 194). Our results show that performance on the BPT was associated with a range of descriptive, neuropsychological and clinical characteristics and that poor test performance appeared to be more common in patients with etiologies that have an increased risk of bilateral damage. Furthermore, we assume a high correspondence between test performance on the BPT and the assessor's clinical judgment of likely having simultanagnosia in preliminary analyses. This study shows the potential usefulness of the BPT to support diagnostic decision making in simultanagnosia. The BPT is made freely available to facilitate its broad application in the clinical assessment of patients with visual impairment and to enable a further evaluation of its utility and validity in future studies.


The management of a completely edentulous patient with tardive dyskinesia.
Tardive dyskinesia (TD) is an involuntary movement disorder of neurologic origin caused by the use of neuroleptic drugs known as dopamine receptor antagonists. The condition may adversely affect prosthodontic interventions and their possible merits. In this case history description, the rigor of scrupulous history-taking and clinical evaluation of patients with TD or neurologic disorders is emphasized. The successful prosthodontic management of a 74-year-old completely edentulous TD patient is presented, with the conclusion that a prosthodontic intervention may aid symptom reduction and contribute to improvement in a TD patient's quality of life.


Prevalence and incidence of severe sepsis in Dutch intensive care units.
Severe sepsis is a dreaded consequence of infection and necessitates intensive care treatment. Severe sepsis has a profound impact on mortality and on hospital costs, but recent incidence data from The Netherlands are not available. The purpose of the present study was to determine the prevalence and incidence of severe sepsis occurring during the first 24 hours of admission in Dutch intensive care units (ICUs). Forty-seven ICUs in The Netherlands participated in a point prevalence survey and included patients with infection at the time of ICU admission. Clinical symptoms of severe sepsis during the first 24 hours of each patient's ICU stay were recorded and the prevalence of severe sepsis was calculated. Then, the annual incidence of severe sepsis in The Netherlands was estimated, based on the prevalence, the estimated length of stay, and the capacity of the participating ICUs relative to the national intensive care capacity. The participating ICUs had 442 beds available for admissions, which was estimated to be 42% of the national ICU capacity. At the time of the survey, 455 patients were currently admitted and 151 were included in the analysis; 134 (29.5%) patients met criteria for severe sepsis. The most common failing organ system was the respiratory system (90%), and most patients were admitted following surgery (37%) and were admitted because of acute infection (62%). The most prevalent source of infection was the lung (47%). The estimated duration of ICU stay for severe sepsis patients was 13.3 +/- 1.1 days. The annual number of admissions for severe sepsis in Dutch ICUs was calculated at 8643 +/- 929 cases/year, which is 0.054% of the population, 0.61% of hospital admissions and 11% of ICU admissions.


Bilateral acetabular fractures induced by an epileptic seizure in a paediatric patient: a unique case and its management.
Bilateral acetabular fractures following epileptic seizures are a rare but known occurrence in adults, with an 18.5% mortality rate. These fractures occurring post epileptic seizures have not been previously documented in children. We report a case of a 13-year-old boy who presented to hospital via ambulance following two violent generalised tonic-clonic seizures in a postictal state, metabolically acidotic and a low haemoglobin. Acute abdomen was suspected and the patient underwent a CT scan which showed bilateral acetabular fractures with central dislocations of both femoral heads and free fluid in the abdomen. The patient underwent initial damage control intervention with insertion of bilateral distal femur skeletal traction. Definitive fixation of the acetabular fractures occurred 1 week later with an open reduction internal fixation with novel supra-pectineal plates using a Pfannenstiel incision. We use this report to increase awareness of significant pelvic injuries in paediatric patients post epileptic seizures.


Plasmid-linked ampicillin resistance in haempohilus influenza type b.
Four ampicillin-resistant, beta-lactamase-producing strains of Haempohilus influenzae type b were examined for the presence of plasmid deoxyribonucleic acid (DNA). Three resistant strains contained a 30 x 10-6-dalton (30Mdal) plasmid and one resitant strain contained a 3-Mdal plasmid. The ampicillin-sensitive Haemophilus strains examined did not contain plasmid DNA. Transformation of a sensitive H. influenzae strain to ampicillin resistance with isolated plasmid DNA preparations revealed that the structural gene for beta-lactamase resided on both plasmid species. DNA-DNA hybridization studies showed that the 30-Mdal Haemophilus plasmid contained the ampicillin translocation DNA segment (TnA) found on some R-factors of enteric origin of the H. influenzae plasmids.


[Uterine prolapse after episiotomy].
The value of episiotomy in regard to the prevention of descensus vagina et uteri is examined in a statistically reliable number of patients (64 cases). Women who were delivered without episiotomy provided the control group (70 cases). In both groups factors promoting pelvic relaxation were taken into consideration. According to the results of this examination the importance of episiotomy as prophylaxis of pelvic relaxation does not justify any obligatory use.


Hyponatremia due to psychotropic drugs.
The syndrome of hyponatremia in psychiatric patients is described, and cases associated with psychotropic drug treatment are reviewed. The causative role of the drug should be documented by rechallenge or a water loading test. In some instances it is possible to continue psychotropic treatment by restricting fluids or administering demeclocycline.


Mechanism of arginine-stimulated Ca2+ influx into pancreatic B cell.
The mechanism by which arginine stimulates Ca2+ inflow into the pancreatic B cell was investigated. Arginine (10 mM) increased 86Rb outflow from perifused rat pancreatic islets, suggesting that arginine-stimulated Ca2+ influx into the B cell does not result from a decrease in K+ conductance. Arginine stimulated Ca2+ uptake in isolated islets over short incubation periods and increased 45Ca outflow from perifused islets in a Ca2+-dependent manner. The calcium channel blocker verapamil inhibited both arginine-stimulated 45Ca uptake and 45Ca outflow. However, the sensitivity toward verapamil of arginine-stimulated islets was lower than that of islets stimulated by 20 mM K+, which gates voltage-sensitive Ca2+ channels. It was similar to that of islets stimulated by 8.3 mM glucose, which is thought to mainly gate voltage-insensitive Ca2+ channels. It is suggested that arginine stimulates Ca2+ inflow into the B cell by gating voltage-insensitive Ca2+ channels. The arginine-induced stimulation of Ca2+ inflow could participate in the depolarizing action of the amino acid on the B cell membrane.


Financial model calibration using consistency hints.
We introduce a technique for forcing the calibration of a financial model to produce valid parameters. The technique is based on learning from hints. It converts simple curve fitting into genuine calibration, where broad conclusions can be inferred from parameter values. The technique augments the error function of curve fitting with consistency hint error functions based on the Kullback-Leibler distance. We introduce an efficient EM-type optimization algorithm tailored to this technique. We also introduce other consistency hints, and balance their weights using canonical errors. We calibrate the correlated multifactor Vasicek model of interest rates, and apply it successfully to Japanese Yen swaps market and US dollar yield market.


Assessing the impact of corn variety and Texas terroir on flavor and alcohol yield in new-make bourbon whiskey.
The whiskey industry is dominated by whiskey styles with recipes that contain corn as the primary grain. However, little research has been conducted to investigate whiskey specific distinctions arising from different corn varieties and growing environments (i.e. terroir). Further, no studies have investigated the aroma or flavor impacts of different varieties and terroirs. Here, three different commodity yellow dent hybrid corn varieties were grown on different farms in Texas, spanning from the Texas Panhandle to the Mexico-United States border. Using novel small-batch mashing techniques, a newly developed new-make (i.e. unaged whiskey,immediate by-product of distillation) bourbon sensory lexicon, a trained sensory panel, high-performance liquid chromatography, and gas chromatography-mass spectrometry/olfactometry (GC-MS/O), we report for the first time a method for evaluating sample effects on alcohol yield and flavor in new-make bourbon whiskey. We discover that variety, terroir and their interactions, previously ignored, can substantially affect valuable sensory aspects of whiskey, suggesting the importance of scientifically evaluating corn genetics and agronomy for developing better whiskey. Excitingly, our data suggest milled corn with higher levels of benzadehyde, readily measured by GC-MS/O, correlates with improved sensory aspects of distillate, which must be expensively evaluated using a trained human sensory panel.


Maternal microvascular dysfunction during preeclamptic pregnancy.
Preeclampsia is a hypertensive disorder of pregnancy effecting ∼5-8% of pregnancies in the United States, and ∼8 million pregnancies worldwide. Preeclampsia is clinically diagnosed after the 20th week of gestation and is characterized by new onset hypertension accompanied by proteinuria and/or thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual symptoms. This broad definition emphasizes the heterogeneity of the clinical presentation of preeclampsia, but also underscores the role of the microvascular beds, specifically the renal, cerebral, and hepatic circulations, in the pathophysiology of the disease. While the diagnostic criteria for preeclampsia relies on the development of de novo hypertension and accompanying clinical symptoms after 20-week gestation, it is likely that subclinical dysfunction of the maternal microvascular beds occurs in parallel and may even precede the development of overt cardiovascular symptoms in these women. However, little is known about the physiology of the non-reproductive maternal microvascular beds during preeclampsia, and the mechanism(s) mediating microvascular dysfunction during preeclamptic pregnancy are largely unexplored in humans despite their integral role in the pathophysiology of the disease. Therefore, the purpose of this review is to provide a summary of the existing literature on maternal microvascular dysfunction during preeclamptic pregnancy by reviewing the functional evidence in humans, highlighting potential mechanisms, and providing recommendations for future work in this area.


Effects of castration and chronic morphine administration on liver alcohol dehydrogenase and the metabolism of ethanol in the male Sprague-Dawley rat.
The effects of castration on liver alcohol dehydrogenase (ADH) activity and the in vivo metabolism of ethanol were examined in the male Sprague-Dawley-derived rat. It was found that castration led to immediate (24 hr) increases in the ADH-dependent metabolism of ethanol which persisted for at least 6 weeks postcastration. Testosterone completely reversed the effects of castration. Moreover, when increases in liver ADH activity and the metabolism of ethanol were allowed to develop to maximal levels (2 weeks), a single s.c. injection of testosterone promptly reversed the effects of castration, such that by 24 hr castrated animals were indistinguishable from controls. Thus, it appears that in the male Sprague-Dawley-derived rat liver ADH activity and the in vivo metabolism of ethanol are under the control of testosterone. Because narcotics have also been shown to depress serum testosterone levels, and there is good evidence of significant pharmacological and biochemical interactions between the narcotics and ethanol, we examined whether chronic administration of morphine led to testosterone-reversible increases in the ADH-dependent metabolic disposition of ethanol. We found that chronic morphine administration, at doses sufficient to markedly depress serum testosterone levels (> 85%), produced large increases in liver ADH activity and the clearance of ethanol. Concurrent administration of testosterone completely abolished this effect. These data may, therefore, provide the first evidence of a biochemical mechanism involved in the interactions between morphine and ethanol. Furthermore, our results suggest that drug-induced reductions in serum testosterone may serve as an important mechanism involved in the cross-tolerance observed between ethanol and many abused, sedative-hypnotic drugs which share the common ability to decrease serum testosterone.


Location and consequences of 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane uptake by Bacillus megaterium.
No detrimental effects of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) were observed when cells of Bacillus megaterium were grown from small inocula in nutrient media containing up to 100 mug of DDT/ml. However, when the ratio of DDT to biomass of resting cells was held constant, levels of DDT as low as 1 mug/ml (0.5 mug/mg of cell dry weight) enhanced the rate of death in the population. The lethal action of DDT was both time- and dose-dependent so that higher doses required less time to effect the same killing than did lower doses. Intact cells bound a maximum of about 1.7 mug of DDT/mg of cell dry weight, of which about 75% was localized in the protoplast membrane. Much of the bound DDT was subsequently lost to the suspending medium and the aqueous stability of the returned DDT was enhanced, possibly by association with solubilized cell materials. A small quantity of bound DDT was converted to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane, which was released from cells somewhat faster than DDT. Apparently the lethal action of DDT was related to its binding in the membrane, but respiration was not inhibited. The atypical macroscopic appearance of membranes isolated from treated cells suggested that cell death may result from altered membrane chemistry.


Rapid monoterpene induction promotes the susceptibility of a novel host pine to mountain pine beetle colonization but not to beetle-vectored fungi.
Chemical induction can drive tree susceptibility to and host range expansions of attacking insects and fungi. Recently, mountain pine beetle (Dendroctonus ponderosae Hopkins; MPB) has expanded its host range from its historic host lodgepole pine (Pinus contorta var. latifolia Douglas ex Loudon) to jack pine (Pinus banksiana Lamb) in western Canada. Beetle success in jack pine forests likely depends upon the suitability of tree chemistry to MPB and its symbiotic phytopathogenic fungi. In particular, how rapid induced defenses of jack pine affect MPB colonization and the beetle's symbionts is unknown. In the field, we characterized and compared differences in rapid induced phloem monoterpenes between lodgepole and jack pines in response to various densities of Grosmannia clavigera (Robinson-Jeffery and Davidson)-a MPB symbiotic fungus used to simulate beetle attack-inoculations. Overall, lodgepole pine had higher limonene and myrcene, but lower α-pinene, concentrations than jack pine. However, myrcene concentrations in jack pine increased with inoculation density, while that in lodgepole pine did not respond to density treatments. We compared the growth and reproduction of MPB's symbiotic fungi, G. clavigera, Ophiostoma montium (Rumford) von Arx and Leptographium longiclavatum Lee, Kim and Breuil, grown on media amended with myrcene, α-pinene and limonene at concentrations reflecting two induction levels from each pine species. Myrcene and α-pinene amendments inhibited the growth but stimulated the reproduction of G. clavigera, whereas limonene stimulated its growth while inhibiting its reproduction. However, the growth and reproduction of the other fungi were generally stimulated by monoterpene amendments. Overall, our results suggest that jack pine rapid induction could promote MPB aggregation due to high levels of α-pinene (pheromone precursor), a positive feedback of myrcene (pheromone synergist) and low levels of limonene (resistance). Jack pine is likely as susceptible to MPB-vectored fungi as lodgepole pine, indicating that jack pine induction will likely not adversely affect symbiont activities enough to inhibit the invasion of MPB into jack pine forests.


Orientation-dependent interfacial mobility governs the anisotropic swelling in lithiated silicon nanowires.
Recent independent experiments demonstrated that the lithiation-induced volume expansion in silicon nanowires, nanopillars, and microslabs is highly anisotropic, with predominant expansion along the <110> direction but negligibly small expansion along the <111> direction. The origin of such anisotropic behavior remains elusive. Here, we develop a chemomechanical model to study the phase evolution and morphological changes in lithiated silicon nanowires. The model couples the diffusive reaction of lithium with the lithiation-induced elasto-plastic deformation. We show that the apparent anisotropic swelling is critically controlled by the orientation-dependent mobility of the core-shell interface, i.e., the lithiation reaction rate at the atomically sharp phase boundary between the crystalline core and the amorphous shell. Our results also underscore the importance of structural relaxation by plastic flow behind the moving phase boundary, which is essential to quantitative prediction of the experimentally observed morphologies of lithiated silicon nanowires. The study sheds light on the lithiation-mediated failure in nanowire-based electrodes, and the modeling framework provides a basis for simulating the morphological evolution, stress generation, and fracture in high-capacity electrodes for the next-generation lithium-ion batteries.


Polymorphisms in the amino acid transporter solute carrier family 6 (neurotransmitter transporter) member 14 gene contribute to polygenic obesity in French Caucasians.
Positional candidate gene analysis of the obesity-linked chromosome Xq24 locus identified two obesity-associated single nucleotide polymorphisms (SNPs) in the membrane amino acid transporter encoding the SLC6A14 (solute carrier family 6 [neurotransmitter transporter], member 14) gene in the Finnish population. Since we previously reported a modest evidence of linkage for this region in French obese families, we analyzed these SNPs in 1,267 obese adult case and 649 lean control subjects. SNPs 20649 C>T (odds ratio 1.23, 95% CI 1.04-1.45; P = 0.013) and 22510 C>G (1.36, 1.16-1.59; P = 0.0001) were shown to be associated with obesity in the French population. In addition, pedigree disequilibrium test results showed a modest excess of both at-risk SNP alleles in affected offspring (P = 0.05 and P = 0.08 for SNPs 20649 C>T and 22510 C>G, respectively). The SNP 22510 C>G at-risk G allele was associated, both in adult women with moderate obesity and in 234 obese girls, with higher body fat and modified perception of hunger and satiety (0.003 < P < 0.06). In conclusion, these data confirm an association of the SLC6A14 gene locus with obesity.


[Mental health of homeless persons. Critical review of the Anglo-Saxon literature].
Because the visibility of homeless persons congregating in urban areas has increased since the 1980's, the relationship between homelessness and mental illness has caused more and more concern. A multitude of epidemiological surveys have been organized in Great Britain, Australia, Canada, and mainly in United States, and have attempted to evaluate scientifically the psychiatric morbidity of this population. This literature review reveals disparity of epidemiological methods in assessing the type and extent of mental illness among homeless adults. The lack of consensual definition of homelessness, the choice of different settings in which the research is organized (street, health centres, shelters), and the use of diverse instruments of psychiatric evaluation (diagnosis by clinician, by scale or by structured diagnostic interview) lead to a great disparity of the results. Thus, 1/3 of the homeless adults had prior history of psychiatric hospitalisation. Rates of psychosis range to 70% and it is estimated that 4% to 74% of the homeless persons suffer from affective disorders. Substance abuse disorder remains a problem for a significant number of these individuals, with a high frequency of dual diagnosis. Such divergent data highlight the anglo-saxon debate between those who accuse desinstitutionnalisation as a reason of homelessness, and those who blame the socioeconomic background.


Transplantation of Skeletal Muscle-Derived Sca-1+/PW1+/Pax7- Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction.
We have previously shown that skeletal muscle-derived Sca-1+/PW1+/Pax7- interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL/6 mice. 5 × 105 eGFP-labelled PICs (MI + PICs; n = 7) or PBS (MI-PBS; n = 7) were injected intramyocardially into the border zone. Sham mice (n = 8) were not subjected to MI, or the transplantation of PICs or PBS. BrdU was administered via osmotic mini-pump for 14 days. Echocardiography was performed prior to surgery (baseline), and 1-, 3- and 6-weeks post-MI and PICs transplantation. Mice were sacrificed at 6 weeks post-MI + PICs transplantation, and heart sections were analysed for fibrosis, hypertrophy, engraftment, proliferation, and differentiation of PICs. A significant (p < 0.05) improvement in ejection fraction (EF) and fractional shortening was observed in the MI-PICs group, compared to MI + PBS group at 6-weeks post MI + PICs transplantation. Infarct size/fibrosis of the left ventricle significantly (p < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (p < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 µM2 vs. 543.5 ± 26.6 µm2), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (p < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 1.0%). PICs expressed and secreted pro-survival and reparative growth factors, supporting a paracrine effect of PICs during recovery/remodeling. Skeletal muscle-derived PICs show significant reparative potential, attenuating cardiac remodelling following transplantation into the infarcted myocardium. PICs can be easily sourced from skeletal muscle and therefore show promise as a potential cell candidate for supporting the reparative and regenerative effects of cell therapies.


Surface Plasmon assisted Cu(x)O photocatalyst for pure water splitting.
In this paper, Cu(x)O photocatalyst on plasmonic nanoporous Au film is proposed to enhancing the H(2) evolution rate of pure water splitting. The nanoporous Au film can simultaneously provide surface-enhanced absorption and built-in potential. The reflection spectrum shows that the surface plasmon (SP) assisted absorption wavelength of the Cu(x)O on the nanoporous Au film can be modified by changing the annealing temperature. It is found that the enhancement of the H(2) evolution rate highly depends on the SP-assisted absorption. As the annealing temperature is 220 ° C, the H(2) evolution rate is 58 μmol hr(-1) under the condition that the device area is 0.25 cm(2).


Predicting Nodal Positivity in Women 70 Years of Age and Older with Hormone Receptor-Positive Breast Cancer to Aid Incorporation of a Society of Surgical Oncology Choosing Wisely Guideline into Clinical Practice.
One of the Society of Surgical Oncology Choosing Wisely guidelines recommends avoiding routine sentinel lymph node (SLN) surgery in clinically node-negative women ≥70 years of age with hormone receptor-positive (HR+) breast cancer. We sought to assess the impact of tumor stage and grade on nodal positivity, and to develop a model to identify patients at low-risk of nodal positivity to aid adoption of the guideline. We identified women ≥70 years of age with HR+ cN0 invasive breast cancer in the National Cancer Database (NCDB; 2010-2013) and examined the impact of tumor stage and grade on nodal positivity to identify low-risk combinations. A multivariable logistic regression model was developed to incorporate additional factors. The area under the curve (AUC) and relative risks (RR) were used to assess performance. Among 71,834 cases, the pathologic nodal positivity (pN+) rate was 15.3%. We identified low-risk criteria as grade 1, cT1mi-T1c (≤2.0 cm), or grade 2, cT1mi-T1b (≤1.0 cm), with pN+ rates of 7.8% compared with 22.3% in patients not meeting these criteria (RR 2.86, p < 0.001). On multivariable analysis, factors associated with pN+ status included clinical T stage, grade, and histology (each p < 0.001). The resulting model had AUC 0.70 and identified women with low predicted probability (<10%) of positive nodes, of whom 6.3% were pN+, versus 21.2% in those with predicted probability ≥10% (RR 3.34, p < 0.001). The simple clinical rule (grade 1, cT1mi-T1c, or grade 2, cT1mi-T1b), as well as the predictive model, both identify women at low risk of nodal positivity where SLN surgery can be omitted.


Extracellular Matrix Deposition Defines the Duration of Cell Sheet Assembly from Human Adipose-Derived MSC.
Cell sheet (CS) engineering using mesenchymal stromal cells (MSC) draws significant interest for regenerative medicine and this approach translates to clinical use for numerous indications. However, little is known of factors that define the timing of CS assembly from primary cultures. This aspect is important for planning CS delivery in autologous and allogeneic modes of use. We used a comparative in vitro approach with primary donors' (n = 14) adipose-derived MSCs and evaluated the impact of healthy subject's sex, MSC culture features (population doubling time and lag-phase), and extracellular matrix (ECM) composition along with factors related to connective tissue formations (α-SMA and FAP-α) on CS assembly duration. Using qualitative and quantitative analysis methods, we found that, in seeded MSCs, high contents of collagen I and collagen IV had a direct correlation with longer CS assembly duration. We found that short lag-phase cultures faster turned to a ready-to-use CS, while age, sex, fibronectin, laminin, α-SMA, and FAP-α failed to provide a significant correlation with the timing of assembly. In detachable CSs, FAP-α was negatively correlated with the duration of assembly, suggesting that its concentration rose over time and contributed to MSC activation, transitioning to α-SMA-positive myofibroblasts and ECM turnover. Preliminary data on cell density and collagen I deposition suggested that the TGF-β1 signaling axis is of pivotal importance for ECM composition and construct maturation.


PuTmiR: a database for extracting neighboring transcription factors of human microRNAs.
Some of the recent investigations in systems biology have revealed the existence of a complex regulatory network between genes, microRNAs (miRNAs) and transcription factors (TFs). In this paper, we focus on TF to miRNA regulation and provide a novel interface for extracting the list of putative TFs for human miRNAs. A putative TF of an miRNA is considered here as those binding within the close genomic locality of that miRNA with respect to its starting or ending base pair on the chromosome. Recent studies suggest that these putative TFs are possible regulators of those miRNAs. The interface is built around two datasets that consist of the exhaustive lists of putative TFs binding respectively in the 10 kb upstream region (USR) and downstream region (DSR) of human miRNAs. A web server, named as PuTmiR, is designed. It provides an option for extracting the putative TFs for human miRNAs, as per the requirement of a user, based on genomic locality, i.e., any upstream or downstream region of interest less than 10 kb. The degree distributions of the number of putative TFs and miRNAs against each other for the 10 kb USR and DSR are analyzed from the data and they explore some interesting results. We also report about the finding of a significant regulatory activity of the YY1 protein over a set of oncomiRNAs related to the colon cancer. The interface provided by the PuTmiR web server provides an important resource for analyzing the direct and indirect regulation of human miRNAs. While it is already an established fact that miRNAs are regulated by TFs binding to their USR, this database might possibly help to study whether an miRNA can also be regulated by the TFs binding to their DSR.


CD27 promotes survival of activated T cells and complements CD28 in generation and establishment of the effector T cell pool.
CD27, like CD28, acts in concert with the T cell receptor to support T cell expansion. Using CD27(-/-) mice, we have shown earlier that CD27 determines the magnitude of primary and memory T cell responses to influenza virus. Here, we have examined the relative contributions of CD27 and CD28 to generation of the virus-specific effector T cell pool and its establishment at the site of infection (the lung), using CD27(-/-), CD28(-/-), and CD27/CD28(-/-) mice. We find that primary and memory CD8+ T cell responses to influenza virus are dependent on the collective contribution of both receptors. In the primary response, CD27 and CD28 impact to a similar extent on expansion of virus-specific T cells in draining lymph nodes. CD27 is the principle determinant for accumulation of virus-specific T cells in the lung because it can sustain this response in CD28(-/-) mice. Unlike CD28, CD27 does not affect cell cycle activity, but promotes survival of activated T cells throughout successive rounds of division at the site of priming and may do so at the site of infection as well. CD27 was found to rescue CD28(-/-) T cells from death at the onset of division, explaining its capacity to support a T cell response in absence of CD28.


Food insecurity, COVID-19 and diets in Fiji - a cross-sectional survey of over 500 adults.
Food insecurity is associated with inadequate nutrition and increased rates of chronic disease. The primary aim of this study was to assess self-reported food insecurity and the perceived impact of COVID-19 on food security, in two regional districts of Central Fiji, as part of a broader program of work on strengthening and monitoring food policy interventions. The secondary aim was to explore the relationship between food insecurity and salt, sugar and fruit and vegetable intake. Seven hundred adults were randomly sampled from the Deuba and Waidamudamu districts of Viti Levu, Fiji. Interview administered surveys were conducted by trained research assistants with data collected electronically. Information was collected on demographics and health status, food security, the perceived impact of COVID-19 on food security, and dietary intake. Food insecurity was assessed using nine questions adapted from Fiji's 2014/5 national nutrition survey, measuring markers of food insecurity over the last 12 months. Additional questions were added to assess the perceived effect of COVID-19 on responses. To address the secondary aim, interview administered 24-hour diet recalls were conducted using Intake24 (a computerised dietary recall system) allowing the calculation of salt, sugar and fruit and vegetable intakes for each person. Weighted linear regression models were used to determine the relationship between food insecurity and salt, sugar and fruit and vegetable intake. 534 people participated in the survey (response rate 76%, 50.4% female, mean age 42 years). 75% (75.3%, 95% CI, 71.4 to 78.8%) of people reported experiencing food insecurity in the 12 months prior to the survey. Around one fifth of people reported running out of foods (16.8%, 13.9 to 20.2%), having to skip meals (19.3%, 16.2 to 22.9%), limiting variety of foods (19.0%, 15.9 to 22.5%), or feeling stressed due to lack of ability to meet food needs (19.5%, 16.4 to 23.0%). 67% (66.9%, 62.9 to 70.7%) reported becoming more food insecure and changing what they ate due to COVID-19. However, people also reported positive changes such as making a home garden (67.8%, 63.7 to 71.6%), growing fruit and vegetables (59.5%, 55.6 to 63.8%), or trying to eat healthier (14.7%, 12.0 to 18.0%). There were no significant associations between food insecurity and intakes of salt, sugar or fruit and vegetables. Participants reported high levels of food insecurity, exceeding recommendations for salt and sugar intake and not meeting fruit and vegetable recommendations, and becoming more food insecure due to COVID-19. Most participants reported making home gardens and/or growing fruit and vegetables in response to the pandemic. There is an opportunity for these activities to be fostered in addressing food insecurity in Fiji, with likely relevance to the Pacific region and other Small Island Developing States who face similar food insecurity challenges.


Studies on the enhancement of allergic lung sensitization by inhalation of ozone and sulfuric acid aerosol.
Air pollutants were found to enhance the allergic sensitization of mice to an inhaled antigen. Aerosolized ovalbumin was used to mimic the inhalation of an environmental allergen. In three experiments the antigenic contact was repeated at 4 to 7 times over a period of approximately a month. Groups of mice were intermittently exposed to ozone at 0.5 and 0.8 ppm, sulfuric acid aerosol (1 mg/m3), and a combination of the two air pollutants. Antigenically sensitized mice showed some evidence of atopic reactivity to the inhaled antigen, but the interpretation of these responses was difficult to evaluate by observation alone. Clear evidence of allergic sensitization was obtained by injecting the antigen intravenously and recording the instances of systemic anaphylaxis. Allergic mice demonstrated anaphylactic shock within a few minutes of the injection, and fatally shocked animals died within 20 to 40 min. Significant increases in the levels of sensitization were obtained in animals exposed to ozone and the combination of ozone and sulfuric acid aerosol.


An Efficient Bifunctional Electrocatalyst of Phosphorous Carbon Co-doped MOFs.
It is eager to develop high-performance and cheap bifunctional electrochemical catalysts for both of the oxygen reduction reaction (ORR) or oxygen evolution reaction (OER) for the energy crisis and environmental problems. Herein, we report a series of ZIF-derived Co-P-C co-doped polyhedral materials with a well-defined morphology. The optimized catalyst Co/P/MOFs-CNTs-700 exhibited favorable electrochemical activities with the lowest overpotential of 420 mV to achieve the current density of 10 mA cm-2 for OER and the half potential of 0.8 V for ORR in 0.1 M NaOH. The performance can be well improved by doping phosphorous resource which greatly changed its morphology. Meanwhile, the doped carbon resources also improve the conductivity, which makes it a promising bifunctional electrochemical catalyst and can be comparable with the commercial electrocatalysts.


The association between breastmilk oligosaccharides and faecal microbiota in healthy breastfed infants at two, six, and twelve weeks of age.
Several factors affect gut microbiota development in early life, among which breastfeeding plays a key role. We followed 24 mother-infant pairs to investigate the associations between concentrations of selected human milk oligosaccharides (HMOs) in breastmilk, infant faeces, and the faecal microbiota composition in healthy, breastfed infants at two, six and 12 weeks of age. Lactation duration had a significant effect on breastmilk HMO content, which decreased with time, except for 3-fucosyllactose (3FL) and Lacto-N-fucopentaose III (LNFP III). We confirmed that microbiota composition was strongly influenced by infant age and was associated with mode of delivery and breastmilk LNFP III concentration at two weeks, with infant sex, delivery mode, and concentrations of 3'sialyllactose (3'SL) in milk at six weeks, and infant sex and Lacto-N-hexaose (LNH) in milk at 12 weeks of age. Correlations between levels of individual breastmilk HMOs and relative abundance of OTUs found in infant faeces, including the most predominant Bifidobacterium OTUs, were weak and varied with age. The faecal concentration of HMOs decreased with age and were strongly and negatively correlated with relative abundance of OTUs within genera Bifidobacterium, Parabacteroides, Escherichia-Shigella, Bacteroides, Actinomyces, Veillonella, Lachnospiraceae Incertae Sedis, and Erysipelotrichaceae Incertae Sedis, indicating the likely importance of these taxa for HMO metabolism in vivo.


The incidence of neurologic injury in paediatric forearm fractures requiring manipulation.
This study sought to evaluate the incidence of neurologic injury in children referred for manipulation in our hospital. A retrospective chart analysis of the first 100 children to be referred with a fracture of any segment of the radius and/or ulna was performed. The incidence of neurologic injury was found to be 15.6%. Neurological injury occurs most frequently with distal physeal fractures with an incidence of 37%. Clinicians require a high index of suspicion when evaluating forearm fractures. If neurologic injury is missed at initial assessment, the child may not receive a prompt reduction, thus increasing the likelihood of long-term sequelae.


Respiratory bronchiolitis following long-term ozone exposure in bonnet monkeys: a morphometric study.
To quantitate the response of respiratory bronchiolar (RB) epithelium and peribronchiolar connective tissue (PCT) to chronic exposure to high ambient levels of ozone, two groups of 8 adult male bonnet monkeys each were subjected 8 h daily for one year to 0.64 ppm (UV standard) ozone or filtered air, respectively. Blocks of tissue selected throughout the lung and from first generation RBs following airway microdissection had the following significant exposure-related changes: 57% greater volume of RB in the lung, 27% smaller diameter of RB lumen, 179% thicker media and intima of peribronchiolar arterioles, 61% thicker RB epithelium, and 77% thicker PCT. The increase in thickness of the RB wall resulted primarily from an 84% increase in PCT, with the remainder from the epithelium. Estimates of cellular numerical density showed an 81% increase in cuboidal bronchiolar cells and an 87% decrease in type 1 pneumocytes in the exposed group. Cell volumes from serial section reconstruction showed significantly larger cuboidal bronchiolar (79%), ciliated (117%), and type 2 (66%) cells over controls. Significant PCT changes included more amorphous extracellular matrix (288%), neutrophils (1523%), and lymphocytes/plasma cells (307%). The number of fibroblasts and the volume of extracellular fibers were larger than control values by 44% and 31% in the exposed group, but these changes were not statistically significant. Centriacinar changes due to exposure to long-term, high ambient ozone in bonnet monkeys results in narrowing of respiratory bronchioles primarily by peribronchiolar inflammation (inflammatory cells, fibers, amorphous matrix) and secondarily through hyperplasia of cuboidal bronchiolar cells.


Tailoring adipose stem cell trophic factor production with differentiation medium components to regenerate chondral defects.
Recent endeavors to use stem cells as trophic factor production sources have the potential to translate into viable therapies for damaged or diseased musculoskeletal tissues. Adipose stem cells (ASCs) can be differentiated into chondrocytes using the chondrogenic medium (CM), but it is unknown if this approach can optimize ASC growth factor secretion for cartilage regeneration by increasing the chondrogenic factor production, while decreasing angiogenic and hypertrophic factor production. The objective of this study was to determine the effects the CM and its components have on growth factor production from ASCs to promote cartilage regeneration. ASCs isolated from male Sprague-Dawley rats and cultured in monolayer or alginate microbeads were treated with either the growth medium (GM) or the CM for 5 days. In subsequent studies, ASC monolayers were treated with either the GM supplemented with different combinations of 50 μg/mL ascorbic acid-2-phosphate (AA2P), 100 nM dexamethasone (Dex), 10 ng/mL transforming growth factor (TGF)-β1, and 100 ng/mL bone morphogenetic protein (BMP)-6 or with the CM excluding different combinations of AA2P, Dex, TGF-β1, and BMP-6. mRNA levels and growth factor production were quantified at 8 and 24 h after the last media change, respectively. The CM increased chondrogenic factor secretion (TGF-β2, TGF-β3, and insulin-like growth factor [IGF]-I) and decreased angiogenic factor production (the vascular endothelial growth factor [VEGF]-A, the fibroblast growth factor [FGF]-2). Microencapsulation in the GM increased production of the chondrogenic (IGF-I, TGF-β2) and angiogenic (VEGF-A) factors. AA2P increased secretion of chondrogenic factors (IGF-I, TGF-β2), and decreased angiogenic factor (VEGF-A) secretion, in addition to decreasing mRNA levels for factors associated with chondrocyte hypertrophy (FGF-18). Dex increased mRNA levels for hypertrophic factors (BMP-2, FGF-18) and decreased angiogenic factor secretion (VEGF-A). TGF-β1 increased angiogenic factor production (FGF-2, VEGF-A) and decreased chondrogenic factor mRNA levels (IGF-I, PTHrP). BMP-6 increased hypertrophic mRNA levels (FGF-18) and chondrogenic factor production (TGF-β2). When ASC microbeads preconditioned with the CM were implanted in a focal cartilage defect and immobilized within an RGD-conjugated hydrogel, tissue infiltration from the edges of the defect and perichondrium was observed. These results show that differentiation media components have distinct effects on ASC's production of angiogenic, chondrogenic, and hypertrophic factors and that AA2P may be the most beneficial CM component for preconditioning ASCs to stimulate cartilage regeneration.


Preliminary crystallographic analysis of two oligomerization-deficient mutants of the aerolysin toxin, H132D and H132N, in their proteolyzed forms.
Aerolysin is a major virulence factor produced by the Gram-negative bacterium Aeromonas hydrophila and is a member of the β-pore-forming toxin family. Two oligomerization-deficient aerolysin mutants, H132D and H132N, have been overproduced, proteolyzed by trypsin digestion and purified. Crystals were grown from the proteolyzed forms and diffraction data were collected for the two mutants to 2.1 and 2.3 Å resolution, respectively. The prism-shaped crystals belonged to space group C2. The crystal structure of the mutants in the mature, but not heptameric, aerolysin form will provide insight into the intermediate states in the oligomerization process of a pore-forming toxin.


The relationship between inpatient cardiac surgery mortality and nurse numbers and educational level: analysis of administrative data.
In most multicenter studies that examine the relationship between nurse staffing and patient safety, nurse-staffing levels are measured per hospital. This can obscure relationships between staffing and outcomes at the unit level and lead to invalid inferences. In the present study, we examined the association between nurse-staffing levels in nursing units that treat postoperative cardiac surgery patients and the in-hospital mortality of these patients. DESIGN-SETTING-PARTICIPANTS: We illustrated our approach by using administrative databases (Year 2003) representing all Belgian cardiac centers (n=28), which included data from 58 intensive care and 75 general nursing units and 9054 patients. We used multilevel logistic regression models and controlled for differences in patient characteristics, nursing care intensity, and cardiac procedural volume. Increased nurse staffing in postoperative general nursing units was significantly associated with decreased mortality. Nurse staffing in postoperative intensive care units was not significantly associated with in-hospital mortality possibly due to lack of variation in ICU staffing across hospitals. This study, together with the international body of evidence, suggests that nurse staffing is one of several variables influencing patient safety. These findings further suggest the need to study the impact of nurse-staffing levels on in-hospital mortality using nursing-unit-level specific data.


Neuroprotective effects of melanocortins in CNS injury.
New compounds having affinity to various melanocortin receptors have recently been identified as possible neuroprotective agents. This review is focused on the role of neuroprotective effects of melanocortins in CNS injury and repair mechanisms. Using selective non-peptidic compounds with varying affinity to melanocortin receptors, our laboratory has shown their anti-edematous effects in the spinal cord injury. This effect of the compounds is related with their ability to attenuate blood-spinal cord barrier permeability. The functional significance and possible therapeutic strategies of these compounds in CNS injury are discussed.


Microplastics in sediments of the Changjiang Estuary, China.
Microplastics are plastics that measure less than 5 mm in diameter. They enter the marine environment as primary sources directly from industrial uses, as well as secondary sources resulting from the degradation of large plastic debris. To improve the knowledge of microplastic pollution in China, we investigated samples from 53 estuarine sediment locations collected with a box corer within the Changjiang Estuary. Microplastics (<5 mm) were extracted from sediments by density separation, after which they were observed under a microscope and categorized according to shape, color and size. Identification was carried out using Micro-Fourier-Transform Infrared Spectroscopy (μ-FT-IR). The abundance of microplastics in the Changjiang Estuary was mapped. The mean concentration was 121 ± 9 items per kg of dry weight, varying from 20 to 340 items per kg of dry weight. It was found that the concentration of microplastics was the highest on the southeast coast of Shanghai. The distribution pattern of microplastics may be affected by the Changjiang diluted water in summer. All of the microplastics collected were categorized according to shape, color and size. Among which fiber (93%), transparent (42%) and small microplastics (<1 mm) (58%) were the most abundant types. No clear correlation between microplastics and the finer sediment fraction was found. Rayon, polyester, and acrylic were the most abundant types of microplastics identified, indicating that the main source of microplastics in the Changjiang Estuary was from washing clothes (the primary source). It is possible to compare microplastic abundance in this study with the results of other related studies using the same quantification method. The identification of microplastics raises the awareness of microplastic pollution from drainage systems. The prevalence of microplastic pollution calls for monitoring microplastics at a national scale on a regular basis.


Fluid intake during wheelchair exercise in the heat: effects of localized cooling garments.
Wheelchair tennis players, competing in hot and humid environments, are faced with an increased risk of heat-related illness and impaired performance. This study examined the effects of head and neck cooling garments on perceptions of exertion (RPE), thermal sensation (TS), and water consumption during wheelchair exercise at 30.4 +/- 0.6 degrees C. Eight highly trained wheelchair tennis players (1 amputee and 7 spinal cord injured) completed two 60-min, intermittent sprint trials; once with cooling (COOL) and once without cooling (CON) in a balanced cross-over design. Players could drink water ad libitum at five predetermined intervals during each trial. Heart rate, blood lactate concentration, peak speed, TS, and RPE were recorded during the trials. Body mass and water consumption were measured before and after each trial. Water consumption was lower in COOL compared with CON (700 +/- 393 mL vs. 1198 +/- 675 mL respectively; P = 0.042). Trends in data suggested lower RPE and TS under COOL conditions (N.S.). Total sweat losses ranged from 200 to 1300 mL; this equated to approximately 1% dehydration after water consumption had been accounted for when averaged across all trials. The ad libitum drinking volumes matched and, in some cases, were greater than the total sweat losses. These results suggest that there is a counterproductive effect of head and neck cooling garments on water consumption. However, despite consuming volumes of water at least equivalent to total sweat loss, changes in body mass suggest an incidence of mild dehydration during wheelchair tennis in the heat.


Investigation of regulation and mechanism of miR-223 on autophagy of CD4 + T lymphocytes in septic mice.
T-lymphocyte dysfunction is most important part of immune dysfunction in sepsis, where dynamic change, especially autophagy of CD4+T lymphocytes is found to be related to disease fate. Our study is to i nvestigate the changes of CD4 + T lymphocytes and their autophagy levels in septic miR-223 -/- mouse model injected intraperitoneally with E. coli.120 male C57BL/6J wild-type. Twenty male miR-223 knockout(miR-223-/-) mice were randomly divided into, according to intraperitoneal injection of normal saline (NS) and E. coli solution, normal saline (WT NS) group, sepsis (WT Sep) group, miR-223 -/- NS group and miR-223 -/- Sep group, respectively. The autophagy related protein was monitored with flow cytometry to observe the autophagy of CD4+T lymphocytes. Flow cytometry showed the proportion of CD4 + T lymphocytes in peripheral blood circulation, alveoli, and spleen of mice in the WT Sep group gradually decreased after surgery, the proportion of cells with autophagic activity in this population of cells was significantly higher than that in the WT NS group, and the proportion of CD4 + T lymphocytes with active autophagic activity in miR-223 -/- mice were significantly decreased, but higher than that in the miR-223 -/- NS group and lower than the level of autophagy in CD4 + T cells of wild-type mice. Thus, miR-223 can up-regulate the level of autophagy in CD4 + T lymphocytes of septic mice, suggesting that miR-223 may be used as a potential target for the prevention and treatment of sepsis.


Intervention models for the management of children with signs of pneumonia or malaria by community health workers.
A systematic review was conducted to categorize and describe Intervention Models involving community health workers (CHWs) that aim to improve case management of sick children at the household and community levels. The review focused on management of children with signs of malaria or pneumonia. Seven Intervention Models were identified, and classified according to: (1) the role of CHWs and families in assessment and treatment of children, (2) system of referral to the nearest health facility (verbal or facilitated), and (3) the location in the community of the drug stock. Standardization of terminology for Intervention Models using this or a similar classification could facilitate comparison and selection of models, including deciding how to modify programmes when policies change concerning first-line drugs, and setting priorities for further research. Of the seven models, that of CHW pneumonia case management (Model 6) has the strongest evidence for an impact on mortality. Pneumonia case management by CHWs is a child health intervention that warrants considerably more attention, particularly in Africa and South Asia.


Outcome measures in burn care. Is mortality dead?
Health care systems constantly struggle with ways to provide higher quality care in a cost-effective manner. Outcome measures serve to evaluate what works and what does not. Whether they are used for research or for the improvement of clinical practice, they are as such, efficiency markers and the first step in determining the consequences of health care. The accomplishments of the past decade have placed us in the midst of an exciting paradigm shift from what used to be primary concern (i.e. mortality), to areas that are more likely to enhance the quality of life of burn survivors. Optimal management of severely burned persons is enormously expensive, and even after survival is ensured, may require a protracted period of surgical, medical and psychological rehabilitative measures for many years. This article aims to review the outcome measures in the acute phase of burn management (mortality and morbidity from the post-burn hypermetabolic response). We further discuss long-term outcome measures (such as, quality of life measures, exercise tolerance and evaluation of return to pre-burn activities) that are now becoming of equal importance as the numbers of burn survivors increase.


Discrimination in waiting times by insurance type and financial soundness of German acute care hospitals.
This paper shows that patients with private health insurance (PHI) are being offered significantly shorter waiting times than patients with statutory health insurance (SHI) in German acute hospital care. This behavior may be driven by the higher expected profitability of PHI relative to SHI holders. Further, we find that hospitals offering private insurees shorter waiting times when compared with SHI holders have a significantly better financial performance than those abstaining from or with less discrimination.


Serum magnesium level and vascular stiffness in children with chronic kidney disease on regular hemodialysis.
Chronic kidney disease (CKD) patients have a high prevalence of vascular calcifications, and cardiovascular disease is the leading cause of death in this population. Magnesium (Mg) depletion may be the missing link between multiple cardiovascular risk factors and the development of atherosclerosis. In this study, we aimed to assess the relationship between serum Mg levels and vascular stiffness in children with CKD on regular hemodialysis (HD). The study included 25 children with CKD on regular HD in our center; the study included also 25 healthy children age-and sex-matched as a control group. Serum Mg levels were measured, and Doppler ultrasound assessment of the intima-media thickness (IMT) and the peak systolic velocities (PSVs) of the main arteries including the (aorta, carotid, and femoral) arteries were recorded in the study patients. There were significantly lower serum Mg levels in children on regular HD than in the controls (1.7 ± 0.43 mg/dL vs. 2.31 ± 0.12 mg/dL, respectively, P = 0.001). There was a significant increase in the aorta and carotid IMT in the study group than in the controls (0.45 ± 0.07 mm vs. 0.40 ± 0.09 mm; 0.98 ± 0.57 mm vs. 0.55 ± 0.1 mm, P = 0.034 and 0.001, respectively), whereas there were no significant differences regarding the PSV of the carotid, aorta, and femoral arteries between the study patients and the controls (P >0.05). A negative correlation was found between serum Mg level with aortic IMT (AIMT) (r = -0.682; P = 0.000). In addition, a significant negative correlation was found between the AIMT with systolic and diastolic blood pressure (r = 0.447, P = 0.025, 0.472, P = 0.017), respectively. We conclude that lower serum Mg levels were associated with vascular calcification in chronic HD children. Confirmation of our results warrants further study.


Tomographic PIV in a model of the left ventricle: 3D flow past biological and mechanical heart valves.
Left ventricular flow is intrinsically complex, three-dimensional and unsteady. Its features are susceptible to cardiovascular pathology and treatment, in particular to surgical interventions involving the valves (mitral valve replacement). To improve our understanding of intraventricular fluid mechanics and the impact of various types of prosthetic valves thereon, we have developed a custom-designed versatile left ventricular phantom with anatomically realistic moving left ventricular membrane. A biological, a tilting disc and a bileaflet valve (in two different orientations) were mounted in the mitral position and tested under the same settings. To investigate 3D flow within the phantom, a four-view tomographic particle image velocimetry setup has been implemented. The results compare side-by-side the evolution of the 3D flow topology, vortical structures and kinetic energy in the left ventricle domain during the cardiac cycle. Except for the tilting disc valve, all tested prosthetic valves induced a crossed flow path, where the outflow crosses the inflow path, passing under the mitral valve. The biological valve shows a strong jet with a peak velocity about twice as high compared to all mechanical heart valves, which makes it easier to penetrate deeply into the cavity. Accordingly, the peak kinetic energy in the left ventricle in case of the biological valve is about four times higher than the mechanical heart valves. We conclude that the tomographic particle imaging velocimetry setup provides a useful ground truth measurement of flow features and allows a comparison of the effects of different valve types on left ventricular flow patterns.


Phosphorylation of threonine in the proline-rich carboxy-terminal region of simian virus 40 large T antigen.
The position of phosphothreonine in the predicted primary structure of simian virus 40 large T antigen was determined by different methods. After digestion of large T antigen with trypsin and subsequent two-dimensional peptide mapping, a single peptide containing phosphothreonine could be separated from the bulk of phosphoserine-containing peptides. Its amino acid composition was determined by differential labeling with various amino acids in vivo. The high yield of proline (4.5 mol) within the phosphothreonine peptide indicated that it was derived from the carboxy terminus of large T antigen and had in its unphosphorylated form the sequence Lys-Pro-Pro-Thr-Pro-Pro-Pro-Glu-Pro-Glu-Thr-COOH. A phosphopeptide generated by chymotrypsin could be converted into the tryptic phosphothreonine peptide, indicating that the latter was part of the chymotryptic peptide. The origin of the phosphothreonine-containing peptides was independently confirmed by using an antiserum directed against the carboxy terminus of large T antigen. This serum reacted specifically with the proline-rich, phosphothreonine-containing peptides. Further analysis by partial acid hydrolysis indicated that the internal threonine was phosphorylated. The unusual amino acid composition on both sides of the phosphothreonine and the possible function of this phosphorylation site are discussed.


Sexually transmitted infections among married women in Dhaka, Bangladesh: unexpected high prevalence of herpes simplex type 2 infection.
To document the prevalence of reproductive tract infections (RTI) and sexually transmitted infections (STI) among women attending a basic healthcare clinic in Dhaka, Bangladesh, to identify risk factors associated with the diseases and to estimate the incidence of syphilis, hepatitis C (HCV), hepatitis B (HBV), and herpes simplex type 2 (HSV-2) infection. A cross sectional sample of 2335 consecutive women was examined during 1996-8. Women were interviewed about risk factors for RTI/STI and tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, HIV, HCV, HBV, HSV-1 and HSV-2 infection as well as vaginal candidosis and bacterial vaginosis. Women with antibodies to T pallidum were retested at regular intervals. One year after ending the study seroconversion for syphilis, HBV, HCV, and HSV-2 infection was detected among women initially negative for the respective diseases. The overall prevalence rate of N gonorrhoeae, C trachomatis, T vaginalis, and T pallidum infection was 0.5%, 1.9%, 2.0%, and 2.9% respectively. Overall, 35% of the women had antibodies to hepatitis B core antigen, 0.9% had HCV, and 12% HSV-2 infection. Risk factors for gonorrhoea/C trachomatis infection were a husband not living at home or suspected of being unfaithful. HSV-2 infection was associated with the same risk factors and with a polygamous marriage. The prevalence of HSV-2 infection among women "at risk" was 23%. HIV infection was not diagnosed. Repeated serological examination indicated that only 32% of women with serological evidence of syphilis had active disease. The seroincidences of HBV, HCV, and HSV-2 were 0.03, 0.007, and 0.009 per person year. Seroconversion for syphilis was not observed.


Molecular characterization and functional analysis of sheep thyroid transcription factor-1.
Thyroid transcription factor-1 (TTF-1), a member of the Nkx2 family of homeodomain-containing proteins, is involved in binding to and in activating the promoters of several important genes in the thyroid, lungs, and brain, and in regulating expression of these tissue-specific genes. We investigated potential roles of sheep (Ovis aries) TTF-1 in regulating cell fate and organ morphogenesis and in controlling puberty and reproductive capability of females. We amplified and cloned the sheep TTF-1 full-length DNA for the first time, analyzed its functional domains and regions, predicted molecular structure of its homeodomain and DNA-binding sites, and examined its expression in pituitary, brain, thyroid gland, ovary, and hypothalamus. We found that sheep TTF-1 has a high degree of homologous identity with that of other mammals, and it has several important domains including domain N, DNA-binding domain, domain C, TN-domain, domain I, and NK2-SD. The DNA-binding domain of sheep TTF-1 has 10 potential DNA-binding sites and is a novel mammalian homeodomain that shows considerable sequence homology with the corresponding rat homeodomain. Several functional regions in sheep TTF-1 share high sequence identity with rat TTF-1, indicating that these regions may have the same activity as in the rat. Expression of TTF-1 in several specific tissues implies that sheep TTF-1 in involved in sheep sexual development and reproductive capability. These results suggest a role of sheep TTF-1 in enhancing sheep reproduction performance and we propose it as a candidate gene for selection.


Progression of age-related macular degeneration: prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular biomarkers.
Age-related macular degeneration (AMD) and cardiovascular disease share common risk factors. Inflammatory biomarkers, including C-reactive protein (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor alpha receptor 2, soluble intercellular and vascular adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and lipid biomarkers, including lipoprotein(a) and apolipoprotein B, have all been associated with cardiovascular disease. We previously found an association between AMD and CRP in a cross-sectional analysis, but the prospective relationships between AMD, CRP, and the other cardiovascular disease markers are unknown. To test the hypothesis that baseline cardiovascular disease biomarkers are associated with subsequent increased risk for progression of AMD. This prospective cohort study involved 251 participants aged 60 years and older who had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least one eye at baseline. The AMD status was assessed by standardized grading of fundus photographs, and stored fasting blood specimens obtained at baseline were analyzed for levels of the various biomarkers. The average follow-up time was 4.6 years. Relationship between biomarkers and incidence rates of progression of AMD. Comparing the highest quartile with the lowest quartile, CRP was associated with progression of AMD, with a multivariate adjusted relative risk (RR) of 2.10 (95% confidence interval [CI], 1.06-4.18; P for trend, .046) controlling for body mass index, smoking, and other cardiovascular variables and a multivariate adjusted RR of 2.02 (95% CI, 1.00-4.04; P for trend, .06) controlling additionally for antioxidant nutrients. Interleukin 6 was also related to progression of AMD, with a multivariate adjusted RR of 1.81 (95% CI, 0.97-3.36; P for trend, .03). Comparing the highest quartile with the lowest quartile, the effect estimates for vascular cell adhesion molecule 1 (multivariate adjusted RR, 1.94) and apolipoprotein B (adjusted RR, 1.39) were in the positive direction but were not statistically significant (P for trend, .08 and .24, respectively). The CRP and IL-6 levels were both significantly related to higher body mass index and current smoking. Higher levels of the systemic inflammatory markers CRP and IL-6 are independently associated with progression of AMD.


Risks of hazardous waste sites versus asteroid and comet impacts: accounting for the discrepancies in U.S. resource allocation.
Approximately $6 billion is spent annually in the United States on the cleanup of sites regulated under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA, or Superfund). The current health risks posed by such sites are thought to be quite small; the expenditures are justified primarily as protecting hypothetical future residents of these sites. Approximately 0.05% of this amount, or $3 million, is spent annually by the U.S. government on the detection of asteroids or comets that could strike the earth. Such damaging impacts do occur from time to time--most recently in 1908 in an unpopulated region of Siberia--but no person is confirmed ever to have died as a result. Anticipated impacts over the course of 1 million years would yield deaths that, when annualized, total approximately 4,000 per year. The risk reduction goal for CERCLA is 15 orders of magnitude greater than that for asteroid/comet detection. A modest increase in resources devoted to asteroid detection would greatly increase the chances of early detection of a threatening object, allowing an effective defense to be attempted. This article argues that the much lower risk-to-resources ratio for CERCLA cleanups than for asteroid and comet detection can be explained by four primary factors: (1) the regard for future generations, since CERCLA benefits mainly the unborn; (2) concrete fears, since toxics are much more feared than asteroids or comets; (3) the source of the threat, since toxic contamination is caused by human beings, unlike impacts from space objects; and (4) the greater political constituencies for hazardous waste cleanup than for space object detection.